MEDICINAL FORM FOR EYES IN CONDITIONS OF PHARMACY PRODUCTION. EYE DROPS, OPHTHALMIC SOLUTIONS. REQUIREMENTS. TECHNOLOGICAL SCHEME FOR PRODUCING EYE DROPS. EYE OILS. BASES FOR EYE OILS. FEATURES OF EYE OILS TECHNOLOGY. IMPROVEMENT OF OPHTHALMIC FORMS. PREPARED: STUDENT 4 COURSES OF GROUP 10 MOHAMMAD NARGIS CHECKED: Pozdnyakova T. A.
THE BASIC DEFICIENCY OF EYE DROPS IS THE MAJOR DEFICIENCY OF EYE DROPS IS A LOW BIOACCESSIBILITY OF MEDICINES AS A RESULT OF A COMPLEX MEMBRANISM OF SORROWS (SLEEP) ESTABLISHED THAT ONLY ONE TEN DOSE OF A MEDICINE DOSES INTO THE EYE. THEREFORE, THE EMPLOYEE OF A PHARMACY INSTITUTION IS OBLIGED TO INFORM THE PATIENT HOW TO APPLY EYE DROPS CORRECTLY.
GF REQUIREMENTS FOR EYE DROPS EYE DROPS MUST: - BE PREPARED UNDER ASEptic CONDITIONS AND BE STERILE; - SUPPORT TEST ON MECHANICAL INCLUSIONS; - TO BE COMFORTABLE AT RECEPTION (ISOTONIC, ISOHYDRIC WITH TARPLE LIQUID); - BE STABLE UNDER FREQUENCY OPEN PACKAGING. FOR STABILIZATION OF PHYSICAL - CHEMICAL, MICROBIOLOGICAL AND RHEOLOGICAL PROPERTIES AUXILIARY SUBSTANCES ARE INCLUDED IN THE COMPOSITION OF THE DROP: CONSERVANTS, ANTI-OXIDIZERS, THICKENERS, STABILIZER. Order of MOH 214 established: the concentration and volume (or mass) of isotonic and stabilizing substances added to eye drops should be indicated not only in passports, but also on recipes.
THE TECHNOLOGY OF MANUFACTURE OF EYE DROPS DRAWING PRODUCTION AND QUALITY CONTROL OF STERILE SOLUTIONS IN PHARMACIES ARE PERFORMED IN ACCORDANCE WITH THE REQUIREMENTS OF THE OPERATING GF, METHODOLOGICAL INSTRUCTIONS FOR COOKING. STERILITY ACCORDING TO THE GF, STERILITY IS A NECESSARY REQUIREMENT FOR ALL EYE DOSAGE FORMS. STERILITY - NO VIABLE MICROBIAL CONTAMINATION. EXCHANGEED PREPARATIONS MAY CAUSE EYE INFECTION, WHICH MAY RESULT IN VISION LOSS. EYE DOSAGE FORMS ARE PREPARED IN ASEPTIC CONDITIONS IN SIMILAR TO AN INJECTIONAL SOLUTIONS. FOR PREPARING EYE DROPS USE STERILE SOLVENTS: CLEANED WATER, ISOTONIC BUFFER SOLUTIONS, OILS AND OTHERS. STERILE SOLUTIONS ARE PACKED IN STERILE BOTTLES. EYE DROPS MUST BE STERILE. METHOD FOR EYE DROPTER STERILIZATION DEPENDS ON THE STABILITY OF MEDICINES IN SOLUTIONS TO TEMPERATURE EFFECTS AND IS DETERMINED BY ORDER MZ 214 FROM G. (SIMILAR INJECTION).
BY THE STERILIZATION MODE ESTABLISHED BY ORDER M З 214, EYE DROPS CAN BE SEPARATED IN 3 GROUPS: 1. Drops without the addition of stabilizers, sterilized with steam at a pressure of 1.1 atm and 120 ° C for 8-12 minutes or fluid steam for 30 minutes. - -This method sterilizes solutions of atropine sulfate, boric acid, dicain, potassium iodide, calcium chloride, sodium chloride, nicotinic acid, pilocarpine hydrochloride, proserin, riboflavin, sulfapyridazine sodium, furacilin, zinc sulfate, ephedrine hydrochloride, as well as eye drops containing riboflavin in combination with ascorbic acid and glucose, etc. 2. Drops with the addition of stabilizers that can be sterilized with steam under pressure or with flowing steam (see the appendix to the order of the Ministry of Health of the Russian Federation 214). 3. Drops containing thermolabile substances that cannot be sterilized by thermal methods. Sterilizing filtration is carried out through 0.22 μm membranes. The following solutions are made using this technology: benzylpenicillin, streptomycin sulfate, collargol, protargol, resorcinol, adrenaline hydrochloride, citral, etc. Sterility testing eye dropsmanufactured in pharmacies is assigned to the district centers for sanitary and epidemiological surveillance (TsGSEN).
EYE DROPS SHOULD KEEP STERILE UNDER FREQUENCY OPEN PACKAGING. EYE DROPS INDEPENDENT ON THE CONDITIONS OF STERILIZATION MAY BE CONTAMINATED BY MICRO-ORGANISMS IN THE PROCESS OF USE (REPEATED APPLICATION FROM ONE Vial). TO PREVENT MICROBIAL POLLUTION OF EYE DROPS IN THE APPLICATION PROCESS, IT IS PROPOSED TO ADD TO THE COMPOSITION OF THE FOLLOWING PRESERVATIVES: CHLOROBUTANOL HYDRATE (0.5%), BENZYL ALCOHOL (0.9%) SULPHANOUS Quaternary Ammonium Bases (Benzalkonium Chloride, 0.01%), Sorbic Acid (0.05-0.2%), etc.
PRESERVATIVES DO NOT PRODUCE STERILIZING EFFECTS. INTRODUCTION OF PRESERVATIVES DOES NOT GUARANTEE STERILITY, BUT SUPPORTS A STABLE LEVEL OF MICROBIAL CONTAMINATION UNDER THE CONDITIONS OF FREQUENCY OPEN PACKAGING. Regardless of the presence of preservatives in patients, patients should be advised to seal the vial after use and boil the pipettes.
ENSURING THE LACK OF MECHANICAL INCLUSIONS WHEN MANUFACTURING THE INTERNAL PHARMACEUTICAL PREPARATION APPLY EQUIPMENT FOR FILTRATION OF INJECTION SOLUTIONS. IN CASE OF PRODUCTION OF SMALL VOLUMES (10-30 ML) USE PRELIMINARY WET AND WASHED PAPER FILTER. FILTRATION IS PREPARED IN A PRELIMINALLY RINSED FILTERED WATER BOTTLE. IN THE PROCESS OF MANUFACTURE, SOLUTIONS ARE PRIMARY AND SECONDARY CONTROL FOR LACK OF MECHANICAL INCLUSIONS, ACCORDING TO THE INSTRUCTIONS OF THE ORDER OF THE MZ OF THE RUSSIAN FEDERATION 214. THE PRIMARY CONTROL IS CARRIED OUT. AT THIS EACH BOTTLE WITH SOLUTION IS VIEWED. IF MECHANICAL INCLUSIONS ARE DETECTED, THE SOLUTION IS FILTERED AGAIN, REVIEWED, CUPS, LABELED AND STERILIZED. SECONDARY CONTROLS ARE ALSO SUBJECT TO 100% BOTTLES WITH SOLUTIONS THAT HAVE PASSED TO THE STERILIZATION STAGE BEFORE THEIR DESIGNING AND PACKING. CHECKING THE QUALITY OF THE INTERNAL PHARMACEUTICAL PREPARATION IS CARRIED OUT BY THE VIEW OF 30 BOTTLES FOR THE ABSENCE OF MECHANICAL INCLUSIONS. CONTROL TIME ACCORDINGLY TO: FROM 2 TO 5 BOTTLES WITH A CAPACITY OF 5-50 ML S.
MAKING THE ACCURACY OF DOSING OF MEDICINES ON THE ACCURACY OF THE CONCENTRATION OF MEDICINES IN EYE DROPS IS INFLUENCED BY THE ACCURACY OF WEIGHTING THE SUBSTANCE, ESPECIALLY WHEN ITS AMOUNT IS MORE THAN 0.05. REQUIREMENTS FOR MANUFACTURE, PACKAGING, CAPPING AND STORAGE OF CONCENTRATED SOLUTIONS ARE SIMILAR TO REQUIREMENTS FOR EYE DROPS. TO PRODUCE EYE DROPS, USE: 0.02% RIBOFLAVIN SOLUTION, 4% BORIC ACID SOLUTION, 2% SULFATE ZINC SOLUTION, 2, 10% ASKORBINIC ACID OR COMBINED SOLUTIONS 2 MORTAR SOLUTIONS. LIST OF CONCENTRATES AND THE TERMS OF THEIR STORAGE ARE SPECIFIED IN ORDER M З 214.
ENSURING COMFORT COMFORTABLE APPLICATION OF EYE DROPS - ONE OF THE BIOPHARMACEUTICAL FACTORS DETERMINING THE ABSENCE OF AN UNFAMILIARY SENSITIVES DURING INSTALLATION OF THE MEDICINAL PRODUCT. Is achieved by isotonizing the eye drops or by adjusting the pH to the pH of the tear fluid. ISOTONING IS CARRIED OUT BY INTRODUCING IN THE COMPOSITION OF THE SOLUTION OF THE CALCULATED NUMBER OF SODIUM CHLORIDE (see. INFUSION SOLUTIONS). It was shown that the eye drops do not cause unpleasant sensations, if their osmotic pressure corresponds to the osmotic pressure of sodium chloride in a concentration of 0.7 to 1.1% of the solution. APPLICATION OF SOLUTIONS WITH A VALUE OF OSMOTIC PRESSURE EXCEEDING THE SPECIFIED LIMITS RESULTS IN A MURNING AND IRRITATED Mucosa OF THE EYE
REGULATION OF PH ON THE COMFORT OF EYE DROPS A BIG INFLUENCE HAS A VALUE OF PH. THE AVERAGE VALUE OF PH OF THE TRIMAL LIQUID - 7.4. RELATIVELY COMFORTABLE IN THE APPLICATION OF THE DROPS HAVING A PH FROM 4.5 TO 9.0 TO REGULATE THE VALUE OF THE PH OF THE EYE DROPS, USE SODIUM HYDROCARBONATE AND BORNIC ACID. PREFERREDLY, AS A SOLVENT, USE BUFFER SOLUTIONS: BORNO ACETIC AND PHOSPHATE APPLICATION OF ACID CHLORISTO - HYDROGEN OR ALKALINE IS IMPOSSIBLE, IF USE.
PH LEVELS INFLUENCE ON THE SOLUBILITY OF MEDICINES. TO PREVENT HYDROLYSIS AND TRANSITION OF SALTS TO THE BASIS, PH OPHTHALMIC SOLUTIONS MUST BE ADJUSTED. SOME MEDICINES MAY BE SUBJECT TO OXIDATIVE DESTRUCTION. TO PREVENT THIS IN THE COMPOSITION OF OPHTHALMIC SOLUTIONS, ANTioxIDANTS AND ANTI-CATALYSTS ARE INTRODUCED. AT THIS SHOULD BE CONSIDERED THAT THE INTRODUCTION OF LOW VALENCY SULFUR DERIVATIVES MAY RESULT IN ALLERGIC REACTIONS, ESPECIALLY IN CHILDREN.
STABILIZATION OF SODIUM SULFACIL SOLUTIONS BY REGULATING PH AND ADMINISTRATION OF ANTIOXIDANTS 30% solution of sulfacyl - sodium according to the recipe for factory manufacture 10; 20; 30% solution of sulfacyl - sodium, including 10 and 20% - for newborns, according to the pharmacy prescription Sulfacil - sodium g Sodium metabisulfite - 5 g Caustic soda solution - 1 g to pH 7.7-8.0 Water for injection - up to 1 l Packing: bottles for running-in Sterilization conditions: temperature 100? C - 30 min. Shelf life - 26 months. Sulfacyl - sodium g, 200 g, 300 g. Sodium thiosulfate - 1.5 g, 1.5 g, 1.5 g. 1 M hydrochloric acid solution: 3.5 ml; 3.5 ml; 3.5 ml of purified water - up to 1 liter. The pH of the solution is 7.5-8.5. Packaging: bottles for running in. Sterilization conditions: temperature 120? C - 8 min. Shelf life - 1 month. Feature: Reducing the irritating effect of alkali and sodium metabisulfite on the mucous membrane of the eye.
PROVIDING PROLONGING OF ACTION THE FIRST WAY OF PROLONGING IS THE INCLUSION OF VISCOUS SOLVENTS IN THE COMPOSITION OF EYE DROPS, WHICH Slow down the QUICK RINSING OF MEDICINES FROM KONJEN. AS LIKE EYE DROP COMPONENTS USE OIL (REFINED SUNFLOWER, PEACH OR APRICOT, FISH FAT). The second way to prolong the action of eye drops is to increase the viscosity of the solutions by introducing synthetic thickeners. NATURAL THICKENERS REDUCE THE MICROBIOLOGICAL STABILITY OF THE PRODUCT, SO DO NOT APPLY.
TARE AND PACKAGING FOR PACKING OF OPHTHALMIC SOLUTIONS Caps aluminum K-l (TU). They are made of aluminum foil with a thickness of 0.2 mm. Bottles - droppers from polyethylene and glass.
TECHNOLOGICAL SCHEME FOR PRODUCING EYE DROPS AND SOLUTIONS FOR NEW DISHES OUTDOOR AND INSIDE WASHED WITH WATER WATER, SOAKED FOR MIN IN WASHING SOLUTIONS, HEATED UP TO? C. MUST BEAR ALSO USED 1: 20, 0.25% DESMOL SOLUTION, 0.5% PROGRESS, LOTOS, ASTRA SOLUTIONS, 1% SP M C SOLUTION (SULFANOL MIXTURE WITH SODIUM TRIPOLIFOIS: 10). FOR SEVERE CONTAMINATION, DISHES FOR 2–3 HOURS SOAK IN 5% SUSPENSION OF THE MUSTARD OR THE SOLUTION OF THE WASHING PRODUCTS IN ACCORDANCE WITH THE SPECIAL INSTRUCTIONS. Washed dishes sterilized with hot air at 260? WITH 60 MIN. TABLEWARE USED DEFINITELY 1% SOLUTION
Adaptations POK-1 of activated chloramine - 30 min; 3% freshly prepared hydrogen peroxide solution with the addition of 0.5% detergents - 80 minutes or 0.5% Desmol solution - 80 minutes. Purified water is used freshly prepared and sterilized in the appropriate mode.
FOR CAPPING OF BOTTLES USE PLUGS OF SPECIAL RUBBER VARIETIES: IR -21 (SILICONE), IR -119, IR -119 A (BUTYL RUBBER). NEW RUBBER TUBES ARE PROCESSED FOR THE REMOVAL OF SULFUR, ZINC AND OTHER SUBSTANCES FROM THEIR SURFACE ACCORDING TO THE INSTRUCTIONS. CONSUMPTIONS USED, RINSED WITH PURIFIED WATER AND BOILED IN IT 2 TIMES FOR 20 MIN, STERILIZED WITH? WITH 45 MIN. SOLUTION VALVES CAPPED WITH RUBBER CONNECTORS CONTROL FOR ABSENCE OF MECHANICAL INCLUSIONS. IF THE MECHANICAL INCLUSIONS ARE DETECTED, IN THE PRIMARY CONTROL OF THE SOLUTION, IT IS REFILTERED. AFTER PRODUCTION, THE SOLUTIONS ARE SUBJECTED TO CHEMICAL ANALYSIS CONCLUDING IN THE DETERMINATION OF AUTHENTICITY (QUALITATIVE ANALYSIS) AND THE QUANTITATIVE CONTENT OF MEDICINES INCLUDING THE COMPOSITION OF THE COMPOSITION. FOR POSITIVE RESULTS, WRAP INTO METAL CAPS. SOLUTION VALVES WITH SOLUTIONS LABEL ON THE ALUMINUM CAP, INDICATING THE NAME, SERIES NUMBER. LABELED Vials are placed in an autoclave and sterilized in accordance with the instructions of the Global Fund, taking into account the volume of solution in the vessel. AFTER STERILIZATION, THE SOLUTIONS ARE ANALYZED FOR THE CONTENT OF MECHANICAL INCLUSIONS BY ORDER 308. DEFINED BOTTLES ARE NOT SUBJECT TO PROCESSING. DEFINED BOTTLES SEND FOR A FULL ANALYSIS IN ACCORDANCE WITH THE REQUIREMENTS OF THE GF OR FS. TAKE A SAMPLE FOR ANALYSIS OF STERILITY. IN THE EVENT OF A POSITIVE RESULT, MARK AND PACK IN CROP BOXES.
SO THE TECHNOLOGY OF ophthalmic solution is practically no different from the technology give an injection EXCEPT THAT DUE small volumes of eye drops is often necessary to weighing SUSPENSION list of substances A and B weight of less than 0.05 g, which is forbidden by the requirement Pharmacopoeia. To overcome this obstacle, it is recommended to use concentrated solutions, the composition and technology of which are presented in the order of the Ministry of Health of the Russian Federation 214.
EYE OINTMENTS IN ADDITION TO SOLUTIONS AND THIN SUSPUSIONS, IN THE FORM OF EYE MEDICINAL FORMS, OILS ARE USED BY MORTGAGING FOR EYE. COMPOSITION OF OILS ARE VARIOUS. EYE OILS OF ANTIBIOTICS, SULFANILAMIDES AND OTHERS FREQUENTLY MEET THE PURPOSE OF APPLICATION MAY BE VARIOUS (DISINFECTION, ANESTHESIA, EXTENSION OR CONSTRUCTION OF THE PUPPLE, REDUCING IN-ORGANIC PRESSURE, etc.).
An eye ointments, in addition to general requirements (uniform distribution of the drug substance and the indifferent RESISTANCE BASES), presents a number of additional requirements, which explains how to use them: 1. The ointment base must be free - no foreign impurities, must be neutral, sterile, UNIFORMLY DISTRIBUTE ON THE MURAL EYE. 2. EYE OILS MUST BE PREPARED WITH RESPECT FOR ASEPTIC CONDITIONS. 3. THE SIZE OF PARTICLES OF MEDICINES MUST BE MINIMUM TO PREVENT AN IRRITANT EYE. Grinding to a particle size of less than 10 microns is recommended.
BASES FOR EYE OILS FOR EYE OILS AS A BASIS USE VASELIN WIDELY FROM - FOR THE ABSENCE OF AN IRRITANT PROPERTIES, RESISTANCE AND CHEMICAL INDIFERENCE. BUT VASELIN, IN VIEW OF HYDROPHOBICITY, BADLY MIXES WITH A TRYAL LIQUID, WASHING THE EYE CORNAL, AND AS A BASIS FOR EYE OILS, UNCOMFORTABLE. GF PROVIDES AS THE BASIS OF THE MIXTURE CONSISTING OF 10 PIECES OF LANOLINE Anhydrous and 90 PARTS OF VASELIN (VARIETY FOR EYE OILS). IN THE ABSENCE OF VASELIN OF SUCH VARIETY, A VEGETABLE VASELINE IS CLEANED AS FOLLOWING: VASELIN IS MELTED IN AN ENAMELED VESSEL AND ADD 1-2% OF ACTIVATED CARBON. MIX TEMPERATURE RISE TO 150? C AND CONTINUE HEATING FOR 1- 2 HOURS. HOT VASELIN FILTERED THROUGH PAPER FILTER AND PILLED IN STERILE BANKS. AFTER CHEMICAL ANALYSIS FOR THE ABSENCE OF ORGANIC IMPURITIES AND NEUTRALIZATION OF VASELINS, APPLY AS A BASIS.
EYE OILS PRODUCTION TECHNOLOGY EYE OILS ARE PREPARED AS DermATOLOGIC OILS ARE, BUT ACCEPTING ASEPTIC CONDITIONS. ALL AUXILIARY MATERIALS, OILY BASIS, MEDICINES SUPPORTING HIGH TEMPERATURE, BANKS ARE STERILIZED BY THE METHODS SPECIFIED IN THE GF. An IMPORTANT FACTOR IN THE PRODUCTION OF EYE OILS IS THE ACHIEVEMENT OF THE OPTIMAL DEGREE OF DISPERSION OF INJECTED MEDICINES. THE REQUIRED DISPERSITY OF SUBSTANCES IS REACHED BY PRELIMINARY DISSOLUTION OR CARE OF THEM WITH A LITTLE QUANTITY OF LIQUID, A RELATED BASIS. SUBSTANCES SOLUBLE IN WATER, FOR EXAMPLE, SALTS OF ALKALOIDS, NOVOCAINE, PROTARGOL AND OTHERS, DISSOLVE IN MINIMUM NUMBER OF STERILE WATER, AND THEN MIX WITH OILY BASIC.
Insoluble or hard-soluble substances (XEROFORM, ZIN OXIDE) are included in the composition of eye ointments in the form of minute powders after a thorough dispersion of them with a small amount of sterilegium sulfide. Particular attention is paid to the manufacture of ointments containing substances that can cause burns (zinc sulfate, tarball) and others. They are injected into the eye ointments, only previously dissolved in water, excluding the ingress of crystals on the mucous membrane of the eye.
EXAMPLE RP .: UNGUENTI ZINCI SULFATIS 0.5% - 10.0 D.S. EYE OINTMENT. FOR THE CENTURY OF THE RIGHT EYE 2 TIMES A DAY. Under aseptic conditions, 0.05 g of sulphate zinc is dissolved in sterile mortar in several drops of purified sterile water (in contrast to dermatological ointments, it is very small for carbohydrates). OINTMENT IS TRANSFERRED INTO A STERILIZED GLASS BANK, WHICH ARE CUKED WITH A SPINNED PLASTIC COVER WITH A STERILIZED GASKET, ROOFED WITH PINK ROSE.
When making eye ointments, as well as eye drops, it is advisable to add preservatives, what are the indications in the Global Fund of the latest edition and in pharmacopoeias of foreign countries. FOR THIS PURPOSE, BENZALCONIUM CHLORIDE 1: 1000, MIXTURE OF NIPAGIN AND NIPAZOLE IN THE RELATIONSHIP OF NIPAGIN 0.12% AND NIPAZOLE 0.02%, SORBIC ACID (0.1-0.2%) AND OTHER PRESERVATED RESOURCES ARE PROPOSED.
PACKAGING EYE OINTS ARE RELEASED IN STERILE GLASS OR PORCELAIN JARS WITH TIGHT-CLOSING COVERS. So that during use, the ointment is not contaminated, it is advisable to release it with a sterile spatula, with the help of which the patient should lay the ointment for an eyelid. IT IS RECOMMENDED TO USE EYE PIPES WITH A NARROW TIP, ALLOWING TO INPUT OINTMENT FOR EYE, AND LOW CAPACITY (UP TO 3.5 G OINT). QUALITY CONTROL QUALITY CONTROL IS PERFORMED IN ACCORDANCE WITH THE REQUIREMENTS OF THE PHARMACOPEIA AND ORDERS OF MZ 305 AND 214.
The technological process for the production of eye drops in industrial conditions
Eye drops in the factory are prepared in compliance with all requirements of the factory technology of injection solutions. In the factory, eye drops are prepared in the form of aqueous solutions in water for injection, as well as in the form of oil solutions in sterile fatty oils (peach, almond), liquid paraffin (oil pyrophos solution 0.01% and 0.02%), and in the form of suspensions and emulsions.
Features of industrial production of eye drops
The following features are distinguished:
the use of antioxidants and gas protection for readily oxidizing substances (sodium sulfacyl, ascorbic acid);
the introduction of preservatives: the preservative benzalkonium chloride is part of the eye drops Allergodil / azelastine / 0.05% solution - made in Germany;
Introduction of prolongators (MC - for the preparation of eye drops of pilocarpine hydrochloride, sodium CMC, polyvinyl alcohol - forpreparation of Ophthalmic Ophthalmic Gel - manufactured in Finland);
Improving packaging: dropper tube, dropper bottles.
Eye ointments
Ophthalmic ointments are a dosage form of soft consistency that can form a uniform continuous film when applied to the conjunctiva of the eye. Eye ointments are prescribed for laying the floor of the lower eyelid in the conjunctival sac or for lubricating the skin and edges of the eyelids
Requirements for eye ointments . For eye ointments, in addition to the general requirements for dermatological ointments, a number of additional requirements are made:
The ointment base should not have foreign inclusions and impurities, it should be sterile, neutral and evenly distributed over the mucous membrane of the eye;
Medicinal substances administered by the type of suspension should be crushed to a minimum degree of dispersion in order to avoid damage to the mucous membrane of the eye and the absence of discomfort;
The pH of the ointment should correspond to the pH of the tear fluid in order to avoid lacrimation and leaching medicinal substance.
Eye ointments, like others dosage forms for eyes, prepared under aseptic conditions.
Ointment Foundation
As a basis for ophthalmic ointments, GF XI recommends the use of an alloy of vaseline grade “for eye ointments” (90 parts) and anhydrous lanolin (10 parts) if the ointment is unofficial (the base is lipophilic-hydrophilic, absorption). The mixture is melted, filtered while hot to release mechanical impurities in sterile jars and sterilized by air at 180 ° or 200 ° (the time varies depending on the mass of the base). The basis due to the content of lanolin in it contributes to the fixation of the ointment on the mucous membrane of the eye and a more complete return of medicinal substances. For the preparation of eye ointments, petroleum jelly of the “for eye ointments” variety is used. In its absence, ordinary petrolatum is subjected to special cleaning according to the Weissman method of reducing substances with activated carbon in an amount of 1-2% at a temperature of 150 ° for 1-2 hours with stirring in an air sterilizer. Hot petrolatum is filtered and checked for the absence of reducing substances. Many eye ointments with antibiotics are prepared on the basis of an alloy of anhydrous lanolin with petrolatum in a ratio of 4: 6. Also, gels of macromolecular compounds - hydrophilic bases (methyl cellulose, sodium CMC, sodium alginate, etc.) are proposed as bases for eye ointments. The basics are well distributed over the mucous membrane of the eye, they easily give up medicinal substances, but they undergo microbial contamination. Therefore, preservatives are introduced into their composition: sorbic acid, benzalkonium chloride, etc. The use of polyethylene oxide bases is not recommended because of the sharp difference in osmotic pressure. Emulsion bases such as m / v are not very suitable due to strong blurred vision and the need for stabilization,
Eye ointment technology in conditions pharmacies
Substances in the composition of eye ointments are administered according to the general rules for their introduction into dermatological ointments. Water-soluble medicinal substances (salts of alkaloids, novocaine, etc.) are dissolved in a minimum amount of water, mixed with the base, adding it in parts (ointment-emulsion).
Resorcinol and zinc sulfate, unlike dermatological ointments, are dissolved in water. Insoluble or insoluble drug substances: xeroform, zinc oxide, mercury oxide yellow are introduced into the base in the form of fine powders when dispersed with a liquid, related base (liquid paraffin, glycerin or purified water). Substances soluble in the base are dissolved in it.
Ophthalmic ointment is an ointment of yellow mercury oxide 2% (HF X), which is prepared on the basis of vaseline oil-2 parts (for dispersing a medicinal substance), anhydrous lanolin-16 parts and Vaseline varieties for eye ointments -80 parts. Preparation: yellow mercury oxide is carefully dispersed with an equal amount of sterile liquid paraffin, after which the finished sterile base is added in parts. In all cases when a yellow mercury ointment is prescribed (regardless of concentration), it is always prepared on a pharmacopeia basis for an eye ointment. Standard prescriptions according to order No. 214 are: pilocarpic ointment 1 and 2% and thiamine ointment 0.5 and 1%, which is prepared on an ophthalmic basis - petrolatum with anhydrous lanolin (90:10). Quality control of eye ointments is carried out similarly to dermatological ointments, including checking the uniformity with the microscopic method for heterogeneous ointments. Eye ointments prepared in pharmacies are dispensed in sterilized jars with screw-on plastic lids with sterile parchment pads.
Features of the production of eye ointments in the factory
These include:
grinding medicinal substances insoluble in an ointment base using appropriate equipment and sieving them through sieves with a hole diameter of 0.1 mm,
expanding the range of bases due to the widespread use of emulsion bases of the IM type, since their use can significantly reduce the dose of a drug substance by increasing the efficiency of their release from the bases,
metal tubes with a varnished inner surface are used to package eye ointments in order to prevent metal from contacting with the medicinal substance; polymeric materials for packaging a single dose of ointment are becoming more common.
As a result of scientific research to find more advanced ophthalmic dosage forms, domestic researchers have proposed a new dosage form - ophthalmic dosage films.
Ophthalmic drug films (HFP), characteristic
HLPs are oval-shaped mechanically strong solid plates with smooth edges and flat surfaces 6–9 mm long, 3–4.5 mm wide, 0.35 mm thick, and an average weight of 0.015 g.
Benefits of Ophthalmic Medicinal Filmsare:
Exact dosage of drugs;
Prolongation of the action of drugs and increase themtherapeutic concentration in the tissues of the eye;
a decrease in the number of injections of the drug to 1-2 times a day;
reduction of the course of treatment by 2-3 times;
Convenience in transportation, economical use of medicinal substances.
Polyacrylamide or its copolymers with monomers of acrylic and vinyl series, polyvinyl alcohol, sodium CMC are used as film-forming agents.
The stages of the technological process for the production of HFPThese include: preparing a polymer solution, preparing a drug solution, mixing solutions, deaerating, casting a film web, producing films — stamping, packaging, sterilization, quality control. HFP quality assessment is carried out according to physicochemical properties: gloss, surface roughness, cracks, tears, elasticity, strength. Ophthalmic films are produced with pilocarpine hydrochloride, dicain, atropine sulfate, fibrinolysin (400 units), SILP Pilaren (pilocarpine hydrochloride with adrenaline hydrotartrate), etc.
The main directions of improving technology and quality ophthalmic dosage forms
development of devices and apparatus for filtering, dosing, packaging and sterilizing eye drops;
expansion of the range of excipients: preservatives, stabilizers, prolongators;
unification of the formulation, expansion of the intra-pharmacy procurement of eye drops, solutions;
expansion of the range of ophthalmic dosage forms of factory production in single-use packaging.
Ophthalmic single-use dosage forms are:
Lamels- gelatinous oval disks with a diameter of 3 mm, containing various medicinal substances in the composition of the gelatinous mass.
Minima- containers made of polymer with a capacity of 4-12 drops of solution or 0.5 g of ointment. The shape of the container makes it easy to open and dose the drug by squeezing the contents onto the mucous membrane. After opening the minima are thrown out. They are made on a special molding machine from granular high-pressure polyethylene, which is sterilized with ethylene oxide. Fill with a dosing machine sterile solution or ointment. After filling, they are sealed under aseptic conditions and sterilized again.
The release of eye drops in lyophilized form (eye drops of complex composition with riboflavin based on polyglucin), liposomal eye drops of Cyclolip, etc., has been mastered.
Eye Drop Stability
Under the influence of various physicochemical factors during production and storage, the components of eye drops can undergo hydrolysis, oxidize, and as a result lose their activity. In order to avoid such adverse reactions, antioxidants and auxiliary substances that regulate the pH of the medium began to be added to the eye drops. According to the degree of stability, the medicinal substances that make up the eye drops are divided into three groups (according to the pH of the solution environment):1) substances resistant to hydrolysis and oxidation in an acidic environment. This group includes salts of alkaloids and synthetic nitrogenous bases. They are usually stabilized with boric acid of isotonic concentration and other buffer solutions that increase the stability of the reaction medium:
2) substances that are stable in an alkaline environment. for example, sulfacyl sodium. In this case, stabilizers will be solutions with an alkaline pH value (sodium bicarbonate, sodium hydroxide, sodium tetraborate):
3) easily oxidizable substances. Antioxidants are used as stabilizers for such substances.
When preparing eye drops, comfort during application is taken into account: To achieve comfort during the use of eye drops, buffers such as:
1) isotonic buffer solution of boric acid with chloramphenicol (0.2%);
2) a borate buffer solution consisting of boric acid (1.85%), sodium tetraborate (0.15%), chloramphenicol (0.2%);
3) phosphate buffer solution, consisting of a solution of sodium phosphate monosubstituted (0.5%) and a solution of sodium phosphate disubstituted (0.9%).
Prolonging the action of eye drops
The disadvantage of solutions of drugs used as eye drops is that the manifestation and therapeutic effect directly depends on the time spent in the conjunctival sac. To maintain the required concentration, frequent instillation of the drug substance is required, since aqueous solutions are quickly washed out by tear fluid. Frequent mechanical action on pathologically altered eye tissues can lead to adverse effects.It was possible to prolong the effect of eye drops by introducing prolongation agents into the composition of the solution that increase the viscosity of the solutions.
Requirements for substances acting as prolongators:
1) to provide the necessary contact of the drug substance with the tissues of the eye;
2) do not irritate the mucous membrane of the eye;
3) do not distort visual sensations;
4) be compatible with the medicinal substance and preservatives;
5) accelerate the epithelization of the eroded cornea, if possible;
6) sterilize well;
7) maintain their properties during storage.
Initially, the role of such substances was played by oils (apricot, peach, fish oil), but synthetic hydrophilic high-molecular compounds replaced them:
Methyl cellulose (0.5 - 2%);
Sodium salt of carboxymethyl cellulose - NaKMTS (0.5-2%);
Polyvinyl alcohol (1.5%);
Microbial polysaccharide aubazidan (0.1 - 0.3%).
Lack of mechanical inclusions
Eye drops are aqueous solutions of medicinal substances and are largely similar in terms of requirements to injection solutions, so the absence of mechanical impurities is provided by filtering through glass (No. 3), porcelain or paper filters with simultaneous sterilization. To achieve the desired quality, thorough filtering is used through the best grades of filter paper and long-fiber cotton wool or No. 3 glass filter.
Packaging and storage of eye drops
Packaging for eye drops should meet the following requirements: to ensure sterility and stability during storage and use, to have a device for installation.
Eye drops are dispensed in neutral glass vials with a capacity of 5-10 ml, sealed with rubber stoppers, closed on top with metal caps.
Eye drops are instilled using pipettes or plastic drip nozzles placed on the bottle. A tube is made in an industrial way - droppers from polyethylene, consisting of a body and a cap with a pin for calcination. Tube - droppers are most convenient to use.
Keep eye drops in a cool, dark place. For holidays, they are issued with the main pink label “Eye Drops” and the warning label “Store in a cool, dark place.”
I. Preparation of eye drops
dissolution of drugs.
As an example, consider the preparation of a solution of diphenhydramine and pilocarpine hydrochloride.
1. Rp: Dimedroli 0.05
Natrii chloridi quantum satis
Ut fiat solutio isotonica
Misce. Da Signa Eye drops.
Ensuring isotonicity is carried out by adding sodium chloride, sodium nitrate or sodium sulfate to the eye drops.
The isotonic equivalent of sodium diphenhydramine is E \u003d 0.2.
To make an isotonic solution of only sodium chloride, you need to take 0.09 g per 10 ml of solution. The diphenhydramine contained in the recipe creates a certain osmotic pressure, therefore, sodium chloride must be taken correspondingly less. Since the isotonic equivalent of diphenhydramide for sodium chloride is 0.2, 0.05 g of diphenhydramine will create an osmotic pressure equal to the osmotic pressure of 0.01 g of sodium chloride:
1.0 g of diphenhydramine - 0.2
0.01 g NaCl
0.2 · 0.05
0.05 g of diphenhydramine - X 1
therefore, sodium chloride must be taken 0.09 - 0.01 \u003d 0.08 g.
2. Rp: Sol. Pilocarpini hydrochloridi - 1% - 10.0
Da Signa 2 drops 3 times a day in the right eye.
This solution is hypotonic and causes an unpleasant sensation when instilled into the eye, so it must be isotonized with sodium chloride. E - pilocarpine hydrochloride for sodium chloride is 0.22 i.e.
1.0 g of pilocarpine - creates the same osmotic pressure as 0.22 g of NaCl, therefore, to bring the solution to isotonicity of sodium chloride,
1g - 0.22
0.022 g
, 1 g - X 0.1 0.22
0.09 - 0.022g \u003d 0.068g \u003d 0.07g NaCl.
Passport:
Pilocarpine hydrochloride 0.1g
Sodium chloride 0.07g
Water for injection 10 ml
Total volume 10 ml
Under aseptic conditions, 0.1 g of pilocarpine hydrochloride and 0.07 g of sodium chloride are dissolved in a sterile stand in approximately 5 ml of water for injection. The solution is filtered through pre-washed sterile filter paper and a cotton swab into a sterile neutral glass bottle, and the remaining amount of water for injection is filtered through the same filter. The bottle with the solution is sealed with a sterile rubber stopper, the solution is examined for the absence of mechanical impurities. The bottle is corked "for running." Next, the bottle is tied with parchment paper, on which an inscription is made with the name and concentration of the solution.
The solution is sterilized by flowing steam at 100 ° C for 30 minutes. or steam under pressure at 120 ° C for 8 minutes. After sterilization, the solution is checked for mechanical impurities, color, and quality of capping.
Then it is decorated with a pink label, which indicates the number of pharmacies, prescription date, full name patient, method of application. Stick warning labels “Keep in a cool and dark place”, “Handle with care”. The bottle is sealed with sealing wax. Write out a signature.
3. Rp: Sol. Sulfacуili - natrii - 20% - 10 ml
Da Signa Eye drops.
Under aseptic conditions, 2 g of sulfacyl sodium are dissolved in 5 ml of water for injection and the solution is filtered through a small paper filter pre-washed with water for injection into a dry, sterile flask. Then the rest of the water is added to the solution, passing it through the same filter until 10 ml of solution is obtained.
II.Ocular solutions
Range of application of ophthalmic solutions:
lotions;
washing;
irrigation solutions;
solutions for cleaning, disinfecting and storing soft contact lenses.
These are aqueous solutions of medicinal substances used to provide a disinfectant, anti-inflammatory and astringent effect. Most often, solutions of furacilin, boric acid, sodium bicarbonate, ethacridine lactate are prescribed. They are applied to the eyes in the form of gauze or cotton swabs moistened with a heated solution of a medicinal substance. Solutions for washing are used for extinguishing (irrigation of the eyelids in an inverted state), washing the lacrimal passages and conjunctival sac with the help of cans, drops and syringes.
For chemical eye burns, a stable sterile phosphate buffer solution with a pH value of 7.2 is used for irrigation and instillation. Solutions for the processing and storage of contact lenses include antiseptic substances, cellulose derivatives, polyvinyl, nonionic surfactants, polyethylene glycols, and isotonic buffer solvents.
Using the sodium tetraborate solution as an example, consider the preparation of eye lotions:
1. Rp: Sol. Natrii tetraboratis - 2.5% - 100 ml
Da Signa Eye lotion.
The isotonic equivalent of sodium tetraborate for sodium chloride is E - 0.34, 2.5 x 0.34 \u003d 0.86 g, so a 2.5% sodium tetraborate solution corresponds to a 0.86% sodium chloride solution, i.e. is almost isotonic.
Passport:
Sodium tetraborate 2.5 g.
Water for injection 100 mg
The total volume of 100 ml.
Under aseptic conditions, 2.5 g of sodium tetraborate are dissolved in a sterile stand in 100 ml of hot water for injection. The solution is filtered into a sterile neutral glass vial. The bottle with the solution is sealed with a sterile rubber stopper, the solution is examined for the absence of mechanical impurities. The vial with the solution is tied with parchment paper, the name and concentration of the solution, your name are inscribed on the strapping, sterilized at 120 0 C for 8 minutes. After sterilization, the solution is re-checked for the absence of mechanical impurities, color, quality of corking the bottle, and draw up as indicated earlier.
2. Rp: Sol. Furacilini - 1: 5000 - 200 ml
Da Signa Eye lotion.
Under aseptic conditions, in a sterile stand, 0.04 g of furatsillin and 0.85 g of sodium chloride are dissolved in 200 ml of hot water for injection. The solution is filtered into a sterile bottle of NS, checked for the absence of mechanical impurities. The vial with the solution is sealed with a rubber stopper “under the run-in”, sterilized at 120 0 C for 8 minutes. After sterilization, they again check for the absence of mechanical impurities. Make out for vacation.
III. Eye drops preparation
from concentrated solutions
To accelerate the preparation of eye drops in frequently repeated prescriptions, concentrated solutions of medicinal substances (concentrates): riboflavin (0.02%), potassium iodide (10%), ascorbic acid (10%), glucose (20%) are pre-prepared under aseptic conditions. , sodium iodide (10%), calcium chloride (10%), zinc sulfate (1%), boric acid (4%), etc.
1. Rp: Riboflavini 0.001
Acidi Vorici 0.2
Aquae pro injectionibus 10 ml
Misce. Da Signa Eye drops
To prepare the solution, you can use a concentrate of riboflavin 0.02% and boric acid 4%:
1) Riboflavin Concentrate:
0.001 - x X \u003d 0.001 · 100 \u003d 5 ml
0.02% Riboflavin Solution
2) Boric acid concentrate:
0.2 –x X \u003d 0.2 · 100 \u003d 5 ml boric acid concentrate
Passport: Riboflavin - 5 ml from 0.02%
Boric acid from 4% - 5 ml.
Under aseptic conditions, 5 ml of a 0.02% riboflavin concentrate and 5 ml of a 4% boric acid concentrate are measured with a sterile pipette into a sterile dispensing flask.
The flask is sealed with a sterile rubber stopper, checked for the absence of mechanical impurities and wrapped in an aluminum cap, drawn up for vacation.
2. Rp: Sol. Riboflavini 0.02% - 10.0
Acidi ascorbinici 0.04
Acidi borici 0.2
Misce. Da Signa 2 drops in both eyes 3 times in
For convenience, two-component concentrates are used.
One-component concentrates:
Glucose 20%
Potassium iodide 10%
Calcium Chloride 10%
Boric acid 4%
Ascorbic Acid 10%
Sodium Chloride 10%
Sodium iodide 10%
Riboflavin 0.02%
Zinc sulfate 1%
Concentrates made on 0.02% riboflavin solution
Glucose 20%
Potassium iodide 10%
Ascorbic Acid 10%
Boric acid 4%
Sodium Chloride 10%
Passport recipe number 2.
Riboflavin solution 0.02% \u003d 10 ml
Ascorbic acid solution 10% \u003d 0.4 ml
Boric acid solution 4% \u003d 5 ml.
Total volume 15.4 ml
In this case, using one-component concentrates, the volume of eye drops is overestimated. Therefore, it is necessary to prepare a solution by dissolving ascorbic and boric acids in a 0.02% riboflavin solution or, more specifically, to use two-component concentrates.
Passport:
A solution of ascorbic acid 10% in a 0.02% solution of riboflavin 0.4 ml.
Boric acid solution 4% to 0.02%
Riboflavin solution 5 ml.
Riboflavin solution 0.02% 4.6 ml.
The total volume of 10 ml.
Under aseptic conditions, 4.6 ml of riboflavin concentrate, 0.4 ml of ascorbic acid concentrate and 5 ml of boric acid concentrate made on a riboflavin solution are pipetted into a sterile vial with a sterile pipette. The solution is corked and formalized and leave.
In the manufacture of a 1% suspension of hydrocortisone, which doctors prescribe in the form of eye drops, a ready-made 2.5% suspension of hydrocortisone acetate for injection can be used. A sterile isotonic sodium chloride solution is added to the calculated amount of suspension under aseptic conditions.
3. Rp: Sol. Zinci sulfatis 0.25% - 10 ml
Da Signa 2 drops in both eyes 3 times a day.
It is not possible to accurately weigh 0.025 g of zinc sulfate on all types of BP. There is a zinc sulfate concentrate 1% (or 1: 100). In 2.5 ml of this concentrate contains 0.025 g of zinc sulfate. This solution is hypotonic, since 0.025 g of zinc sulfate creates the same osmotic pressure in the solution as 0.003 g of sodium chloride. Therefore, 0.087 g of sodium chloride or 0.87 ml of its 10% concentrate should be added to the zinc sulfate solution.
Passport:
Zinc sulfate solution 1% -2.5 ml
A solution of sodium chloride 10% -0.9 ml (0.8087 · 10) \u003d 0.87 \u003d 0.9 ml
Water for injection 6.6 ml
The total volume of 10 ml.
Under aseptic conditions, 6.6 ml of sterile water for injection, 2.5 ml of zinc sulfate concentrate and 0.9 ml of sodium chloride concentrate are measured in a sterile vial with a sterile pipette. The solution is corked for running in and made out for vacation.
Eye drops preparation
with extension components
A type of eye drops made from concentrated solutions is drops, which include prolongators - methyl cellulose (MC), sodium salt of carbomethyl cellulose, polyvinyl alcohol.
2. Rp: Sol. Zinci sulfatis 0.025
Acidi borici 0.2
Solutionis Methylcellulosae 1% - 10 ml
Misce. Da tales doses No. 2
Da Signa 2 drops once a day at night.
Passport (for 2 bottles)
Zinc sulfate 0.05 g
Boric acid 0.4 g
Nipagina 0.02
Cellulose 0.2 g
Water for injection 10 ml
Total volume 20 ml
A) Preparation of a solution of methyl cellulose.
Under aseptic conditions, 0.2 g of MC are poured into 5 ml of water for injection, heated to a temperature of 80 - 90 0 C and left to swell. After two hours, the remaining amount of water is added, mix thoroughly and left in the refrigerator for 10-12 hours until the end of dissolution of the MC, then the solution is filtered through a No. 2 sterile glass filter under vacuum, and the solution is checked for mechanical impurities.
B) Preparation of a solution of the remaining components.
Separately, in about 9 ml of hot water for injection under aseptic conditions, 0.02 g of nipagin is dissolved with vigorous agitation, then 0.4 g of boric acid and 0.05 g of zinc sulfate are dissolved in a warm solution. After cooling, the solution was adjusted with water to a volume of 10 ml, filtered.
Both solutions are combined, thoroughly mixed, the solution is poured into 10 ml into sterile vials, and they are sealed “under running”.
Vials with a solution are sterilized at 120 ° C for 5 minutes. Bottles issue for vacation.
IV. Eye ointments
Ophthalmic ointments (Ungenta ophtalmicae) are soft dosage forms that form a continuous film when applied to the conjunctiva of the eye. Ointments are used by laying behind the eyelid through eye spatulas. These dosage forms are intended to reduce inflammatory reactions, disinfection, anesthesia, dilate or narrow the pupil, and reduce intraocular pressure. Eye ointments consist of a base and medicinal substances, the choice of which depends on the desired therapeutic effect.
The State Pharmacopoeia sets out manufacturing guidelines and requirements for ointments.
The eye tissues are distinguished by their increased sensitivity and vulnerability, therefore, special requirements are placed on eye ointments, because of which the dosage form is allocated to a special group.
The main requirements are:
1) sterility (manufacturing is carried out only under aseptic conditions);
2) the minimum degree of dispersion of drugs in eye suspensions;
3) the ease and uniformity of distribution on the mucous membrane of the conjunctiva and eyes, provided by the structure of the eye ointment;
4) the absence of irritating components in the composition of the ointment (especially acids);
5) the necessary pH value of the eye ointment in the range of 4.5 - 9.0, otherwise tearing and leaching of the ointment from the eye is possible.
Ointment Foundation
Requirements for the bases for eye ointments:
sterility;
lack of irritating properties;
chemical indifference;
good distribution ability;
hydrophilicity, providing emulsification with tear fluid;
the melting point of the base 32-34 0 C.
In the absence of petroleum jelly of the grade “For eye ointments” it is obtained as a result of additional purification of ordinary petroleum jelly. In pharmacy conditions, it is melted, 2% activated carbon is added, then the mixture is heated to 150 0 C for 1 hour, and then filtered through a pleated filter into sterilized jars and sealed.
If the doctor has not indicated the basis in the prescription, then, according to the Global Fund, you should use a sterile mixture of 10 parts of anhydrous lanolin and 90 parts of Vaseline grade “For eye ointments. The mixture is sterilized at 150 ° C for 30 minutes. or at 200 ° C for 15 minutes in an air sterilizer. Store in a dark place at a temperature of no higher than 25 0 C for 2 days or at 3-5 0 C no more than 30 days.
Hydrophilic bases are also used as the basis for eye ointments. For example, methyl cellulose base. They are physiological in a number of indicators: neutral, well release medicinal substances, but at the same time require additional stabilization (adding preservatives).
The technology of preparation of eye ointments
Medicinal substances are introduced into the base according to the general rules for the preparation of dermatological ointments. Water-soluble drug substances are pre-dissolved in sterile water. Water and base insoluble medicinal substances are ground into a fine powder with auxiliary liquid. All auxiliary materials, ointment base, medicinal substances. (thermostable), banks are sterilized according to the instructions of the State Pharmacopoeia. When preparing ointments, the administered medicinal substances must have an optimal degree of dispersion. The required degree of dispersion is achieved by dissolving in sterile water or thoroughly grinding in a small amount of water or a related base, and then mixing with an ointment base.
Packing eye ointments
Ophthalmic ointments are released in sterile jars, with screw-on plastic caps with sterilized parchment pads. For vacation draw up a pink label. "Eye ointment" and the necessary warning labels. Store eye ointments in well-sealed jars in a cool, dark place. The shelf life of ophthalmic ointments in pharmacy production is approved by regulatory documentation.
Examples of the preparation of eye ointments
1. Rp: Unguenti Zinci sulfatis 0.5% -10.0
Da Signa Eye ointment.
Under aseptic conditions, 0.05 g of zinc sulfate is dissolved in a sterile mortar in a few drops of water for injection, 10 g of a sterile base for ophthalmic ointments are added, and mixed thoroughly. The ointment is transferred to a glass jar with a screw-on plastic lid. They are decorated with a pink eye ointment label.
2. Rp: Ung. Hydrargyri oxydi flavi 20.0
Da Signa Eye ointment.
This ointment is standard and it is prepared on the basis that is indicated in the recipe. This ointment is called ophthalmic - “Mercury yellow ointment” of the following composition (Article 343 GFH):
Yellow oxide mercury 2.0 g
Petroleum jelly 2.0 g
Vaseline 80 g
Lanolin without water 16.0 g
Passport:
Yellow mercury oxide 0.4 g
Petroleum jelly oil 0.4 g
Vaseline 16.0 g
Lanolin without water 3.20 g
Total weight 20.0 g
The yellow mercury oxide is thoroughly triturated with an equal amount of sterile liquid paraffin, after which filtered sterile, almost cooled base is mixed in parts. The ointment is prepared "ex tempore" because mercury oxide decomposes under the influence of light with the release of metallic mercury.
Decorate the jar with a pink label "Eye Ointment." Stick warning labels “Store in a cool place”, “Store in a dark place.”
If the prescription of the ointment is non-standard and the doctor’s prescription does not indicate which basis to take, then for the manufacture of eye ointments GF X recommends a mixture of 10 g. anhydrous lanolin and 90g. Vaseline varieties "For eye ointments." The mixture is melted, filtered and sterilized.
3. Rp: Ung. Xeroformii 0.5% -10.0
Da Signa Eye ointment.
In a sterile mortar, 0.05 g of xeroform is thoroughly ground with a few drops of sterile liquid paraffin and 10 g of a base consisting of 1 g of anhydrous lanolin and 9 g of petroleum jelly are added in parts, achieving an even distribution of xeroform throughout the base. Transfer the ointment into a sterile jar and arrange for vacation.
4.Rp: Unguenti Sulfacyli - Natrii 30% -20.0
Da Signa Eye ointment.
VFS 42 - 92 - 72 is approved for sulfacyl ointment 30%.
Composition: sulfacyl - sodium 30 g
Water for injection 20 g
Lanolin without water 20 g
Vaseline oil 15 g
Vaseline (varieties for eye ointments) 15 g
Therefore, to prepare 20 g - 30% sulfacyl ointment, take 6 g of sulfacyl sodium and dissolve in 4 ml of hot water for injection, then the resulting solution is emulsified with a sterile alloy of anhydrous lanolin (4 g), Vaseline "For eye ointments" (3 g) and vaseline oil (3 g). The finished ointment is transferred to a sterile jar, issued for vacation.
Self-help questions
What is the characteristic of ophthalmic dosage forms? What are the requirements for eye dropslotions?
Compare the quality of eye drops and injectable solutions. What conclusions can be drawn from this comparison?
What are the possible causes of unpleasant sensations arising after instillations of eye drops and what are the ways to eliminate these phenomena?
Compare the quality indicators of ophthalmic solutions (prolonged action and stability). Give examples of ensuring these indicators?
What is the similarity of technology of dermatological and eye ointments? How to explain the difference in their technology?
What concentrated solutions are used in the manufacture of eye drops. Examples.
What are the requirements for eye ointments? What is the feature of technology. Examples of the preparation of eye ointments?
What are the requirements for ointment bases for eye ointments?
What is the importance of rational packaging of eye ointments.
How to assess the quality of ophthalmic dosage forms (drops, ointments).
1. Rp: Solutionis Dicaini 1% - 10 ml.
Da Signa 2 drops 3 times a day in the left eye.
2. Rp: Solutionis Kalii iodidi 3% - 10 ml.
3. Rp: Riboflavini 0.001
Acidi ascorbinici 0.01
Aq. pro injectionibus 10 ml
4. Rp: Solutionis Zinci sulfatis 0.25% - 10 ml.
Acidi borici 0.2
Misce. Da Signa 2 drops 3 times a day in both eyes.
5. Rp: Riboflavini 0.002
Triloni B 0.003
Sol. Methylcellulosae 1% - 10 ml
Misce. Da Signa 2 drops 3 times a day in both eyes.
6. Rp: Riboflavini 0.002
Acidi ascorbinici 0.02
Natrii metabisulfiti 0.01
Triloni B 0.003
Solutionis Methylcellulosae 1% - 10 ml
Misce. Da Signa 2 drops 3 times a day in both eyes
For the night.
7. Rp: Riboflavini 0.002
Acidi ascorbinici 0.01
Kalii iodidi 0.2
Solutionis Acidi borici 2% - 10 ml
Misce. Da Signa 2 drops 3 times a day in both eyes.
8. Rp: Riboflavini 0.002
Solutionis Acidi borici 3% - 10 ml
Misce. Da Signa 2 drops 3 times a day in both eyes.
9. Rp: Riboflavini 0.002
Acidi ascorbinici 0.03
Solutionis Glucosi 2% - 10 ml
Misce. Da Signa 2 drops 3 times a day in both eyes.
10. Rp: Riboflavini 0.002
Solutionis Kalii iodidi 2% - 10 ml
Misce. Da Signa 2 drops 3 times a day in both
11. Rp: Solutionis Aethacridini lactatis 1% - 100 ml
Da Signa 2 drops 3 times a day in both eyes.
12. Rp: Solutionis Aethacridini lactatis 1% - 100 ml
Da Signa Eye lotion.
13. Rp: Unguenti Collargoli 3% - 10 ml
Da Signa Eye ointment
14. Rp: Ung. Thiamini bromidi 0.5% - 10.0
Da Signa Eye ointment.
15. Rp: Zinci sulfatis 0.05
Lanolini aa 10.0
Misce. fiat unguentum
Da Signa Eye ointment.
16. Rp: Unguentum Atropini sulfatis 0.5% - 10.0
Da Signa Eye ointment.
17. Rp: Unguentum Pilocarpini hydrochloridi 2% - 10.0
Da Signa Eye ointment (at night).
18. Rp: Unguentum Hydrargyri oxydi flavi 10.0
Da Signa Eye ointment.
To increase durability to some eye drops it is proposed to add small amounts of preservatives, for example: nipagin, sodium formaldehyde sulfoxylate, phenylethyl alcohol, etc.
B. L. Polyak with employees suggested as a preservative for eye drops apply a mixture of 0.2% chloramphenicol and 2% boric acid. According to the authors, this preservative is reliable and completely harmless. To stabilize eye drops abroad, they resort to their preparation on buffer solutions. There are several prescriptions for such solvents.
In some cases, it is required that eye solutions were tear fluid isotonic and had a pH close to it. Isotonicity is often required for solutions used for washing the eyes, since in these cases large quantities of the solution come into contact with the mucous membrane of the eye. The isotonicity of the solutions is achieved by adding a certain amount of sodium chloride. If sodium chloride is incompatible with the drugs that make up the drug, then some other pharmacologically indifferent substances (glucose, etc.) are sometimes added.
For isotonic calculations concentrations of ophthalmic solutions use the above methods.
Very significant It also has the exact concentration of dissolved medicinal substances.
Drop eye drops It should be in sterile bottles - droppers or in special bottles with ground pipettes.
When dropping drops in ordinary flasks, parchment is placed under the cork. Do not lay waxed paper on it, as it may contaminate the solution.
Example. Rp .: Zinci sulfurici 0.025
Solutionis Acidi borici 2% - 10.0
Misce. Da Signa Eye drops
Accurately weigh 0,025 zinc sulfate on hand scales, it is impossible, therefore, this solution should be prepared in double quantity. 0.4 boric acid is dissolved in 19.6 warm sterile freshly distilled water and 0.05 zinc sulfate is added upon cooling. The solution is filtered through a small pleated filter with a cotton ball attached. The filter is washed with the same solution, since when washing the filter with water, there is some dilution of the solution concentration due to the fact that part of the water is retained by the filter. 10.0 was released from the filtered solution.
Example. Rp .: Pilocarpini hydrochlorici 0.1
Aquae destillatae 10.0
Misce. Da Signa Eye drops.
Eye drops this recipe is also prepared in compliance with all asepsis rules. 0.1 pilocarpine hydrochloride is dissolved in half (5.0) freshly distilled sterile water, filtered, and then water is added to the solution to 10.0 (passing it through the same filter). The bottle with these drops is sealed.
Example. Rp .: Solutionis Sulfacyli solubile 20% - 10.0
Da Signa Eye drops
2.0 Sulfacyl Soluble dissolve in 5.0 sterile freshly distilled water and the resulting solution is filtered through a small paper filter into a pre-calibrated dry sterile bottle. Then water is added to the solution, passing it through the same filter to obtain a 10.0 solution. Release the solution in a dark bottle or with a warning label "Keep in a dark place."
For the preparation of eye drops in pharmacies sometimes use concentrated solutions (solutions of solfacil soluble 20% and 30%, atropine sulfate 1%, boric acid 4%, zinc sulfate 1% and some others). Such concentrated solutions may only be prepared for a short time. Each of these solutions has a specific shelf life in days (for example, 2 days for a solution of resorcinol 10%, 14 days for a solution of zinc sulfate 1% and atropine sulfate 1%, 7 days for a solution of potassium iodide 10%). Glucose solution for the preparation of eye drops should be used only freshly prepared.
Concentrated solutions, which have changes in appearance (discoloration, the appearance of turbidity, flakes, films, etc.) are not allowed to be used.
State budget educational institution secondary vocational education
Syzran College of Medicine and Humanities
Specialties 060301 Pharmacy
Graduation work (thesis)
Manufacture and manufacture of ophthalmic dosage forms
Artist: Second year student
Blokhina Elena Aleksandrovna
Teacher: Sorokina R.A.
syzran - 2013
Introduction
Chapter 1. Requirements for eye drops, ophthalmic solutions and intra-pharmaceutical preparations
1 Sterility
2 Isotonicity
3 Isohydricity
4 Stability
5 Transparency
6 Rollover
7 Internal pharmacy blanks
Chapter 2. Production ophthalmic solutions
1 Preparation of eye drops by dissolving medicinal and excipients
2. The manufacture of eye drops using concentrated solutions
Chapter 3. Quality Control
1 Organoleptic control
2 Physical control
3 Chemical control
4 Control when leaving the pharmacy
Chapter 4. Requirements for pharmacies
4.1 Composition of premises and equipment of the pharmacy
4.2 Pharmacy operations
Chapter 5. Industrial production of eye drops
5.1 Technology for the production of eye drops
2 Control of ophthalmic solutions for mechanical inclusion
Chapter 6. Analysis of the implementation of ophthalmic dosage forms
1 Research Methods
2 Analysis of the shelf life of ophthalmic dosage forms manufactured in pharmacies and in industrial conditions
Conclusion
List of references
application
Introduction
Relevance - The chosen topic consists in the need for a detailed study of the technology for the manufacture and production of ophthalmic dosage forms in view of the fact that eye diseases remain a serious social problem in practical ophthalmology as a cause of temporary disability in 80% and as a cause of blindness in 20% of cases. All medications for eye practice constitute a special group medicines. This is determined by a number of reasons of a social, medical and pharmaceutical nature: the exclusive role of the organ of vision in ensuring the level and quality of human life; the special complexity and specificity of the anatomical, biophysical and physico-optical mechanisms of vision; opportunity and necessity drug exposure on the front of the eye; strict requirements for the quality and safety of ophthalmic dosage forms; significant technological difficulties in the development of compositions and technologies and their introduction into production associated with a fairly narrow range of active pharmacological substances and excipients that are allowed for administration into the eye; high requirements for pH and isotonicity. Most of all, eye drops meet these requirements. The development of original medicines, including ophthalmic, requires a lot of financial and time costs, which is especially expressed in relation to the development of the composition and the creation of optimal technology for ophthalmic dosage forms, among which eye drops still dominate. The object of study is the process of industrial production of ophthalmic dosage forms. Subject of study - ophthalmic dosage forms. Purpose of the study - To achieve the goal, it is necessary to solve the following tasks: To study the theoretical literature on the research problem; To study the requirements for eye drops and pharmacy preparations; Consider making eye drops by dissolving drugs and excipients; To analyze the composition of concentrated solutions of medicinal substances used in the manufacture of ophthalmic solutions; Consider making eye drops using concentrated solutions; 6. consider the types of quality control when leaving the pharmacy; To study the requirements for pharmacies; To analyze the dynamics of the implementation of ophthalmic dosage forms manufactured in a pharmacy and in an industrial environment. Practical relevance - the results of the study allow a wide approach to the production and manufacture of ophthalmic dosage forms .
Research Methods: Study and analysis of scientific literature. The study of the requirements for eye drops and pharmacy preparations. Analysis of the composition of concentrated solutions of medicinal substances used in the manufacture of ophthalmic solutions. Making eye drops using concentrated solutions. 5. Consider the types of quality control when leaving the pharmacy. Studying the requirements for pharmacies. Analysis of the dynamics of sales of ophthalmic dosage forms manufactured in the pharmacy and in industrial conditions. Analysis of the shelf life of ophthalmic dosage forms manufactured in pharmacies and in industrial conditions. When writing a thesis, the following regulatory documentation was studied: The State Pharmacopoeia of the Russian Federation 12-part 1 / M .: Scientific Center for Expertise of Medical Devices, 2008. - 704 p. Order of the Ministry of Health of Russia “On the schedule for prescribing and prescribing medicines, medical devices and specialized medical nutrition products” dated February 12, 2007 No. 110. Order of the Ministry of Health of Russia "On quality control of medicines manufactured in pharmacies" dated July 16, 1997 No. 214 Order of the Ministry of Health of Russia "On norms of deviations allowed in the manufacture of medicines and packaging of industrial products in pharmacies" dated October 16, 1997 No. 305. In the process of preparing the work, a wide range of sources was used: Guidelines for the manufacture of sterile solutions in a pharmacy. - M., 1994 Workshop on the technology of dosage forms: Textbook. The allowance / I.I. Krasnyuk, G.V. Mikhailova, O.N. Grigoryev et al. // Ed. I.I. Krasnyuk, G.V. Mikhailova. - M.: Publishing Center "Academy", 2006. Technology of drugs<#"justify">- Pharmaceutical technology. The technology of dosage forms: a textbook for stud., Training. by special 040500 - Pharmacy / Ed. I.I. Krasnyuk, G.V. Mikhailova - 2nd ed., Stereotype. - M.: Publ. Center "Academy", 2006. - 592 pp. - (Higher vocational education). Pharmaceutical Technology: Technology of dosage forms. Ed. I.I. Krasnyuk, G.V. Mikhailova, M .: GEOTAR-Media, 2011, D. Muravyova, I. Samylina, G. Yakovlev Pharmacognosy. Textbook for students Pharmaceutical technology All of the above publications and articles used to write the work are written on the basis of existing legislative and normative-methodological acts, the latest literature, study of work experience and are of great interest to pharmacy workers. Work structure: The thesis consists of introduction, five chapters, conclusion, list of references and literature, applications. Chapter 1. Requirements for eye drops, ophthalmic solutions and intra-pharmaceutical preparations Eye drops - as defined in the Global Fund, is an official dosage form intended for installation in the eye. Apply aqueous or oily solutions, the finest suspensions or emulsions of medicinal substances, dosed in drops. They should be made under aseptic conditions. They should not include substances such as essential oils, solutions with strong acid or alkaline properties. Most often, pharmacies produce aqueous solutions of medicinal substances for eye drops, lotions, rinses, irrigation of the mucous membranes of the eyes. .1 Sterility
Normally, the protective function is performed by lysozyme - a natural antibiotic substance contained in the lacrimal fluid, lysing microorganisms that enter the conjunctiva. With eye diseases, the content of lysozyme in the tear fluid usually decreases, and the conjunctiva is unprotected from the effects of microorganisms. Infection of the eye with non-sterile solutions can cause serious consequences, sometimes leading to loss of vision. The main method for sterilizing eye drops is thermal - saturated steam in a steam sterilizer at 120 ± 2 ° C, a number of solutions (atropine sulfate, dicaine, potassium iodide, ascorbic acid, chloramphenicol, sodium iodide, sodium sulfacyl, novocaine, ethylmorphine hydrochloride, drops with complex riboflavin composition and others (Fig. 1) are sterilized by fluid steam at 100C. Figure 1. Solutions that sterilize fluid vapors If the substances cannot withstand even the gentle sterilization mode, or the sterilization mode for the solution is not established, then the eye drops are prepared under aseptic conditions on a sterile Solvent (purified water, 0.9% sodium chloride solution or a solution of a thermostable substance). Apply filter sterilization method. Thermal methods do not sterilize solutions of resorcinol, alum, collargol, protargol, trypsin, lidase, antibiotics (except chloramphenicol), citral, adrenaline hydrochloride and some other substances. Eye drops are dispensed in multi-dose packaging, therefore, when the bottle is opened at home, the drops can be subjected to secondary microbial contamination (on the second day - when using an eye dropper and on the fifth day - when using a dropper). Drops with sodium sulfacil remain sterile until the solution is fully used. To preserve sterility with repeated use of eye drops at home, it is allowed to use (as directed by a doctor) preservatives: nipagin (0.05 - 0.25%), a mixture of nipagin (0.18%) and nipazole (0.02%), chlorobutanol hydrate (0.5%) ; benzyl alcohol (0.9%), sorbic acid (0.1%), benzalkonium chloride (0.01%), dodecyldimethylbenzylammonium chloride (0.01%), etc. Preservatives are used more widely in industrial production, while in the pharmacy the role of preservative in eye drops is played by boric acid (1.9 - 2%), if it is prescribed in a prescription, together with chloramphenicol (0.15%). Boric acid can simultaneously perform the functions of both a stabilizer of a number of substances and an isotonizing component. .2 Isotonicity
Ophthalmic solutions should be isotonic with tear fluid (unless the drug is prescribed in high concentrations, as well as in the preparation of collargol and protargol solutions). Normally, tear fluid and blood plasma have equal osmotic pressure. The same pressure creates a 0.9% solution of sodium chloride, which is on an equal footing with biological fluids. Ophthalmic solutions should have an osmotic pressure like that of a 0.9% sodium chloride solution with permissible fluctuations of ± 0.2%, i.e. ranging from 0.7 to 1.1%. Drops below 0.7% of the equivalent concentration of sodium chloride should be isotonized to 0.9%. At the same time, excipients permitted by GF are added, taking into account the compatibility of the components. Most often, sodium chloride is used for these purposes. With the introduction of hypotonic solutions into the eye, pain appears. In some cases, the use of hypotonic solutions is allowed, which should be indicated in the relevant private articles. Hypertonic solutions prescribed by a doctor in a prescription in a pharmacy are made and dispensed to the patient without changing the composition. Solutions, the components of which together increase the osmotic pressure of the drops by more than 1.1% of the equivalent concentration of sodium chloride, must be considered as special formulations of hypertonic concentration. Medicinal substances, prescribed in small quantities (approximately hundredths of a gram in 10 ml of solution), practically do not affect the osmotic pressure of eye drops. In such cases, eye drops are made on a 0.9% isotonic sodium chloride solution with furatsilin solutions (1: 5000); riboflavin (1: 5000); citral (1: 1 LLC, 1: 2000); chloramphenicol (0.1-0.25%). In some cases, the prescribed medicinal substance itself isotonizes part of the volume; therefore, the remaining volume of the solution is isotonized by adding sodium chloride or other excipients permitted by the pharmacopoeia. The required amount of the isotonizing component is calculated using the isotonic equivalent of sodium chloride. The isotonic equivalent of sodium chloride shows how much sodium chloride in an equal volume and equal conditions creates the same osmotic pressure as 1 g of a drug substance. The GF includes a table of isotonic equivalents for sodium chloride for a number of substances. Isotonic equivalents can be found in other regulatory documents. The principle of calculating the isotonic concentration and mass of the isotonizing substance (sodium chloride) using the isotonic equivalent of sodium chloride will be analyzed using a specific example: Example 1 Rp .: Solutionis Ephedrini hydrochloridi 1% - 10 ml D.S. 2 drops in the right eye 3 times a day. The isotonic equivalent of ephedrine hydrochloride 0.28. By the proportion they find how much sodium chloride is equivalent to the amount of ephedrine hydrochloride written in the recipe (0.1). 0.1XX \u003d 0.028 g. For the solution to be isotonic with the tear fluid, the amount of ephedrine hydrochloride should be equivalent to 0.09 g of sodium chloride (0.9% solution for a volume of 10 ml). The missing amount (0.09 - 0.028 \u003d 0.068) is made up by adding sodium chloride (0.068 or -0.07). The amount of isotonic substance (sodium chloride) can be calculated by the formula M \u003d 0.009 Na aV Rp - (m 1, m 2 / E 1, + t 2E 2 + ...),
where M is the mass of sodium chloride required for isotonation of the solution, g; 009 - mass of sodium chloride in 1 ml of isotonic solution, g; V Rp - the volume of solution prescribed in the recipe, ml; m 1, m 2 - the mass of drugs prescribed in the prescription; E 1, E 2 - Isotonic equivalents of drugs prescribed in the prescription. A qualitative characteristic in terms of “iso-, hypo-, hypertonic solution” is insufficient for use in modern medical and pharmaceutical practice. Currently, the concepts of osmolality and osmolarity are used to express the osmotic activity of ophthalmic, injection and infusion solutions. Molar concentration is the amount of substance in moles contained in 1 liter of solution. Molar concentration is the amount of substance in moles contained in 1 kg of solution. Osmolality or osmolarity indicates the content in the molar (molar) solution of active particles (molecules, ions) that create a certain osmotic pressure. Given that ophthalmic and injection solutions are made in mass-volume concentration, the osmolarity characteristic is more convenient to use. If the amount of osmotically active particles in the osmolar solution is such that the pressure they create is physiological, such solutions are called isosmolar. The unit of measurement of osmolarity is milliosmol (thousandth of the osmolarity concentration). Theoretical osmolarity is calculated by the formula: where rinse - milliosmolarity of the solution (mosmol / l); m is the mass of the substance in solution, g / l; n is the number of particles in solution formed as a result of dissociation upon dissolution (n \u003d I, if the substance in the solution does not dissociate; n \u003d 2 if the substance upon dissociation forms two ions; n \u003d 3 if - three, etc.); M is the molecular weight of a substance in solution. Example 2 Rp .: Solutionis Natrii chloridi 0.9% - 100 ml Da. Signa For infusion. It is known that a 0.9% solution of sodium chloride is isotonic to the lacrimal fluid and blood plasma, therefore, the concentration of 308 mosm is isosmolar. Example 3 (use the copybook in example 2). Rp: Solutionis Ephedrini hydrochloridi 1% - 10 ml. Signa 2 drops in the right eye 3 times a day. So 99.16 my< 308 моем. Следовательно, 1 ный раствор эфедрина гидрохлорида - гипотонический, его следует изотонировать, добавив определенное количество натрия хлорида, который бы создал недостающую до изотонирования концентрацию: 308 - 99,16 = 208,84 моcм: In order for the solution to be isotonic (isosmotic) of the tear fluid, it is necessary to add 6.14 g of sodium chloride per 1 liter of solution or 0.06 g per 10 ml of eye drops. In addition to sodium chloride, sodium sulfate and sodium nitrate are used to isotonize ophthalmic solutions, provided that they are compatible with medicinal substances. For example, sodium sulfate should be used when isotonizing drops with zinc sulfate (in the absence of boric acid in the recipe), since more toxic and slightly dissociable zinc chloride will form with sodium chloride. When isotonizing with other isotonizing substances, the calculations are first carried out with sodium chloride, and then the result is multiplied by a conversion factor, which for sodium sulfate is 4.35, for sodium nitrate - 1.51, for boric acid - 1.89. .3 Isohydricity
It is desirable that the ophthalmic solutions are approximately isohydric to the tear fluid, i.e. had a pH of 7.3-9.7. However, the human eye tolerates a relatively good pH of 5.5-11.4. Lower pH values \u200b\u200b(below 5.5) and higher (above 11.4) can cause pain. The optimal pH value of ophthalmic solutions is created taking into account the need to ensure stability. .4 Stability
Thermal sterilization and long-term storage of solutions in glass containers can lead to the destruction of many drugs due to hydrolysis, oxidation, and other processes. Stabilization can be achieved by the addition of substances that regulate the pH of the medium, antioxidants and preservatives. Medicinal substances used in ophthalmic solutions can be divided into 3 groups depending on pH. The first group includes salts of alkaloids and synthetic nitrogenous bases, as well as other substances resistant to hydrolysis and oxidation in an acidic environment. ) an isotonic solution of boric acid 1.9%, chloramphenicol 0.2% (pH 5.0) - used for eye drops containing dicain, novocaine, mesatone and zinc salts; 2) a buffer solution prepared from boric acid 1.84%, sodium tetraborate 0.14%, chloramphenicol 0.2% (pH 6.8), is used for eye drops containing: atropine sulfate, pilocarpine hydrochloride, scopolamine hydrobromide; 3) buffer solution - a mixture of 70 ml of a 0.8% solution of anhydrous monosubstituted sodium phosphate, 30 ml of a 0.95% solution of anhydrous disubstituted sodium phosphate and 0.5% sodium chloride (pH 6.5) is used for eye drops containing the preparations specified in paragraph 2, as well as ephedrine hydrochloride, homatropine hydrobromide. The second group includes substances that are stable in an alkaline environment: sulfacyl sodium, norsulfazole sodium, etc. They can be stabilized with sodium hydroxide, sodium bicarbonate, sodium tetraborate and buffer mixtures with an alkaline pH. The third group includes easily oxidizing substances. Antioxidants are used to stabilize such eye drops (Table 1). Table 1 Antioxidants used to stabilize eye drops Sodium thiosulfate Sodium metabisulfite Trilon BS,% Drops,% Drops,% Drops 0.05 0.15 Dicaina 1, 2, 3% Sodium sulfacyl 10.20.30% (including for newborns) In a 0.35% solution of 1 M hydrochloric acid 0.1 0.5 0.03 mesatone 1% fetanol 3% sodium sulfacil 20% in a 1.8% solution of 0.1 M sodium physostigmine salicylate 0.25% 0.03 riboflavin 0.02% potassium iodide, glucose equally 2% (including from 1% MC) A complex antioxidant (sodium metabisulfite 0.1% and trilon B 0.03%) is used as part of eye drops: Riboflavin 0.02% Ascorbic acid 0.2% Glucose 2% (including with 1% MC) Prescriptions of drugs for which intra-pharmacy procurement is possible or production under conditions of small-scale production with a shelf life of 30 days or more are given in regulatory documents. Some prescriptions contain stabilizers (Appendix 1.) .5 Transparency
Ophthalmic solutions should be transparent and not contain suspended particles that can cause injury to the membranes of the eye. They need to be filtered through the best grades of filter paper, and under the filter should be placed a small swab of long-fiber wool. It is important that after filtering the concentration of the solution and its volume do not become less than established by the standards, therefore, everything said about filtering small volumes of solutions fully applies to eye drops. Medicinal and auxiliary substances are dissolved in half the volume of the solvent, filtered, the filter is washed with the remaining volume of the solvent, and the absence of mechanical impurities is checked with the UK-2 device. If mechanical impurities are present, they are filtered through the same filter until they are absent. After sterilization, the solution is again checked for mechanical impurities; if it is detected, it is rejected. According to the prescriptions often found in the recipe, it is advisable to resort to the use of concentrated solutions manufactured in the pharmacy for a specified period, which frees the pharmacist from filtering small volumes of liquids. .6 Prolongation
It is advisable that the eye drops be continuous. Extension of action as directed by a physician can be achieved by increasing the viscosity of aqueous solutions. Polyvinyl alcohol, MC and sodium, CMC, polyacrylamide (PAA) are suitable for this purpose. These substances do not affect vision and provide the necessary contact of drugs with the eye without irritating it. The diluted solutions of PVA (1-2%), sodium-CMC (1.5%) and MC (0.5-1%) used are easily sterilized and remain transparent when stored in the refrigerator. .7 Internal pharmacy blank
Small volumes and masses of drugs, prescribed in the form of eye drops, often complicate and slow down the manufacturing process of the drug. Therefore, pharmacies are switching to the intra-pharmacy procurement of eye drops according to the prescriptions most often found in the recipe. This allows us to improve the filtering process, to carry out sterilization in a more organized manner, to organize a full chemical analysis of each series of solutions, thereby significantly reducing the time for the manufacture and dispensing of eye drops. In addition, with an intra-pharmacy blank, drops are simultaneously packaged in standard 5 or 10 ml bottles with a rubber stopper, followed by break-in with aluminum caps. In the appendix to the order “On the quality control of medicines manufactured in pharmacies”, a large list of prescriptions for eye drops prepared in pharmacies for different periods is given. Chapter 2. The manufacture of ophthalmic solutions
.1 Preparation of eye drops by dissolving drugs and excipients
As an example, consider the manufacture of eye drops of pilocarpine hydrochloride. Example 4 Rp. Solutionis Pilocarpini hydrochloridi 1% - 10 ml D. S. 2 drops in the right eye 2 times a day. prescription pharmaceutical examination. The annex to the Instructions for Quality Control of Medicines Manufactured in Pharmacies contains the composition of a 1% pilocarpine hydrochloride solution, quality requirements, sterilization regimen, storage conditions and shelf life. The composition of the drug: Pilocarpine Hydrochloride 0.1 Sodium chloride 0.068 Purified water Up to 10 ml The components of the recipe are compatible. The substance of list A is prescribed in the prescription. Doses are not checked, since eye drops are a dosage form for external use. The release rate of the substance is not regulated. Properties of medicinal and excipients of prescription. Pilocarpinum hydrochloridum. In a private article of the Pilocarpini hydrochloridum GF, it is indicated that this substance is colorless crystals or odorless white crystalline powder, hygroscopic, very easily soluble in water. Sodium chloride (Natrium chloridum). White cubic crystals or a white crystalline powder, odorless, salty taste, soluble in 3 parts of water. The pharmacy may be in the form of a 10% concentrated solution. Purified water (Aqua purificata). In accordance with the order of the Ministry of Health of Russia “On the quality control of medicines manufactured in pharmacies”, purified water intended for the manufacture of sterile solutions, in addition to the previously mentioned tests, should be checked during daily monitoring for the absence of reducing substances, ammonium salts and carbon dioxide. For the manufacture of eye drops, in addition to water for injection, the use of freshly obtained purified water is allowed. Preparatory measures. All ophthalmic solutions are prepared under aseptic conditions, i.e. in an aseptic block. On the bars with medicinal substances intended for the manufacture of sterile dosage forms, there should be a warning sign “For sterile dosage forms”. To ensure the technological process, the following must be prepared: sterile bottles in Bix, from neutral glass of 5, 10, 20 ml or more, AB-1 bottles with a capacity of 150, 250 ml, sterile glass funnels, glass filters, J-10 dispenser, syringe “Record” type, filter nozzle for small-volume microfiltration (filter sterilization) FA-25, pharmacy pipettes, UK-2 device, aluminum caps and gaskets, rubber caps, device for crimping caps POK-1, sterile auxiliary material (medical cotton wool, filter folded paper, gauze napkins), a set of nuclear membranes (CMN), a set of concentrated solutions and excipients, purified or fresh water for injection, freshly prepared or sterile, steam sterilizer (Appendix 3) The calculations. In this case, there is sodium chloride in the recipe to bring the solution to a concentration of isotonic tear fluid, however, for training purposes, appropriate calculations should be made. The isotonic equivalent of pilocarpine hydrochloride in sodium chloride (0.22), which is found in the corresponding GF table, is recorded on the reverse side of the PPC. The prescription contains 0.1 g of pilocarpine hydrochloride. This amount will be equivalent to 0.022 g of sodium chloride. Therefore, to obtain a solution of isotonic concentration, it is necessary to add sodium chloride in an amount of 0.068 (-0.07), i.e. 09 - 0,1 0.22 \u003d 0.068 or 0.09 - 0.022 \u003d 0.068 (0.07) Sodium chloride can be added as a 10% solution (0.7 ml, -14 drops) Technology of the drug. In order to fulfill the requirement of sterility under aseptic conditions, in a sterile stand in 5 ml of purified water is dissolved 0.1 g of pilocarpine hydrochloride, which is obtained according to a prepared recipe. Add 0.07 g of sodium chloride (you can use a 10% concentrated solution of sodium chloride). An example of the use of concentrated solutions will be discussed below. Ophthalmic solutions are filtered through a sterile folded paper filter with a sterile cotton swab attached. The filter is pre-washed with sterile purified water. After filtering the solution, the remaining volume of solvent is passed through the same filter. Glass filters with a pore size of 10-16 microns can be used. When filtering through glass and other fine-porous filtering materials (for example, nuclear membranes), it is necessary to create excess pressure or vacuum. If there are mechanical impurities in the solution, the filtration is repeated. After the manufacture of eye drops fill the front side of the PPK: Date. PPK 20. "A". Aquae purificatae5 mlhydrochloridi0,1chloridi0,07purificatae5 ml V \u003d 10 ml Signatures: and write out the signature. A solution of up to 100 ml is sterilized for 8 min at 120 + 2 ° C. Again check the absence of mechanical impurities, in their absence, the solution is drawn up for vacation. In pharmacies, it is often made not according to individual prescriptions, but in the form of an intra-pharmacy blank and released upon presentation of a prescription. Concentrated solutions. Some medicinal substances in eye drops are contained in small concentrations (0.01; 0.02; 0.1%, etc.). In combination with the small volume of solution prescribed in the recipe, this causes difficulties in weighing and dissolving them (especially moderately, poorly and very poorly soluble medicinal substances). In such cases, it is advisable to use sterile concentrated solutions of medicinal substances (one-component and combined). The nomenclature of ophthalmic concentrated solutions approved for use is approved by the Ministry of Health of Russia and is presented in the Guidelines for the manufacture of sterile solutions in pharmacies. This list includes prescriptions containing compatible medicinal substances, withstanding thermal sterilization methods, having analysis methods for chemical control and established expiration dates (Table 3). Table 3 Thermal sterilization resistant drugs Solution,% Sterilization mode Storage conditions C Time, min. Term, days C Produced on purified water: Potassium iodide Acid of ascorbic acid Boric acid Sodium thiosulfate Sodium chloride Riboflavin Zinc sulfate Citral 20 (1: 5) 2 (1:50) 5 (1:20) 10 (1:10) 4 (1:25) 1 (1: 100) 10 (1:10) 0.02 (1: 5000) 1 (1: 100) 2 (1:50) 0.02 (1: 5000 ) 120 100 120 100 120 120 120 Prepare aseptically 8 30 8 30 8 8 8 30 3030 30; 5 30 30 30 90 90 30 30 225 3-5 25 25 25 25 25 25 3-5 25 3-4 Produced at 0.02% Riboflavin solution: Ascorbic acids Boric acid Nicotinic acid Sodium chloride 2 (1:50) 4 (1:25) 0,1 (1: 1000) 10 (1:10) 100 120 100 12030 8 30 85; 30 30 90 3025; 3-5 25 2 The manufacturing technology of an ophthalmic concentrated solution will be analyzed using the following example: Example 5 Solutionis Acidi nicotinici 0.1% cum Riboflavino 0.02% - 50 ml In a private st. GF indicated that "Riboflavinum" (Vitaminum B 2) - A yellow-orange crystalline powder with a weak specific smell, bitter taste, unstable in the light, very soluble in water (1: 5000). Acidum nicotinicum is an odorless white crystalline powder, slightly acidic taste, sparingly soluble in water, soluble in hot water. Note. Opened vials with sterile ophthalmic concentrates should be used within 24 hours. Sterile concentrated solutions are used for the manufacture of ophthalmic solutions not to be sterilized. The shelf life of eye drops from sterile concentrates according to non-standard prescriptions is 2 days. During the day, concentrated solutions made under aseptic conditions and not subjected to sterilization should be used. Concentrated solutions made under aseptic conditions (non-sterile) (in avoid re-sterilization, which can lead to the decomposition of drugs), is used to make eye drops according to standard prescriptions with the established sterilization mode. * Sterilized volume - up to 100 ml. Riboflavin weight (per 50 ml) 0.01 g. The mass of riboflavin (per volume of 50 ml) is 0.01 g. The mass of nicotinic acid (per volume of 50 ml) is 0.05 g. Calculations are recorded in the book of laboratory and packaging work. Manufacturing technology. Under aseptic conditions, 0.01 g of riboflavin is dissolved by heating. After complete dissolution of riboflavin in 50 ml of a hot solution of riboflavin, 0.05 g of nicotinic acid is dissolved. The solution is filtered through a folded paper, glass or other filter, washed with a 0.02% riboflavin solution. Check for the absence of mechanical impurities. Concentrated solutions are subjected to qualitative and quantitative control. The control results are recorded in the logbook of the results of organoleptic, physical and chemical control. The vial with the solution is sealed with a rubber stopper, a metal cap “running in”, sterilized for 30 minutes at 100 "C. 2.2 the Preparation of eye drops using concentrated solutions
The preparation of concentrated solutions in a pharmacy allows you to speed up the production of eye drops. The use of concentrated solutions made on purified water. Example 6 Rp .: Solutionis Riboflavin 0.01% - 10 ml Acidi ascoibinici 0.05. Da Signa 2 drops 3 times a day in both eyes. All stages of professional activity correspond to the stages described earlier. Let us dwell on the calculations in more detail. The mass of sodium chloride for isotonizing the solution is calculated by the formula: The concentration of drugs prescribed in the prescription is such that it practically does not affect the osmotic pressure, so the solution should be prepared on an isotonic (0.9%) sodium chloride solution. The method for calculating the volumes of concentrated solutions and purified water is similar to the calculations performed in the manufacture of mixtures using a burette system. The volumes of concentrated solutions and purified water: Riboflavin (0.001 5000) 5 ml Ascorbic Acid (0.05 20) 1.0 ml (0,081 10) 0.8 ml (10 - 5 - 1 - 0.8) 3.2 ml After manufacturing from memory fill the front side of the PPK: PPK Date22 Aquae purificatae 3.2 ml Solutionis Riboflavini 0.02% 5 ml Solutionis Acidi ascorbinici 5% 1 ml Solutionis Natrii chloridi 10% 0.8 ml V \u003d 10 ml Signatures: The sterilization regimen for eye drops made according to this recipe is not specified in the regulatory documents, therefore sterile concentrated solutions are used, which are measured under aseptic conditions with pharmacy pipettes in a sterile bottle for dispensing. The use of concentrated solutions made on a 0.02% solution of riboflavin. Example 7 Rp .: Solutionis Riboflavini 0.02% - 10 mlascorbinici 0.03 borici 0.2 Misce. D.S. 2 drops 4 times a day in both eyes. A copy is available in the appendix to the instructions for quality control of medicines manufactured in pharmacies. Sterilization mode: 120 ° C, 8 min. In the manufacture should use concentrated aseptic solutions. The calculations. The isotonic equivalent of boric acid for sodium chloride is 0.53 (Appendix 2.) 0.53-0.2 \u003d 0.106 (1.06%), i.e. the solution is slightly hypertonic, so sodium chloride is not added in this case. Given the limits of isotonic concentration (0.9 + 0.2)%, the solution can be considered as isotonic. When using concentrated solutions made on purified water, the volume of eye drops and the concentration of medicinal substances that do not correspond to the prescription will be obtained, which is unacceptable. Riboflavin solution 0.02% - 10 ml (\u003d 0.002 5000)
A solution of ascorbic acid 5% - 0.6 ml (\u003d 0.03 20)
Boric acid solution 4% - 5 ml (\u003d 0.2 - 25) The calculated volume of 15.6 ml - a lot more sodium chloride Purified water recipe indicated in the recipe. Therefore, concentrated solutions prepared using a 0.02% riboflavin solution are used. After performing the appropriate calculations and manufacturing the solution from memory, fill the front side of the PPC: PPK Date 23. Solutionis Riboflavini 0.02% 3.5 ml Solutionis Acidi ascorbinici 2%
cum0.02% .... 1.5 mlAcidi borici 4% cum 0.02% 5 ml V \u003d 10 ml Concentrated solutions are measured in a bottle for dispensing, corked, checked for the absence of mechanical impurities, drawn up for sterilization, sterilized and drawn up for dispensing. Eye lotions, solutions for irrigation of the mucous membrane of the eyes, solutions for washing and storing contact lenses and other ophthalmic solutions are made in the same way as eye drops, subject to the requirements of sterility, stability, the absence of suspended particles visible to the naked eye, isotonicity and, if necessary, prolonged action . Most often, lotions are used for lotions and rinses: solutions of boric acid, sodium bicarbonate, furacilin, ethacridine lactate, in extreme cases (for example, in case of eye lesions with drip-poisoning substances), a 2% solution of gramicidin can be prescribed. Packaging, corking. The bottle is corked with a rubber stopper and wrapped in an aluminum cap. If required (in accordance with ND), they are drawn up for sterilization by strengthening a special tag or tying with wet parchment indicating the name, concentration of the solution, last name and date of manufacture. Sterilization. Solutions are dispensed from the pharmacy aseptically made or sterilized by the method specified in regulatory documents. After sterilization, the solutions are again checked for mechanical impurities. Clearance for a vacation from a pharmacy. The vial with the solution is sealed (if the substance of list A is present in the recipe) without removing the parchment bandage used to design the vial for sterilization. If the solution has not been sterilized, the lid of the bottle (aluminum cap) is tied with wet Parchment, the thread is fixed on top with a wax seal. The bottle is supplied with the main pink label “Eye drops”, which indicates the number of the pharmacy, date of manufacture, name and initials of the patient, method of use, analysis number, expiration date, and the warning label “Handle with care”. A prescription containing in the recipe substances that are subject to quantitative registration remains in the pharmacy, unless the recipe has the special inscription “For prolonged use", For example, a prescription containing pilocarpine hydrochloride (for the treatment of glaucoma). Chapter 3. Quality Control
.1 Organoleptic control
At the manufacturing stage, solutions are subjected to organoleptic control according to indicators: color, smell, completeness of dissolution, transparency. Mechanical inclusions in the solution are determined on a UK-2 device (before and after sterilization). The verification procedure is described in the Instructions for the control of mechanical inclusions in injection and ophthalmic solutions and eye drops pharmacy manufacturing, (Appendix to the Guidelines for the manufacture of sterile solutions in pharmacies). . Modern devices operate on the basis of the photoelectric effect. .2 Physical control
is to check the total volume. Check each series of intra-pharmacy blanks and dosage forms. Dosage forms made according to individual recipes (requirements) are checked selectively, at least 3% of the total quantity produced per day. .3 Chemical control
Particular attention in the qualitative and quantitative control should be paid to drugs used in ocular practice (including for children) containing narcotic and toxic substances (for example, silver nitrate solutions), as well as to all concentrated solutions. When analyzing eye drops, the content of isotonic and stabilizing substances is determined before sterilization. 3.4 Control when leaving the pharmacy
It consists in verifying the compliance of the package with the physicochemical properties of the ingredients, the number on the prescription, receipt, label, signature, patient name on the prescription, label, signature, receipt; compliance of the signature with the recipe, preparation of the drug with current requirements. Chapter 4. Requirements for pharmacies
.1 Composition of premises and equipment of the pharmacy
In accordance with the planned volume of work and the nature of production activities, the composition of the premises and the equipment of the pharmacy is determined taking into account the recommendations of the Ministry of Health of the Russian Federation and SNiP. The minimum composition of pharmacy premises includes: a trading room, a room for preparing medicines, a room for receiving distilled water, a washing room, a manager’s office, a staff room, a room for storing medicines, a toilet, and a dressing room. It is mandatory that the pharmacy has water supply, sewage, a telephone, electricity, gas, stove heating (in the absence of other types of energy resources). The minimum size of the trading floor is 20 square meters. m In a pharmacy with a minimum size of the trading floor there can be one workplace. Payment of the cost of medicines by the population should be carried out through a cash register. The area for the preparation of medicines should be at least 15 square meters. m and is equipped with special pharmacy furniture, appliances, equipment for the preparation, mixing, filtering, packaging, labeling, packaging and corking of medicines, safes (special cabinets) for storing poisonous and narcotic drugs, ethyl alcohol, bar-eyes, measuring instruments for weight, volume, beats weight, reagents for chemical control of drugs. In the room for the preparation of medicines, workplaces should be organized for the preparation and quality control of medicines. Depending on the volume of work and the increase in the area of \u200b\u200bthe assistant room, specialized workplaces for the manufacture of various dosage forms can be created. The minimum area for receiving distilled water is 5 sq.m. It must be equipped with devices for receiving and containers for storing distilled water in accordance with the current rules on the sanitary regime of pharmacies. The minimum area of \u200b\u200bthe washing room is 5 sq.m. Its equipment must ensure compliance with the sanitary requirements of pharmacies. The area of \u200b\u200bthe autoclave is at least 10 sq.m. Premises for storing stocks of medicines and medical devices should have a minimum area of \u200b\u200bat least 36 sq.m and should be equipped with racks, cabinets and other necessary equipment to ensure the preservation of toxic, narcotic, potent, flammable, thermolabile and other medicines, medicinal products plant materials, medical devices in accordance with their physicochemical properties. Staff room - at least 8 square meters. m and is equipped with furniture for eating and relaxing staff. The area of \u200b\u200bthe dressing room should ensure the storage of home and work clothes in accordance with the requirements for the sanitary regime of pharmacies. ophthalmic drug industrial pharmacy 4.2 Pharmacy operations
By the nature of production activities, pharmacies are divided into: manufacturing medicines according to prescriptions of doctors and the requirements of medical institutions and implementing the implementation of finished medicines (manufacturing pharmacy); selling finished medicines to the population and medical institutions (pharmacy of finished medicines). Mandatory for the pharmacy is the presence of the State Pharmacopoeia, regulatory and technical documentation, reference books on manufacturing technology, quality control, storage conditions, and the rules for dispensing medicines. To perform its main task, a production pharmacy should have additional premises: aseptic unit for the preparation of aseptic and sterile dosage forms; autoclave; chemist's office - analytics; a room for pyrogen-free water; storage facilities for flammable, thermolabile and other medicines requiring special storage conditions in accordance with their physicochemical properties. The location of production facilities should exclude oncoming flows of the manufacturing process of sterile and non-sterile medicines. The organization of jobs should ensure compliance with sanitary and pharmaceutical requirements, the technology for the manufacture of dosage forms and their quality control. The quality control of medicines and distilled water is regulated by regulatory documents of the Ministry of Health of the Russian Federation. In industrial pharmacies manufacturing eye drops and sterile dosage forms, physico-chemical and microbiological quality control of distilled water and medicines should be carried out. To pack manufactured medicines, a pharmacy must have packaging material and glassware, as well as special equipment for its disinfection, washing, drying, and sterilization. Equipment intended for the manufacture of sterile dosage forms must be validated - confirmation of the ability of the equipment and auxiliary systems in the reliability of work, taking into account permissible deviations. The pharmacy must strictly comply with pharmaceutical and sanitary requirements. Pharmacy employees engaged in the manufacture and quality control of sterile medicines must undergo certification to assess knowledge and practical skills in the manner prescribed by applicable law. Technical and economic equipment of pharmacies should be carried out in accordance with regulatory documents. All devices, apparatuses available in the pharmacy must have technical passports, and their maintenance and repair must be done in a timely manner. To perform the main task, a pharmacy must have a stock of medicines approved for use in the Russian Federation, including vital medicines, according to the list approved by the Ministry of Health of the Russian Federation. As directed by local health authorities, individual pharmacies should have a minimum supply of vaccines and serums. Chapter 5. Industrial production of eye drops
.1 Eye Drop Technology
In industrial production, eye drops in a dropper tube are prepared in rooms of the II class of cleanliness under aseptic conditions. The room and equipment are wet-cleaned, disinfected with a 3-5% phenol solution and sterilized with bactericidal lamps for 2 hours. The dissolution is carried out in stirred tank reactors, then analyzed and subjected to filtering in turn (first for purification from mechanical impurities, and then for sterilization). The resulting solution is placed in a sterilized apparatus for filling tube droppers. In parallel with this, cases and caps are made of tube droppers. A case with a capacity of 1.5 ± 0.15 ml and a wall thickness of 0.5 ± 0.1 mm is formed on the machine in several stages by blowing and stamping from granules of high-pressure polyethylene grade 15803-020 or 16803-070. Caps with a pin for puncturing are poured under pressure from the molten granules of low pressure polyethylene grade 20906-040 or 20506-007. After manufacturing, they are washed with distilled water, dried and subjected to gas sterilization at 40-50 with a mixture of ethylene oxide and 10% carbon dioxide for 2 hours. Ethylene oxide is removed from the products by keeping them for 12 hours in a sterile room. Further, under aseptic conditions in a unit with excess pressure of sterile air, the caps are screwed onto the body, filled with a solution of a medicinal substance using metering pumps and sealed by heat sealing. On a printing machine, an inscription with the name of the drug is applied to the body on both sides, indicating its concentration and volume. Filled tube droppers are visually checked for the absence of mechanical impurities on a black and white background when illuminated with a 60 W electric lamp, 5% of each batch is subjected to a complete analysis. The dropper tube is packed in single cases, in cardboard boxes or in polyvinyl chloride film. In addition to this package, according to GOST 17768-80, glass bottles with a stopper-pipette from unstabilized low-density polyethylene are recommended for eye drops. Before filling, the solution is sterilized by filtration, and pipette tubes by gas sterilization with ethylene oxide with 10% carbon dioxide. .2 Monitoring of ophthalmic solutions for mechanical impurities
Eye drops should be completely transparent and not containing any suspended particles that can cause mechanical damage to the membranes of the eye. Eye drops should be filtered through the best grades of filter paper, with a small lump of long-fiber wool placed under the filter. It is important that after filtration, the concentration of the solution and its total mass do not decrease more than is allowed by established standards. All that has been said about filtering small amounts of solutions fully and primarily relates to eye drops. According to the recipes that are often found in the recipe, it is advisable to resort to the help of intra-pharmacy blanks - concentrates prepared on time, which frees from filtering small amounts of liquids. The nomenclature of eye drops produced in tube droppers and vials. The range of dosage forms for the eyes, currently produced in the factory in tube droppers, is still small and, of course, needs further expansion. However, this problem is not simple and easily solvable, since the development of technical standards for each new name of a medicinal substance is associated with the solution of a number of issues. First of all, from a huge number of prescriptions of ophthalmic medicines, one should select and analyze those that are constantly found in the eye practice of the whole country or, at least, in large settlements. Next, it is necessary to determine the most commonly used concentrations of the drug substance, and these values \u200b\u200bmust be sufficiently stable or maintained at a constant level by the addition of stabilizers. Finally, appropriate analysis techniques should be available or developed, both for the drug substance itself and for other components of the drug. Only after this can we begin to study the interaction of polymer packaging materials with a solution of a medicinal substance during production, sterilization and storage conditions. It should be borne in mind that at the final stage of these studies, which sometimes continue for a long time, negative results can be obtained. In this case, you have to start all over again and continue to search for other optimal options. Methods for cleaning solutions of medicinal substances, along with ensuring sterility, an equally important problem in the industrial production of ophthalmic drugs in new forms of packaging is the absence of mechanical impurities in solutions. To solve it, it is planned to carry out appropriate measures in two directions: cleaning solutions of medicinal substances and maintaining industrial cleanliness in industrial premises. Based on the results of work on the influence of the process of freezing eye drop solutions on their physicochemical properties, notes were made in the Storage section of the relevant pharmacopeia article: “Freezing during transportation and storage is not a contraindication to its use.” At the same time, additional experiments were put on storing eye drops in polymer packaging in a frozen state in order to study the possibility of extending their shelf life. For the experiments, preparations of sulfacyl sodium (20%) and zinc sulfate (0.25%) with boric acid (2%) produced by industry on a wide [industrial scale] were selected. Eye drops were stored at a temperature of - 10 ± 2 ° C, checking at certain intervals their qualitative and quantitative indicators for compliance with the requirements of pharmacopoeial articles. Currently, work in this direction is ongoing. Increased shelf life of eye drops and improved technology for the production of plastic containers Figure 3. Pharmaceutical equipment Chapter 6. Analysis of the implementation of ophthalmic dosage forms
.1 Research Methods
For achievement set goals and decisions tasks it is necessary to analyze the implementation of ophthalmic dosage forms manufactured in pharmacies and in industrial settings. Compare the expiration dates of ophthalmic dosage forms manufactured in a pharmacy and in an industrial environment. Consider the sales of ophthalmic dosage forms over five years (2008-2012) in production pharmacies (No. 262) and selling finished dosage forms (Pharmacy LLC Soglasie and Pharmacy Implosiya) (table 5). Table 5 Implementation of ophthalmic dosage forms 2008-2012 g Pharmacy 262 (Central City Hospital), LLC “CONSENT” Pharmacy Implosiya2008, 3423176719562009, 228229321842010, 2506242824892011, 1682296429582012, 129929463057 We calculate the dynamics of sales. If we take the testimony of 2008 for 100%, and the rest of the indicators recounted as a percentage in relation to it: Pharmacy No. 262 of the Central City Hospital where 3423 -100%; g. \u003d (2328 x100) / 3423 \u003d 68%; g. \u003d (2506x100) / 3423 \u003d 73%; d. \u003d (1682x100) / 3423 \u003d 49%; g. \u003d (1299x100) / 3423 \u003d 38%; Based on the calculations, we see that in pharmacy No. 262 in 2009, sales of ophthalmic dosage forms fell by 32% compared to 2008, which is 1095 packages less than what was sold in 2008. In 2010, there was a decline in sales by 27% (917 packages). In 2011, the decline was 51% (174 packages) and in 2012 - 62% (2124 packages). Figure 4. Indicators of sales dynamics of Pharmacy No. 262 Figure 4 shows us that over the past five years, there has been a decline in sales of ophthalmic dosage forms Pharmacy LLC "Consent" where 1767-100%; g. \u003d (2293x100) / 1767 \u003d 129%; g. \u003d (2428x100) / 1767 \u003d 137%; g. \u003d (2964x100) / 1767 \u003d 168%; d. \u003d (2946 x100) / 1767 \u003d 167%; Based on the calculations, we see that in the pharmacy of Soglasie LLC the sales of ophthalmic dosage forms in 2009, compared to 2008, increased by 29%, i.e. 526 packs more than was sold in 2008. In 2010, the percentage of sales increased by 37% (661 packages); 2011 68% (1197 packs); 2012 67% (1179 packs). Here we are witnessing a steady increase in the volume of sales of ophthalmic dosage forms, although 2012 indicators are lower than 2011 by 1%, but this can be explained by the presence of a competitive neighbor, the Implosia pharmacy Figure 5. Indicators of sales dynamics Pharmacy LLC "Consent" Figure 5 shows that over the past five years, there has been an increase in sales of ophthalmic dosage forms relative to 2008. Pharmacy "Implosion" where 1956 -100%; g. \u003d (2189x100) / 1956 \u003d 112%; g. \u003d (2489x100) / 1956 \u003d 127%; g. \u003d (2958x100) / 1956 \u003d 151%; g. \u003d (3057x100) / 1956 \u003d 156%; Figure 6 Indicators of sales dynamics Pharmacy "Implosia" Based on the calculations, we see in the implosion pharmacy selling ophthalmic dosage forms in 2009, compared to 2008. increased by 12%, i.e. 228 packs more than in 2008. In 2010 sales grew by 27% (533 packs); in 2011 by 51% (1,002 packages) and in 2012 by 56% (1,101 packages). There is also a steady increase in sales of ophthalmic dosage forms compared to 2008. Figure 6 shows that over the course of five years, there has also been an increase in sales of ophthalmic dosage forms relative to 2008. Figure 7. Dynamics of sales by pharmacies In Figure 7 we see that the dynamics of sales in manufacturing pharmacies (Pharmacy No. 262) decreased markedly in relation to 2008, and the dynamics of sales in pharmacies selling finished medicinal ophthalmic forms increased in relation to 2008. From which we can conclude that the population’s need for manufacturing pharmacies is declining. .2 Analysis of the shelf life of ophthalmic dosage forms manufactured in pharmacies and in industrial settings
To achieve this goal and solve problems, we consider the shelf life of ophthalmic dosage forms manufactured in the pharmacy and in industrial conditions, using atropine 1%, chloramphenicol 0.2%, pilocarpine 1%, zinc sulfate and sulfacyl sodium 20% (table 6) (Figure 3) Table 6 Shelf life of ophthalmic dosage forms manufactured in the pharmacy and industrial conditions Eye drops Shelf life of HF manufactured in a pharmacy Shelf life of HF industrial production (year) Atropine 1% 30 days 2 years Levomycetin 0.2% 7 days 2 years Pilocarpine 1% 30 days 3 years Zinc sulfate 30 days 2 years 6 months Sulfacil sodium 20% 30 days 30 days 2 years Based on the indicators, we can say for sure that the shelf life of ophthalmic dosage forms of industrial production significantly exceeds the shelf life of eye drops made in a manufacturing pharmacy. Figure 8. Ophthalmic dosage forms drug production
In accordance with the order of the Ministry of Health of the Russian Federation dated July 16, 1997 “On Quality Control of Medicines Manufactured in a Pharmacy”, the expiration dates of eye drops and ophthalmic solutions hermetically sealed in bottles with rubber stoppers for “run-in” are from 7 to 30 days, moreover they depend on the temperature during storage. Solutions containing drugs that are sensitive to light are stored in a dark place. Solutions of citral 0.01%, fetanol 3%, riboflavin 0.01-0.02%, ascorbic acid 0.2%, as well as eye drops, capped "under the wrap", have a shelf life of no more than 2 days. What we can see in table No. 6, which shows examples of the most common ophthalmic dosage forms manufactured in a pharmacy and their factory analogues, which have a shelf life of two, and provided glass packaging is up to three years (Fig. 9.1; 9.2). Figure 9.1 Dropper Bottle Figure 9.2 Glass packaging From which we can assume that the reason for the transition of pharmacies from the production format to pharmacies that sell ready-made ophthalmic dosage forms is the more advantageous storage of medicines. That is, the pharmacy does not bear the cost of equipping additional production facilities, as a rule there are no losses of raw materials, except for the expired shelf life. But if you follow the “first come, first leave” rule and timely sell these drugs, before the expiration date, the losses will be minimal or reduced to zero. Also, packages with a longer shelf life are beneficial for purchasers, since in most cases people with chronic eye diseases buy eye drops and take 1-2 packs “in reserve”. Conclusion
The main purpose of this course work - identification and analysis of patterns of industrial production and pharmacy manufacturing of ophthalmic dosage forms. To achieve this goal, the following tasks were solved: The theoretical literature on the research topic has been studied. The requirements for eye drops and pharmaceutical preparations were studied. The manufacture of eye drops by dissolving medicinal and auxiliary substances is considered. The composition of concentrated solutions of medicinal substances used in the manufacture of ophthalmic solutions is analyzed. The manufacture of eye drops using concentrated solutions is considered. 6. The types of quality control during the vacation from the pharmacy are considered. Studied the requirements for pharmacies. At the end of the work, we can draw the following conclusions: at present, the manufacture of ophthalmic dosage forms in Syzran, as well as other forms, under pharmaceutical prescriptions by a doctor’s prescription, has noticeably decreased, for example, in production pharmacy No. 262 in 2009, sales of ophthalmic dosage forms fell by 32 % in relation to 2008, which is 1095 packages less than what was sold in 2008. In 2010, there was a decline in sales by 27% (917 packages). In 2011, the decline was 51% (174 packages) and in 2012 - 62% (2124 packages). Despite this, some drugs, with today's abundance of drugs, still have no factory analogues. Production pharmacies have the opportunity to independently prepare individual medicines for a patient who has applied to a pharmacy, taking into account his illness, age, and individual intolerance. We must not forget that a person has his own individual characteristics, and some component of the finished product can cause intolerance. In this case, an individual medicine is prepared without such a component. However, the manufacture of prescription drugs requires a manufacturing base and appropriate staff qualifications. In view of this, far from all pharmacies have the ability and the right to make medicines. This situation is typical for a number of other territories of the region. Pharmacies where there is a prescription and production department are closed. In the city and the district, three pharmacies make dosage forms, since it is economically unprofitable. To make production worthy, it is necessary to observe high requirements, create sterility conditions, and carry out constant monitoring of dosage forms. In pharmacy conditions, medical equipment is used for manufacturing - autoclaves, drying ovens, which are very expensive to maintain. The problem of pharmacy production is currently acute. Transitioning to market relations forces pharmacists to be economically literate. If we consider the problem from the standpoint of profitability, then everything is clear: on 20 square meters you can place racks and display cases with a thousand preparations, but this place is not enough to be able to prepare potion and ointment in accordance with regulatory requirements. The rent is the same, moreover, it is constantly growing, as well as utility bills. With prescriptions for the day, much fewer patients come to the pharmacy than for ready-made medicines, and the manufacturing process is laborious. Considerable funds are required to maintain a separate production facility in accordance with sanitary regulations. List of references:
1.Bykov V.A. [and etc.]. Pharmaceutical technology. A guide to laboratory studies: a textbook / - M.: GEOTAR-Media, 2009. - 304p. 2.Bykov V.A. [and etc.]. Pharmaceutical technology. A guide to laboratory studies: a training manual / - M.: GEOTAR-Media, 2010. - 304p. 3.State Pharmacopoeia of the Russian Federation 12-part 1 / M .: Scientific Center for Expertise of Medical Devices, 2008. - 704 p.: Silt 4.Grossman V.A. Pharmaceutical Technology Author: Publisher: GEOTAR-Media; 2012 Series: Didactics: 320 pp. .Denisova T.V. [and etc.]. Technology of dosage forms. Textbook, Abstract to the book "Pharmaceutical technology. Medicine, hardcover, 2007 .Guidelines for the manufacture of sterile solutions in a pharmacy. - M., 1994 .New technologies in medicine and pharmacy. Tizol .: collection of scientific articles. Materials of the interregional scientific-practical conference. / Ed. O.P. Kovtun. - Yekaterinburg: UGMA, 2010 .-- 160 p.: Ill. 8.Nikolsky V.S. Pharmaceutical technology. Guide to laboratory exercises.<#"justify">10.Workshop on the technology of dosage forms: a study guide for students studying in special. 060108 - Pharmacy / Ed. I.I. Krasnyuk, G.V. Mikhailova. - 3rd ed., Revised. and add. - M.: Publ. Center "Academy", 2007. - 432. 11.Order of the Ministry of Health of Russia “On the schedule of prescribing and prescribing medicines, medical devices and specialized medical nutrition products” dated February 12, 2007 No. 110 .Order of the Ministry of Health of Russia "On quality control of medicines manufactured in pharmacies" dated July 16, 1997 No. 214 Order of the Ministry of Health of Russia "On norms of deviations allowed in the manufacture of medicines and packaging of industrial products in pharmacies" dated October 16, 1997 No. 305. .Textbook for students of pharmaceutical universities and faculties. Authors: Ed. A.I. Tikhonov. 11/06/2007. Pharmaceutical Technology Guide. 14.Pharmaceutical technology. The technology of dosage forms: a textbook for stud., Training. by special 040500 - Pharmacy / Ed. I.I. Krasnyuk, G.V. Mikhailova. - 2nd ed., Stereotype. - M.: Publ. Center "Academy", 2006. - 592.- (Higher vocational education). 15.Pharmaceutical technology. The technology of dosage forms: a textbook for stud., Training. by special 040500 - Pharmacy / Ed. I.I. Krasnyuk, G.V. Mikhailova. - 3rd ed., Revised. and add. - M.: Publ. Center "Academy", 2007. - 592 p. - (Higher vocational education). .Pharmaceutical Technology: Technology of dosage forms. Ed. I.I. Krasnyuk, G.V. Mikhailova, M .: GEOTAR-Media, 2011. D. Muravyova, I. Samylina, G. Yakovlev. Pharmacognosy. Textbook for students. Annex 1
Prescription eye drops and ophthalmic irrigation solutions containing stabilizers Name and composition of solutions Sterilization mode Storage temperature Shelf life, days Note * Dicaine solution 0.5%, 1%, 2%, 3% Dicaine 00.5 g, 0.1 g, 0.2 g, 0.3 g. Sodium chloride 0.081 g, 0.072 g, 0.053 g, 0.035 g Sodium thiosulfate 0.005 g, 0.005 g, 0.005 g, Purified water to 10 ml 120 about . 8 min< 25 3-5120 302% и 3% р-ра хранить в холодильнике нельзяMesatone solution 1% Mesatone 0.1 g Sodium chloride 0.056 g. Sodium metabisulfite 0.01 g. Purified water up to 10 ml 120 about . 8 min< 25 3-530 30__**Riboflavin 0.002 g Potassium iodide 0.2 g Glucose (anhydrous) 0.2 g Trilon 0.003 Sodium metabisulfite 0.01 Water purified to 10 ml 100 about . 30 minutes__** Riboflavin 0.002 g Ascorbic acid 0.02 g Glucose (anhydrous) 0.2 g Trilon 0.003 Sodium metabisulfite 0.01 Water purified to 10 ml 100 about . 30 minutes< 25 3-530 30Раствор изготавливают на свеже-прокипяченой воде очищенной.Sulfacyl sodium solution 20% Sulfacyl sodium solution 2 g Sodium metabisulfite 0.05 g Sodium hydroxide solution (one mol / l). 0.18 ml of purified water to 10 ml100 about . 30 min 3-5-5 __ ** Sulfacyl sodium solution 10%, 20%, 30% Sulfacyl sodium 1 g, 2 g, 3 g Sodium thiosulfate 0.015 g Hydrochloric acid solution (one mol / l). 0.035 ml of purified water to 10 ml120 about . 8 min< 25 3-530 30Раствор можно использовать для инсталляции новорожденным**Fetanol solution 3% Fetanol 0.3 g Sodium metabisulfite 0.01 g Purified water up to 10 ml 120 about . 8 min< 25 3-530 30__**Physostigmine salicylate solution 0.25% Physostigmine salicylate 0.025 g Nicotinic acid 0.003 g Sodium metabisulfite 0.003 g Sodium chloride 0.08 g, Purified water to 10 ml120 about . 8 min< 25 3-530 30__**Ophthalmic saline solution Sodium chloride 5.30 g Potassium chloride 0.75 g Calcium chloride (anhydrous) 0.48 Sodium acetate (anhydrous) 3, 90 Glucose (anhydrous)) 0.80 Diluted hydrochloric acid (8%) 0.05 ml Purified water to 1 liter Sodium chloride 5.30 g Potassium chloride 0.75 g Calcium chloride (anhydrous) 0.48 Sodium acetate (anhydrous) 3, 90 Glucose (anhydrous)) 0.80 Magnesium chloride (anhydrous) 0.30 Acids diluted hydrochloric (8%) 0.05 ml of purified water to 1 l about . 12 min< 2530
Table of isotonic equivalents for sodium chloride (1 g of drug substance - equivalent amount of sodium chloride in grams) Name of the medicinal substance (1 g) Equivalent to the amount of sodium chloride (in g) Name of the medicinal substance (1 g) Equivalent to the amount of NaCl (in g) Aminazine Amidopyrine Amizil Glucose (anhydrous) Homatropine hydrobromide Dikain Diphenhydramine Potassium iodide chloride Calcium chloride Acid aminocaproic ascorbic boron nicotinic cocaine hydrochloride Caffeine - sodium benzoate Lobelin hydrochloride Magnesium sulfate Copper sulfate Mesatone Morphine hydrochloride Sodium acetate benzoate bisulfite bromide bicarbonate iodide metabisulfite nitrite Sodium p ara-aminosalicylate Sodium salicylate 0.10 0.15 0.19 0.18 0.16 0.18 0.20 0.35 0.76 0.36 0.27 0.18 0.53 0.25 0.14 0 , 23 0.14 0.14 0.13 0.28 0.15 0.46 0.40 0.60 0.62 0.65 0.38 0.65 0.83 0.27 0.35 Apomorphine hydrochloride Atropine sulfate Aceclidine Sodium tetraborate thiosulfate phosphate (disubstituted) chloride citrate for injection Nicotinamide Novocaine Novocainamide Papaverine hydrochloride Pilocarpine Platifillina hydrotartrate Proserin Promedol Silver nitrate Scopolamine hydrobromide sovcainine sorbitol Strichinum hydrochloride hydrochloride trichloride nitrate tina hydrochloride Ethyl morphine hydrochloride Eufillin Ephedrine hydrochloride 0.14 0.10 0.20 0.34 0.30 1.00 1.00 0.30 0.20 0.18 0.22 0.10 0.22 0.13 0, 19 0.22 0.33 0.11 0.13 0.19 0.12 0.21 0.21 0.716 0.31 0.12 0.28 0.10 0.15 0.17 0.28 Appendix 3 .. . Assortment management functions at the enterprise level is an important element in the operational study of the degree of development of production and circulation. Packaging and closures for medicines in a pharmacy polymers are used for the production of syringe tubes (for dosage forms intended for injection); a dropper tube is used to pack eye drops; contours used for packaging suppositories
