Semisolids PDF

UNIVERSITY OF SOUTHERN MINDANAO SEMISOLIDS ▪ Ointments ▪ Creams ▪ Cream Emulsions ▪ Gels ▪ Rigid Foams ▪ Common Property ▪ Ability to cling to the surface of application for reasonable duration before they are worn off ▪ Uses of Semisolids 1. Vehicles for topically applied drugs 2...

UNIVERSITY OF SOUTHERN MINDANAO SEMISOLIDS ▪ Ointments ▪ Creams ▪ Cream Emulsions ▪ Gels ▪ Rigid Foams ▪ Common Property ▪ Ability to cling to the surface of application for reasonable duration before they are worn off ▪ Uses of Semisolids 1. Vehicles for topically applied drugs 2. Emollients 3. Protective or occlusive dressing on the skin Raw Materials for Semisolids 1. Hydrocarbons 2. Hydrocarbon waxes 3. Oleaginous substances 4. Fatty acids and alcohols 5. Emulsifiers 6. Polyols 7. Insoluble Compounds Hydrocarbons 1. Petrolatum ▪ Complex mixture of semisolids containing hydrocarbon aliphatic, cyclic, saturated, unsaturated branch and unbranched in varying proportion 2. Mineral Oil ▪ Obtained from petroleum acid the lower viscosity is more preferred since it is less tacky(sticky) and greasy. Hydrocarbon waxes ▪ Are frequently employed to increase the viscosity of mineral oils to prevent separation from an ointment. ▪ Paraffin ▪ Ceresin Wax (mixture of paraffin wax and ozokerite) Oleagenous Substance ▪ Vegetable Oils ▪ Peanut Oils Glycerides of mixtures of ▪ Almond Oils saturated and unsaturated ▪ Sesame Oils fatty acids ▪ Olive Oils Fatty Acids and Alcohols 1. Stearic Acids ▪ Used in water-removal Creams as an emulsifiers to develop a certain consistency in the creams 2. Stearyl Alcohols and Cetyl Alcohols (Palmityl Alcohol) ▪ Used as Auxiliary emulsifiers and emollients ▪ In sufficient Quantity of Stearyl Alcohol produces a firm cream which may be softened by cetyl alcohol Emulsifiers ▪ Triethanolamine Stearate Soap (water soluble Soap) ▪ 1st Emulsifier used for semisolid in O/W Emulsions ▪ The viscosity of the cream or ointment prevents coalescence of the emulsified phase and helps to stabilize the emulsion. ▪ The interfacial film formed around the dispersed phase globules is generally solid making the emulsified preparation more rigid. Polyols ▪ Glycerine ▪ PG ▪ Sorbitol 70% Used as Humectantans ▪ LMW PEG Insoluble Powders ▪ Uniformly dispersed throughout the vehicle to ensure homogeneity of the product. ▪ The solid must be impalpable to the touch → Grittiness ▪ Particles less than 74 microns in size equivalent to the mesh opening in a number 200 mesh sieve of the US standard series are considered impalpable to most people. Types of Vehicles ▪ The vehicle used for a semisolid pharmaceutical preparation differs from the used for cosmetics → penetration into the skin is not desired. ▪ Both effective therapeutically and cosmetically apealing Factors which influence the choice of semisolids vehicle: 1. Nature of the skin lesion 2. Solubility and stability of the drug in the base Four Classes of semisolids vehicles recognized by USP 1. Hydrocarbon Bases 2. Absorption Bases 3. Water removal Bases 4. Water soluble Bases Hydrocarbon Bases 1. Petrolatum ▪ Most used in ointment vehicles 2. White Ointment Petrolatum with 5% beeswax are typically lipophilic vehicles Absorption Bases ▪ Hydrophilic mixtures formed by the addition of substance miscible with hydrocarbons and possesing polar grouping such sulphates, Sulfonate, Carboxyl or an ether linkage (R-O-R’). ▪ Lanolin, cholesterol, sterol, sorbitan monostearate or Monoleate ▪ Maybe added to make hydrocarbon bases hydrophilic Cold Cream type of W/O emulsions Water removable Bases ▪ O/W ▪ Referred to as “Creams” ▪ Example: Vanishing Creams Water Soluble Bases ▪ Prepared from the mixtures if HMW and LMW PEG ▪ Characteristics of this bases ▪ LMW are liquids; moderately HMW are unctuous; HMW are Solids ▪ No water is required for their Preparations ▪ Suitable combination of HLMW PEG yields products having ointment-like consistency which softens or melt when applied to the skin. ▪ Many polar groups and other linkage ▪ Greaseless ointment bases Ophthalmic Ointments ▪ Ophthalmic vehicles frequently contains soft petrolatum, a bland absorption base, or a water-soluble base. ▪ Prepared with PEG or with water soluble gums. ▪ Mineral oil is frequently added to petrolatum to lower its fusion point. ▪ All materials should be impalpable to avoid eye discomfort and irritation. ▪ For injured eye - STERILE Prevention from microbial Spoilage ▪ Quality of chemical preservatives: 1. Stability with regards to other components of the formula 2. Containers to be used Parabens (para-hydroxybenzoate Esters) General Consideration of Preservatives ▪ Containers – source of contamination by harboring bacterial spores or by sorption or chemical interaction between preservatives like plastic, rubber seals, and closure. Characteristics of Preservatives: ▪ Some preservatives become inactivate in the presence of other ingredients ▪ 5% tween 80 inactivates 80% of the total methyl paraben present such that higher concentration of preservatives is required. ▪ Boric Acids maybe used in ophthalmic preparation but not for nasal products due to possible toxic effect when absorbed in large quantities. ▪ To measure the effectiveness of the preservatives against a bacterial or fungal contamination, the semisolids is contaminated with suitable organism and then count is made over a period with the original cream without preservatives as the control. Antioxidants ▪ Choice of antioxidants is made depending on the following factors: ▪ Toxicity ▪ Irritating potency BHA ▪ Compatibility BHT ▪ Odor Propyl Gallate ▪ Discoloration ▪ Solubility and stability Industrial Processing ▪ Pilot Pant or small-scale production equipment is essential in developing a manufacturing procedure for a production-size batch. ▪ Mixing and stirring operations are critical in preparation of semisolids ▪ Aeration should be prevented for stability and consistency in density ▪ Introducing one phase below the surface of the other liquid or phase and mixing carefully. Manufacture of Ointments: ▪ Fusion Methods ▪ Anhydrous Ointments ▪ Dissolving the active ingredient in the melted fats and waxes or in the vehicle and then mixed while cooling to ensure homogenous distribution of ingredients Manufacture of emulsified Semisolids 3 factors to be controlled during manufacture 1. Time of mixing 2. Temperature 3. Mechanical works include rate of agitation Tonicity Contributors: ▪ Compounds contributing to the isotonicity of a product reduce the pain of injection in area with nerve endings. ▪ Buffer may be severe as tonicity contributors as well as stabilizers for the pH. Containers Production 1. Compounding 2. Filtration 3. Filling 4. Sealing 5. Sterilization Compounding ▪ Processing of sterile preparations follow normal manufacturing procedures which must be done in aseptic condition ▪ all conditions must be carefully designed and controlled to prevent the entrance of microorganisms to a product To achieve this, there must be good environmental control. ▪ Personnel implementing this must understand and practice the standard operating procedures from preventing contamination. ▪ All equipment's and materials used whenever possible must be sterile. Filling ▪ Membrane filters are used for clarification when a highly polished solution is desired ▪ Remove particulates at least 3 microns ▪ Sterilization by filtration is achieved when viable microorganism and spores of approximately 0.3 microns are removed. ▪ Membrane with porosity ratings 0.22 or 0.45 microns are usually specified in sterile filtration Filling ▪ The larger size has a faster flow rate (3 times) but would require the use of prefilter to remove some colloidal matter which cause rapid clogging and thus reduce the filtration cycle. ▪ Bubble test – efficiency of the membrane Filling ▪ Bulk – Subdivided into unit dose containers during filling ▪ To measure the volume – aid of Gravity, vacuum, or pressure pump Sealing ▪ To assure temper-proof ▪ Sealed in an aseptic technique ▪ Ampoule are sealed by heating with high temperature gas-oxygen 1.Tip Seals 2.Pull-seals Sterilization 1. Physical 2. Chemical