Pharmaceutics Exam 4 Study Guide PDF

Pharmaceutics Exam 4 Study Guide Topic 1: Semisolid Dosage Forms 1. Define & classify semisolid dosage forms. a. Ointments – greasy, used for protective or therapeutic purposes, often composed of a petrolatum or lanolin base, provide a barrier to help drug penetrate the skin b. Creams – emulsions of...

Pharmaceutics Exam 4 Study Guide Topic 1: Semisolid Dosage Forms 1. Define & classify semisolid dosage forms. a. Ointments – greasy, used for protective or therapeutic purposes, often composed of a petrolatum or lanolin base, provide a barrier to help drug penetrate the skin b. Creams – emulsions of oil & water with an added thickening agent for consistency, used for many purposes including moisturizing, treating skin conditions, & delivering drug through the skin c. Pastes – thick preparations that contain a high proportion of solid materials dispersed within liquid, used for protective or soothing purposes d. Gels – jelly substance in which a liquid is dispersed within a solid, used for their cooling sensation e. Suppositories – both solid & semisolid depending on their formulation 2. What are basic principles of drug delivery to the skin, mucous membranes, & body cavities? a. Skin surface i. Dermal, provides local action 1. Surface - protective film, sunscreen, cleansing, antiseptic 2. Within stratum corneum – psoriasis, eczema, xerosis, moisturizer 3. Deep – acne, cellulitis, dermatitis ii. Transdermal, provides systemic effect 1. Most absorbed via epidermis due to large surface area b. Mucous membranes i. Ophthalmic, nasal, oral, rectal, vaginal c. Body cavities i. Rectal, vaginal, urethral 3. Describe properties of semisolid dosage forms. a. Smooth texture, elegant appearance, hydrating, non-gritty, non-greasy/staining, non-hygroscopic, don’t alter membrane/skin function, miscible with skin secretions b. Easily applicable w/ efficient drug release, water washability, c. Bases should be inert, non-irritating, compatible w/ skin pH, good as a solvent & emulsifying agent, emollient, protective, non-greasy, easily removable 4. What are advantages & disadvantages of semisolid dosage forms? a. Advantages i. Ointments easily spread on skin (external, local, site specific) ii. Lubricating/emollient effects iii. Persist at site of application iv. Avoids first-pass effect & GI v. Convenient (pts who can’t swallow, polypharmacy) b. Disadvantages i. Dose accuracy is highly variable ii. Irritation, dermatitis, allergic reactions iii. Bulky, can cause staining/grease spots iv. Poor permeability of some drugs v. Only for drugs that require small plasma concentration for action (TD) vi. Large molecules cannot easily penetrate vii. Difficult to remove 5. Review properties of the skin layers and their role in drug penetration & absorption. a. Stratum corneum is the most difficult epidermal barrier for drugs to cross i. The largest part of the epidermis ii. The other layers are much easier to pass through Commented [JF1]: done iii. Intracellular lipids are barrier for hydrophilic drugs b. Dermis has no protective mechanisms, very easy to pass drug into systemic circulation c. Natural moisturizing factor (NMF) i. Complex mix of low-molecular weight, water-soluble compounds 6. Describe physiochemical principles behind the design of semisolid dosage forms. a. Partition coefficient, lipophilicity, solubility b. Drug concentration, type of dosage form, type of base c. Molecule size, pH, ionization (opposite charges can enhance penetration & lengthen drug release) d. Excipients (penetration enhancers, antioxidants) 7. What are commonly used excipients in semisolids? a. Permeation enhancers – oleic acid, pyrrolindones (PCA), ethanol, glycol, PEGs, propylene glycols, surfactants b. Humectants (increase solubility, penetration, & hydration) – glycerin, urea, hyaluronic acid, glycolic acid, propylene glycol, sorbitol, olive oil, honey Topic 2: Ointments & Creams 1. What is the USP definition of ointments & creams? a. Ointments - 50% hydrocarbons, waxes, or polyols (can be used ophthalmically) b. Creams – o/w emulsions or aqueoud microcrystalline dispersions of long fatty acids or alcohols, up to 50% water content 2. What are different types of ointment bases? Describe their properties & applications. a. Hydrocarbon base i. Oleaginous: no or small amounts of aqueous/water parts, can keep drug in prolonged contact w/ skin, emollient, don’t dry out (longer shelf-life) b. Absorption base i. Anhydrous: incorporates aqueous solutions to form w/o emulsion ii. Water-in-oil emulsion: incorporates additional aqueous solutions c. Water-removable base i. Oil-in-water emulsion base: washable, creams, more acceptable for cosmetic uses, some drugs may be more effective in this form, can be diluted w/ water & can absorb skin discharges d. Water-soluble base i. Polyethylene glycol: “grease-less”, non-occlusive, similar to gels 3. Discuss strategies & criteria for selecting the appropriate ointment bases. a. Desired action (site of application) b. Nature of the drug to be included (drug properties, chemical stability) c. Bioavailability (rate of release) d. Effect of therapeutic agent on finished product quality (viscosity) Commented [JF2]: done 4. Describe the formulation considerations of ointments & the criteria for selecting the appropriate formulation method? a. Levigation – drug is levigated w/ small amount of base to form a concentrate that is then geometrically diluted with remaining base b. Fusion – base components are melted and congealed at a constant cooling rate, the heat-liable substances or volatile substances are added when the temperature is cool enough 5. Discuss the preparation & production of creams. a. Preparation of the oil phase – melting ingredients (highest MP first) b. Hydrating the aqueous phase – emulsifiers, stabilizers, and preservatives are dispersed in water, heating can accelerate process & helps mix with oils c. Forming emulsion – the two phases are blended under vigorous agitation d. Dispersion of active ingredient & excipients 6. What are factors that control the release of drugs for ointments & creams, & their penetration/absorption into or through the skin? a. An ointment’s hydrophobic nature allows for increased adhesive properties to mucosal membranes (great for hemorrhoids & eyelid mucosa) 7. Explain Fick’s law of diffusion as related to percutaneous drug absorption. a. Dissolution & release of drug from the vehicle or formulation b. Partition of the drug into the stratum corneum c. Diffusion of solubilized drug across stratum corneum d. Penetration of the drug into skin layers 8. What are emulgels? What are their advantages? a. Compound with properties of both and emulsion and gel i. Once you have an emulsion, add into a gel (via a gelling agent or an already made gel), dualrelease control system for delivering hydrophobic drugs ii. Better penetration & non-greasy feel, easy to spread & remove iii. Prepared via incorporation method Topic 3: Pastes & Gels 1. Define pastes. What is the difference between these and ointments? a. Pastes – semisolid dosage form that contains a high percentage up to 50% of finely dispersed solids i. Pastes have increased viscosity à ensures thick film is applied (great for eczema & psoriasis) ii. Stiff consistency, doesn’t spread well, serves as protective coating (but not occlusive), treats oozing lesions iii. Can come in aqueous/single-phase or fatty 2. What are common excipients in pastes? What are the different types of antioxidants in pastes? How do we select between lipo & hydrophilic antioxidants? a. Aqueous paste ingredients i. Gelatin, pectin, carboxymethylcellulose sodium, plasticized hydrocarbon gel b. Fatty paste ingredients i. Castor seed oil, mineral oil, paraffin, balsam tolu resin, petrolatum, cod liver oil, lanolin, methylparaben, soy ii. No preservatives needed!! c. Common excipients i. Hydrophobic solvents 1. Polydimethylsiloxane, vegetable oils, isopropyl myristate ii. Preservatives (fatty pastes) 1. Phenol, benzoic acid, methylparabens, benzyl alcohol, phenoxyethanol iii. Antioxidants 1. Lipophilic - BHA, BHT 2. Hydrophilic - sodium metabisulfite 3. Describe the manufacturing/preparation of pastes. a. Fusion method – melt bases & wax, add powdered ingredients, constant stirring b. Fusion & tituration – melt base, triturate powder w/ small amount of base, mix w/ remaining base 4. What is the USP definition of gels? What are magmas? a. Gels – semisolids consisting of colloids as either small inorganic or large organic molecules b. Magmas – particle size of dispersed phase is larger 5. What are the differences between hydrogels & organogels? a. Hydrogels – polar & aqueous, small & inorganic molecules i. Contains natural polymers, semisynthetic & synthetic ii. Insoluble due to crosslinks b. Organogels – non-polar & lipid-based, large organic molecules i. Contains lecithin, fatty acids, sorbitan esters 6. Describe the main classes of gelling agents. a. Aqueous gelling agents i. Natural - gelatin, gums, starch ii. Semi-synthetic – cellulose derivatives, sodium alginate iii. Synthetic - carbomer, povidone, polyvinyl alcohol, poloxamer, silicon dioxide b. Órgano solvents i. Hexane, isopropyl myristate, sunflower or corn oil 7. What are some semisolid patient counseling points? a. Occlusive vehicles enhance penetration, vehicle can be protective &/or cause side effects b. Clean & dry the area before application, wash hands c. Instruct pt on proper amount/dose Topic 4: Semisolids for special use 1. Define foams, plasters, dressings, and suppositories. a. Foam – dispersion of a gas in a liquid, forms a fluffy semisolid i. Can offer cooling, soothing, emollient, or moisturizing effects ii. Can aid highly inflamed, swollen, abraded, infected, or sensitive skin iii. Can be used rectally, vaginally, or topically b. Plaster – mass that adheres to skin, usually a piece of fabric with a layer of medication (salonpas) i. Can offer protection/mechanical support, occlusive, macerating effects c. Dressing – external application like ointment, covering or protection i. Dressing w/ gauze, used as a bandage or skin graft d. Suppositories – semisolid for insertion into body cavity (rectum, vagina, urethra) i. Melt or dissolve, can provide local or systemic effect 2. What are the different types of foams? Describe advantage of rectal foams compared to suppositories. a. Solid foams – transformed liquid foam into solid or gel b. Liquid foams i. Propellant-based – pressurized aerosols, 2 or 3 phases ii. Propellant-free – microemulsions w/ large portion of surfactants c. Rectal foams can have a better coverage area over suppositories 3. What are hydrogel dressings & hydrocolloid dressings? Describe their advantages. a. Hydrogel – hydrated 3D network of hydrophilic polymers, keep wound moist & absorb exudate i. Also include antibacterial agents, growth factors, & molecules to help wound healing b. Hydrocolloid – self-adhering, made of gelatin, pectin, or carboxymethylcellulose, provide a moist & insulating environment for healing, great due to not having to change as often i. Contain gel-forming agents, have a waterproof backing, come in many shapes/sizes, come with/without an adhesive border, made for difficult to dress wound areas 4. What are the types of suppositories? Describe various routes of administration & advantages. a. Fatty base or water-soluble base suppositories b. Rectal, vaginal (aka pessaries), & urethral (aka bougie) c. Great for pts who cannot swallow, post-op, nausea or vomiting, avoiding GI/liver, stomach irritation, unconscious, or seizures 5. Discuss types of suppository bases. a. Glycerol-gelatin bases i. Retain moisture, lubrication & aid in insertion b. PEG bases i. Water-soluble, suitable for hydrophilic & lipophilic drugs, good bioavailability c. Surfactant bases i. Facilitate drug delivery 6. Describe various methods of preparation of suppositories extemporaneously. a. Hand-rolling i. Used to make a few suppositories ii. Base & active ingredients are titrated in a mortar, rolled into a cylinder, & cut b. Compression molding i. Mixed mass of base & active ingredients forced into a compression mold ii. Avoids heat (great for flammable drugs) c. Fusion molding i. Melt the base & disperse or dissolve the active ingredients, remove from heat & pour into a suppository mold 7. What are quality attributes of suppositories? a. Hardness (handling & delivery) b. Shape (comfortable insertion & retention) c. Solubilization of drug d. Rapid melting/dissolving after application Topic 5: Stability, Expiration, & BUDs 1. What is the difference between shelf life & expiration date? How do manufacturers establish shelf life & expiration. a. Shelf-life – duration for which product meets specifications after manufacturing (when stored/used as directed) b. Expiration date – date (month & year) until batch meets specifications (when stored/used as directed) c. Established via “stress test” 2. What are types of drug stability? Describe types of degradation reactions that cause instability. a. Chemical i. Hydrolysis – when a drug molecule interacts with water (groups: esters, sub. Amide, lactone, lactam) ii. Oxidation – process of electron loss, interaction w/ oxygen (groups: aldehyde, alcohol, phenol, sucrose, oleic acid) iii. Photolysis – degradation via absorption of UV light (should pack these products in amber bottles, tablet coatings, or capsules) iv. Epimerization – epimer is transformed, action of drug on receptor is stereoselective (Ex. Lepinephrine is the only form that works for anaphylaxis) b. Physical i. Changes in strength, appearance, odor, taste, texture, uniformity c. Microbiological i. Applies to sterile products, & preservative-free products ii. Can add antimicrobial preservatives to multi-dose products iii. Aid via refrigeration or freezing product (when appropriate) 3. Discuss how proper design of a drug product, packaging, and storage can improve chemical stability of drug products. a. Understanding drug reactivity b. Protect from moisture, light, oxygen via packaging c. Storage conditions (room temp, fridge, freezer) d. Appropriate dosage form, excipients, & manufacturing 4. What is the difference between primary and secondary packages? Explain the functions of appropriate primary packaging for a drug product & define these terms. a. Primary package – in direct contact with drug product b. Secondary package – outside of the primary package, usually not critical to product stability 5. What is the acceptable range for the potency of a stable drug product? a. Active ingredient potency range = 90-110% of label strength (+/-10% variation is general) 6. Define drug recall, withdrawal, and discontinuation. a. Recall – batch/lot specific, problem w/ manufacture, stability, package, &/or label b. Withdrawal – product specific, problem w/ safety or efficacy c. Discontinuation – product specific, company stops sale of product