UNIT 5 Pharmaceutics (Imperfect Pharmacy) PDF

# Semi-Solids ## Semi-Solid Dosage Forms - Topical (dermatological) preparations - Used for therapeutic, protectives or cosmetic function - Generally applied over the skin but can also be applied nasally, vaginally or rectally - Include ointments, pastes, creams and gels - Contain one or more activ...

# Semi-Solids ## Semi-Solid Dosage Forms - Topical (dermatological) preparations - Used for therapeutic, protectives or cosmetic function - Generally applied over the skin but can also be applied nasally, vaginally or rectally - Include ointments, pastes, creams and gels - Contain one or more active pharmaceutical ingredients (API) dissolved or uniformly dispersed in a suitable base ### Advantages - Used externally hence probability of side effects are very less - First pass metabolism is avoided - Suitable for unconscious patients - Suitable dosage form for bitter drugs - More stable than liquid dosage form ### Disadvantages - No dose accuracy - Bulky to handle - Application with finger may cause contamination - Physio-chemically less stable compared to solid dosage form - May cause irritation or allergy in some patients ## Ideal Properties of Semi-Solid Dosage Forms - Can be defined on the basis of 3 parameters: - Physical properties - Physiological properties - Application properties ### Physical Properties - Should have smooth texture - Should be elegant in appearance - Should be non-dehydrating - Should be non-gritty in nature - Should have non-greasy and non-staining properties - Should be non-hygroscopic in nature ### Physiological Properties - Should be non-irritating in nature - Should not alter skin membrane - Should be easily miscible with skin secretions ### Application Properties - Should be easily applicable with efficient drug release - Should have high aqueous washability ## Mechanism of Drug Permeation - Also known as dermal penetration of drugs - The skin has two main layers: - Epidermis (outermost layer) - Dermis (active part of skin containing hair follicles and blood supply) - Epidermis itself divides into 5 other parts but the main layer that controls the penetration of drugs is called stratum corneum - The permeation/penetration of drugs occurs through three major routes: - Transcellular - Intercellular - Appendageal ## Factors Influencing Dermal Penetration of Drugs - Can be further divided into two categories: - Biological factors - Physiochemical factors ### Biological Factors - Mainly includes: - Skin condition - Skin age - Blood flow - Regional skin sites - Skin metabolism - Species difference - Skin hydration #### Skin Hydration - When the amount of water is sufficient or in excess, the tissue swells and softens - Drugs through this softened tissue easily penetrate the skin - Hydration increases drug penetration #### Skin Condition - The penetration of drugs through skin is affected by age, disease, climate and injury - Drug absorption occurs rapidly in children - Diseases and injured skin increases drug penetration - Drug penetration is less in healthy skin #### Skin Age - The young skin is more permeable than older - The skin of the children are more sensitive to the toxic effects of drugs - Skin age plays an important role in dermal penetration of drugs #### Blood Flow - Blood flow through the skin also affects the dermal penetration of drugs - When blood flow is reduced, amount of drug penetration increases #### Regional Skin Site - Dermal penetration of drugs changes with varying of skin thickness - Facial skin is generally more permeable compare to other body sites #### Skin Metabolism - The skin metabolizes steroid hormones, chemical carcinogens and some other drugs - Skin metabolism determines efficacy of drug permeated through skin #### Species Difference - The condition and thickness of skin varies in different species - Mice, rat, rabbits have more hair follicles but they lack sweat glands, so drug penetration is different in their skin compare to human skin ### Physiochemical Factors - Mainly includes: - Temperature and pH - Drug concentration - Solubility of drugs - Diffusion coefficient - Molecular size and shape #### Temperature and pH - The increase in temperature increases the dermal penetration of drugs through skin - Drug with pH value near 5 easily penetrates the skin #### Drug Concentration - The drug penetration is depends upon the concentration gradient - Concentration gradient will be higher if concentration of drug will be more across the barrier. #### Solubility of Drugs - Highly lipid soluble drugs easily penetrates the skin compare to hydrophilic drugs #### Diffusion Coefficient - The diffusion coefficient of drug depends on the properties of drugs and diffusion medium #### Size and Shape - Penetration of drugs is inversely depends on size - Small molecules penetrates faster than larger ones ## Preparation of Semisolids Dosage Forms ### Ingredients Used in Preparation - Bases - Preservative - Humectants - Antioxidants - Emulsifier - Gelling agent - Permeation enhancer - Buffers ### Bases - It is one of the most important ingredient used in formulation of semisolid dosage form - Ointment bases do not merely act as the carriers of the medicaments, but they also control the extent of absorption of medicaments incorporated in them #### Ideal Properties of a Base - Should be: - Inert, non-irritating and non-sensitizing - Compatible with skin pH and the drug - Good solvent and/or emulsifying agent - Emollient, protective, non-greasy and easily removable - Release medicament readily at the site of application - Pharmaceutically elegant and possess good stability #### Types of Bases - Oleaginous/ hydrocarbon bases - Absorption/emulsifiable bases - Emulsifying bases - Water soluble bases ##### 1. Oleaginous (hydrocarbon) Bases - Consist of a combination of more than one oleaginous material such as water insoluble hydrophobic oils and fats - Disadvantages - Greasy, sticky-non washable - Retain body heat - Do not increase absorption - Prevent drainage on oozing area - Anhydrous, do not absorb water and insoluble in water - Hydrocarbons, such as: - Paraffin wax Soft paraffin, Liquid paraffin - Vegetable oils and animal fats, such as: - Peanut oil, Coconut oil, Lanolin, Bees wax - Hydrogenated & sulfated oils, such as: - Hydrogenated castor oil, Hydrogenated & sulfated castor oil - Acids, Alcohols & Esters, such as: - Stearic acid, Stearyl alcohol, Isopropyl Myristicate - Silicones, such as: Dimethyl polysiloxanes ##### 2. Absorption (Emulsifiable) base - Qualities: - Anhydrous - Forms w/o emulsion - Absorbs 50% water - Easily removable by water - Classification: - Non-emulsified bases: Absorb water and aqueous solutions to produce w/o emulsions, such as: Wool fat, wool alcohol, beeswax, cholesterol - W/O emulsions: Absorb more water than non-emulsified bases. Eg. Hydrous wool fat (lanolin) ##### 3. Emulsion Bases: - Ability to absorb water, serum discharges and forms o/w and w/o emulsions - Classified as either W/O or O/W - W/O - greasy, sticky, such as: Sulfur & zinc ointments - O/W - easily removed from skin, such as: vanishing cream - Advantages: - Miscible with exudates from lesions - Do not interfere with skin function - Good contact with skin because of surfactant content - High cosmetic acceptability - Easy removable from the hair - Disadvantages: - W/o emulsion greasy and sticky - Acceptance is less - Difficult to remove from body and clothing ##### 4. Water Soluble Bases: (Grease less Base) - As the name 'greaseless' suggests, these bases are oil free - Hydrous as well as anhydrous in nature - Show complete solubility in water - Carbo waxes (for viscous liquids and solids) - Pectin, Tragacanth & Cellulose derivates (form plants) - Gelatin (animal) - Silica Gel, Bentonite - For low viscosity: Glycerin, Glyceryl mono stearate ### Methods of Preparation of Ointments & Creams - Trituration - Fusion - Chemical reaction - Emulsification ### Methods of Preparation of Pastes - Trituration - Fusion ### Method of Preparation of Gels - General method #### 1. Trituration Method - Widely used method for extemporaneous preparation of ointments - When the base is soft and medicament is solid insoluble, small amount of liquid to incorporated in the base - Advantage: Involves mixing as well as size reduction - Procedure: - Reduce the solid medicament to fine powder - Mix medicament with small amount of base on ointment slab with a stainless steel spatula until a homogeneous product is formed - Add remaining quantities of base with uniform mixing - Incorporate any liquid ingredient if present (mortar and pestle should be used in case of large quantity of liquid) - Steps: - Size Reduction - Levigation - Mixing with base - Spatulation or trituration - Mixing base to produce final weight - Homogenization - Filling #### 2. Fusion Method: - Suitable when ointment base contains number of solid ingredients of different melting points. - Procedure: - Melt ointment base in decreasing order of their melting point: Highest melting point should be melted first, low melting point next - This avoids over heating of substances of low melting point - Incorporate medicament slowly to the melted mass - Stir thoroughly until mass cools down and a homogeneous product is formed. - Liquid ingredients or aqueous substance should be heated to the same temperature as the melted bases before addition - If not, wax or solids will cool down quickly and get separated - Precautions: - Stirring is done continuously - a homogeneous mass - Vigorous stirring should be avoided to prevent entrapment of air - Rapid cooling should be avoided to get a uniform product - To remove the dust or foreign particles, strain through muslin cloth - Steps: - Grate the waxy base - Melt using water bath - High M.P base 1st, mix low M.P in it - Melt base together - Dissolve oil soluble drug - Add small volume phase in large volume phase - Cooling under stirring - Soft mass of 40°c - Homogenization - Filling #### 3. Chemical Reaction Method - Preparation of some ointment involves chemical reactions - Eg - (a)Iodine ointment (iodine free form) - (b)Iodine ointment (iodine combined form with ointment base) - (a) Ointments containing free iodine: - Iodine is slightly soluble in fats and vegetable oils - Readily soluble is potassium iodide solution in water due to formation of polyiodides - Poly iodides are readily soluble in water, alcohol and glycerin - These solutions may be incorporated with the molten absorption type ointment base - (b) Ointments containing combined iodine: - Fixed oils and many fats obtained from vegetable and animal sources contain unsaturated constituents - Iodine combines with double bonds - Free iodine is not available, so ointments appear dark, greenish black in colour - Leaves no stain when rubbed into the skin, Hence known as non-staining iodine ointment #### 4. Emulsification Method - Facts, oils and waxes are melted together to a temperature of 70°c - Aqueous solution of the heat stable, water soluble compounds is also heated to the same temperature - Aqueous Solution is slowly added to the melted bases, with continuous stirring until cool - Emulsifying agent is needed to make a stable emulsion - . Water soluble soaps are commonly used as emulsifier for semisolid o/w emulsions - Combination of triethanolamine stearate soap and cetyl alcohol is used in o/w emulsion - Bees wax and divalent calcium ions used in w/o emulsion