Compounding Exam #2
hard gelatin capsule parts
(1) base (2) cap (3) composition of gelatin capsule shell
synthetic emulsifying agents
(1) cationic (2) anionic (3) nonionic
desired properties of powders
(1) particle size - the larger the mesh number, the smaller the particles must be to pass through the sieve (2) free flowing
identify mortar and pestle
(1) porcelain (middle) (2) wedge wood (rough) (3) glass (smooth) --> if you want to break up very small, use wedgewood --> when making capsules, you should use glass because the least amount of drug will be lost --> if colored or dyed -- use glass
ALWAYS PUT ON THE LABEL
(1) preservatives (2) alcohol content (% v/v)
how to figure out aliquot example
(1) total weight of atropine sulfate required (this is C in the proportion) 0.6 mg/capsule x 10 capsules = 6 mg (2) select some multiple of 6 mg that can be weighed with the desired degree of accuracy (this is A in the proportion) -- eg. select multiple of 20 6 mg x 20 = 120 mg atropine sulfate (3) select the size of the aliquot portion to be taken to contain the 6 mg of the drug (this is D in the proportion) selecto 120 mg aliquot (4) since we now have A, C, and D in our formula, we can solve for B (trituration weight) 120 / x = 6 / 120 --> x = 2400 mg trituration (drug + diluent) (5) determine the weight of diluent (lactose) required to prepare the trituration by subtracting the weight of stropping sulfate from the trituration weight 2400 mg trituration - 120 mg atropine sulfate = 2280 mg lactose (6) determine the weight of lactose which must be added to the aliquot portion of trituration to complete the prescription, so that each capsule weighs 200 mg 200 mg/capsule x 10 capsules = 2000 mg (drug + lactose) 200 mg - 120 mg aliquot = 1880 mg lactose *method* (1) weigh a suitable amount of drug (at least 120 mg) and reduce it to a fine powder in a mortar (triturate it) (2) weight a suitable amount of diluent (3) mix the drug and diluent by *geometric dilution* (4) weight an aliquot of the trituration containing the desired weight of drug (save left over trituration for refills) (5) weight amount of diluent and mix with amount of aliquot from #4 by geometric dilution (6) prepare capsules weighing specific amount each
natural emulsifying agents
(1) vegetable derivatives (2) animal derivatives (3) semi-synthetic agents
method to identify oil and water phase
(1) weight cetyl alcohol, put this in a small beaker and heat to melting (45º and 50º) using a hot water bath (2) weight stearic acid and measure the glycerin and add to some purified water; heat to about 50º-55º in the microwave (3) add the melted cetyl alcohol and stir until cooled and thickened (4) ass triethanolamine solution and qs in a 2 oz container with purified water
ointment: method
(1) weight urea and dissolve in purified water (may use warm water to speed the dissolution) (2) weight hydrocortisone and incorporate it by using geometric dilution into hydrophilic petrolatum (may use a levigating agent if desired, must show calculations for the weight of the levigating agent) (3) weigh methyl paraben (4) sprinkle this on top of the ointment while gradually adding the urea solution to the hydrophilic petrolatum
ethyl alcohol (ethanol): *alcohol USP*
*95% ethanol and 5% purified water* - content: not less than 92.3% and not more than 93.8%, by weight (w/w), corresponding to not less than 94.9% and not more than 96% by volume (v/v) of C2H5OH
absorption bases
*AQUAPHOR and EUCERIN* - two subgroups: (1) *anhydrous absorption bases*: there are hydrocarbon bases that contain an emulsifier or emulsifiers that form water in oil emulsions when water is added (2) *water in oil emulsions*: these are absorption bases that contain water, the amount depending on the base
hydrocarbon / oleaginous bases
*VASELINE* - inexpensive - non-reactive - non-irritating - good emollient (with addition of emulsifier) - are *not water-washable*, so they stay on the skin and keep incorporated medications in contact with the skin - have poor patient acceptance because of their greasy nature - are not removed easily with washing when this is desired -- they may be removed with mineral oil - *cannot absorb water and can only absorb very limited amounts of alcoholic solutions*, so most liquid ingredients are difficult to incorporate and skin secretions do not readily dissipate
serial dilution
*am I comfortable doing this?* -- similar to aliquots, just need to do it multiple times - notice that in the table of values, the minimum amount given in the "Amount of Drug Needed column is 1.2 mg - this is because, as a general rule, an amount of drug requiring a dilution of greater than 100:1 is usually not done with a single dilution because homogeneous mixing at this level is difficult - furthermore, the amount of diluent needed becomes unreasonably large - when very small quantities of drug are needed (eg. less than 1 mg) a serial dilution is usually used *this method is avoided when possible because the mathematics is more difficult, and it is easy to get confused)
Rx: HCl 0.1 mEq/kg/hr dispense 500 mL or 1N solution sig: administer by IV for treatment of metabolic acidosis
*calculating volume of concentrated acid needed for desired quantity of diluted acid* 1 N = 36.46 g / 1000 mL = xg / 100 mL --> x = 3.7 g 3.7 g / 100 mL = x g / 500 mL --> x = 18.5 g *how many mL of 37% w/w hydrochloride acid having a specific gravity of 1.20 are required to make 500 mL of diluted hydrochloride acid solution 37 g / 100 g = 18.5 g / x g --> x = 50 g 1.2 g/mL = 50 g / x mL --> x = 41.7 mL *OR* 1 N = 36.46 g / 1000 mL = xg / 100 mL --> x = 3.7 g 3.7 g / 100 mL = 3.7% 37% * x = 3.7% * 500 g --> x = 50 g 1.2 g/mL = 50 g / x mL --> x = 41.7 mL
natural emulsifying agents: *semi-synthetic agents*
*cellulose derivatives* *eg* methylcellulose, carboxymethylcelllulose
serial dilution: example
*drug/amount desired: hyoscine HBr 0.35 mg* 0.35 / 120 = 120 / x = 41,143 mg dilution --> dilution factor ~ 343 (1) weight the MWQ of hyoscine 120 mg (2) weigh an arbitrary amount of lactose that is ≥ MWQ -- in this case, because we need such a small quantity of drug, choose a larger quantity of lactose: 3000 mg (3) thoroughly mix the two powders by triturating in a mortar -- remember to use geometric dilution (4) calculate the total weight of the dilution: 120 mg + 3000 mg = 3120 mg dilution 1 (5) weight the MWQ, 120 mg, of dilution 1 (6) calculate the number of mg of hyoscine that will be contained in 120 mg of dilution a 120 mg hyoscine / 3120 mg dilution A = x mg hyoscine / 120 mg dilution A --> x = 4.6 mg hyoscine (7) weight a second amount of lactose that is ≥ MWQ -- again, because we need such a small quantity of drug, choose a moderate quantity of lactose: 3000 mg (8) thoroughly mix the 120 mg of dilution A with the 3 g of lactose by triturating in a mortar (9) calculate the total weight of the second dilution 120 mg + 3000 mg = 3120 mg dilution B (10) calculate the number of mg of dilution B that contains the desired 0.35 mg of hyoscine (remember that, although you weighed 120 mg of dilution A, it only contained 4.6 mg of hyoscine) 4.6 mg hyoscine / 3120 mg dilution B = 0.35 mg hyoscine / x mg dilution B --> x = 237 mg dilution (11) weight this calculated amount of dilution B (237 mg) to get the desired 0.35 mg of hyoscine
synthetic emulsifying agents: *anionic*
*eg* - alkali soaps (sodium or potassium oleate) - amine soaps (triethanolamine stearate) - detergents (sodium laurel sulfate, sodium dactyl sulfosuccinate, sodium docusate)
synthetic emulsifying agents: *cationic*
*eg* - benzalkonium chloride - benzethonium chloride
synthetic emulsifying agents: *nonionic*
*eg* - sorbitan esters (Spans) - polyoxyethylene derivatives of sorbitan esters (Tweens) - glyceryl esters
natural emulsifying agents: *vegetable derivatives*
*eg* acacia, tragacanth, agar, pectin, carrageenan, lecithin
natural emulsifying agents: *animal derivatives*
*eg* gelatin, lanolin (sheep fat), cholesterol (parenteral emulsions)
capsule: *sizes*
*identified by different numbers -- small number = bigger capsule volume*
liquid aliquot example: prepare 100 mL of a solution containing 0.2 mg/mL clonidine
*need 100 mL x 0.2 mg/mL = 20 mg clonidine) (1) select a suitable solvent (based on drug solubility and stability, route of administration, and potential toxicity of the solvent) *select water (or possibly ethanol)* (2) select the aliquot volume (D) in which the desired amount of drug (C) will be contained -- this establishes the concentration of the solution to be prepared -- volume must be large enough that concentration does not exceed the solubility of the drug, but small enough that it does not exceed the total volume of the prescriptions (*HINT*: check Remintons or Merck Index for solubility data, then pick a concentration that is less than this solubility) *select 5 ml, then concentration = 20 mg/5ml = 4mg/ml (3) select weight of drug (120 mg) to prepare the solution -- whenever practical, use the least weighable quantity so as to minimize waster (this is A in the proportion) *select 120 mg* (4) calculate the total volume (B) of solution to be prepared *120/x = 20/5 --> x = 30 mL* (5) removed aliquot of solution and qs to total Rx volume with the appropriate vehicle
dilution of acids
*remember* - for official undiluted acids (concentrated) strength is expressed as w/w - the strength of official diluted acids is express as *w/v* - it is necessary to consider the specific gravity of concentrated acids in calculating the volume to be use in preparing diluted acids
alternate materials for capsules
*will alter the bioavailabiltiy* - pullulan, a water soluble polysaccharide --> eg. Capsugel -- NPcaps - HPMC, a water soluble polymer --> eg. Capsugel -- Vcaps
isopropyl alcohol (2-propanol): *isopropyl rubbing alcohol USP*
- *70% isopropyl alcohol* - content: not less than 68% and not more than 72% of isopropyl alcohol by volume (v/v), the remainder consisting of water, with or without suitable stabilizers, perfume oils, and color additives certified by the FDA or use in drugs
glycols
- *glycerin USP (glycerol)*: has local anesthetic for children that are teething - *propylene glycol USP* - *polyethylene glycol NF* -- go-litely
storage: emulsions
- *internal preparations* should be stored in a refrigerator - *external preparations* should be stored at room temperature - the preparation beyond-use date depends on the stability of the ingredients - if all ingredients are chemically stable, a 14-day dating is acceptable for internal use preparations - the usual maximum dating for chemically stable external preparations is 1 month
ethyl alcohol (ethanol): *dehydrated alcohol USP*
- *just alcohol -- no water* - not less than 99.2% by weight (w/w), corresponding to not less than 99.5% by volume (v/v) of C2H5OH
water-removable bases: *disadvantages*
- *less protective, less emollient, and less occlusive* than hydrocarbon or absorption bases - those with soap-type emulsifiers can have compatibility problems - those that contain water may have stability problems with ingredients that are sensitive to hydrolysis - those containing water are *subject to microbial growth*; manufactured bases of this type contain preservatives - because water is the external phase, *these products "dry out" if exposed to air* - *humectants* may be added to retard dehydration -- silica is the most common to trap the water
water-removable bases: *advantages*
- *non-greasy* and therefore aesthetically pleasing - can be removed form the skin by washing - *can absorb some water or alcohol*; if the amount of liquid added reaches a critical amount, the base will thin out to a lotion - *will allow the dissipation of fluids from injured skin*
levigation of coal tar
- *remember weigh coal tar* and polysorbate 80 - weight coal tar directly on top of the polysorbate 80 - levigate the two together
ethyl alcohol (ethanol): *rubbing alcohol USP*
- *rubbing alcohol USP = 70% ethanol* - alcohol content: 68.5-71.5% by volume of dehydrated alcohol
where to find HLB
- *table 29.1* practical guide -- gives HLB values for some common non-ionic surfactants used in compounding - span and arlacel surfactants are considered lipophilic with HLB numbers in the range of 1.8-8.6 --> they tend to form water in oil emulsions - tween emulsifiers have HLB numbers in the range of 9.6-16.7 --> they are more hydrophilic and favor oil in water emulsions
capsules: *quality control*
- *uniformity*: check capsules for uniformity in appearance and color -- weigh them - *extent of fill*: check capsules for uniformity of extent of fill to ensure that ll capsules have been filled - *locked*: check capsules to ensure that they have all been tightly closed and locked
ointment bases: *water soluble*
- *water soluble* - water washable - *may* contain water - can absorb water *(limited)* - non-occlusive - non-greasy - *lipid-free* *eg* polyethylene glycol ointment
types of solvents
- *water-miscible solvents* include water, alcohol, isopropyl alcohol, glycerin, propylene glycol, and polyethylene glycol 400 - *lipophilic solvents* include mineral oil and the various fixed oils, including castor oil, cottonseed oil, olive oil, and corn oil
isopropyl alcohol: summary
- 2-propanol CH3CHOHCH3 - isopropyl alcohol is for external use only - it may be used as a solvent-vehicle for drugs that are being formulated into topical products - in concentrations ≥70% it is an effective disinfectant - it is somewhat superior to ethyl alcohol as an antiseptic *isopropyl alcohol is about twice as toxic as ethanol*
ingredients of a typical hard capsule formulation
- API - diluent (lactose -- most common) - glidant (silica) - lubricant --helps with flow and sticks them together (magnesium sulfate) - stearate = fatty material -- very good at coating
special levigating agents
- Tween 80 is used as a levigating agent for coal tar - coal tar ointment USP contains an amount of tween 80 equal to one-half the weight of coal tar - coal tar solution will not mix with mineral oil or glycerin, but it can be directly incorporated into may ointment bases - castor oil is recommended for levigating peruvian balsam - ichthammol is levigate with glycerin
locking hard gelatin capsules
- Tylenol incident in 1982 - GlaxoSmithKline: bevels edges, flat ends and fuses cap to the base - caplets
water for pharmaceutical use purpose -- USP
- USP purified water - USP water for injection (WFI) - USP sterile water for injection - USP sterile water for inhalation - USP bacteriostatic water for injection - USP sterile water for irrigation
total amount of emulsifier needed
- a 2-5% w/v emulsifier combination has been recommended for liquid emulsions --> some sources report that using an amount in the upper range gives more stable preparations - other references recommend that the emulsifier used should depend on the amount of internal phase to be emulsified --> in this case, 10-20% w/v of the internal phase is a suggested guideline *we put 5% in lab!!! --> total amount of the two emulsifiers combined*
aliquot method of weighing and measuring
- a method by which small quantities of a substance may be obtained within the degree of accuracy desired - *step 1*: select some multiple of the desired quantity that can be weighed with the required precision -- weigh this multiple - *step 2*: using an inert substance that is compatible with the given preparation, dilute the multiple quantity - *step 3*: weigh an aliquot part of the dilution that contains the desired quantity *needs to be a homogeneous mixture so you know that you are obtaining the desired amounts of each ingredient*
pharmaceutical eutectic mixture
- a mixture of two or more substances that may liquify when intimately mixed at room temperature - liquification depends on: (1) ambient room temperature (2) original melting points of the substances (3) the proportions in which th substances are mixed (4) the extent and degree of pressure used in trituration (5) the presence of other ingredients which may sorb any liquid formed - separately, they may have higher melting points than room temperature -- but together, they would reduce the melting point
relative amounts go emulsifier combinations
- a system was needed to aid formulators in making systematic decisions for amounts and types of surfactants to use in giving products of maximum stability - the HLB (hydrophily - lipophile - balance) system was developed by Griffin - it is based on the fact that all surfactant molecules have both hydrophilic (water-loving) and lipophilic (oil-loving) portions - the balance between these two parts varies with the surfactant - numbers from 1 to 20 were assigned to surfactants based on the balance --> lower number = lipophilic compounds --> higher numbers = hydrophilic compounds
emulsion
- a thermodynamically unstable two-phase system consisting of at least two immiscible liquids, one of which is dispersed in the form of small droplets throughout the other, and an emulsifying agent - the dispersed liquid is known as the *internal or discontinuous phase*, whereas the dispersion medium is known as the *external or continuous phase*
how to handle hygroscopic and deliquescent drugs
- add a powdered ingredient to the formulation that will absorb the water which is attracted to the problem solid -- light magnesium oxide is sometimes used for this purpose and is acceptable, provided the aunty needed is not sufficient to impart a therapeutic laxative effect - dispense in a tight contained - counsel the patient to store the product in a low humidity environment
common gelling agents
- alginic acid - bentonite - *carbopols* (now known as *carbomers*) - carboxymethylcellulose - ethylcellulose - gelatin - hydroxyethylcellulose - hydroxypropyl cellulose - magnesium aluminum silicate (veegum) - *1% methylcellulose* - poloxamers (pluronics) - polyvinyl alcohol - sodium alginate - tragacanth -- natural - xanthan gum -- natural
measurement of polysorbate-sorbitan ester emulsifiers
- all are customarily measured by weight, not by volume - this is because, at room temperature, some of these emulsifiers are solids and others are thick liquids
label: emulsions
- all emulsions are disperse systems and need a *SHAKE WELL* auxiliary label - external use emulsions should be labeled for *EXTERNAL USE ONLY*
oils
- almond oil NF - castor oil USP -- very powerful laxative - corn oil NF - cottonseed oil NF - mineral oil USP -- can be used on skin - light mineral oil NF - olive oil NF - peanut oil NF - safflower oil USP - sesame oil NF - soybean oil USP
order of mixing
- although some sources recommend dissolving the oil-soluble sorbitan ester portions (the spans) in the oil, and the water-soluble polysorbate part (the tweens) in the water, many pharmacists find it much easier to dissolve or dispense both emulsifiers in the oil phase - although the polysorbate compound eventually dissolves in water, it tends to "lump up" initially, making it difficult to work with
strategies for handling efflorescent powders
- always store and dispense these powders in tight containers - the anhydrous form of the drug may be substituted for the hydrate, but be sure to make appropriate dose corrections
ALLIGATION
- an old and practical method of solving arithmetic problems related to mixtures of ingredients - two types of alligation: (1) *alligation medial*, used to find the quantity of a mixture given the quantities of its ingredients -- merely a matter of finding a weighted mean (2) *alligation alternate*, used to find the amount of each ingredient needed to make a mixture of a given quantity -- more complicated and involves organizing the ingredients into high and low pairs which are then traded off
coal tar
- antipruritic, antipsoriatic, antiseborrheic, keratolytic - coal tar is the tar obtained as a by-product during the destructive distillation of bituminous coal at temperatures in the range of 900 to 1100 ºC - *coal tar topical solution (LCD = liquid carbonic detergens): coal tar -- 200 g, polysorbate 80:50 g; alcohol qs 1000 mL*
issues related to the use of hard capsules
- capsules are generally less popular than tablets - if the compression properties of the drug are poor and high dose is required, they offer a practical alternative to tablets - capsules are larger than a tablet - some concern for ability for tampering - *traditional use of gelatin capsules* is under question because of formaldehyde-induced cross-linking and bovine sources of gelatin (mad cow disease) - people are trying to find different materials to make capsules
capsules
- capsules are solid dosage forms in which the drug is enclosed within either a hard or soft soluble container or "shell" - the shells are usually formed from *gelatin*; however, they also may be made from *starch* or other suitable substances (USP) - dry powders, semi-solids, and liquids that do not dissolve gelatin may be encapsulated in capsules - capsules account for about 20% of all prescriptions dispensed - hard gelatin, soft gelatin (eg. fish oil), due to chemical processes
strategies to add an aqueous or alcoholic solution to a base
- change the ointment base - ass a nonionic auxiliary emulsifier or emulsifier combination, such as a tween/span-type - add stearyl or cetyl alcohol to water-soluble polyethylene glycol bases to improve water or alcohol absorption - spatulate the solution and ointment base until a sufficient amount of the solvent evaporate
single-phase systems
- contain linear or branched polymer macromolecules that dissolve in water and have no apparent boundary with the dispensing medium - these macromolecules are classed as natural polymers (eg. tragacanth), semisynthetic cellulose derivatives (eg. methyl cellulose) or synthetic polymers (eg. carbomer polymers) - single-phase gels made from synthetic or natural macromolecules are called mucilages
water-in-oil (W/O)
- conversely, where water or aqueous solutions are *dispersed* in an oleaginous medium - generally formed if the aqueous phase constitutes < 45% of the total weight and a lipophilic emulsifier is used
amount of excess product to make to compensate for loss during compounding
- depending on factors such as compounding technique, number and type of ointment ingredients, and difficulty of the compounding process, *between 2 and 4 grams of an ointment may be lost in the compounding process* - either a *percentage* or excess or a given *amount* of excess product is usually made to compensate for this loss - the amount of excess made is based on the pharmacist's own experience and professional judgment
advantages of solid dosage forms
- drugs and chemicals are most stable as dry solids - because they are dry and compact, tablets, capsules and divided powders are packaged, transported, administered, and stored more easily than are liquids - undesirable taste is more noticeable when substances are in solution than when in solid form -- objectionablee taste can be concelared completely by enclosing the solid drug in capsules or coated tablets - accurate dosing is easier to achieve with dosage forms furnished as individual units, such as tablets, capsules and divided powder - controlled release is must easier to achieve with solid dosage forms than with liquids
unique advantages of powders
- each dose can contain a different amount of active drug - can be administered easily to infants and young children who cannot swallow tablets or capsules - drug will have a rapid onset of action since disintegration is not required - can be applied to many body cavities such as ears, not, tooth socket, throat - drugs tend to be most stable as a solid - can be made into many different dosage formulations (capsules, tablets, powders for reconstitution, dusting powders, bulk powders, powders for inhalation, etc.
topical emulsions (creams and ointments)
- emollient (soothing of the skin) or protective properties are often desired of topical preparations, and oils can serve these functions - when the oils are emulsified, they feel less greasy and are more aesthetically appealing to patients
ethanol: summary
- ethyl alcohol: CH3CH2OH - it is used as a solvent-vehicle for the preparation of pharmaceutical dosage forms for internal or external use - it is an effective antiseptic-disinfectant, being germicidal in concentrations above 60% - its usual concentration as an antiseptic-disinfectant is 70%
percentage weight-in-weight
- expressed the number of grams of a constituent in 100 g of solution or preparation (w/w). usually used for mixtures of solids and semisolids - for these types of calculations a pharmacist needs to know: (1) weight of active ingredient in a specific weight of solution or liquid preparation given its weight-in-weight percentage ratio (2) weight of either active ingredient or diluent, given weight of the other and percentage strength (w/w) of solution (3) percentage strength (w/w) of solution, given weight of active ingredient and weight of solution
percentage weight in volume
- expresses the number of grams of a constituent in 100 mL of solution of liquid preparation and is used regardless of whether water or another liquid is the solvent or vehicle (w/v) - for these types of calculations a pharmacist needs to know: (1) weight of active ingredient in a specific volume, given its percentage weight-in-volume (2) percentage weight-in-volume of solution, given weight of solute or constituent and volume of solution or liquid preparation (3) volume of solution or liquid preparation, given percentage strength weight-in-volume and weight of solute
percentage volume
- expresses the number of mL of a constituent in 100 mL of solution or liquid preparation (v/v) - for these types of calculations a pharmacist needs to know: (1) volume of ingredient in a specific volume, given percentage strength volume-in-volume (2) percentage volume-in-volume of solution, given volume of active ingredient and volume of solution or liquid preparation (3) volume of solution or liquid preparation, given volume of active ingredient and its percentage (v/v)
insufflations
- extremely fine powders to be introduced into body cavities - to administer: the powder is placed in the insufflator, and when the bulb is squeezed, the air current carries the fine particles through the nozzle to the region for which the medication is intended - all extemporaneously compounded insufflations must be passed through a 100 mesh sieve
desired properties of a liquid emulsion -- oral or topical
- fine droplets - slow aggregation of the droplets and creaming of the product - ease of re-dispersion when shaken
dusting powders
- fine medicinal (ulk) powders intended to be dusted on the skin by means of sifter-top containers - a single medicinal agent may be used as a dusting powder; however, a base is frequently used to apply a medicinal agent and to protect the skin from irritation and friction
strategies for handling drugs that form liquid eutectic mixtures
- force the liquid eutectic to form, then sorb the liquid onto an inert, high melting, finley divided solid -- magnesium carbonate is reported to be the agent of choice, but light or heavy magnesium oxide, calcium phosphate, starch, talc, and lactose may also be suitable - an alternative method is to separately triturate each potential eutectic former with an inert powder, such as one of those given above; then the protected powders are mixed together by gentle spatulation - when you add extra ingredients, consult with the prescribed -- if necessary, make adjustments to maintain the intended dose
incorporation of liquids
- formulations that include liquids must use ointment bases that will absorb the liquid -- if a liquid must be added to a base that will not absorb it, one of the strategies given above for incorporating solutions may be used - certain thick liquids are measured by weight rather than by volume -- eg. coal tar, peru balsam, ichthammol, and the polysorbate-sorbitan type emulsifiers - some liquids require special levigating agents -- several of these are listed above in the section on levigating agents - some liquids, especially aqueous and alcoholic solutions, soak into the paper of ointment pads -- ointment slabs are the preferred equipment for these products
ointment bases
- four general classes: (1) *hydrocarbon* (2) *absorption* (3) *water-removable* (4) *water-soluble* - pastes and gels are classified separately by the USP - although creams have been given a separate class by the USP, the term is now commonly reserved for ointment bases that are water-removable
gels: *advantages*
- gels are an excellent formulation for several routs of administration - they are useful as liquid formulations in oral, topical, vaginal, and rectal administration - gels can be clear formulations when all of the particles completely dissolve in the dispersing medium - but this doesn't occur in all gels, and some are therefore turbid - clear gels are preferred by patients
gelling agents
- gels are made using substances (called gelling agents) that undergo a higher degree of cross-linking os association when hydrated and dispersed in the dispersing medium, or wen dissolved in the dispersing medium - this cross-linking or association of the dispersed phase will alter the viscosity of the dispersing medium - the movement of the dispersing medium is restricted by the dispersed phase, and the viscosity is increased
carbomers
- generic name for a family of polymers known as Carbopol first used in the mid 1950s - as a group, they are dry powders with high bulk densities, and form acidic aqueous solutions (pH around 3) - they thicken at higher pHs (around 5 or 6) - they will also swell in aqueous solution of that pH as much as 1000 times their original volume - their solutions range in viscosity from 0 to 80,000 centipoise (cps)
selecting inert ingredient: *sodium carboxymethylcellulose* (CMC)
- granular material - have good flow properties, but, depending on the other ingredient in the formulation, they may change the dissolution and absorption characteristics of the drug - unless specifically called for, natural and synthetic gum powders should be avoided as diluents because they may form thick viscous barriers around the drug particles when exposed to the aqueous fluid in the stomach and may prevent the drug from being released from the dosage form - some sustained release capsule formulations use synthetic gums to modify drug release, but these formulations should always be thoroughly tested before use
water-soluble bases or gels
- greaseless ointment bases that are water soluble -- most are polyethylene glycol-type ointment bases - eg. poly-ethylene glycol and chapstick *PROS* - soluble in water so they are easily removed by washing - leave no oil residue - can absorb some water or alcohol; as the amount of liquid added increases, the base begins to thin out and eventually dissolves *CONS* - irritating, 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 the compatibility and stability problems associated with water
selecting inert ingredient: *microcrystalline cellulose*
- has been used successfully as a diluent for capsule filling machines - it is a free flowing powder classified by the NF as a tablet disintegrate and tablet and capsule diluent - *water INSOLUBLE* -- may slow down release
absorption bases: *advantages*
- have moderately *good protective, occlusive, and emollient properties* - *do not wash off easily* so they hold incorporated medications in contact with the skin - *can absorb liquids* --> anhydrous absorption bases: can absorb significant amounts of water and moderate amount of alcoholic solutions --> water in oil emulsions: because they already contain water, emulsion absorption bases absorb variable amounts of water and/or alcohol - come lanolin-types have compositions somewhat like the *sebaceous secretions of the skin* -- there are though to have superior emollient properties
based on their make-up, ointment bases have varying capacities to absorb liquids
- hydrocarbon bases do not absorb any water and only very limited amounts of alcoholic solutions - anhydrous absorption bases can absorb large quantities of aqueous solutions and lesser amounts of alcoholic solutions - water in oil emulsion bases accept varied amounts of water alcoholic solutions - water removable oil in water emulsion bases accept water or water-miscible liquids in their external phase, but eventually thin out to a fluid lotion with the addition of significant amounts of these liquids - as their name indicates, water-soluble bases are soluble in water -- they are also soluble in alcohol -- they accept a very limited amount of water without loss of viscosity
meaning of HLB values
- if an emulsifier has a *low HLB number*, there is a *low number of hydrophilic groups* on the molecule and it will have more of a *lipophilic character* --> eg. the Spans generally have low HLB number and they are also oil soluble --> because of their oil soluble character, Spans will cause the oil phase to predominate the form a w/o emulsion - if an emulsifier has a *high HLB number*, there is a *large number of hydrophilic groups* on the molecule and it will have more of a *hydrophilic character* --> the Tweens have higher HLB numbers and they are also water soluble --> because of their water soluble character, Tweens will cause the water phase to predominate and form an o/w emulsion
incorporation of solid drugs and chemicals
- if possible, pick a form of the drug that is a fine powder - *use levigation*
choosing a levigating agent -- table 30.1 practical guide
- if the formulation already contains an ingredient that is a suitable levigating agent, that liquid should be used - for an added levigating agent, check for compatibility with the other ointment ingredients an with the ointment base *general rule* - assuming that there are no compatibility problems with other ointment ingredients, *levigating agents are usually chosen to be chemically similar to the ointment base* - eg. *mineral oil* is the levigating agent of choice for oily bases, such as hydrocarbon, absorption and water in oil emulsion bases - *glycerin*, which is miscible with water, is usually used for water-removable with water-soluble bases
two-phase systems
- if the gel contains small discrete particles, the gel is called a two-phase system - if the gel does not appear to have discrete particles, it is called as a one-phase system - two-phase systems are thixotropic -- eg. they are semisolid on standing but liquefy when shaken - if the particle size in a two-phase system is large, the gel is referred to as a magma - *eg* of two-phase systems include aluminum hydroxide gel and bentonite magma
clumping
- if the gelling agent is added to the dispersing medium in a haphazard manner, there is a tendency for the agent to "clump" - the outer molecules of the gelling agent contact the medium first and hydrate forming a surface layer that is more difficult for the medium to penetrate - the clumps will ultimately hydrate, but it will take more time - a much more efficient manner is to sieve the agents onto the surface of the medium a little at a time as the medium is stirring - using glycerin as a wetting agent will sometimes minimize clump formation *want to prevent clumping!!!* *GO SLOW* -- incorporate a little at a time
ointment slabs or pads
- in the US, an *ointment slab (porcelain/glass tile) or pad is usually preferred - although ointment pads are nice because they minimize cleanup, they do have some limitations - *ointment slabs* are preferred when a liquid ingredient must be incorporated into the ointment, especially if the liquid is an aqueous solution - *liquids soak into the parchment paper of ointment pads*, and excess weight can be lost - *very stick or thick ointments are often more easily made on a slab* - loss is usually less when an ointment is compounded on an ointment slab than on a pad
ointment bases: *water-removable (oil in water emulsion)*
- insoluble in water - *water washable* - *contains water* - *can absorb water* - *non-occlusive* - *non-greasy* *eg* - hydrophilic ointment - vanishing cream - derma base - velvachol
ointment bases: *water-in-oil emulsion absorption*
- insoluble in water - not water-washable - *contains water* - *can absorb water (limited)* - emollient - occlusive - greasy *eg* - hydrous lanolin - cold cream - eucerin - hydrocream - rose water ointment
ointment bases: *anhydrous absorption*
- insoluble in water - not water-washable - anhydrous - *can absorb water* - emollient - occlusive - greasy *eg* - hydrophilic petrolatum - lanolin - aquaphor - aqua base - polysorb
ointment bases: *hydrocarbon (oleaginous)*
- insoluble in water - not water-washable - anhydrous - will not absorb water - emollient - occlusive - greasy *eg* - white petrolatum - white ointment - vegetable shortening (eg. Crisco) - vaseline
powders
- intimate mixtures of dry, finely divided drugs and/or chemical that may be intended for internal (oral powders) or external (topical powders)use - "powder" refers to a chemical or mixture that is solid in physical state - in compounding: "powder refers to a dosage formulation that is solid in physical state - however, the formulation may be composed of only the active drug or may be a mixture of the active drug and other ingredients
trituration
- is the preferred method of blending under most circumstances because it mixes powders more intimately than other methods - it should always be used when making mixtures that contain small quantities of potent drugs - because trituration accomplishes two processes at the same time -- namely, particle size reduction and blending -- this method saves time when powders of unequal particle size are being combined
parenteral emulsions
- lipid emulsions containing a physical mixture of medium and long chain triglycerides (MCT/LCT) are a well-proven concept in parenteral nutrition of critically ill patients *eg* - o/w sustained-release depot preparations (I.M.) - w/o emulsions of allergenic extract (S.C.)
PLO gel
- made by combining a pluronic F-127 gel and a lecithin/isopropyl palmitate syrup - the two components are made and stored separately - when it is time to compound a formulation, water soluble drugs are dissolved in the pluronic gel or oil soluble drugs are dissolved in the lecithin syrup - if a small quantity of formulation is to be made, each of the components is put into a syringe and two syringes are connected by an adapter - the mixture is forced between the two syringes and the shear caused by passing the mixture through the adapter will create the PLO gel
stability: emulsions
- maintenance of small droplets and ease of redispersion are both essential to the physical stability of the system - because emulsions are, by nature, physically unstable systems, beyond-use dates for there preparations should be conservative - the USP 23 states that all emulsions require an antimicrobial agent because the aqueous phase is favorable to the growth of microorganisms
percentage
- means "by the hundred" or "in a hundred" - 50% is 50 parts in 100 - solutions / suspensions solids in liquid = w/v - solution liquid in liquid = v/v - mixture solids and semi-solids = w/w - solutions gases in liquids = w/v
cellulose derivatives
- methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and carboxymethylcellulose - all of the derivatives except carboxymethylcellulose (CMC) maintain their viscosity over a wide pH range (3-11) - CMC has its ideal viscosity at pH 7-9; the viscosity dramatically decreases below pH 4 and above pH 10
inverse relationships
- most pharmaceutical calculations deal with simple, direct relationships: twice the cause, double the effect, etc - BUT occasionally they deal with inverse relationships: twice the cause, half the effect, etc. --> *eg* - when you decrease the strength of a solution by increasing the amount of diluent - if 10 L of a 10% solution are diluted to 25 L, what is the percentage strength of the dilution Q1C1 = Q2C2 10 L * 10% = 25 L * C2 C2 = 4%
label for powders
- needs to include the AMOUNT of each ingredient per dose *(ORAL)* - needs to include the percentage of each ingredient per dose *(TOPICAL)*
bulk powders
- non potent - can be dosed with acceptable accuracy and safety using measuring devices such as the teaspoon, cup, or insufflator - this practically limits the use of orally administered bulk powders to antacids, dietary supplements, laxatives, and a few analgesics - many bulk powders are used topically
oral emulsions
- oral liquid emulsions are less acceptable to patients than solutions or suspensions because of the objectionable oily feel of emulsions in the mouth - therefore, an oral emulsion is formulated only when it is necessary to make a liquid product of an oil or when the solubility of bioavailability characteristics of a drug make this delivery system clearly superior
things to remember
- percent without classification means w/w for solids and semisolids -- w/v for solutions of solids in liquids -- v/v for liquids in liquids - mg percent (mg %) expresses the number of mg of a substance in 100 mL of liquid --> 30 mg % means 30 mg of drug in each 100 mL of blood - for dilute solutions concentration expressed as ppm -- 6 ppm = 0.006%
examples of hygroscopic and deliquescent drugs
- phenobarbital sodium - ephedrine sulfate - hyoscyamine hydrobromide - zinc chloride
diabetic foot ulcers
- phenytoin promotes granulation in a wound while counteracting inflammation - misoprostol is a synthetic prostaglandin that accelerates wound healing - metronidazole exerts an antimicrobial effect to assist in wound care - nifedipine blocks the calcium influx into smooth muscles, thereby decreasing the vascular tone, which in turn increases blood flow
poloxamer gels
- pluronics are copolymers of polyoxyethylene and polyoxypropylene - they will form thermoreversible gels in concentration ranging from 15% to 50% - this means they are liquids at cool (refrigerator) temperature, but are gels at room or body temperature - poloxamer copolymers are white, waxy granules that form clear liquids when dispersed in cold water or cooled to 0-10º overnight - pluronic F-127 is often combined with a lecithin and isopropyl palmitate solution to make a *PLO gel* - GALLIPOT -- Polox and Lipiol
powder sprays
- powders dispensed under pressure and will deliver targeted and uniform application at the desired site - in an aerosol container, medicated powders may be maintained in a sterile condition - the powder particles must be a definite size range to prevent clogging of the valve orifice and to provide uniformity of application - in general, powders that are to be packaged as powder sprays must not contain particles greater than 50 microns if they are to be sprayed successfully
preservatives: *acacia emulsions*
- preservatives are *required* for acacia emulsions because of their susceptibility to microbial (especially mold) growth - unless the formulation contains an additive that would alter the pH, acacia emulsions have a pH in the range of 4.5-5 - therefore, preservatives that require a slightly acidic pH, such as benzoic acid or sorbic acid, are effective preservatives for acacia emulsions
proof strength
- proof spirit is aqueous solution containing 50% v/v of absolute alcohol - above or below proof - proof strength 50% -- proof spirit = 100 proof --> 100% or absolute alcohol = 200 proof --> 25% = 50 proof
ointment: stability
- semisolid dosage forms and are therefore usually more physically stable than are suspensions or emulsions -- this allows more flexibility with assigning expiration dates - "bleeding" of liquid ingredients and phase separation can occur -- special levigating agent, as outline previously, may be helpful - glycerin or propylene glycol may be added as humectants to ointment bases containing water to retard evaporation of the water and drying out of the ointment base
creams
- semisolid dosage forms containing one or more drug substances dissolved or dispersed in a suitable base - the term has traditionally been applied to semisolids that possess a relatively fluid consistency formulated as either wait in oil (eg. cold cream) or oil in water (eg. fluocinolone acetone cream) emulsions - however, more recently the term has been restricted to products consisting of oil in water emulsions or aqueous microcrystalline dispersions of long chains fatty acids or alcohols that are water washable and more cosmetically and aesthetically acceptable
pastes
- semisolid dosage forms that contain one or more drug substances intended for topical application - one class is made from a *single phase aqueous gel* (eg. carboxymethylcellulose sodium paste) - the other class, *the fatty pastes* (eg. zinc oxide paste), consist of thick, stiff ointments that do not ordinarily flow at body temperature, and therefore serve as protective coatings over the areas to which they are applied
ointments
- semisolid preparations intended for external application to the skin or mucous membranes - although the word "ointment" has this official general meaning, the term is also used as part of a drug product name to indicate that the drug is incorporated into a specific base type, a hydrocarbon base (fluocinolone acetonide ointment)
neutralizers: gelling agents
- some gelling agents (carbomers) require a "neutralizer" or a pH adjusting chemical to create the gel after the gelling agent has been water in the dispersing medium --> sodium hydroxide --> triethanolamine (trolamine)
solubility: gelling agents
- some gelling agents are more soluble in cold water than in hot water --> methylcellulose and poloxamers have better solubility in cold water - bentonite, gelatin, and sodium carboxymethylcellulose are more schedule in hot water - carbomers, tragacanth, and alginic acid gels are made with lukewarm water
absorption bases: *disadvantages*
- some have *poor patient acceptance* --> the anhydrous absorption bases have a greasy nature similar to that of hydrocarbon bases --> some lanolin-type bases may be somewhat sticky and some are not odor-free - *are not easily removed with washing* -- similar to hydrocarbon bases, they may be removed with mineral oil - *those bases containing wool wax or wool wax alcohols may be sensitizing* - those with soap-type emulsifiers (eg. cold cream, rose water ointment) can have compatibility problems - those that contain water may have stability problems with ingredients that are sensitive to hydrolysis - those containing water are subject to microbial growth; manufactured bases of this type contain preservatives
gels
- sometimes called jellies - are semisolid systems consisting of either suspensions made up of small inorganic particles or large organic molecules interpenetrated by a liquid - this official meaning of gel encompasses both two-phase systems, which are thixotropic suspensions (eg. aluminum hydroxide gel and bentonite magma)that are semisolids on standing but liquids on being shaken, and single-phase systems of synthetic macromolecules (eg. carbomer) or natural gum (eg. tragacanth) - here we will focus only on gels that are semisolids
black rubber or plastic spatulas
- special purpose spatulas that are used when an ingredient (eg. iodine) reacts with a metal spatula - not for general use in compounding ointments because they do not have the proper combination of flexibility and strength to give adequate shear and mixing
prepare acacia emulsion by the dry gum method
- the calculated amount of acacia and all the oil contained in the formulation are put in a Wedgwood mortar and triturated until a month slurry results and all the acacia is properly "wet" by the oil - the amount of the aqueous phase, which is calculated from the ratio given before, is measured in a *clean and dry* graduated cylinder and is added, all at once, with *hard and fast* trituration - trituration is continued until the primary emulsion is formed - you know this has occurred when the system changes from a translucent, oily-appearing liquid into a thick, white liquid - the sound of trituration also changes to give a "crackling" sound - once the primary emulsion is formed, other ingredients may be added
WARNING: cellulose derivatives
- the cellulose derivatives ability to hydrate is reduced by the addition of salts - some derivatives are more sensitive to divalent and trivalent inorganic salts - *the most difficult task is to introduce the compounds into solvents without clumping*
incorporating a drug into an ointment example
- the drug is usually the smaller quantity of the two ingredients, so geometric dilution will be used to dilute the small quantity drug into the ointment *eg* calamine powder and ointment base (1) add an amount of the ointment that is approximately equal in size to the calamine (2) spatulate the mixture (3) add a second portion of the ointment to the spatulate mixture that is about the same size (4) spatulate that mixture (5) continue adding portion of the ointment to the spatulate mixture in approximately equal sized until all of the ointment is use -- spatulate after each addition
non-ionic surfactant emulsions
- the most common non-ionic emulsifying agents for liquid emulsions are combinations of: (1) polysorbates (2) sorbitan esters (3) Span-Tween surfactants
levigation
- the process where we reduce the particle size of a powder by triturating it in a mortar and pestle or spatulating it on an ointment slab or pad with a small amount of a liquid in which the solid is not soluble (mineral oil and glycerin - this process is used for incorporating solids into ointments, pastes, and gels
factors that determine the amount of levigating agent needed include
- the quantity and properties of the solids to be incorporated - the levigating agent selected - the properties of the ointment base - the desired spreading consistency of the ointment - amounts of levigating agents used in official products can serve as a guide, but these vary considerably
a levigating agent is *NOT* use when:
- the solid being incorporated has a very fine particle size - the quantity of solid to incorporate is small - the ointment base is soft - the final product is to be a stiff ointment or paste
important to remember: *emulsions*
- the term *primary emulsions* is used to describe the initial emulsion formed with a prescribed ratio of ingredients --> if a prescription asks for 20 mL mineral oil -- use 40 mL mineral oil, 20 mL water and 10 g acacia (4 : 2 : 1) - this prescribed set of ingredients gives a system of optimal viscosity and consistency so that the shearing force exerted in the mortar is maximized to allow the formation of an emulsion
water-removable bases
- these are *oil in water emulsions* or *CREAMS* - in former times, the term "cream" was used for *either* oil in water (eg. vanishing cream) *or* water in oil (eg. cold cream) emulsion bases, and it usually was used for bases with a more fluid consistency - now the term is reserved for water removable oil in water emulsion bases or microcrystalline dispersions of long chain fatty acids or alcohols in water
efflorescent powders
- these are drugs or chemicals that *contain water of hydration* which may be releases when the powders are manipulated or are stored under conditions of low relative humidity - the water liberate when the drug or chemical is triturated may cause the powders to become damp or pasty - if water is released to the atmosphere because of low relative humidity, the drug loses its crystallinity and becomes powdery - furthermore, if water of hydration is given off, a given weight of the resulting powder no longer contains the same amount of drug - eg. caffeine, codeine phosphate, cocaine, codeine, citric acid
emulsifying agents
- these are surfactants which concentrate at the interface of the two immiscible phases and prevent coalescence of the droplets - some emulsifying agents also increase the viscosity of the system, slowing aggregation of the droplets and decreasing the rate of creaming -- some put a charge on the particles to repel each other
capsules: *disadvantages or limitations*
- they are easily tampered with (although techniques exist for preventing this) -- over come at the moment - they are subject to the effects of relative humidity and to microbial contamination - they may be difficult for some people to swallow - more expensive (commercially)
capsules: *advantages*
- they may be used to mask the unpleasant tastes, aromas, or appearance of a drug - they allow powders to be dispensed in an uncompressed form, thus allowing for quicker dissolution and absorption of the drug following oral dosing (as compared with tablets) - they offer the pharmacist versatility to prepare any dose desired for a variety of administration routes (eg. oral, inhalation, rectal, or to be diluted for vaginal, rectal, oral or topical use - they may be easier than tablets for some people to swallow - they can be made to alter the release rate of the drug
instability: *creaming* emulsions
- this is migration of the droplets of the internal phase to the top or bottom of the emulsion - the direction of the movement depends on whether the internal phase is more or less dense than the continuous or external phase
instability: *coalescence* emulsions
- this is the merging of small droplets into larger droplets with eventual complete separation of phases so that the droplets cannot be re-emulsified by simple shaking of the product - irreversible coalescence of the droplets is also called "cracking"
typical use of *O/W*
- this is the most common emulsion type - it is always preferred for oral products where an oily feel in the mouth is objectionable - it is also used for external products when ease of removal and/or a non-greasy feeling preparation is desired
liquid aliquot method
- this technique is similar to the solid method but employs liquid rather than solid diluents - it is used only when the product to be dispensed is a liquid - a weighable quantity of drug is dissolved in a calculated volume or a suitable solvent, usually water or ethanol - then, an aliquot of the solution containing the desired amount of drug is removed - both the total volume of solution and the aliquot volume should be such that they are emily and accurately measured (preferably who number multiple of 5 mL)
folded powder papers disadvantages compared to divided powders packaged in polybags
- time consuming preparation - poor moisture barriers - failure to safety packaging regulations
uses of ointments, creams, gels, and pastes
- to protect skin or mucous membrane from chemical or physical irritants in the environment and to permit rejuvenation of the tissue - to provide hydration of the skin or an emollients effect - to provide a vehicle for applying a medication either for local or systemic effect (eg. local -- a topical antibiotic; systemic -- a nitroglycerin ointment for treating angina)
factors that determine emulsion type
- type of emulsifier - phase ratio, that is, relative amounts of oil and water - order of mixing
dissolution
- under certain circumstances, dissolving a solid ingredient in a solvent or oil and subsequent incorporation of the solution into the ointment base if the preferred treatment - certain crystalline ingredients such as urea and camphor are difficult or impossible to levigate to a fine powder and should be dissolved in a suitable solvent before incorporation in the ointment base - testosterone is an example of a compound that gives gritty ointments unless it is first dissolved in an appropriate vegetable oil -- it is not soluble in mineral oil
acacia emulsions
- unique among the natural polymer emulsifiers in its ability to form emulsions using only a Wedgwood mortar and pestle - it is therefore a useful ingredient for extemporaneous compounding of emulsion - *the emulsification process does require the formation of a primary emulsion*
general rule: levigating agents
- unless a prescription order specifically calls for a given amount of levigating agent, *the MINIMUM AMOUNT of levigating agent necessary to lubricate the powders is generally recommended* - *documentation*: the name of the levigating agent and the quantity used should be noted on the face of the prescription order or the compounding record
amount of solvent to add: *general rule*
- unless a prescription order specifically calls for a given amount of the solvent, use the *MINIMUM AMOUNT necessary to dissolve the powders* -- SOLUBILITY - *documentation*: the name of the solvent and the quantity used should be noted on the face of the prescription order or in the compounding record
ointments: things to look out for?
- urea is available as hard crystals which are very difficult to pulverize - it is usually dissolved first in water and the solution is incorporated - look up the solubility of urea and calculate the number of milliliters of water needed
topics use of *W/O*
- used for external products when emollient, lubricating, or protective properties are desired - many ointments which are emulsion systems are w/o emulsions
primary emulsions
- used to describe the initial emulsion formed with a prescribed ratio of ingredients - this prescribed set of ingredients gives a system of optimal viscosity and consistency so that they shearing force exerted in the mortar is maximized to allow the formation of an emulsion
how to figure out an aliquot
- using ratio and proportion, we can determine the weight of drug and lactose required to make the trituration as well as the weight of the aliquot to the used to fill the prescription: (A) / (B) = (C) / (D) *(A)* = weight of drug in trituration *(B)* = weight of trituration *(C)* = weight of the drug in aliquot *(D)* = weight of aliquot - *keep in mind that any substance that must be weighed on the balance (drug, lactose, and aliquot) must be at least 120 mg)*
selecting inert ingredient: *lactose*
- very common inert diluent - it is commonly available as the monohydrate, and some suppliers sell the monohydrate in two forms, regular and spray-dried - spray-dried lactose monohydrate has been modified through processing to give a powder with improved flow characteristics - *water soluble* - extremely low incidence of side effects, readily available, low cost
preferred solvents -- USP
- water - alcohols - glycols - oils
gels -- single-phase systems
- water soluble - water washable - contain water - may contain alcohol - can absorb additional water - non-occlusive - non-greasy - lipid free *eg* - methylcellulose gel - sodium carboxymethylcellulose gel - hydroxypropyl methyl cellulose gel (liqua-gel) - hydroxypropyl cellulose gel - carbomer gel - poloxamer gel
USP zinc oxide paste
- weight zinc oxide and starch, spatulate together - weigh white petrolatum and gradually incorporate the powders in the white petrolatum and spatulate well until a smooth and uniform paste is obtained - label and dispense
alcohol USP
- when a prescription order or pharmaceutical formula calls for alcohol, the monograph product Alcohol USP is to be used - content: not less thant 92.3% and not more than 93.8% by weight (w/w) corresponding to not less than 94.9% and not more than 96% by volume (v/v) of C2H5OH - the content of alcohol in a liquid preparation shall be states on the label as a percentage (v/v) of C2H5OH
two rules of dilution and concentration
- when ratio strengths are given, convert to percentage strength before setting up a proportion --> 1 in 10 = 1:10 = 1/10 = 10% - whenever proportional parts are entered into a calculation, reduce them to lowest term: --> 75:25 simplify to 3:1 -- (better -- convert to percentage)
oil-in-water (O/W)
- where oils, petroleum hydrocarbons, and/or waxes tare the *dispersed phase*, and water or an aqueous solution is the *continuous phase*, the system is called an oil-in-water (o/w) emulsion - generally formed if the aqueous phase constitutes > 45% of the total weight, and a hydrophilic emulsifier is used
in preparing 250 mL of a certain lotion the pharmacist used 4 mL of liquefied phenol. what is the v/v strength of the lotion?
1.6 mL ~ 1.6% v/v liquefied phenol
how many grams of a drug should be added to 240 mL water to make a 4% w/w solution
10 g of the drug
allegation medial: you have three ointments: 200 g of 10%, 50 g of a 20% and 100 g of 5% oil in water emulsion. how much oil is in a product produced by mixing the ointments?
10% v/v
what is the HLB of a mixture of 40% Span 60 and 60% Tween 60 --> HLB Span 60 = 4.7 --> HLB Tween 60 = 14.9
10.8
how many grams of aminobenzoic acid should be used to prepare 8 fluid ounces of a 5% solution in 70% alcohol
12 g aminobenzoic acid
- how many grams of phenol should be used to prepare 240 g of a 5% w/w solution in water? - how much water is needed?
12 g of phenol 228 g water
how many mg of hydrocortisone should be used in compounding: - hydrocortisone 1/8% - hydrophilic ointment ad. 10 g
12.5 mg hydrocortisone
what is the percentage strength of a solution of urea, if 80 mL contain 12 g?
15% w/v urea in water
a hospital pharmacist whats to use three lots of ichthammol creams containing 50%, 20% and 5% ichthammol to produce a 10% ointment. in what proportion should they be mixed?
1:10:1
in what proportion should 20% benzocaine ointment be mixed with an ointment base to produce a 2.5% benzocaine ointment?
1:7
ratio for primary acacia emulsions: *for essential oils*
2 : 2 : 1
how many grams of dextrose are required to prepare 4000 mL of a 5% solution?
200 g w/v dextrose
how many milliliters of 37% w/w hydrochloride acid having a specific gravity of 1.20 are required to make 100 mL of diluted hydrochloride acid 10% w/v?
22.5 mL
allegation medial: what is the percentage v/v of alcohol in a mixture containing 500 mL of tenpin hydrate elixir (40% v/v alcohol), 400 mL of theophylline sodium glycerinate elixir (21% v/v alcohol) and sufficient simple syrup to make 1000 mL?
28.4%
ratio for primary acacia emulsions: *for volatile oils*
3 : 2 : 1
ratio for primary acacia emulsions: *for fixed oils, such as vegetable oils and mineral oil, the oil to water to acacia ratio (O : W : A) is...*
4 : 2 : 1
if 5 g of boric acid is added to 100 mL water what is the % w/w strength of the solution
4.76 g ~ 4.76 w/w boric acid
in what proportion should 95% and 50% alcohol be mixed to give 70% alcohol?
4:5
if 1500 g of a solution contain 75 g of drug what is the % w/w strength of the solution
5% w/w of drug
allegation medial: what is the percentage strength v/v of alcohol in a mixture of 3000 mL of 40% v/v alcohol, 1000 mL or 60% v/v alcohol, and 1000 mL of 70% v/v alcohol?
50% v/v
how many mL of liquefied phenol should be used to compound the following prescription: liquefied phenol 2.5% calamine lotion ad. 240 mL
6 mL of liquefied phenol
how many milliliters of 85% w/w phosphoric acid with a density of 1.71 g/mL should be used to prepare 1 gallon of a 1/4% w/v phosphoric acid solution?
6.5 mL
in what proportion should Tween 80 and Span 80 be blended to obtain a required HLB of 12? --> HLB of tween 80 = 15 --> HLB of Span 80 = 4.3
72:28
peppermint spirit contains 10% v/v peppermint oil. what volume of the spirit will contain 75 mL peppermint oil?
750 mL of a 10% v/v peppermint spirit solution
in what proportions may a 20%, 15%, 5% and 3% zinc oxide ointments be mixed to give a 10% ointment?
7:10:5:5
how many mL of a 3% solution can be made from 27 g of ephedrine sulfate?
900 mL of a 3% w/v solution of ephedrine sulfate in water
actions of unmedicated creams: *protective*
a substance that protects injured or exposed skin surfaces from harmful or annoying stimuli
actions of unmedicated creams: *emollient*
an agent that softens the skin or soothes irritation in skin or mucous membrane
toxicity of ethanol and isopropyl
are COMPLETELY different!!!
natural emulsifying agents: *synthetic agents*
carbopols
particles size reduction
comminution
ethyl alcohol (ethanol): *diluted alcohol NF*
content: a mixture of alcohol and water with not less than 41% and not more than 42% by weight (w/w), corresponding to not less than 48.4% and not more than 49.5% by volume (v/v) of C2C5OH
how much?: gelling agents
gelling agents are used in concentrations of 0.5% up to 10% depending on the agent
when to add drug: gelling agents
it is easier to add the active drug before the gel is formed if the drug doesn't interfere with the gel formation
aliquot example:
make 10 capsules, each containing 0.6 mg atropine sulfate and watch weighing a total of 200 mg
ointments: preservatives
methyl paraben 0.2%
patience: gelling agents
most gelling agents require 24-48 hours to completely hydrate and reach maximum viscosity and clarity
isopropyl alcohol (2-propanol): *azeotropic isopropyl alcohol USP*
not less than 91% and not more than 93% os isopropyl alcohol, by volume (v/v), the remainder consisting of water
isopropyl alcohol (2-propanol): *isopropyl alcohol USP*
not less than 99% of C3H8O
can we ingest gels?
only carbopol 934P, methyl cellulose, hydroxypropylmethylcellulose, and sodium carboxymethylcellulose are recommended for oral administration
levigating agent for coal tar
polysorbate 80 (tween 80)
divided powders (chartulae; charts; powder papers)
single doses of powdered medicinals individually wrapped in cellophane, metallic foil, or paper
hygroscopic powders
solid drugs or chemical that absorb moisture from the air
ingredient ratio for primary acacia emulsions
the amounts in the ratio are predicated on the total amount of oil in the formulation
ethyl alcohol (ethanol): *dehydrated alcohol injection USP*
the injection is dehydrated alcohol which is suitable for parenteral use
spatulation
the process of mixing powders on an ointment slab or pad using a spatula -- this process *does not reduce the particle size*
pulverization by intervention
the process whereby we dissolve a coarse powders in a volatile solvent (ethanol, acetone) and then rapidly evaporate the solvent to leave a fine powdered precipitate
deliquescent powders
these are hygroscopic powders that may absorb sufficient moisture from the air to dissolve and form a solution
large metal spatulas
used for levigation, spatulation, and incorporation of solid and liquid ingredients
cetyl alcohol
used in the cosmetic industry as a surfactant in shampoos and hair conditioners, as an emollient and as an emulsifier and thickening agent in the manufacture of skin creams and lotions
smaller metal spatulas
useful for removing product from the large spatula and for transferring product from the ointment slab or pad to the ointment jar
pulverization
when very large, rough particles are crushed
