Semisolid Dosage Forms PDF

Schedule of Topics Week 7: Semi-solids Week 8: Transdermal Semisolid Dosage Forms:...

Schedule of Topics Week 7: Semi-solids Week 8: Transdermal Semisolid Dosage Forms: Week 9: Pulmonary Week 10: Radioactivity Ointment, creams, gels Week 11: Parenterals ***Homework has been posted on-line ***Quizzes: Do you guys want weekly quizzes, 2 quizzes, 1 big quiz? Objectives Objectives What are the distinguishing features of ointments, creams, gels, and pastes? How are they different from the other? Be able to select the correct product Understand the limitations of suppository and the bases! Understand which for a patient. type of base should be chosen depending on the drug solubility (see the There are 5 types of ointment bases, understand their unique characteristics chart within the lecture). and be able to select the correct base based on a patients needs. Be able to describe the two methods used to compound ointments. What is an emulsion? Which phase is the internal phase of an emulsion, The Be able to describe how you perform geometric dilution. And why do we use bulk phase? Which phase is it easier to add components/chemicals to and it? why? Which suppository base is a polymorph? Which suppository base is stored in Understand each type of flow (rheology) and the examples of dosage forms the fridge? What (ingredient) can you add to the suppository to raise the for each. melting point? Understand how viscosity affects the rate of sedimentation. Know the BUD’s. What does BUD stand for? Know the types of suppository bases. Which base melts at body temp vs which one dissolves? Understand what is meant by penetration, permeation, and absorption. Know and understand the following terms: syneresis, swelling, imhibition  Semi-Solids Function of Dermatologicals 4th state of matter Protect injured areas from the environment Hold their shape when undisturbed Skin hydration (emollient) -Whip cream to Chapstick Can be pharmaceutical OR cosmetic Vehicle for medication transport (either local or systemic) Prophylactic (example: Neosporin) http:// www.americanpharmaceuticalreview.com/ Featured-Articles/170872-Lipids-in- Transdermal-and-Topical-Drug-Delivery/ Mechanism of Skin Penetration Types of Semi-Solids Creams Gels Ointments Pastes Can contain one or more active ingredient Typically contains excipients: emulsifiers, viscosity increasing agents, antimicrobials, antioxidants Will be on the exam but will cover in greater detail in the transdermal lecture  Special Attributes Signs of Physical Instability Bioavailability: depends on: area of application, thickness of residue left after application, formulation itself. Change in consistency Free of pathogens and remain so but no need to be sterile* Discoloration Free of contamination Emulsion breakdown Chemical stability; solution vs decomposition Crystal growth Physical deterioration: separation Shrinking due to water evaporation Local or systemic effect Microbial growth is present or suspected Ointments, creams, lotions, pastes Change in odor Factors to Consider Factors to Consider 1. Treating skin disease? What must occur? 2. Need both aqueous and lipid solubility (for absorption) -We will discuss the log P ratio next lecture 3. Animal fats (lard and wool) when combined with water, *Very important penetrate the skin. (ex: Type of emulsion base and drug to understand release) the difference in 4. Greasy bases interfere with normal skin functions. these 3 terms! (sweating?) Institute for Dermopharmacy Gmb H  For formulations that exert a topical effect (not systemic), the Pharmaceutical factors: effective drug concentration is subjective: Drug penetration depends on: physicochemical properties of the drug and the vehicle; the condition of the skin -based on qualitative measures. and specifically: -Clinical effect varies. Stability of the base: rancidity of base, use of antioxidants Oleaginous bases provide greater occlusion and emollient Rate of drug release effects Solvent properties: most medications used in ointments are Pastes offer the best occlusion and are more effective than insoluble in the ointment base ** ointments at absorbing serous discharge Emulsifying properties: (H20) Creams-more easily spreadable, water-soluble Consistency-able to withstand changes in temperature, maintain physical properties Emulsions Emulsion- a thermodynamically unstable system consisting of at least 2 immiscible liquid phases; one of which is dispersed as globules in the other liquid phase. 1. Oil-in-water (o/w) 2. Water-in-oil (w/o) 3. Multiple emulsions (w/o/w or o/w/o): delayed action delivery systems. Oil in water (o/w): water is the bulk phase. (example: salad 4. Microemulsions: spontaneously formed when the components are dressing, milk) mixed in the appropriate ratios. Water in oil (w/o): oil is the bulk phase Churned cream is o/w becomes butter (w/o; an inverse emulsion)  Rheology and the Types of Flow Pseudoplastic flow-observed in systems that deform and flow instantaneously with applied stress. Viscosity decreases with increasing shear stress-it is a shear thinning system. (Common It is the study of deformation and flow properties of matter. with polymers in solution, ex: creams) Can be applied to a solid, liquid or gas Dilatant flow-the deformation and flow occurs Viscosity is a measure of resistance to flow or thickness. instantaneously upon the application of stress. But this is a Newtonian fluid- any fluid that exhibits a viscosity that shear-thickening system. (ex: whipping cream, pastes, remains constant regardless of any external stress that is suspensions with a high % of dispersed solids that exhibit an applied on it. (the amount of stress applied is proportional to increase in resistance to flow. Viscosity increases with the flow) increasing shear rate.) Non-Newtonian flow: Plastic flow-a situation in which no flow occurs in response to shear stress until a certain transition point is reached. Example: ointments Thixotropy- a time-dependent shear thinning property. Occurs Negative Thixotropy- (aka antithixotropy) an when gels or fluids that are viscous under static conditions will increase in thickness or resistance to flow with an become less viscous over time, when shaken or agitated and increased time of shear. Can occur as a result from then becomes easily pourable. (ex: gels, lotions) an increased collision frequency of dispersed particles in suspension.  Ointments USP definition: semisolid preparations intended for Types of ointment bases external application to the skin or mucus membranes. Distinguished based on their composition. 1. Oleaginous bases Viscous 2. Absorption bases 3. W/O emulsion bases Oleaginous or polymeric 4. O/W emulsion bases. 5. Water-soluble bases May contain drug Used to Treat ADVANTAGES Avoids first pass metabolism Minor skin infections Site specific action of drug on affected area Itching Convenient for treatment of topical conditions associated with membranes Burns More stable than liquid dosage forms Diaper rash Insect stings/bites DISADVANTAGES Poison ivy May cause staining Athlete’s foot Bulky to handle Corns Application with finger may cause contamination Calluses Physico-chemically less stable than solid dosage forms (i.e. tablets) Warts Can be greasy/not preferred (ointments) May cause irritation (face vs body lotion) Acne, psoriasis, eczema Some patients may be allergic *Not all inclusive  Ideal Properties Ointments Physical Properties Smooth texture A viscous oleaginous or polymeric semisolid dosage form. Elegant in appearance Non-dehydrating Intended for external application to the skin or mucous Not gritty, greasy and does not stain membranes that soften or melt at body temperature. Not hygroscopic What does this word mean? Smell (Recall from pharmaceutics I) They should spread easily and be non-gritty. Physiological Properties Non-irritating Semisolid plastic flow characteristics Does not alter membrane or skin function Miscible with skin secretions More viscous Has a low sensitization index Resistance to flow drops as application continues Application Properties Easily applicable with efficient drug release High aqueous washability In this picture, can you tell which one is the oleaginous base? Oleaginous bases Hydrophobic and anhydrous Water insoluble Not water washable Cannot absorb water Oily, occlusive, lack cosmetic appeal Difficult to spread, greasy, thick, stiff Poor drug release Uses: protectants, emollients and vehicles for solid drugs Hydrocarbons Animal/vegetable fats/oils (castor oil, cotton seed oil, olive oil) Synthetic esters (glyceryl monostearate, butyl stearate, isopropyl lanolate, cetyl alcohol, stearyl alcohol) White petroleum (Vasoline), white ointment  Aquaphor Absorption bases (an exception) Absorption bases have properties in-between Aquaphor contains 41% petrolatum oleaginous bases and w/o bases Capable of absorbing up to 3 times its weight in water W/O bases: Emulsion bases Two Types: Contains 0.6. Aw stands for water activity. or refrigerator. (Examples: elixir) Use this when the Aw is 0.6. Aw stands for water activity. days, whichever is earlier. Controlled room temperature or refrigerator. (Examples: capsules, tablets, suppositories, ointments, granules, powders) Use this when the Aw is