Compounding

dermatological preparations

broad term that covers forms for external administration on skin; dermatologicals that are compounded=solutions, suspensions and gels, emulsions, lotions, creams, ointments, and pastes and others that are manufactured=aerosols and devices such as transdermal patches, tapes, and gauzes; ointments=semisolid dosage forms for skin and mucus membranes, creams meet the general definition but separate class=semisolid dosage forms containing one or more drug substance dissolved or dispersed in suitable base, formulated as either water in oil (cold cream) or oil in water (fluocinolone acetone cream) emulsion; pastes=semisolid that contain one or more drug substances intended for topical application, contain more solid material than ointments, at least 20% solids (zinc oxide paste); o, c, and applied to skin, surface of eye, used nasally, vaginally, or rectally, medicated or not, unmedicated=protectants, emollients, or lubricants; emollient=softens skin or soothes irritation, protective=protects injured or exposed skin from stimuli, occlusive=promotes retention of water by forming hydrophobic barrier that prevents moisture from evaporative, humectant=causes water to be retained

Elixir

clear, sweetened, flavored hydroalcoholic solutions for oral administration, most widely used liquid oral dosage form, popular=pleasant flavor, stability, and ease of preparation, not as sweet and viscous as syrups and less effective at masking the taste of APIs, because of alcohol=better solvents for most APIs than syrup and can contain both water soluble and alcohol soluble solutes; if alcohol content too high=unpleasant to take and have CNS depressant effect, normally just enough alcohol present to dissolve API and any volatile flavoring oil present=each one needs different blend of alcohol why varies 4-20%; glycerin and/or propylene glycol=third cosolvent with alcohol and water to decrease concentration of alcohol; volatile flavoring oils, sweeteners, and colorants=improve taste and appearance; first dissolved in alcohol if soluble in alcohol and dissolved in water if soluble in water, then co solvent added to alcohol, water added to aldol with stirring=high concentration of alcohol, qs to volume with water, if reduced for dilution=same concentration of alcohol and co-solvents

emulsions

coarse dispersion of liquid dispersed in a liquid; diff tween suspension=ohysical state of dispersed susbtance=solid v liquid; consist of an aqueous and oil phase; can be liquids (oral liquids, IV emulsion, topical lotions) and semisolids (creams); two types: O/W=oil is dispersed phase (internal) and water=dispersion medium (external), primarily has properties of aqueous system since water is external phase and oil droplets are hidden within he water, orally, topically, and IV; W/O=water dispersed through oil, internal=water and external=oil, primarily has properties of oil since water droplets are hidden, exclusively topical; adv=O/W hide taste and feel of orally administered oil (mineral oil), allows uniform product of two immiscible liquids, small droplet size of dispersed phase may increase efficiency of dispersed phase compared to administration of bulk oil, preparation of O/W makes IV administration of oil possible (IV fat emulsion for TPN or poorly water soluble, and particle size less than 5 microns) because oil alone would block capillaries=death, biggest overall use of both=dermatological products (lotions and ointments); packaged and stored like suspensions

colloids

colloidal dispersions: 0.1 to 0.5 microns (1nm to 500 nm), particles larger than atoms, ions, or molecules and consist of a single, large molecule of high molecular weight (insulin, plasma proteins) or aggregate of smaller molecules (micelles); more than one shape=globules, rods, flakes, threats, and branched rods and threads, associated colloids=dispersion of micelles (aggregates of 30-100 surfactant molecules) and size is 10 nm=lower colloidal size range, may appear translucent, opalescent, or cloudy depending on type of colloid and extent of particle concentration and dispersion, light scattering effect of colloids can be used to determine the MW, size, and shape; brownian movement=bombardment of colloidal particles by molecules of dispersion medium so no settling because gravity no effect, like solutions=colligative properties

Compounded tablets

commercially manufactured only in fixed dosage strengths and combos; compounded tablet provide more flexibility; pharmacists can prepare molded tablets with tablet triturate mold; molded tablets=small tablets made by molding a soft mass that usually consists of a potent med diluted with lactose and moistened with alcohol and they: quickly disintegrate in moisture, poor physical strength, limited size, easy to adjust composition; prepare: mix drug + diluent, moisten with alcohol, mix into pasty mass, fill holes in top portion of mold, all cavities are packed, place cavity plate on peg plate, tablets removed from cavity plate, tablets dry on pegs

Manual methods of comminution

comminution=process fo reducing the particle size of a solid substance to a finer state of subdivision; trituration=continuous rubbing or grinding of powder in a mortar with a pestle (reduce size and mix), suitable for hard and factorable powders, tools: pill tile and spatula or mortar and pestle (same type and normally porcelain to get small unless stain or smell cuz absorptive); legation: triturating while moistened with a liquid in which the powder is insoluble, mineral oil or glycerin, after get paste or suspension or incorporate into ointment or gel; Pulverization by intervention: comminution by utilizing a solvent that can be easily removed, ethanol and menthol because has to evaporate easily; not all can reduce size directly and why have other two; smaller size=increase dissolution and absorption and F and more consistent dose

Powder formulation abbreviations and directions

default unit is g for weight and mL for volume; M.Ft=mix and make; Pulv=powder, Sig=write on label; p.a.a.=to be applied to affected part, t.i.d.=three times a day; qs=a sufficient quantity; aa=of each (if see below one then the same amount applies for one above); DTD=of such dose, Ex: of such dose that prepares 10 capsules; mixture should be prepared of ingredients in amounts listed and divided into number of dosage forms indicated

defloc vs flocc suspension

deflocc: particles exist in suspension in separate entities, rate of sedimentation is slow and each particle settles separately and particle is small, sediment formed slowly, sediment becomes very closely packed due to weight of upper layers of sedimenting material and repulsive forces between particles overcome due to gravity and hard cake formed=difficult/impossible to disperse, supernatant has cloudy appearance when settling is apparent (large first and small left in solution), flocc: particles loose aggregates, rate of sedimentation is high=settle as floc=collection of particles, sediment formed rapidly, sediment formed loosely and possesses a scaffold like structure=particles not bonded tightly and hard, dense cake does not form, easy to redisperse so as to reform the original suspension, supernatant clear and volume of sediment is large due to loose structure

stokes' law

describes rate of settling of particles (in a dilute dispersion of spheres of uniform size); V=d2 (roe1-roe2)g and all/18n; V=velocity of settling, d-diameter of dispersed (increased=increase settling), roe 1-density of dispersed particle (increased=increased settling), roe 2=density of dispersion medium (increased=decreased settling), g=gravitational constant (9.81 m/sec2), n=viscosity of dispersion medium (increase=decreased settling); particle size=important especially because d is squared=decrease in particle size improves content uniformity and decreases rate of settling and can be reduced in pharmacy by mortar and pestle but large scale=different milling and pulverization equipment; density of vehicle=suspension can be increased by adding these substances alone or in combo: Polyethylene glycol, glycerin, sorbitol, and sugar; viscosity of vehicle=viscosity of a suspension is increased by adding suspending agents=methyl cellulose, carboxymethyl cellulose sodium, acacia tragacanth, majority of suspensions contain suspending agents to minimize sedimentation; rate can be decreased by decrease in particle size, increase density of liquid, and increase viscosity of liquid; for emulsions: V has negative value at creaming, to decrease rate of creaming=increase viscosity and decrease droplet size (g=0 and roe1=roe2)

selection of appropriate base and factors that affect percutaneous absorption of drugs from ointments

desired release rate of drug substance from the ointment base, desirability of topical or percutaneous drug absorption, desirability of occlusion of moisture from skin, stability of the drug in the ointment base, effect of the drug on the consistency of the ointment base, desire for a base that is easily removed by washing with water, characteristics of the surface to which it is applied; factors=method of application, type of ointment base, degree of skin occlusion, condition of skin, site of application, relative affinity of drug for base and skin

Compounded capsules preparation

developing filling contents formulation: anything that won't dissolve capsule like powders, granules, pastes, caplets, tablets, liquids, etc and majority are powder or granules and include drug (active ingredient) and excipients (inactive ingredients): fillers (or diluents), glints, surfactants; selecting capsule size: from 000 to 5 with 5 being the smallest and compounded capsules usually size 0 to 3 and choose perfect size based on volume (total contents of each pill/bulk density powder which is density=fit volume of one capsule); capsule filling; capsule sealing=mechanically interlocking caps and bodies, interlocking rings or bumps molded into the cap and body side walls (Psilok (shionogi), Snap-fit and Coni-Snap (capsugel), Lox-it (pharmaphil); capsule clean=cleaned with a cloth or paper towel prior to dispensing to remove any powder on outside of capsules and powder looks bad and may also have unpleasant taste and/or odor; capsule package=industry in plastic wrapping and compounding in bottle to keep away from O2, light, and moisture

Granules

diff from powders because powders=0.1 to 10 micrometers and granules=0.5-10 mm; adv over powders (most based on SA): granules flow better, granules prevent un mixing (stratification) of powder blends, dust problems associated with the handling and processing of fine powders are minimized b granulation, granules are more stable to atmospheric water and oxygen (cuz increased SA and do not absorb as easily), granules are more easily wetted by water; effervescent granules: contain mixture of citric acid (acidulant), tartaric acid (acidulant), with bicarbonate (source of CO2) and a medicinal agent, carbonated solution is pleasant vehicle and lessens bitter, amount of vehicle needed, subtract amount of total by the amount of active drug, ratio: citric acid monohydrate: 1, tartaric acid: 2, sodium bicarbonate: 3.4 g, citric alone=sticky mixture that will not easily granulate and tartaric acid=not used alone because granules too friable and crumble

Excipients for tablets (diluent, binders, disintegrants)

diluents=fillers, to increase bulk of tablet formulation to a practical size for compression and administration (most compressed at least 250 mg) ex: dicalcium phosphate (CaHPO4) lactose=equal parts lactose and dicalcium, microcrystalline cellulose (avicel)=direct compression, mannitol=in chewable and ODT and buccal and sweet taste and readily undergoes disintegration (also sucrose and normally one with highest amount); binders=impart cohesive qualities to powdered material to facilitate formulation of granules of desired hardness and size and insures tablet remaining intact after compression, ex: starch paste, gelatin solution, PVP, microcrystalline cellulose; disintegrants=disintegrators=disintegrating agents=promote disintegration into small particles after ingestion, ex: starch (most popular), super disintegrates=small amount needed ( 2 to 8% of tablet)=cross linked PVP and Croscarmellose sodium, disintegrates have great affinity for water, absorb water in large amounts, swell, and break tablet apart (alginic acid also disintegrate)

physical state of dispersed systems and based on particle size

dispersion can be throughout solid, liquid, and gas; solid in solid=solid suspension (zinc oxide paste) solid in liquid=suspension (tetracycline oral suspension USP), solon in gas=solid aerosol (epinephrine bitartrate inhalation aerosol USP), liquid in solid=solid emulsion (hydrophilic petrolatum USP, liquid in liquid=emulsion (mineral oil emulsion USP), liquid in gas==liquid aerials (nasal sprays), gas in solid=solid foam (foamed plastics), gas in liquid=foam (effervescent salts in water), gas in gas=none; particle size: coarse=particle size range from 0.5 to 50 microns (suspensions and emulsions), fine=size from 0.5 to 10 microns (magmas and gels), colloidal=size from 0.1 to 0.5 microns (1nm to 500nm and colloids)

Powders as a dosage form

divided powders=powders dispensed in form of individual doses: oral divided powders (charts)=dispensed in folded powder papers as individual dose, powders for inhalation=intended to be inhaled deep into lungs with the use of special metered dose inhalers; bulk powders=powders dispensed in a bulk container containing multiple doses: oral bulk powders=intended for oral administration, dentifrice powders=used in cleaning of teeth, douche powders=dissolved in water prior to use as cleansing agents and vaginal use, dusting powders=applied to skin, fine powder to be dusted on skin by means of sifter top containers, powder base: bentonite, kaolin, Kieselguhr, magnesium carbonate, starch and these vehicles will absorb secretions and dry area and impart a cooling effect, small particle size to be grit free and avoid irritation; powder insufflations=finely divided powders introduced (blown) into body cavities=extremely fine powder is placed in vessel, when rubber bulb is depressed, internal turbulence blow powder through orifice into nose, throat, tooth socket, or skin; aerosol powders=powder for inhalation and dispensed under pressure, delivery through mouthpiece to throat and lung, dry powder inhalers

geometric dilution

a process that thoroughly mixes a small amount of a drug with an appropriate amount of diluent; when have a small amount of drug and a lot of diluent; when both same color so cannot differentiate; in order to have it uniform because otherwise will not; start by mixing with mortar and pestle equal sizes of API and diluent and then add equal size to mixture of diluent (2 times before) and mix with mortar and pestle, scraping down sides of mortar and pestle between addition and continue until all mixed; Ex: 100 mg API + 100 Mg L, next 200 mg L, next 400 mg L; difficult to mix and clump if do all at once

suspending agents examples

acacia NF, agar NF, alginic acid NF, attapulgite (colloidal/activated), bentonite NF, carbomer NF, carboxymethylcellulose calcium, caboxymethylcellulose sodium, carrageenan NG, cellulose=microcrystalline and NF, microcrystalline cellulose and carboxymethylcellulose sodium NF, dextrin NF, guar gum NF, hydroxyethyl cellulose NF, hydroxypropyl cellulose NF, hydroxypropylmethyl cellulose USP, mangesium aluminum silicate NF, methylcellulose USP, pectin USP, poloxamer NF, polyethylene oxide NF, polyvinyl alcohol USP, providone USP, propylene glycole alginate NF, silicone dioxide NF colloidal, sodium alginate NF, tragacanth NF, Xantham gum NF

description of flocculation

addition of small amount of electrolye reduces zeta potential; when goes below critical value, attractive forces supersede the repulsive forces and flocculation occurs; loosely packed particles or flocs settle faster and form clear supernatant than deflocculated because larger size; unlike deflocc=don't form solid cake; sediment of flocks easy to redisperse by minute agitation (shaking), defloccs should be avoided=formation of solid hard cake; sedimentation of flocks can be minimized by adding suspending agents to increase viscosity of surrounding vehicle; experimental determination: sedimentation volume=F used to measure flock and is fraction of total volume occupied by the flocculated sediment and higher=better so if F=1 then the total volume is occupied by flocc sediment, degree of flocculation=beta which is sedimentation volume of flock suspension divided by sedimentation volume of defloc and want higher so more see volume of suspension

Importance of particle size and categories

affects rate of drug dissolution and bioavailability; ensure content from dose to dose; penetrability of particles to be inhaled for deposition in respiratory track (Deposition); non grittiness of solid particles in dermal ointments, creams, and opthalmic preparation (fine powder so on skin does not irritate); imp for eye and topical=no irritation so decrease size; USP/NF categories: very coarse is over 1000 microns and mesh size number is 2-10, coarse is 355-1000 microns and mesh 20-40; moderately coarse is 180-355 and mesh size is 40-80; fine is 125-180 microns and mesh size 80-120, very fine is 90-125 microns and mesh size 120-200; mesh size: #10 sieve has 10 openings per inch in screen mesh and if can sift through=10 mesh size, larger number of mesh size=smaller particle

Lozenges

also called cough drops, troches, or pastilles; flavored, sweetened base plus medicine; slowly dissolved in mouth for localized to treat sore throat and colds (systemic effect possible); adv: easy to administer to ped and geriatric patients, having formulas that are easy to change and can be patient specific, keeping the drug in contact with the oral cavity for an extended period of time; disadv: may perceive a gummy type as candy and not a serious dosage form; compounded: by molding mixtures of ingredients containing: sugars to form hard lozenge, PEG to form soft lozenge, gelatin to form chewable lozenge

Soft gelatin capsules

also known as soft gels; attractive, odorless, and tasteless dosage form, invented before hard gelatin capsules; majority intended for oral use; adv compared to hard gelatin: hermetically sealed (airtight)=may contain liquids, suspensions, and pasty materials, as well as dry powders, tamper resistant because cannot be taken apart and put back together, better content uniformity of liquid filled soft gelatin capsules than powder filled hard gelatin capsules, soft gelatin capsules may result in better bioavailability (liquids inside and skip dissolution), disadv: special equipment needed to make so more expensive and less commonly used; typical composition: polymer base (gelatin 66.3%), plasticizer (glycerin 33%), Preservative (methyl paraben 0.1%), colorant (color 0.1%), opacifier (titanium dioxide 0.5%), solvent/process aid (water qs); preparation: rotary die process, fill tank and pump to leads to injection wedge to die and chutes

Emulsification

emulsifiers prevent coalescence by forming a film around the droplets of the internal phase;e three types of films: monomolecular film=surfactants with one layer surrounding (oil in middle); multi molecular film=hydrophilic colloids such as acacia with multiple layers syrrounding(oil in middle); solid particle film=bentonite (oil or H2O in middle);determining types: dilution method=based on fact external phase of an emulsion is easily diluted with more external phase, additional water=blends into O/W=dilute emulsion so if O/W=miscible with water and W/immiscible with water, dye method=add small amount of oil soluble dye to small sample and if O/W=dye disappear into internal phase or not mix with product at all; if emulsifier has low HLB (below 6)= mostly lipophilic/lipid soluble and forms W/O emulsions, if emulsifier has high HLB (over 8)=hydrophilic/water soluble and forms O/W emulsions

Suppository bases

fatty or oleaginous: cocoa butter, refrigeration needed because when melted and chilled=forms metastable crystalline with melting point much lower than normal so can not remain solid at room ten or can not harden easily in suppository mold, phenol and chloral hydrate=lower melting point of cocoa butter, fattibases (triglycerides fro palm, coconut oils with self emulsifying glycerol monostearate), wecovee bases (triglycerides from coconut oil), witepsol bases (triglycerides of saturated fatty acids); water soluble and water miscible bases: glycerinated gelatin bases=uncommon and base from granulated gelatin and glycerin and water, mostly used in vaginal=prolonged localized action and soften slowly and base is slower to soften and mix with physiologic fluids and slower release and tendency to absorb moisture so should be protected from atmosphere, polyethylene glycol bases=common, may be blended to get right consistency, do not melt at body temp but dissolve slowly in body fluids, no refrigeration, those that do not contain at least 20% water should be dipped ins ager before use to avoid irritation to mucous membranes after insertion

Excipients added to filling contents

fillers (or diluents): to increase bulk of formulation: lactose, microcrystalline cellulose, mannitol, starch; glints: improve flow rate form hopper and into body of capsule during filling process, flowability, colloidal silicon dioxide, starch, talc; lubricants=reduce powder adhesion to machine parts, hydrophobia steatites such as magnesium stearate and calcium stearate and stearic acid; surfactants and wetting agents: increase wettability of drug particles and enhance drug dissolution, sodium laurel sulfate

Hard Gelatin Capsules

gelatin: bone gelatin (type B) or skin gelatin (type A), dyes and other colorants, opacifying agent or opacifier: titanium dioxide (TiO2), protect capsule content form light, preservative: sulfur dioxide, water 10 to 15%: high humidity=too soft and sticky, lose rigid shape, dry or low moisture=brittle and crumble when handled; made from other material: starch (capill), HPMC (Vegicaps, V-caps), PVA capsule; manufacturing: 1) mixing gelatin with hot water and adding dyes and other components, 2) capsules molded into pin bars, 3) dying of capsules, 4) once drying is complete, capsule halves individually stripped from pins, 5) cap and body lengths precisely timed, 6) capsule bodies and caps joined automatically in joiner blocks, 9) finished capsules pushed onto a conveyer belt which carries them out to a container

Excipients for tablets (glidants and lubricants, miscllaneous)

glidants=improve granulation flow into die, lubricants=prevent sticking of compressed tablet to punches and die of tablet machine and ex of both: magnesium stearate, calcium stearate, and stearic acid and colloidal silicon dioxide, starch, and talc; miscellaneous=colorants, sweeteners, and flavor ants and those used to coat, colorants=dyes=improve appearance, aid in product ID, and hide color differences in various tablet combos=F & C (food, drug, and cosmetic) dyes or D & C (drug and cosmetic) dyes, sweetening and flavoring=only in chewable and ODT (effervescent, buccal, and SL also possibilities as well as tablet film coatings)=sucralose (splenda), saccharin (sweet N low), and aspartame (nutrasweet equal)

Compressed tablet manufacture

granulation methods: granulation through wet granulation or dry granulation and then compression of granulation into tablet; direct compression=compressing tablets directly form powdered material with a lubricant and a disintegrate; tablet machines: contain lower punch, die, and upper punch; powder filled in the die and lower punch at bottom and upper punch over die, lower moves up to remove excess powder and upper moves inside die and force applied to compress powder into tablet, upper moves outside die and lower punch moves up to eject tablet; with rotary tablet machine

USP 795

guidelines for compounding; physical/environmental requirements: separate area and need washable ceiling tiles and food and need a dedicated barrier but more intense for sterile compounding=regulate airflow; standard operating procedures (SOPs); MSDS data sheets; training; Documentation: each time compounded have to do compounding log and have to include for API NDC number, Lot number for internal tracking of product, Expiration date, manufacturer, amount used and for excipient used: NDC number, Lot number, Expiration date, manufacturer, amount used and overall: pharmacist pre check by with signature and pharmacist final check by with signature, so you can track it back; some facilities have stricter standards than required by law: two different check neonatal dose or 3 pharmacists check if less than 0.1 mL; now titer regulations and insurance bans because of inflation of prices and unnecessary compounding

Types of Lozenges

hard=made by heating sugars and other ingredients together and pouring mixture into a mold and mold can shape mixture to look like sucker or lollipop and will not disintegrate in mouth but will erode or dissolve over 5-10 minutes period and not suitable for heat liable drugs because high temps required to prepare; soft=easily compounded and can be colored and flavored, chewed or allowed to slowly dissolve in mouth, typical ingredients are PEG 1000 or 1450, chocolate, or sugar-acacia base, dispensing method: pour warm mass (50C) into plastic mold; chewable: chewed and swallowed, popular with pecs, gummy-type, formulation based on glycerinated gelatin suppository formula: glycerin, gelatin, water, flavoring agents, and sweetener

Electronic balance

have digital displays and internal calibration capabilities; have a larger capacity range; min weight that can be discriminated is 3 mg; never weight less than 60 mg; follow aliquot method for weighing less than 60 mg; do not require daily calibration; instructions: level balance by a dusting feet until air bubble is centered, of 5 buttons, never use zero button, only large T, place weighing paper and press red T to zero appears, place weighed material in center, add new weighing paper and press red T for next weighing; can also do tablet counting

hydrocarbon ointment base

hydrocarbon=oleaginous bases, adv=inexpensive, nonreactive and nonirritating, good emollient, protective, and occlusive properties, are not water-washable so stay on skin and keep meds in contact with skin, disadv=poor patient acceptance cuz greasy, not removed easily with washing, not absorb water and can absorb limited alcoholic solutions=most liquid ingredients difficult to incorporate and aqueous skin secretions do not readil dissipate, petrolatum USP=purified mixture of semisolid hydrocarbons from petroleum and greasy and used alone or in combo (solid or liquid paraffin, yellow ointment=yellow wax 5% and petrolatum 95%=slightly greater viscosity than petrolatum, white ointmendiffers from yellow by substitution of white wax and white petrolatum

preparation of suppositories

mineral oil is lubricant and not needed for cocoa butter and polyethylene glycol because separate out with cooling but is for glycerinated gelatin; every base has different density and added drug affects density=proper amount of drug and suppository mold has to be calibrated for each base; determining amount of vase: different methods of weighing the base; hand rolling method=finely powdered drug mixed with grated base in mortar and pestle using levigation and geometric dilution and small amount of fixed oil may be added to facilitate, mass hand rolled into suppositories; fusion method=melting base, incorporating meds, pouring melt into molds, allow melt and congeal, remove formed, principle way made commercially, primarily if con taint cocoa butter, PEG, glycerin-gelatin bases, can make 650 at a time and molds=brass, aluminum, or nickel-copper alloys; compression method=uniform drug and base produced by hand rolling, mixture into suppository compression device=mixture into lubricated compression mold cavities, mold cooled and suppositories ejected, compression for heat liable medicinal substances or those insoluble in the base, permits no likelihood of insoluble matter settling, disadv=special machine and limited shapes, for heat soluble=melt and mix and cool and compress=uniform granules

solution

mixture of two or more components which forms homogenous molecular dispersion, components=solvent and solute; classified as oral, otic, opthalmic, topical, nasal, inhalants, irrigating=clean bod cavities and during surgery, parenteral; adv relative to solids=faster onset of action because API already dissolved and easy to swallow (biggest adv and for pecs and beds), disadv: many APIs chemically unstable in solution=short shelf life, flavoring problems, inaccuracy of dose especially when household spoon is used, liquids bulky (higher shipping costs), spill able, and inconvenient to carry around; both syrups and elixirs are solutions; packaged=plastic or glass bottles protected from light, primary concern=potential for microbial growth and default USP NF BUD for aqueous solutions without preservatives=14 days if stored at cold temperature, sign of instability=precipitation in solution; most preferred if can formulate but if taste bad or not chemically stable=can't make

components of a prescription/med order

name of prescriber, credentials of prescriber (MD), full address of prescriber's practice, phone number of prescriber's practice, date of issue, patient's name, patient's address, name of drug (generic or brand name of medication), strength of dosage form (in compounding show what ingredient to include and amount), quantity to dispense, Sig (instructions for use), number of refills/refill instructions, dispense in childproof container mandated (optional), messages to pharmacist (optional), signature of prescriber (required to have two signature lines in alabama: substitution allowed or substation not allowed), DEA number of prescriber=required for CS; prescriber's state license number=NPI number; in compounding can have QS=quantum sufficient (fill to that); in compounding have weight to know if right

Weighing Machines

non-automatic (mechanical beam, class III) and automatic (electronic) balances; pharmacies that specialize in compounding have electronic balances but until recently majority of pharmacies (esp built before 1999) used class III; guidance: leveled and stable surface for balance, cover pans with weighing paper/boats, fold weighing paper diagonally, every time use clean weighing paper to avoid contamination, always readjust balance with new paper and boats, always arrest torsion balance to protect and maintain accuracy, weights on right hand pan, do not pour or dump, use spatula, always wight legal minimum quantity (decided on sensitivity requirement/SR), in compounding, max 5% weighing error is allowed, calibrate monthly and service yearly

Gel method of preparation

non-solvent method=levigate powder with a water miscible non solvent (alcohol, glycerin, or propylene glycol), use blender to mix powder and solvent (sodium carboxymethylcellulose); cold water method=some gelling agents more soluble in cold water than in hot water (methyl cellulose and poloxamers), hot water method=some gelling agents gel only in hot water than in cold water (starch and gelatin), neutralization method=some gelling agents acidic in nature, readily dissolved in tepid water to form solution and need alkali to neutralize to produce sparkling clear gels (carbomers), medicated=API may be dissolved before or after gel formed depending on interference, basic drugs dissolved in organic solvent such as alcohol and added to carbomer solutions=spontaneous gels; package=air tight container, refrigerated or at room temp, tubes, jars, squeeze bottles or pump dispensers with applicator or syringes, observed for shrinkage, separation of liquid, discoloration, and microbial contamination

emulsifying agents (nonionic surfactants, natural, solids)

nonionic surfactants=no incompatibilities with charged drugs or preservatives, esters of same 4 fatty acids (slop) with glycerin, glycol, or sorbitol and mostly lipophilic and form W/O, esters of these fatty acids and large polar groups=PEG or PEG bonded to sorbitol=hydrophilic and form O/W, glycerol fatty acid esters=W/O, propylene glycol fatty acid esters=W/O, sorbitan fatty acid esters=arlacels form W/O, polyoxyl fatty acid esters=form O/W, polyoxyethylene sorbitan fatty acid esters=polysorbates form O/W and most commonly used nonionic, poloxamers=series of compounds; natural=acacia=carbohydrate gum that forms hydrophilic colloidal solutions=O/W, cholesterol=steroid alcohol (wool fat=lanolin) and lipophilic so W/O, phospholipids like lecthins form emulsions and IV; finely dispersed solids=particles insoluble in water and oil and pushed to interface=film that prevents coalescence, betonite=colloidal clay, if water first and then oil=O/W but if oil first and then water=W/O, veegum=colloidal clay similar to bentonite

Water soluble bases

not contain oleaginous components; completely water washable and soluble and greaseless; soften greatly with addition of water, large amounts of aqueous solutions not effectively incorporated into these bases, mostly used for incorporation of solid substance, polyethylene glycol ointment NF=prototype ex; adv: soluble in water and easily removed by washing, no oil residue, can absorb some water or alcohol and as the amount of liquid added increases=base thins out and eventually dissolves; disadv: cause irritation, especially on denuded or abraded skin or mucous membranes, have little to no emollient properties, PEG type bases may have compatibility problems with incorporated drugs that are subject to oxidation, those that contain water may have compatibility and stability problems associated with ager and a preservative is required; PEG=polymer of ethylene oxide

desirable properties of suspension

not settle rapidly=if settle at bottom, should be re-dispersed by rapidly shaking container, correct viscosity to pour freely form bottles and/or to flow through administration needle, if used in dermatology=must be sufficiently fluid to spread over the skin with no resistance and adhere to the skin after application; upon storage=when particles settle to bottom=not form hard cake that is difficult to re disperse by shaking

preparation of ointments

incorporation method (mechanical bleeding): mixing of components using glass mortar and pestle and/or ointment slab and spatula, solid should be added as solution to have uniform blend and no grittiness and if not=powder levigated to minimize grittiness and increase effectiveness, prepared by thoroughly rubbing and wokring the components together on the hard surface until product is smooth and uniform, to avoid grittiness of final product=API levigated (mineral oil for oil as external phase and glycerin for water as external phase) and levigating agent=equal volume to solid material and mortar and pestle for this=reduction in particle size and dispersion and not affect viscosity and after=dispersion incorporated to base by spatulation or mortar and pestle, for gummy=pulverization by intervention; fusion method (melting)=only compound ointments when incorporation can't be used= spatulation cannot be used to incorporate white wax or stiffening agent, most common to prepare ointment bases and not add drug to base, water bath=melt components and blended bus tiring and API added as solution or levigated powder, if heat liable and any volatile components=added last when temp low, ointments with beeswax, paraffin, stearyl alcohol, and high MW PEGS use fusion, highest melting point=heated to lowest possible

capsule filling

individual hand filling (punch method)=place the triturated powder on a pill tile and flatten powder with a metal spatula (no specks observed and proper mixing to ensure proper distribution of all ingredients so uniform dose) and then fill capsule by holding it with the open end and punching it into the powder and will require repeated punching and then check weight by skipping cap on and not locking and if weight not right=add or remove and when weight correct=press on cap until hear click or hand operated capsule filling machine=load capsules into machine, separate capsule caps with capsule bodies, powder placed on unit and capsule bodies filled, capsule caps reattached

Oswald ripening

instability in suspensions; rare; particle (Crystal) growth in suspension=destabilization process which occurs due to temperature fluctuation during storage=may change particle size distribution and polymorphic form of drug, if solubility of drug is temperature dependent; methods to overcome: selection of particles of narrow size range, selection of more stable crystalline form of drug, avoidance of high energy milling during particle size reduction, incorporation of wetting agent (surfactant or protective colloid), increase in viscosity of vehicle to retard particle dissolution and subsequent crystal growth, avoidance of temp extremes during storage

suspensions

liquid preparations containing undissolved solid drug particles=dispersed phase throughout a liquid=dispersion medium; intended for oral as sweetened, flavored that may be swallowed, through NG tube, or swished for topical mucosal treatment, or can be topical (skin, eye)=lotions in that case or can be non-sweetened, non-flavored for parenteral routes (IO, IN, IV, IM, SQ); why have one? some drugs insoluble in all therapeutically acceptable solvents and as a liquid=ideal for those who have difficulty swallowing, disagreeable tastes can be masked (many no taste as insoluble dispersed phase), drugs in suspension=chemically more stable than in solution, oral suspensions=systemic and local effects, greater flexibility in administration of doses; disadv=physical instability as dispersed particles settle over time=lack of uniformity of dose, texture may be unpleasant to patients

Weighing

metric system=most preferred in healthcare, based on multiples or fractions of ten, gram, liter, meter; apothecary system=commonly used in past, largely replaced by metric, roman rather than arabic numerals, gallon, quart, pint and have to do conversion: 1 fl oz=29.57 mL, 1 kg=2.2 lb, 1 lb= 453.59g, 1 oz= 28.35 g; avoirdupois system: weight measurement only, basic unit is grain, pound is most common

source of active ingredient for compounding

obtaining pure powder form of an API for average retail or hospital is difficult, time consuming and expensive; best source of API=commercially prepared product: tablets and capsules; tablets may normally be comminuted and capsule contents emptied for use in compounding pharmacy; can also use sterile IV liquid for oral but not the other way around

water-removable bases

oil in water emulsions, also known as creams=vanishing cream; because external phase of the emulsion is aqueous=easily washed from skin and often called water-washable bases; adv: non-greasy and aesthetically pleasing, can be removed from skin by washing=water removable, can absorb some water or alcohol, if amount of liquid added reaches critical amount=bases will thin out to a lotion, allow dissipation of fluids from injured skin; disadv=less protective, emollient and occlusive than hydrocarbon or absorption, with soap-type emulsifiers can have compatibility problems (surfactants and emulsifying agents), with water=chemical stability problems with ingredients sensitive to hydrolysis, subject to microbial growth, and USP requires these contain preservative, because water is external phase=bases may dry out due to evaporation and can be minimized by storage in tight containers, humectants can be added to stop too; Ex; hydrophilic ointment USP, vanishing cream

Pastes

ointments with high percentage of insoluble particulate solids (over 20%) and seem stiffer, seem less greasy and more absorptive than ointments, because they contain high concentrations of solid ingredients that absorb water and aqueous solutions, better at absorbing skin secretions and less penetrating and stay in place on skin better than ointments; good protective barriers when placed on skin; like ointments=form unbroken, relatively water impermeable film on the skin surface and thus are emollient and unlink ointments=film is opaque=effective sunblock; effective to absorb serous secretions, not suitable for hairy parts of body

Powders

oldest dosage form; industrially prepared oral powders largely replaced by tablets and capsules; compounding oral powders not unusual=usually for geriatric or pediatric patients; Adv: easy to swallow, relative stability (more stable than liquid), rapid onset of action, large doses possible, avoid irritation caused by very soluble salt tablet; disadv: not suitable for drugs with unpleasant taste/odor, less stable than tablet or capsules, relative expensive than tablet or capsules; powder compounding: reduction of particle size of all ingredients, sieving, weighing of each ingredient, mixing, weighing of individual doses (divided powders only), packaging and labeling

Compounding suspensions

one of easiest and most commonly compounded dosage forms; correct amount of API obtained, pure is preferred but can take commercial tablets and capsules=insoluble excipients less of a problem because API is also insoluble, powder, tablets, or capsule contents 1) levigated in glass mortar (with glycerin or propylene glycerol=decrease particle size for slower settling and more uniform dosing to have more accurate dosing and remove adsorbed air from powder particles and form void spaces for easier wetting with vehicle, viscous levigating agent forced to flow tween particles to displace air, to coat and separate each particle so that they may be wetted by the dispersion medium; 2 q.s. with viscous vehicle to decrease rate of API settling for more accurate dosing; package and storage: packaged in wide mouth containers having adequate air space above liquid (skacking), stored in tight containers to protect from freezing and excessive heat and light, label=shake before use to ensure uniform distribution of solid particles and thereby uniform and proper dosage

Packages of powders

oral bulk powders in cardboard bulk powder boxes or wide mouth screw cap glass jars; dusting powders in sifter top cans or powder blower/insufflator; divided powders: plastic packets: small sealable (zip lock) plastic bags (tiny sandwich bags) the easiest package to use and offer much greater protection from the atmosphere, loss of powder to the packet is a concern OR folded powder papers (more traditional method): 1) white bond: opaque and thus neat professional appearance but NOT moisture resistant; vegetable parchment: semi-opaque and moisture resistant; glassine: newest and most commonly used weighing paper and is glazed, transparent, and moisture resistant; waxed: transparent but waterproof, individual doses of divided powder either folded powder papers or plastic packets traditionally dispensed in powder paper box

semisolid preparation

packaging=detmatologic in jars or tubes, opthalmic, nasal, vaginal, and rectal=tubes; tubes=light in weight, inexpensive, convenient for use, and compatible with most formulative components and provide greater protection against external contamination and environmental conditions than jars; ointment tubes=aluminum or plastic, when ointment for opthalmic, rectal, vaginal, aural, or nasal=special applicator tips, ointment=transferring weighed into jar with spatula at pharmacy or if fusion=poured into jar; evaluation: stability of API and adjuvants, visual color, odor, viscosity, extrudability, loss of water and other volatile components, phase distribution, particle size distribution of dispersed phases, pH, texture and feel upon application, particulate contamination, microbial contamination and sterility, release and bioavailability

Prescribe compound order

paper copy (written or printed) on tamper resistant prescription pads/ printer paper; fax transmission to the pharmacy/pharmacy software; CPOE/e-prescription; phone order from prescriber or prescriber's agent; voicemail from prescriber or prescriber's agent

Flocculation

particles dispersed become charged by: selective adsorption of a particular ionic species present in solution and charges on particles arise from ionization groups; charged particle in aqueous attracts ions of opposite chare/counterions (gegenions)=cloud of counter ions around particle; if zeta potential reduced below certain value (depending on dispersion system)=attractive forces exceed repulsive forces and particles come together=flocculation, stages throughout dispersion and a=potential determining ions and surface charge is nernst potent ion and on b=surface charge is zeta potential; a to b=counter ions and stern layer, b to c=diffuse layer, and a to c=electrical double layer, c to d=electro neutral region because equal number of positive and negative ions; if all have large negative or positive zeta potential will repel and lead to deflocculation so this is +30 and above or -30 and below, if low zeta potential values=no force to prevent particles coming together leading to flocculation so this os around 0 to 30 and to -30

physical stability of emulsions

physically unstable since oil and water are immiscible; chemical dissimilarity=high interfacial tension at interface=causes oil and water to resist mixing and quickly separate into two layers after mixing; coalescence=fusion of the dispersed droplets to form larger droplets which fuse to form even larger droplets, cracking or breaking=result of coalescence and is complete separation of oil and water into two layers (oil on top); important that internal phase be dispersed as small droplets throughout external phase for dose uniformity, important that the dispersed phase remain dispersed for a reasonable period after shaking=dose uniformity in each fraction of liquid; to be physically stable enough=need an emulsifier/emulsifying agent=prevent coalescence by forming a film (physical barrier) around the dispersed droplets and since the droplets can't touch=can't fuse, creaming=not a significant problem in an emulsion ointment base because too high viscosity of external phase would arrest creaming

Divided Powders: chart preparation

place the paper on the counter away from winds or drafts; fold down top long edge of paper one half inch; place weighted dose of drug in center; bring lower edge of paper and insert it completely into top fold of powder paper and make second fold in top edge of paper; center folded paper lengthwise over an open powder box size of intended use, fold equal overhanding ends down while pressing in sides of box, do not press too hard and bend box; fold ends of powder paper completely back and sharply crease end folds, place filed powder paper into box with folds away from you, prepare folded powder paper for each dose, after know length of folds, rest can be folded equally

preservatives and anti-oxidants in suspension

preservatives=chlorocresol, chlorobutanol, benzoate's, phenyl mercuric nitrate and paragons are used and criteria selection=efficacy against wide spectrum of microorganisms, stability (shelf life) toxicity, sensitizing effects, compatibility with other ingredients in the dosage form, taste and odor; coloring agents, flavoring agents; anti-oxidants=many undergo oxidative degradation upon storage and auto oxidation is common, there are three categories: true antioxidants=inhibit oxidation by reacting with free radicals=tocopherols, alkyl callates, BHA, BHT, reducing agents=lower redox potential than the drug or other substances in the formulation, more readily oxidized=ascorbic acid, sulfites, anti oxidant synergists=chelating agents=citric acid, tartaric acid, disodium meditate, lecithin, selection of antioxidant depends on stability, efficacy, toxicity, odor, taste, compatibility with other ingredients

Tablet characteristics

routes: oral, buccal, SL, chewable, ODT, implanted, vaginal; Immediate release, controlled release/extended release=release over long period of time, delayed release=enteric coated; modes of disintegration: effervescent tablet: zantac effervescent tablet, chewable tablet: amoxicillin chewable tablets, dispersible tablet: amoxicillin, aspirin=dissolves too but not specific recipe; coated: sugar, film=polymer film on tablet surface, compress coating=compressing a coating onto compressed tablets, inner core and outer layer, separate chemically incompatible materials, dual release patterns possible, enteric=resists dissolution or disruption in stomach but not in intestines, used for drugs that are unstable or irritating to stomach and has cellulose phthalate based coating, sustained release coating=coated with polymers (ethyl cellulose), control the release of drug from a tablet via diffusion of the drug through the polymer film, reduce dose frequency; preparing methods: compressed tablets (industry) 99%, molded tablets (compounding, 3D printed tablet

Creams

semisolid preparations containing one or more medicinal agents dissolved or dispersant in E/O or O/W emulsion or in another type of water-washable base; vanishing creams=O/W emulsions containing large percentages of water and stearic acid or other oleaginous components, after application of cream=water evaporates and leaves a thin residue film of stearic acid or other oleaginous component, creamy or shiny appearance=reflection of light from emulsified phases; many patients and physicians prefer creams to ointments because easier to spread and remove; frequently manufacture topical preparations of drug in cream and ointment bases=preference of patient and physician; on skin, rectally, and vaginally; NF contains monographs for six polymers=carbomers=gelling agents at concentrations of 0.5 to 2% in water

Gels

semisolid systems consisting organic elongated macromolecules in an aqueous or non aqueous liquid, interlaced and interpenetrated by a liquid with no definite boundary between solid and liquid phases; organic macromolecule=gelling agent; gelling agents: synthetic macromolecule=carbomers, poloxamers, cellulose derivative=methyl cellulose, carboxymethyl cellulose sodium, natural gums=xantham gum, tragacanth; may thicken on standing=forming thixotrope and must be shaken before use to liquify gel and enable pouring; contain gelling agent and water and can have API, solvent (alcohol and/or propylene glycol), antimicrobial preservatives, and stabilizers; adminsitration=skin, eye, nose, vagina, rectum; used as lubricants and carriers of spermicidal agents=intra vaginally as adjunctive form of contraception, some contain anti-info steroids=infl on scalp because cream and ointment too greasy

Caking of suspensions

small individual particles always become charged by their ionic character or by absorption of ions, due to repulsion=suspended particles remain as individual particules=deflocculated=do no aggregate and settle slowly due to gravity; end result=formation of hard and dense cake powder on bottom of container that is not re dispersed by shaking; slow process (left weeks to months undisturbed) and not normally a problem in compounded because prepared immediately prior to use and shaken before each dose, but problem for industrially prepared=stored undisturbed for months or years; to overcome=converting into flocculated suspension

Syringes and smaller volumes

small volumes less than 2 mL=pipette, small syringe, or calibrated dropper=number drops from vertically held dropper in 2 mL of liquid (10 mL graduate) and number of drops different for each dropper type and each liquid; graduated cylinders: level of liquid is read to bottom of meniscus and measure is vertical when reading meniscus=read parallel; smaller diameter=smaller volume errors, volume errors dependent on diameters; syringes=graduated cylinders with plunger, rules for graduates apply here, useful for viscous liquids (glycerin, propylene glycol, or mineral oil) and more accurate because pour slowly in graduate (60 seconds), bottles with special syringe adapter caps=viscous liquids even easier and less messy (attach to cap and pull up form bottom of bottle)

hard gelatin v soft gelatin capsule

soft: plasticized shell (glycerin, propylene, glycol, sorbitol) to make soft and flexible, liquid or suspension content (dry solid possible), manufacture: formed/filled in one operation, closure: hermetically sealed, size and shapes: many: round, tube, oval, oblong; hard: shell not plasticized, content: dry solids (liquid. semi-solid matrices possible, manufacture: shell made first in one operation and filled in a separate process, closure: traditional friction fit; mechanical interlock, banding, and liquid sealing possible, sizes and shapes limited

capsules

solid dosage form in which the active ingredient is enclosed in a gelatin shell; different method of packaging a divided powder; shell made of gelatin usually; dry powders, semi-solids, and liquids that do not dissolve gelatin may be encapsulated; capsules account for 25% of dispensed solid dosage form; primarily intended for oral delivery; two major types: hard gelatin capsules and soft gelatin capsules; adv: hide taste/odor: capsule shell hides any unpleasant taste and/or odor of the active ingredients, appearance: capsules are neat and elegant in appearance, relative swallowing: relatively easy to swallow for average adult (not geriatric), flexibility of content: unique mixed fills possible, role in drug development (early stage), role in clinical tests (double blind clinical trials), compounding lab; disadv: relative swallowing: peds and geriatric patients difficulty swallowing, more expensive (commercially) than tablet, relative size: not suitable when powder volume (bulk) per dose is large

suppositories

solid dosage forms intended for insertion into body orifices=melt, soften, or dissolve and exert localized or systemic effects; commonly rectally, vaginally, and occasionally urethrally; rectal=cylindrical, bullet or torpedo shaped and may weight about 2 g, for infants=pencil like and may weight about 1 g, vaginal=pessaries and urethral=bougies; inserts=compressed tablets used as vaginal suppositories and normally supplied with inserting device for placement of tablet high in vaginal tract; local action=rectal for constipation, pain or irritation, itching, inf with hemorrhoids or ano-rectal conditions, glycerin ones=promote laxation by local irritation of mucous membrane, vaginal=mainly contraceptive, antiseptics, urethra=antibacterials and local anesthetic preparative examination; for systemic: mucous membrane of rectum and vagina=absorption and adv=drugs destroyed or inactivated by pH or enzymes of stomach or intestine not exposed to this, drugs irritating to stomach may be given without this, rectal route=bypass first pass, convenient administration to adults or peds who can't swallow, effective route for vomiting; package=tightly closed to precent moisture change in suppositories, with cocoa butter=individually to prevent contact and adhesion, photosensitive drug=opaque material (metallic foil), polyethylene glycol=stored at room temp without refrigeration

Tablets

solid dosage forms which are prepared by compression (over 99%) or by molding in compounding; most common dosage form in pharmacy; adv: relative=mostly compared to liquids, accuracy of dose, ease of obtaining dose, rapid and inexpensive manufacturing, easy to package, ship, and dispense, stability=more stable than liquids, powders, and granules, easy ID=coated tablets can be imprinted with edible ink and uncoated tablets may be debased (stamped in, using an embossed punch) with an ID code (engraved punches), taste=tablets have bland taste (compared to divided powder or solution) but may be coated to hide bad taste/odor, tamper resistant=substances not easily removed from or added; disadv: difficulty swallowing=some patients (elderly and peds), not practical for large doses=tablets too large to swallow but chewable tablets possible solution, bad taste/odor=require encapsulation or tablets may require coating so capsules=best and lowest cost

storage and stability of powders

store in dry places, protect form light in some cases; keep out of reach of children USP 795: Beyond Use dates=BUD: 6 months for non aqueous formulations, 1 month for water-containing topical/dermal and mucosal liquid semisolid formulations, 2 weeks for water containing oral formulations, OR 25% of expiration date remaining if prepared from commercial product=if tablet will be expired in 4 months then 4 times 25% it expires in 1 month, which ever of the two are shorter

Syrup

sweet, viscous, aqueous solutions; contain flavoring agents and intended for oral use, non medicated=pleasant vehicles in the compounding of liquid oral drug preparations (solutions and suspensions), cuz of sweet taste and absence of alcohol=useful for pediatric, popular for antitussives=sweet, thick syrup has soothing effect on irritated throat issue, any water soluble API that is chemically stable in aqueous solution=formulated as syrup, difficult to determine stability; preservation: highly concentrated aqueous solutions of sucrose and dilute solutions of sucrose=subject to yeast and mold growth and need preservative=benzoic acid, methyl parable with propyl paraben or sorbic acid, for compounded=preservatives omitted if refrigerated; concentrated solutions (over 85% w/v) resistant to mold growth=no refrigeration or preservation; additional chemicals: antioxidants, chelating agents, colorants, sweeteners, pH controlling agents

Pharmaceutical Compounding

the preparation, mixing, assembling, packaging, and labeling of a drug or device in accordance with a licensed practitioner's prescription (outpatient) or med order=inpatient/institutional setting such as hospitals or long term care facilities ands this is under an initiative based on practitioner/patient/pharmacist/compounder relationship in the course of professional practice; compound preparations: compounded dosage forms, compounded drug, compounded formulations, which include powders, tablets, capsules lozenges, solutions, suspensions, emulsions, suppositories, creams, ointments, pastes, topical gels

Measuring

to deliver volumetric: single volume pipet, syringe, calibrated pipet; to contain volumetric: graduated cylinder=accurately measure and transfer, conical graduated cylinder=enable stirring or mixing, volumetric flask, calibrated pipet; small volumes=graduated pipettes (5 mL to 0.1mL) or by a syringe; 5% measuring error so to avoid, never less than 20% of capacity of graduate (not less than 2mL in 10 mL), graduate almost filled to volume should be used than bigger one fro accuracy and read at eye level; don't measure in portions=increases error; smallest measure that will hold desired volume; measure is thoroughly drained=hold inverted for 15 sec (especially viscous 60 second)

Sticks

topical delivery of APIs; 1) very convenient, easily applied and soften at body temp, may deliver med where needed and cannot be seen on skin, can be carried in pocket or purse; 2) have excellent chemical stability, anhydrous sticks have USP/NF BUD of six months but heat to prepare them=concern for heat-liable APIs; relative to an ointment in a jar=reduced risk of contamination by fingers during use; 3) easy to prepare, base components are melted, mix with API and poured/packaged into tubes, identical to ointment compounding by fusion and suppository compounding; bases: opaque=waxes/oils OR PEGs, high melting point waves (or PEGs) blending with low melting point lipids (or PEGs)=soften at body temp for easier spreading, hardness of stick can be modified by chaining percent of highest melting point substance, for wax/oil=aqueous API can be incorporated into lanolin or another absorption ointment base for action and then mix with wax/oil; clear bases=sodium stearate in glycerin and/or propylene glycol (glycerin suppository)

Class III balance

two pan balances, max weight 60 g or 120 g removable weighing pans of equal weight, mechanical beam (oscillation) arrest, still in use in many pharmacies=meets min SR of 6 mg; min weight that can be discriminated is 6 mg, never weigh less than 120 mg and if do=follow aliquot method; not inexpensive; require use of weight set; place weights on right pan; sample to be weighed on left pan; instructions: set bubble to middle of tube by leveling screws, set internal weight to zero by turning calibration dial to zero, lock balance by turning arrest knob, unlock and check pointer rests at center of marker plate, place weighing paper or boat n both side and correct any difference, lock the balance and place weights on right pan, place sample to be weighed on left pan, add, or remove sample till achieve correct weight; 52% compounding use, 65% think teach=remain integral to compounding

Emulsifying agents (anionic and cationic surfactants)

types of emulsion formed depends exclusively on emulsifier used rather than the volumes of the oil and water=ban croft's rule=the phase in which the emulsifier is most soluble will become external phase; if more soluble in water than oil (polysorbate 80)=O/W, if more soluble in oil than water (Span 80)=W/O type; synthetic=biggest group: cationic=not emulsifiers but preservatives because harmful to human cells=hemolysis, anionic surfactants=contains carboxylate ions of fatty acids/soaps and cause GI disturbances=only emulsifiers for external products and incompatible with cationic drugs and cationic preservatives=form insoluble complex that precipitates: soft soaps=salts of fatty acids=stearic, lauric, oleic palmitic (slop) and monovalent cations=Na+, K+, triethanolamine and are water soluble, hard soaps=salts of fatty acids (slop) and di or trivalent cations=Ca, Mg, Al and water insoluble, sodium laurel sulfate=most commonly used anionic emulsifier and found in ointments and lotions and water soluble=O/W emulsions

vaginal and urethral suppositories

vaginal=globular, oviform, or cone shaped and weigh about 5 g when cocoa butter is base, combat female UTI and to restore vaginal mucosa to normal state and contraceptive; ingredients=combos of various molecular weight polyethylene glycol, surfactants, paragons as preservative agents, buffered to acid pH (4.5)=acidity discourages pathogenic organisms and provides favorable environment for recolonization of acid-producing bacilli normally found in vagina; avoid fatty bases because melts within minutes and can leak out, aqueous better because takes hours to dissolve in water and can't leak out; urethral=slender and tapered about 5 mm in diameter and up to 60 mm long, insertion into male or female urethra and used in local infection, much smaller=micro suppository introduced for alprostadil=erectile dysfunction=single use medicated transurethral system to male urethra, suspended in PEG and formed into pellet and administered after urination, vehicle will dissolve in fluid and release drug for absorption

Additives for suspensions

vehicles: water, glycerin, alcohol; wetting agents (surfactants)=degree of wetting a powder can be evaluated by observing a contact angle and 0=extensive interaction and complete wetting and to 90=partial and above 90=non-wetting and 180=completely unbeatable and in suspensions=many hydrophobic solids and aqueous vehicles and nonionic and anionic surfactants (polysorbates and poloxamers) used as wetting agents and adsorption of surfactants alters properties at interface and promotes wetting of dispersed phase in suspensions, suspending agents=to suspend particles as impart viscosity and natural ones=acacia, tragacanth, and bentonite, synthetic=methyl cellulose, carboxymethyl cellulose, sodium carbodymethyl cellulose and natural=nontoxic and inexpensive but may have batch to batch variation and microbial contamination, pH controlling agents=buffers used to maintain pH and important for those that contain ionizable acidic or basic groups in which pH influences stability and solubility of drug, electrolytes, anti-oxidants; preservatives

viscous vehicles for suspension and rheology

viscous vehicles=pseudoplastic (shear thining) flow vest since their viscosity decreases with saking and increases at rest, in past equal mixture 1:1 of methylcelulose (0.5% to 5%) solution and a flavored syrup was commonly used as the viscous vehicle, today=more common to use a commercial suspending vehicle with pseudo plastic flow for 50% total suspension volume and then q.s. to total suspension volume with commercial syrup with newtonian flow, since qs'd to final volume=not worry about volume from powder or levigating agent; rehology: newtonian: viscosity unchanged due to shearing rate=water, alcohol, syrup, glycerol, sodium chloride solution, non-newtonian=viscosity decreases or increases with S and types of non-newtonian: plastic flow=viscosity crops slightly and then remain constant with increase in S=methyl cellulose lotion and colloidal dispersions, pseudo plastic flow=viscosity decreases with increase in S (highly desirable)=concentrated polymer solutions and carbomer gels, dilatant flow=viscosity increases with decrease in S (undesirable)=any suspension with high % of solids and clay suspension

Granule preparation

wet granulation: wet powder with a liquid (water or ethanol) to form a paste; formation of granules starting from the paste, using a granulator or pass through a screen, dry in oven, the classification of the granules with sieve; fusion or dry method (compounding of effervescent granules): the blended powder is heated in a beaker on a water bath while stirring, the heat releases citric acid water of hydration (monohydrate) to the other powders causing them to be sticky, the wet mass is forced through sieve (8) to make granules, which are then allowed to dry before packaging

Aliquot method and trituration

when less than MWQ=cannot be weighed directly so use trituration method=mixtures of drug with inert diluent usually lactose, diluent=expand weight of system and allow accurate and convenient measurements of an aliquot (sample, part or portion), allow us to obtain necessary amount of drug without compromising accuracy; steps: determination of min. weighable amount for instrument, weighing of min weighable amount of substance, mixing diluent with predetermined amount of and inert substance to obtain dilution or mixture, weighing of an aliquot (sample) of mixture which will provide quantity of the substance, all weighed quantities must be equal or greater than the minimum weighable amount; for liquids=less frequent, when smallest measuring tool available makes amount measuring less than 20%

Absorption base

1) anhydrous=permit incorporation of aqueous solutions resulting in formation of W/O emulsions=anhydrous lanolin, hydrophilic petrolatum, aquaphor 2) W/O emulsion absorption bases=W/O emulsions that permit incorporation of additional quantities of aqueous solutions (Lanolin, hydrocream, eucerin); not easily removed from skin with water washing because external phase is oil, useful as adjuncts to incorporate small volumes of aqueous solutions into hydrocarbon bases; adv=moderately good protective, occlusive, and emollient, do not wash off easily=hold incorporated meds in contact with skin, can absorb liquids=anhydrous can with lots of water and moderate alcoholic and because already contain water=emulsion various amounts of water and/or alcohol can be absorbed; some lanolin types=like sebaceous secretions of skin=superior emollient; disadv=some bases=poor patient acceptance=greasy and some sticky and odor, not easily removed by washing, containing wool wax or wool wax alcohols=sensitizing, soap-type emulsifiers (cold cream)=compatibility problems with this type of emulsifying agent, contain water=chemical instability with ingredients that are sensitive to hydrolysis and subject to microbial growth=preservative; Ex: hydrophilic petrolatum USP, aquaphor, lanolin USP, modified lanolin USP, cold cream

Formulation of suspensions

1) use of structured vehicles to maintain deflocculated particles in suspension=entrap particles so that minimum settling occur, shear thinning property of these vehicles facilitate the reformation of a uniform dispersion when shear is applied, disadv of deflocculated system is formation of a compact cake when particles eventually settle and particles have lenity of time to pack tightly by falling over another to form an impacted bed, sedimentation volume of such system is low and sediment is difficult to redisperse, suitable approach for making suspension=prepare flocculated suspension ins structured vehicle; 2) application of principles of flocculation to produce flocs that although settle rapidly, are easily resuspended with a minimum agitation=addition of flocculating agents=electrolyes, polymers and surfactants, electrolytes (NaCl, KCl, citrates, phosphates)=reduce electrical barrier between particles=decreased zeta potential and formation of bridge between adjacent particles so as to link them together in a loosely arranged structure, polymers (cellulose gum, xanthem gum, gelatin)=act as flocculating agents because part of chain adsorbed on particle surface with remaining parts projecting into dispersion medium, bridging between latter portions leads to formation of flocs

Medication use process

1. prescribe: selevt medication based on patient assessment and send otter to pharmacy; transcribe (order verification): enter med order into pharmacy computer, assess appropriateness and address any discrepancies (imp for this unit); dispense=prepare and distribute medication from pharmacy to patient or health care provider (important for this unit); administer=review appropriateness of medication which is then given to or taken by the patient; monitor=assess patient's response to the medication and document outcomes, further interventions are made as needed; mixes people, systems, policies, procedures; goal: safe and effective medication therapy

step 11, 12, and 13 of compounding

11=label the prescription containers to include the following items: name of the preparation, strength of the preparation, internal lot number or ID number of compounded preparation, do not use beyond date, storage instructions (room temp, refrigerator, freezer, light protected, etc), initials of the pharmacist who compounded or verified the prescription, any other statements required by law; extra labels (side effects, storage, use, instructions) print out normally with manufactured but have to be chosen with compounded and the expiration date must be entered manually for compounded, in community dispense all to one patient where at hospital=several patients, stability is different=can't use beyond date, tell patient how to maximize stability; 12=sign and date the prescription, affirming that all procedures were carried out to ensure uniformity, identity, strength, quantity, and purity: right color, right smell, right consistency, right blending and overall quality=appropriate and safe; 13=clean all equipment thoroughly and promptly and more properly

Step 1, 2, 3, 4 in compounding

1=evaluate whether the prescribed compound should be compounded based on intended use, safety of use in the way prescribed, and determine any legal issues in compounding as prescribed; 2=preform all necessary calculations to determine amount of each ingredient for appropriate strength and prescribed quantities, decide most accurate way to measure quantities and ensure you have correct measuring devices available to accurately measure each ingredient; 3=identify what equipment is needed in order to compound the prescription and make sure the equipment is clean and ready to use; 4=wash hands and wear appropriate attire to ensure personal safety

Steps 5, 6, 7 in compounding

5=clean area where compounding will occur with isopropyl alcohol or diluted bleach solution (10% bleach), make sure all compounding equipment is clean; 6=only compound a single prescription within a specified compounding area at a time to avoid errors or possible contamination, never compound neonatal or pediatric concentrations of ingredients in a separate area than the adult concentrations, clean area between compounds; 7=assemble all equipment, active ingredients, excipients, supplies, and materials in the cleaned compounding area

Steps 8, 9, 10 in compounding

8=compound the pharmaceutical preparation according to the prescription orders or the prescription monograph (formula) using the art and science of pharmacy, can have recipes from articles or compounding courses and if don't have, use pharmacy knowledge; 9=ensure that the compounded product meets standards of consistency, blending, color, clarity, odor, pH, and other visual or scientific testing as appropriate for the prescription; 10=document in the compounding log as required by law, including internal lot number for tracking preparation, NDC number, manufacturer, lot number, expiration date, and amount used of each ingredient in the compounded product and signature or initials of the pharmacist

Blending Powders

Mixing; two or more powders combined into a homogenous mixture=consistent dose; 1) reduce particle size until uniform with other ingredients, more uniform=increase accuracy of dose; 2) start with substance present in the smallest amount and add ingredient with next larger quantity (if practical) using geometric dilution technique; 3) Continue adding substances until all are added and uniformly mixed; can blend with geometric dilution; small-scale blending equipment: pill tile and spatula, mortar and pestle, bottle/container, plastic baggie