Chapter 8 medicated applications
Download as PPT, PDF22 likes5,622 views
The document discusses the formulation and manufacturing processes of topical pharmaceuticals, focusing on components such as vehicles, emollients, and absorption factors affecting drug delivery through the skin. It details various raw materials used in medicated semisolid formulations, their functions, and types, alongside preservation methods and the requirements for microbiological testing. Additionally, it outlines specific manufacturing methods, especially the fusion method for semisolids, and emphasizes the importance of adhering to USP standards for quality and safety.
More Related Content
Similar to Chapter 8 medicated applications (20)
Chapter 8 medicated applications
- 1. 1 Presented by: Asst. Prof. MA. LOURDES LICSI-MOJARES, RPh CEU School of Pharmacy
- 2. USES OF TOPICAL PHARMACEUTICALS VEHICLES FOR TOPICALLY – APPLIED DRUGS ( Non-medicated ointment bases) EMOLLIENTS – provide soothing / softening effects on the surface tissues PROTECTIVES / OCCLUSIVE DRESSINGS 2
- 3. FACTORS INFLUENCING ABSORPTION OF DRUGS THROUGH THE SKIN A. Partition Coefficient of Drugs through the Skin Substances possessing both water and lipid solubility are favorably absorbed through the skin. 3
- 4. FACTORS INFLUENCING ABSORPTION OF DRUGS THROUGH THE SKIN B. Moisture and Temperature in the Environment of the Skin B.1 Moisture Balance in the Skin It is found in the stratum corneum layer of the epidermis. It prevents the NMF (Natural Moisturizing Factor) from being stripped from the skin. NMF prevents skin from drying out, even during excessive contact of the skin with water. 4
- 5. FACTORS INFLUENCING ABSORPTION OF DRUGS THROUGH THE SKIN B.2 Insensible Perspiration The skin constantly releases water in the skin surface, which evaporates quickly without being noticed. When the surrounding environment has a high moisture content, the rate of evaporation of sweat is slowed down, and the person becomes aware of the clammy moist sensation on his skin. 5
- 6. FACTORS INFLUENCING ABSORPTION OF DRUGS THROUGH THE SKIN C. Pathological Injury to the Skin Skin penetration has been enhanced by abrasions or when the skin is stripped of its barrier layer. 6
- 7. FACTORS INFLUENCING ABSORPTION OF DRUGS THROUGH THE SKIN D. Type of Vehicle Used Skin penetration of drug substances may be enhanced by the use of a suitable semisolid base. The vehicle may help increase the rate of penetration of a drug substances into the skin. It serves as a carrier for the API. 7
- 8. RAW MATERIALS IN THE FORMULATION OF MEDICATED APPLICATIONS FDA approves chemical substances and states the maximum concentration considered safe for food and cosmetics (GRAS grade). The supplier of these drug substances supplies brochures / information which indicates that FDA APPROVAL SAFETY TESTS are conducted. 8
- 9. THE FREQUENT RAW MATERIALS FOR MEDICATED SEMISOLIDS HYDROCARBONS Petrolatum and Mineral oil are the MOST WIDELY USED substances in semisolids, next to water. PETROLATUM– a complex mixture of semisolids containing hydrocarbon aliphatic, cyclic, saturated, unsaturated, branched and unbranched substances in varying proportions. MINERAL OIL – derived from petroleum acid. It is less tacky and with lower viscosity. 9
- 10. THE FREQUENT RAW MATERIALS FOR MEDICATED SEMISOLIDS HYDROCARBON WAXES 1. Help increase the viscosity of hydrocarbons such as petrolatum and mineral oil 2. prevent separation of hydrocarbons from the ointment. Examples: paraffin, beeswax, ceresin wax (mixture of paraffin and ozokerite). 10
- 11. THE FREQUENT RAW MATERIALS FOR MEDICATED SEMISOLIDS OLEAGINOUS SUBSTANCES Vegetable fixed oils which contain glycerides of mixtures of saturated and unsaturated fatty acids (MCT’s and FA’s). These are employed for its EMOLLIENT and SKIN-LUBRICATING effects. Examples: Fixed oils of peanut, olive, sesame, cottonseed, coconut, corn 11
- 12. THE FREQUENT RAW MATERIALS FOR MEDICATED SEMISOLIDS FATTY ACIDS and ALCOHOLS Functions as; 1. auxiliary emulsifiers 2. viscosity –builders Examples: Stearic acid – emulsifiers in water-removable creams Stearyl / Cetyl Alcohols - emollients, provides the necessary firmness / softness in consistency of creams. 12
- 13. THE FREQUENT RAW MATERIALS FOR MEDICATED SEMISOLIDS EMULSIFIERS Substances that; a. Prevent Coalescence b. act as Product stabilizers Examples: Triethanolamine stearate, SPANS, TWEENS, Carbowax 13
- 14. THE FREQUENT RAW MATERIALS FOR MEDICATED SEMISOLIDS POLYOLS Used as Humectants, prevents dehydration and “Crusting” on top of creams and ointments in jars. Examples: Glycerin, PG, Sorbitol 70%, PEG (lower MW) 14
- 15. THE FREQUENT RAW MATERIALS FOR MEDICATED SEMISOLIDS INSOLUBLE POWDERS These must be uniformly dispersed throughout the semisolid vehicle to assure product homogeneity. These solids must be impalpable to the touch.. Particles less than 74 micronsParticles less than 74 microns (equivalent to 200 mesh) is said to be(equivalent to 200 mesh) is said to be impalpable to most peopleimpalpable to most people.. 15
- 16. TYPES OF SEMISOLID VEHICLES NON-MEDICATED BASES Factors which Influence the Choice of Semisolid Vehicles 1. Nature of the skin lesion 2. Skin Type 3. Solubility of the formulation components 4. Stability of the API’s 16
- 17. TYPES OF SEMISOLID VEHICLES NON-MEDICATED BASES HYDROCARBON BASES Typically lipophilic Spreads easily onto the skin Difficult to remove / wash-off Act as occlusive dressings, since the normal evaporation of insensible perspiration is inhibited. Examples are White petrolatum, Mineral oil, White / Yellow Ointment, USP 17
- 18. TYPES OF SEMISOLID VEHICLES NON-MEDICATED BASES ABSORPTION / EMULSIFIABLE BASES These are hydrophilic mixtures formed by the addition of substances that possess polar groupings ( sulfates, carboxyl, hydroxyl or ether linkages) to a Hydrocarbon Base. Lanolin, Cholesterol, Sorbitan monostearate / monooleate are added to Hydrocarbon bases to make it hydrophilic. 18
- 19. TYPES OF SEMISOLID VEHICLES NON-MEDICATED BASES WATER – REMOVABLE / WASHABLE BASES These are o/w emulsions referred to as Creams. Upon application, there is little or no evidence of its presence onto the skin. Best for moist skin lesions, since its o/w character tend to adsorb serous discharges. 19
- 20. TYPES OF SEMISOLID VEHICLES NON-MEDICATED BASES WATER – REMOVABLE / WASHABLE BASES Vanishing creams, Foundation creams, Shaving Creams. Vanishing creams type of vehicles are of o/w type. Absorption bases are of w/o type. 20
- 21. TYPES OF SEMISOLID VEHICLES NON-MEDICATED BASES WATER-SOLUBLE / GREASELESS BASES Prepared from mixtures of high and low MW PEG No water is required in its preparation Water soluble, due to many polar groups and ether linkages 21
- 22. TYPES OF SEMISOLID VEHICLES NON-MEDICATED BASES WATER-SOLUBLE / GREASELESS BASES Suitable combinations of high and low MW PEG yield products having an ointment-like consistency, which soften or melt when applied topically. Low MW PEG – liquids Moderately high MW PEG – unctuous Very High MW PEG - solids 22
- 23. OPTHALMIC OINTMENTS Semisolid ophthalmic vehicles frequently contain any of the ff. bases that have been sterilized; 1. petroleum jelly 2. absorption base (Lanolin or Lanolin Alcohol) 3. water-soluble base Insoluble API powders should meet the requirements for IMPALPABILITY. Ophthalmic ointments should be rendered STERILE and ISOTONIC. 23
- 24. OTHER OPTHALMIC OINMENT BASES Lanolin Sterilized by Gamma Radiation or Sterilization by Filtration Lanolin Alcohol Possess emollient properties suitable for eye ointment formulation. 24
- 25. 25
- 26. PRESERVATION FROM MICROBIAL SPOILAGE The chemical preservative for semisolids should be evaluated as to: 1. Stability with regard to formulation components 2. Container to be used. 26
- 27. CHARACTERISTICS OF PRESERVATIVES FOR SEMISOLID PRODUCTS Some preservatives become inactive in the presence of other ingredients. Boric acid may be used in ophthalmic ointments against bacterial/ fungal contamination. Bacterial counts should be made on the water supply, RM, pipelines, filling equipment and containers. 27
- 28. USE OF ANTI-OXIDANTS Anti-oxidants are added to semisolids, whenever oxidative deterioration is anticipated. BHA, BHT, Propyl gallate 28
- 29. USE OF ANTI-OXIDANTS The choice of anti-oxidant is made upon consideration of the following factors: 1. toxicity / irritating potency 2. compatibility 3. odor 4. discoloration 5. solubility 6. stability 29
- 30. MANUFACTURING PROCESS OF SEMI-SOLIDS Factors to be controlled during the Fusion Method: 1. Time of mixing 2. Temperature of mixing 3. Rate of agitation ( and other mechanical works) 30
- 31. MANUFACTURING PROCESS OF SEMI-SOLIDS FUSION METHOD ANHYDROUS OINTMENTS are manufactured by this process, which is made by dissolving the API’s in the previously melted fats and waxes. The melted mass must be mixed while cooling to ensure the homogenous distribution of the ingredients. 31
- 32. STEPS IN FUSION METHOD Step 1: PREPARATION OF THE OIL PHASE Flake / pulverize the dry ingredients. Heating is required to melt some ingredients (waxes), usually at 700 C to 750 C. Blend in advance and disperse in mineral oil or silicone oil. 32
- 33. STEPS IN FUSION METHOD Step 2: HYDRATION OF THE INGREDIENTS IN THE AQUEOUS PHASE Emulsifiers, stabilizers, thickening agents are dispersed into water in a separate vessel. Usually followed by a filtration procedure, if needed. Heating may be required to accelerate hydration. 33
- 34. STEPS IN FUSION METHOD Step 3: FOAMING THE EMULSION The aqueous and oil phases are blended under vigorous agitation, to form the emulsion. Temperature is controlled between 300 C to 400 C. Defoaming procedures are done to minimize foam formation after the product has emulsified. 34
- 35. STEPS IN FUSION METHOD Step 4: DISPERSION OF THE ACTIVE/S The API’s make up only a small proportion of the formulation. It must be EFFICIENTLY DISPERSED to maximize yield and product effectiveness. 35
- 36. PROCESS FLOW DIAGRAM of TOPICAL PHARMACEUTICALS MANUFACTURE 36
- 37. PLASTIC TUBE FILLING and SEALING MACHINE 37
- 38. METHODS OF FILLING OPTHALMIC OINTMENTS BLOW FILL SEAL METHOD (BFS) SEQUENCE in ONE EASY OPERATION: 1. Fabrication of containers 2. Filling the product 3. Sealing 38
- 39. METHODS OF FILLING OPTHALMIC OINTMENTS FORM FILL SEAL METHOD (FFS) The conventional method of filling opthalmic ointments. 39
- 40. STRAIGHT- SIDED GLASS and PET JARS for CREAMS and OINTMENTS 40
- 41. FILLING MACHINE OINTMENT FOR OINTMENTS PRODUCTION 41
- 42. COLLAPSIBLE TUBE FILLING AND SEALING MACHINE Makes use of the “Hot Melt” Sealing system. Fills and Seals 85 collapsible tubes per minute. 42
- 43. Specialty packaging for ointments intended for; Nasal Rectal Vaginal Opthalmic 43
- 44. STORAGE and LABELING MICROBIAL SCREENING ( Microbial Limit Tests) 1. Staphylococcus aureus 2. Pseudomonas aeruginosa 44 As per USP Requirements:
- 45. MINIMUM FILL Assessment of the Content Uniformity of semi-solids. Product weighing 60 g or mL – nlt 90% of the labeled amount. Product weighing 60 g or mL to 150 g or mL – nlt 95% of the labeled amount. 45 As per USP Requirements:
- 46. STANDARD ASSAYS of the API’s (Quantitative assay of % Purity or % Content) STERILITY TESTS 1. Membrane Filtration Technique 2. Test Tube Inoculation Method 46 As per USP Requirements:
- 47. In vivo BA/BE – Dermatopharmacokinetic Studies (DPS) Applicable to semisolids that contain: 1. Antifungals 2. Antivirals 3. Corticosteroids 4. Antibiotics 5. Topicals for vaginal use 47 As per USP Requirements:
- 48. In vivo BA/BE – Dermatopharmacokinetic Studies (DPS) Not applicable to semisolids for; a. otic use b. opthalmic use c. that damage the stratum corneum of the skin. 48 As per USP Requirements:
- 49. In vivo BA/BE – Dermatopharmacokinetic Studies (DPS) It involves measurement of the ff.; 1. drug concentration in the stratum corneum 2. drug uptake 3. apparent steady state 4. elimination after drug application onto the skin 49 As per USP Requirements:
- 50. As per Non- USP requirements pH Water Content (Karl Fisher Method) Water affects the; a. physical stability b. chemical stability c. microbial stability 50
- 51. Usual water limit: 0.5% to 1% NMT 0.5% water content for Ointments containing: 1. Bacitracin 2. Chlortetracycline HCl 3. Nystatin 51
- 52. NMT 1% water content for ointments, creams or gels containing; 1. Erythromycin 2. Gentamycin sulfate 3. Neomycin sulfate 4. Tetracycline HCl 52
- 53. Foreign Substances Homogeneity ( also refers to Content Uniformity by Minimum Fill testing) 53
- 54. Metal Particle Detection Test – mandatory for opthalmic ointments only. Limits: NMT 3 tubes out of the 10 tubes tested should contain 8 metal particles. 54
- 55. Leaker Test Mandatory for opthalmic ointments filled in collapsible tubes. By Classical Blotting Paper Method 55
- 56. Specs / Limits: NMT 1 tube out of the 10 tubes should leak. If MT 1 tube leaks, repeat the test on 20 additional tubes. NMT 1 tube out of the 30 tubes should leak. 56
Editor's Notes
- #3: They are generally referred to as therapeutic ointments and creams, pastes and other forms of viscous consistency intended for external application onto the skin.
- #6: There are drug substances which penetrate faster, when the external environment temperature is higher.
- #8: Example; Ethanol generates faster in olive oil, than in NSS, as a topical vehicle.
- #17: Skin penetration is an important consideration in the choice of vehicle for medicated semisolids, but not for cosmetics. A well formulated semisolid should be both therapeutically effective and aesthetically /cosmetically appealing.
- #19: Mineral oil is usually added to reduce the stickiness / tackiness of the hydrocarbon base.
- #25: LANOLIN ALCOHOL – Prepared by saponification of Lanolin. Hydrophobic vehicle ideal for dry skin ointments, w/o creams and for opthalmic use. 0.1% antioxidant should be added.
- #27: Preservatives are added to prevent contamination, deterioration and spoilage by bacteria and molds. Containers may be a contributing source of contamination by harboring bacterial spores or by sorption or by chemical interaction with the preservative like plastics, rubber seals and closures.
- #28: 5% TWEEN 80 inactivates 80% of the total methylparaben present. Thus a higher concentration of a preservative is required.
- #36: THIS CAN BE ASSESSED BY PERFORMING MINIMUM FILL TESTING OF THE PRODUCTS.
- #39: BFS - Cost- effective alternative for sterile-sealing operations, since the product can be sterile-filled.
- #45: MINIMUM FILL – applicable to products NMT 150 gram or ml of the product, assesses the Content Uniformity. If the product weight is less than 60 g or mL, the net content of any single container should not be less than 90% of the labeled amount. If the product weight is between 60 and 150 g or mL, the net content of any single container should not be less than 95% of the labeled amount. If these limits are not met, the test is repeated with an additional 20 containers. BA/BE – Bioavailability / Bioequivalency tests. Mandatory by BFAD. Dermatopharmacokinetic (DPS) studies are required. Dermatopharmacokinetic (DPK) studies are applicable for topical semisolid products that contain antifungals, antivirals, corticosteroids, and antibiotics and vaginally applied products. They are not applicable for ophthalmic, otic, and other products that damage stratum corneum. DPK studies involve measurement of drug concentrations in stratum corneum, drug uptake, apparent steady state, and elimination after application of the test product onto skin. MICROBIAL SCREENING – Staph. aureus and Pseudo. aeruginosa for topical ointments.
- #46: MINIMUM FILL – applicable to products NMT 150 gram or ml of the product, assesses the Content Uniformity. If the product weight is less than 60 g or mL, the net content of any single container should not be less than 90% of the labeled amount. If the product weight is between 60 and 150 g or mL, the net content of any single container should not be less than 95% of the labeled amount. If these limits are not met, the test is repeated with an additional 20 containers. BA/BE – Bioavailability / Bioequivalency tests. Mandatory by BFAD. Dermatopharmacokinetic (DPS) studies are required. Dermatopharmacokinetic (DPK) studies are applicable for topical semisolid products that contain antifungals, antivirals, corticosteroids, and antibiotics and vaginally applied products. They are not applicable for ophthalmic, otic, and other products that damage stratum corneum. DPK studies involve measurement of drug concentrations in stratum corneum, drug uptake, apparent steady state, and elimination after application of the test product onto skin. MICROBIAL SCREENING – Staph. aureus and Pseudo. aeruginosa for topical ointments.
- #47: MINIMUM FILL – applicable to products NMT 150 gram or ml of the product, assesses the Content Uniformity. If the product weight is less than 60 g or mL, the net content of any single container should not be less than 90% of the labeled amount. If the product weight is between 60 and 150 g or mL, the net content of any single container should not be less than 95% of the labeled amount. If these limits are not met, the test is repeated with an additional 20 containers. BA/BE – Bioavailability / Bioequivalency tests. Mandatory by BFAD. Dermatopharmacokinetic (DPS) studies are required. Dermatopharmacokinetic (DPK) studies are applicable for topical semisolid products that contain antifungals, antivirals, corticosteroids, and antibiotics and vaginally applied products. They are not applicable for ophthalmic, otic, and other products that damage stratum corneum. DPK studies involve measurement of drug concentrations in stratum corneum, drug uptake, apparent steady state, and elimination after application of the test product onto skin. MICROBIAL SCREENING – Staph. aureus and Pseudo. aeruginosa for topical ointments.
- #48: MINIMUM FILL – applicable to products NMT 150 gram or ml of the product, assesses the Content Uniformity. If the product weight is less than 60 g or mL, the net content of any single container should not be less than 90% of the labeled amount. If the product weight is between 60 and 150 g or mL, the net content of any single container should not be less than 95% of the labeled amount. If these limits are not met, the test is repeated with an additional 20 containers. BA/BE – Bioavailability / Bioequivalency tests. Mandatory by BFAD. Dermatopharmacokinetic (DPS) studies are required. Dermatopharmacokinetic (DPK) studies are applicable for topical semisolid products that contain antifungals, antivirals, corticosteroids, and antibiotics and vaginally applied products. They are not applicable for ophthalmic, otic, and other products that damage stratum corneum. DPK studies involve measurement of drug concentrations in stratum corneum, drug uptake, apparent steady state, and elimination after application of the test product onto skin. MICROBIAL SCREENING – Staph. aureus and Pseudo. aeruginosa for topical ointments.
- #49: MINIMUM FILL – applicable to products NMT 150 gram or ml of the product, assesses the Content Uniformity. If the product weight is less than 60 g or mL, the net content of any single container should not be less than 90% of the labeled amount. If the product weight is between 60 and 150 g or mL, the net content of any single container should not be less than 95% of the labeled amount. If these limits are not met, the test is repeated with an additional 20 containers. BA/BE – Bioavailability / Bioequivalency tests. Mandatory by BFAD. Dermatopharmacokinetic (DPS) studies are required. Dermatopharmacokinetic (DPK) studies are applicable for topical semisolid products that contain antifungals, antivirals, corticosteroids, and antibiotics and vaginally applied products. They are not applicable for ophthalmic, otic, and other products that damage stratum corneum. DPK studies involve measurement of drug concentrations in stratum corneum, drug uptake, apparent steady state, and elimination after application of the test product onto skin. MICROBIAL SCREENING – Staph. aureus and Pseudo. aeruginosa for topical ointments.
- #50: MINIMUM FILL – applicable to products NMT 150 gram or ml of the product, assesses the Content Uniformity. If the product weight is less than 60 g or mL, the net content of any single container should not be less than 90% of the labeled amount. If the product weight is between 60 and 150 g or mL, the net content of any single container should not be less than 95% of the labeled amount. If these limits are not met, the test is repeated with an additional 20 containers. BA/BE – Bioavailability / Bioequivalency tests. Mandatory by BFAD. Dermatopharmacokinetic (DPS) studies are required. Dermatopharmacokinetic (DPK) studies are applicable for topical semisolid products that contain antifungals, antivirals, corticosteroids, and antibiotics and vaginally applied products. They are not applicable for ophthalmic, otic, and other products that damage stratum corneum. DPK studies involve measurement of drug concentrations in stratum corneum, drug uptake, apparent steady state, and elimination after application of the test product onto skin. MICROBIAL SCREENING – Staph. aureus and Pseudo. aeruginosa for topical ointments.
- #51: WATER CONTENT – by Karl Fisher method. Water affects the physical, chemical and microbial stability of pharmaceuticals. LIMITS:0.5% to 1 % The limit of water in bacitracin, chlortetracycline hydrochloride, and nystatin ointments is not more than 0.5%, whereas amphotericin SEMISOLID DOSAGES: OINTMENTS, CREAMS, AND GELS B, erythromycin, gentamycin sulfate, neomycin sulfate, and tetracycline hydrochloride ointments may contain up to 1% moisture . METAL PARTICLE DETECTION – for opthalmic ointments. LIMITS: nmt 3 tubes are allowed to contain 8 particles. LEAKER TEST – mandatory for opthalmic ointments. LIMITS: nmt 1 tube leaks out of 30 tubes
- #52: WATER CONTENT – by Karl Fisher method. Water affects the physical, chemical and microbial stability of pharmaceuticals. LIMITS:0.5% to 1 % The limit of water in bacitracin, chlortetracycline hydrochloride, and nystatin ointments is not more than 0.5%, whereas amphotericin SEMISOLID DOSAGES: OINTMENTS, CREAMS, AND GELS B, erythromycin, gentamycin sulfate, neomycin sulfate, and tetracycline hydrochloride ointments may contain up to 1% moisture . METAL PARTICLE DETECTION – for opthalmic ointments. LIMITS: nmt 3 tubes are allowed to contain 8 particles. LEAKER TEST – mandatory for opthalmic ointments. LIMITS: nmt 1 tube leaks out of 30 tubes
- #53: WATER CONTENT – by Karl Fisher method. Water affects the physical, chemical and microbial stability of pharmaceuticals. LIMITS:0.5% to 1 % The limit of water in bacitracin, chlortetracycline hydrochloride, and nystatin ointments is not more than 0.5%, whereas amphotericin SEMISOLID DOSAGES: OINTMENTS, CREAMS, AND GELS B, erythromycin, gentamycin sulfate, neomycin sulfate, and tetracycline hydrochloride ointments may contain up to 1% moisture . METAL PARTICLE DETECTION – for opthalmic ointments. LIMITS: nmt 3 tubes are allowed to contain 8 particles. LEAKER TEST – mandatory for opthalmic ointments. LIMITS: nmt 1 tube leaks out of 30 tubes
- #54: WATER CONTENT – by Karl Fisher method. Water affects the physical, chemical and microbial stability of pharmaceuticals. LIMITS:0.5% to 1 % The limit of water in bacitracin, chlortetracycline hydrochloride, and nystatin ointments is not more than 0.5%, whereas amphotericin SEMISOLID DOSAGES: OINTMENTS, CREAMS, AND GELS B, erythromycin, gentamycin sulfate, neomycin sulfate, and tetracycline hydrochloride ointments may contain up to 1% moisture . METAL PARTICLE DETECTION – for opthalmic ointments. LIMITS: nmt 3 tubes are allowed to contain 8 particles. LEAKER TEST – mandatory for opthalmic ointments. LIMITS: nmt 1 tube leaks out of 30 tubes
- #55: WATER CONTENT – by Karl Fisher method. Water affects the physical, chemical and microbial stability of pharmaceuticals. LIMITS:0.5% to 1 % The limit of water in bacitracin, chlortetracycline hydrochloride, and nystatin ointments is not more than 0.5%, whereas amphotericin SEMISOLID DOSAGES: OINTMENTS, CREAMS, AND GELS B, erythromycin, gentamycin sulfate, neomycin sulfate, and tetracycline hydrochloride ointments may contain up to 1% moisture . METAL PARTICLE DETECTION – for opthalmic ointments. LIMITS: nmt 3 tubes are allowed to contain 8 particles. LEAKER TEST – mandatory for opthalmic ointments. LIMITS: nmt 1 tube leaks out of 30 tubes
- #56: WATER CONTENT – by Karl Fisher method. Water affects the physical, chemical and microbial stability of pharmaceuticals. LIMITS:0.5% to 1 % The limit of water in bacitracin, chlortetracycline hydrochloride, and nystatin ointments is not more than 0.5%, whereas amphotericin SEMISOLID DOSAGES: OINTMENTS, CREAMS, AND GELS B, erythromycin, gentamycin sulfate, neomycin sulfate, and tetracycline hydrochloride ointments may contain up to 1% moisture . METAL PARTICLE DETECTION – for opthalmic ointments. LIMITS: nmt 3 tubes are allowed to contain 8 particles. LEAKER TEST – mandatory for opthalmic ointments. LIMITS: nmt 1 tube leaks out of 30 tubes
- #57: WATER CONTENT – by Karl Fisher method. Water affects the physical, chemical and microbial stability of pharmaceuticals. LIMITS:0.5% to 1 % The limit of water in bacitracin, chlortetracycline hydrochloride, and nystatin ointments is not more than 0.5%, whereas amphotericin SEMISOLID DOSAGES: OINTMENTS, CREAMS, AND GELS B, erythromycin, gentamycin sulfate, neomycin sulfate, and tetracycline hydrochloride ointments may contain up to 1% moisture . METAL PARTICLE DETECTION – for opthalmic ointments. LIMITS: nmt 3 tubes are allowed to contain 8 particles. LEAKER TEST – mandatory for opthalmic ointments. LIMITS: nmt 1 tube leaks out of 30 tubes