Suppositories PDF

Suppositories: ​ Solid dosage forms ​ Localized or systemic (faster onset reaction) effects ​ Inserts: solid dosage form and come with an insert, inserted into vagina and urethra ​ Advantages: ○​ Avoidance of oral and parenteral routes: ○​ AVOIDS FIRST PASS EFFECT...

Suppositories: ​ Solid dosage forms ​ Localized or systemic (faster onset reaction) effects ​ Inserts: solid dosage form and come with an insert, inserted into vagina and urethra ​ Advantages: ○​ Avoidance of oral and parenteral routes: ○​ AVOIDS FIRST PASS EFFECT ​ Protect drugs destroyed/ inactivated by the pH of enzymes in the stomach ​ Drugs irritating for the stomach ​ Drugs destroyed by portal circulation may bypass the liver after rectal administration (avoids first pass effect at least partially for those drugs that are administered orally) ○​ Convenient for patients unable to swallow ○​ Achievement of a rapid drug effect systemically ○​ Advantageous if oral form causes nausea/ vomiting ○​ Ability to give large doses of drugs than using oral administration ○​ Good for unconscious patients ○​ Pediatric populations ○​ Good for treating hospice patients ○​ Low cost ○​ Targeted deliver: minimized systemic toxicity and concentrated drug at the site of action ○​ No special technical difficulties in making suppositories ​ Disadvantages: ○​ Messy to apple ○​ Variation of absorption: ​ Colonic content, circulation route, ph ​ If placement too high will go through first pass metabolism ​ Gi problems ○​ Irritation for mucous cause by drugs/ bases ○​ Some suppositories leak or are expelled after inserting ○​ cultural/religious factors ○​ Defecation could interrupt process ​ The rectum has three types of hemorrhoidal veins: ○​ Superior, middle, inferior - its best of the suppository is inserted between the middle and inferior veins to avoid first pass effect ​ Two veins responsible for transport of adi are inferior and middle hemorrhoidal veins ○​ To avoid first pass effect, avoid too high placement of rectal suppository ​ Colonic content ~ greater absorption when rectum is void/ empty ​ Rectal fluids are “aqueous” neutral in nature and have no buffer capacity ​ Oil-soluble drug: oily base Slow release Water-soluble drug: oily base Rapid release  Oil-soluble drug: water-miscible base Moderate release Water-miscible drug: water-miscible base Moderate release ​ Two mechanisms of drug absorption for Vaginal inserts: ○​ Passive diffusion ○​ Para-cellular route ​ Composition: ○​ Active ingredient ○​ Suppository base ○​ Additives (suspending, emulsifying, lubricating agents) ​ Suppository bases act as a vehicle ​ - DESIRED PROPERTIES IS THAT THEY remain solid at room temperature and melt at body temp ○​ Types: ​ Fatty bases or oleaginous bases ​ Cocoa butter (theobroma oil) *has POLYMORPHISM which lowers melting point* B 35-37 Celsius - must heat carefully ​ Hydrogenated vegetable oils (palm, coconut, cottonseed) ​ Disadvantages: can melt in fingertips and be messy, may leak ​ Water- soluble or water miscible bases ​ Glycerinated gelatin bases (do NOT melt but dissolve slowly) ​ Slower release ○​ Why suppositories need to be moistened with water before inserting ​ Polyethylene glycol (PEG) bases (do NOT melt but dissolve in the body fluids) ​ Can also be dipped in water ​ Methods of preparation: ○​ Fusion molding (Common and Uses HEAT) ○​ Compression ○​ Hand rolling and shaping ​ Packaging/ storage: ○​ Cocoa butter in FRIDGE (rub suppositories gently with fingers to melt surface to provide lubrication) ○​ Glycerinated gelatin in controlled room temperature ○​ Containers- tightly closed class ○​ Glycerin is very hygroscopic ​ ​ ​ ​ Semisolids:  ​ Used for topical applications ​ Common sites of application include skin, eye, nose, vagina, rectum ​ Produce local and systemic effects ​ Can be used for topic and transdermal: ○​ Topical product: skin is the target organ, drug should penetrate and must be retained in the skin ○​ Transdermal product: skin is NOT the target organ. Ex. : pluronic lecithin organogel (PLO) ​ Semisolid preparations: ○​ Ointments: ​ Can be medicated or unmedicated ​ Composed of drug and ointment base ​ Ointment base is the vehicle (four types) 1.​ Oleaginous bases 2.​ Absorption bases 3.​ Water-removable bases 4.​ Water-soluble bases Oleaginous bases: ○​ AKA hydrocarbon bases or greasy bases ○​ Excellent emollient effect when applied to skin, protect against moisture escape, remain longer on skin, effective as occlusive dressings ○​ Difficult to wash ​ Examples: ○​ Petrolatum: ​ Aka yellow petroleum or petroleum jelly ○​ White petrolatum: ​ AKA white petroleum jelly ○​ Yellow ointment ○​ White ointment Absorption bases: ​ Absorbs water ​ Two types: 1.​ Emulsifiable bases: ○​ NO water ○​ Becomes W/O when you add aqueous solutions ○​ Ex. hydrophilic petrolatum and anhydrous lanolin 2.​ Emulsion bases: ○​ W/O emulsions ○​ Allow incorporation of additional quantities of aqueous solutions ○​ ex. Lanolin Water-removable bases: ○​ O/W emulsions ○​ Ex. Hydrophilic ointment Water - soluble bases: ○​ No oleaginous bases ○​ Aka Greaseless bases ○​ Large amount of aqueous solutions can not be incorporated effectively ○​ Used for incorporation of solid substances ○​ Ex. PEG Ointment preparations: ​ Incorporation Solids ○​ Levigate to reduce the particle size of a solid by triturating it in a mortar ​ Gummy material ​ Liquids: 1. Aqueous solutions (hydrophilic ointment bases easily accept aqueous solutions) - small amounts only 2. Alcoholic solutions ​ Fusion (involves heat) Preparation with emulsion base ○​ The water soluble ingredients are mixed separately and heated to the same temperature as oleaginous components ○​ The aqueous phase is then added to the oil phase slowly Creams: -​ Soft, spreadable consistency -​ W/O or O/W emulsion Pastes: -​ Larger amount of solids -​ More stiffer than ointments Gels & Magmas: -​ Semi Solid systems consisting of dispersion made up of small inorganic or large organic molecules enclosing and interpenetrated by a liquid -​ Gels can be two-phase or single-phase -​ Two phase gels or magma or milk: -​ Has floccules -​ Single phase gels: -​ Do not have apparent boundaries between them and the liquid ​ Filling of ointments- ○​ Jars  ○​ tubes Know these definitions: ​ Syneresis: upon standing for some time, gels shrinks bc some of the liquid squeezes out of the system ​ Swelling: the opposite of syneresis, gel takes up some liquid and increases in volume ​ Imbibitions: taking up a certain amount of liquid but not measurable increase in volume ​ Thixotropic: semisolid on standing but become liquid on agitation and again becomes semi solid upon standing Commonly used gelling agents in preparation: Acacia Alginic acid Bentonite Carbomer 934 Methylcellulose Carboxymethylcellulose Poloxamer Tragacanth gum Starch Xanthum gum ​ ​ ​ ​ ​ Suspensions: ​ Liquid dosage ​ Disperse systems: ○​ The substance distributed is called dispersed phase and the vehicle is called dispersing phase or dispersion medium. Both are insoluble and together form dispersed or disperse system ​ Available for oral, ocular, topical, rectal and parenteral administration ​ Ophthalmic, vaccines, solid and liquid phase ​ Shake before use ​ Desired properties for good suspension: ○​ Should be readily dispersed ○​ Homogenous ○​ Pour readily and evenly ○​ Particle size of the suspensoid should remain daily constant throughout periods of undisturbed standing ○​ Should not form a solid cake upon standing ​ Flocculated vs deflocculated suspension ○​ Flocculated suspension: -​ DESIRED -​ Particles are bonded weakly and settle rapidly -​ Do not form cakes  -​ The rate of sedimentation is high as particles settle as floc, which is a collection of particles -​ The flocculated particles are easily resuspended -​ The supernatant liquid is clear during the initial stages of settling -​ A distinct boundary exists between the supernatant liquid and sediment ​ Deflocculated suspension: -​ Not desired -​ Particles settle slowly and eventually form a sediment in which aggregation occurs resulting in hard cake which is difficult to resuspend -​ Due to slow rate of sedimentation, each particle settles separately and the particle size is minimal -​ The supernatant is turbid during the initial stage of settling (larger particles settle faster than small ones) -​ No distinct boundary exist between supernatany liquid and sediment Physical features of the dispersed phase of a suspension: ​ Size ​ Micro Pulverization ​ Fluid energy grinding or aka jet milling or micronizing ​ Spray drying Methods of preparing flocculated suspensions: ​ Flocculating agents ​ Altering the ph ​ Use of electrolytes as flocculating agents ​ Surfactants ​ Polymers ​ ​ ​ ​ ​ ​ ​ ​ ​ Emulsions: ​ Two phase heterogenous mixture!!!! THIS IS SO IMPORTANT ​ Stabilized by emulsifying agents ​ Shake before taking ​ Creams ointments, lotions, foams, ointments and commercial vitamin drops are not classified under emulsions even though they are ​ Can be used for Oil soluble vitamins and diagnostic agents Applications and advantages of emulsions~ ​ Emulsion spreads easily and completely over the skin and thus useful for dermatological and cosmetic preparations. ​ Irritation producing drugs are administered as emulsion (drug in the internal phase) to reduce the direct contact with the skin. ​ cold cream  ​ A O/W emulsion can be easily removed if it is desirable for any medical condition Example: vanishing cream ​ Emulsions are also used in aerosol type formulations to form foams Example: Clobetasol topical (against psoriasis, dermatitis) Types of emulsions: Oil in water emulsions and water in oil emulsions -​ Decide based on physicochemical properties of drugs and route of administration -​ Examples: -​ Fats or oils for oral administration are formulated as oil in water emulsions -​ IV emulsions are o/w type emulsion (water external) -​ IM injection that requires depot effect may be formulated as w/o emulsion (long, slow release) -​ Semisolids for external use can be either o/w or w/o emulsions Emulsifying agents: 1.​ Carbohydrate materials: acacia, tragacanth, pectin 2.​ Protein substances: gelatin, egg yolk, casein 3.​ Surfactants 4.​ High molecular weight alcohols 5.​ Finely divided solids ​ HLB scale is 0-20 ○​ LOW HLB: less than 10, more oil soluble, lipophilic, used for water in oil emulsions ○​ HIGH HLB: more than 10, more water soluble, hydrophilic , sued for oil in water emulsions ​ Preparations: 1. Continental or dry gum method -​ Oil then water -​ 4:2:1 (4 parts oil, 2 parts water and 1 part gum) -​ Primary emulsion 2. English or wet gum method -​ Water then oil -​ 4:2:1 Creaming and coalescence: ​ Creaming is OKAY and reversible (Desired) ​ Coalescence NOT DESIRED IRREVERSIBLE -​ the forming of larger droplets and is more destructive to emulsions than creaming. The separation of internal phase from emulsion is called breaking. Irreversible. Breaking - separation of internal phase  ​ ​ ​ ​ ​ ​ ​ Capsules ​ Solid dosage forms ​ Could be hard or soft ​ Shells are formed from gelatin (derived from pork skin or cattle bones) ​ Hard shell : 2 parts (body and cap) ; made up of gelatin , sugar and water ​ Soft shell : one piece capsules; gelatin plus glycerin or sorbitol (plasticize the gel) ​ Vegetable capsule is made up of hydroxypropyl methylcellulose (HMPC) also called hypromellose, alternative to gelatin ​ Gelatin is soluble in warm gastric fluids ​ Capsule size and volume are INVERSELY related -​ As shell size increases volume decreases (shell size 5 has a volume of.21) -​ Largest size is 000 and smallest is 5 ​ Opaquing agents example: titanium dioxide ​ Capsule powder formulations and ingredients: ○​ Fillers or diluents: starch, lactose, microcrystalline cellulose ○​ Disintegrants: assist in breakup and distribution fo the capsules contents in the stomach ○​ Lubricants or glidants: enhances flow properties to allow easy passage of capsules ​ Ex. fumed silicon dioxide, magnesium stearate, calcium stearate, stearic acid ​ Surfactant: sodium lauryl sulfate added as wetting agent -​ Capsule sealing: joining the cap and body -​ Capsule polishing: removing the powder that adheres to the shell outside Soft vs hard gelatine capsules: Soft: ​ One piece ​ Single unit dosage forms that contain liquid or semi solid fill enclosed in one piece hemitally sealed elastic outer layer ​ Composed of glycerin, sorbitol, or propylene glycol (added to plasticize the shell to make it softer) ​ Gelatin is more than plasticizer Quality assurance for capsules (USP requirements): ​ Disintegration ​ Dissolution testing  ​ Weight variation ​ Content uniformity (should be 85%-115%) Major defects for filled hard gelatin capsules: ​ Cracks, pinholes ​ Empty capsules ​ Presence of embedded surface spot and contamination ​ Capsule must have tight closure in the container during normal handling and dispensing ​ Containers are free from particulate substances and undesirable odor ​ Void space of the container should be filled ​ Cap and body of the shell is separated