Question | Answer |
what is pharmaceutical compounding? | the physical and/or chemical modification of a substance (drug or raw chemical) resulting in a drug/dosage form which is suitable for administration to a patient |
what is extemporaneous compounding? | Compounding pursuant to 1) a specific patient, 2)for a specific prescription and 3) for one dispensing of the medication (does not apply to batching, manufacturing, or refills compounded at the same time) |
What is batching? (in terms of pharmaceutical compounding) | compounding 'ahead of time' in anticipation of outstanding refills or unfilled oral prescriptions |
What is manufacturing? (in terms of pharmaceutical compounding) | compounding for long-term inventory and sale. (NOT pursuant to a particular patient, prescription, or within the scope of pharmacy practice) |
Which pharmaceutical dosage forms, discussed in class, are commonly prepared extemporaneously? | lozenges, pills, tablets (uncommon), charts, powder capsules, liquid capsules (uncommon) |
What are the valid justifications for pharmaceutical compounding? (3) | 1) drug or dosage form not commercially available
2)dose unavailable
3)patient comfort and compliance (taste) |
What are the prohibitions to pharmaceutical compounding? | cannot "manufacture" = making more than you need. You can only batch up to a 30 day supply of what you will anticipate needing |
What is stability? | the extent to which a prescription preparation remains within specified limits in terms of: chemical composition, physical composition, and microbiologic activity/contamination |
What general considerations must be taken into account when formulating and assigning expiration dates to extemporaneously compounded pharmaceutical preparations? | Expiration is a function of stability and storage conditions. Base it on published formulation data and stability tests whenever possible |
What is the most important consideration with respect to the storage of pharmaceutical preparations? | keep out of reach of children |
What is an active ingredient? | substances present in the formulation which exist for their direct effect on the patient |
What is an inactive ingredient? | substances present in a formulation which exist solely for their effect on the product |
Can an ingredient have both active and inactive properties? If so how should it be classified? | Yes, if it exerts both direct effects on the patient and for the benefit to the product, it is said to be an active ingredient |
What is refinement? | particle size reduction. (has different ranges of particle sizes than pulverization) |
What is trituration? | verb: refining and mixing of powders |
What is a trituration? | noun: mixed powder product |
What is geometric combination? | visually duplicating an equivalent mass and combining. |
When is geometric combination warranted? | Indicated when mass of powders to be mixed differs by a factor GREATER THAN 3 (if =3 do not need to) |
What is a eutectic? | a combination of 2 or more substances where the melting point is less than that of any part when taken alone |
What factors must be optimized in order to yield a eutectic combination with the lowest possible melting point? | optimum ratio of masses, room temperature, substance melting points, fineness of particle size |
What is the basic principle at play (and responsible for) eutectic formation? | interference with crystalline structure |
What is efflorescence? | contains waters of hydration (stoichiometric). due to hydrogen bonding. The delicate crystal structures may be altered when exposed to stress, humidity, or temperature. ex: cocaine, terpin hydrate, quinine HCl |
What is deliquescence? | hygroscopic (subject to moisturization) but will dissolve and form a water based solution. Ex: lithium bromide |
What is hygroscopicity? | powders subject to moisturization from ambient humidity. (affinity for water, will absorb water from air) |
Be able to derive the Sensitivity of a balance from MWQ and vice versa for a given desired tolerance | Sensitivity/MWQ = %/100 |
Ideal Body weigh Equation (IBW) | Male: 50 + (2.3* inches over 5')
Female: 45.5 + (2.3* inches over 5') |
lb to kg conversion | 2.205 lb = 1 kg |
inch to cm conversion | 1 in = 2.54 cm |
Creatinine Clearance equation | M: (140-age)*IBW / 72*SCr
F: M eq * 0.85 |
Know the BSA equation and how to use a BSA nomogram | sqrt((height in cm * weight in kg)/3600) |
Which pharmaceutical dosage forms are composed of powders? | bulk powders, capsules, charts, tablets(compressed powder) |
Which pharmaceutical dosage forms represent unit dose powders? | capsules, charts, tablets (compressed powders) |
basic characteristics of lozenges | -dissolve/disintegrate in mouth
-local (oral) drug delivery usually
-pastilles (soft, high sugar)
-troches (relatively small)
-analgesics, anesthetics, antimicrobial |
basic characteristics of pills | -small, round, spherical, hard
-cut up a long spherical dough, roll into balls, dry |
basic characteristics of tablets | -compressed unit dose powder
-solidification mold (less common, extemporaneous)
-can extemporaneously prepare, but uncommon |
basic characteristics of charts | -contains specific dose of medication
-loose powder in a paper envelope |
basic characteristics of powder capsules | -solid and non-rigid
-shell usually molded gelatin |
basic characteristics of liquid capsules | -nonsolid and non-rigid
-can extemporaneously compound, but not common
-need to use liquid that will not dissolve capsule - some alcohols (not EtOH, fixed oil, volatile oil) |
basic characteristics of gel capsules | - cannot be extemporaneously prepared
-semisolid and non-rigid
-beads of gel inside |
Rule of 7s (backward and forward) | 7 - grains = capsule size, 1 g = 15.43 gr |
Active ingredients in an oral, unit dose powder should have what units? | mass/dose |
Active ingredients in a topical powder should have what units? | mass of drug/mass of product (concentration, %w/w) |
What physical forms may potentially be found as ingredients in commercially available capsules? | powders, liquids, gels |
what physical forms are commonly used as ingredients in commercially available capsules? | powders. liquids are uncommon |
What general advantages do capsules have over other solid oral dosage forms? | custom dosing, multiple drugs in one capsule, easy to swallow, taste concealment, rapid drug release |
What is an excipient? | inactive ingredient with a purpose to the preparation: fillers, binders, glidants, disintegrants, coloring agents, flavoring agents |
What is ratio strength? | X g of drug in Y g or ml of product (X:Y)
1: Y = 1 g of drug for every Y g or ml of product |
% w/v | g/100 ml |
% w/w | g/100g |
% v/w | ml/100g |
% v/v | ml/100ml |
Freezer/frozen temperature | -20 to - 10 degrees C |
Cold temperature | 8 degrees C or less |
Refrigerated** temperature | 2 - 4 degrees C |
Cool temperature | 8 = 15 degrees C |
Room temperature ** | 20 - 25 degrees C |
warm temperature | 30 - 40 degrees C |
excessive heat | above 40 degrees C |
all liquid dosage forms | suspensions (lotions), solutions (syrups, elixirs, spirits, tinctures, lotions), emulsions (O/w, w/o) |
the basic characteristics of a simple solution | all ingredients are molecularly dispersed, does not need to be maintained by shaking. |
definition of a solute | substance which is dissolved in a solvent |
definition of solvent | base liquid, pure or mixture of miscible liquids, contains no active ingredients |
USP definition of solution | liquid preparations that contain one or more chemical substances dissolved in a suitable solvent or mixture of mutually miscible solvents |
functional definition of solution | molecular dispersion of a solute in solvent |
Basic characteristics of a true pharmaceutical syrup | concentrated aqueous preparation of sugar or sugar substitute, highly concentrated = viscous. sugar at near saturation |
advantage of liquid over solid dosage forms (3) | -dose determined by volume measurement
-precise dosing (custom dosing)
-nonstandard dosing easy (ex: pediatric)
-easy to swallow |
dosage for examples, which are solutions | solutions = syrups, elixirs, tinctures, lotions, non-solutions = suspensions and emulsions |
disadvantages of liquid dosage forms compared to solid (5) | -inconvenient dosing (need to teach pt.)
-prone to error
-unpleasant taste difficult to mask
-specific storage conditions
-drug is often less stable than dry form |
stability of active ingredients in a liquid dosage form compared to dry dosage forms or suspensions | theoretically maximum surface area of the drug in contact with solvent = less stable |
examples of water soluble dissociable ionic substances | potassium citrate, sodium chloride, potassium chloride |
water soluble non dissociable substnaces | glucose |
definiition of solubility | the degree or extent to which a solute will dissolve in a solvent |
general solubility notations | freely soluble, sparingly soluble, very slightly soluble |
exact solubility notation | 1 g of X in ___ ml of Y |
What is a eutectic | a combination of 2 or more substances where the melting point is less than that of any part when taken alone |
can a solution be part of a suspension | yes, a suspension can contain dissolved things |
can a suspension be part of a solution | no, a solution cannot contain undissolved things. not molecularly dispersed |
can a syrup be part of a suspension? | yes, a suspension may have some soluble components |
can a suspension be part of a syrup? | no, syrups are solutions, and they need to be molecularly dispersed |
various routes of administration for solution | IV, IM, Sq, epidural, intrathecal, rectal, ophthalmic, otic, topical |
various routes of administration by which liquid dosage forms in general can be administered | Sq, IM, rectal, ophthalmic, otic, topical |
routes of administration inappropriate or dangerous for some specific dosage forms | IV,intrathecal, epidural = not safe for suspensions |
In which particular case is the use of preservatives dangerous and tragic? | intrathecal preparations, never use bacteriostatic water for injection. preservatives will destroy motor neurons and permanently paralyze |
advantages of solutions over suspensions | suspending agents not required, easily absorbed |
disadvantage of solutions in respect to suspensions | generally less stable |
what is the general effect of temperature on a solution system | increasing solubility with increasing temperature |
what is meant by saturation in a solution system | cannot dissolve anymore: maximum concentration acheived |
what is miscibility? | 2 liquids soluble in each other in all proportions |
Exact composition of alcohol USP | 94.9% w/v ethyl alcohol |
FDA ruling march 1995 | Maximum alcohol content in OTC products: Children <6 years old = 0.5%, 6-12 years = 5%, >12 years 10% |
mg % | x mg/100 ml |
shaking solutions and simple syrups? | not needed for patients but RPh may need to shake to prepare |
Shaking suspensions? | always! |
20% rule? | smallest volume that can be measured is 20% of its full rated volume |
difference between a volumetric measuring device and a holding vessel | measure precisely vs just use to hold the liquid. ex: graduated cylinders vs beakers |
be able to convert between mg % and ratio strength | mg% = x g/100 ml, ratio strength = 1 g//x ml |
what is the simplest form of ratio strength | X:Y |
what is parts strength? | X parts + Z parts = Ytotal |
convert between ratio strength and parts strength | X:Y, and X:Z where X parts + Z parts = Y total |
know the concept of equivalence | MW = g/mol, valence = Eq/Mol, EW=MW/valence = g/Eq |
units for molecular weight | g/mol |
units for equivalent weight | g/Eq |
what is an equivalent? | a unit once dissolved |
isotonic | same osmolarity |
hypotonic | less osmolarity |
hypertonic | more osmolarity |
preservation paradox for syrups | contain a lot of sugar, but are actually a preservative. this is because there is not a lot of free water |
free water | water available that is not involved in solubilizing the sugar |
know the effect of temperature on free water | as temp increases, free water increases |
know the effect of increasing solute concentrations on dissolution time | increasing solute concentration increases dissolution time |
effect of increasing sugar content of a syrup | -sugar may precipitate
-drug may precipitate |
effect of decreasing the sugar content of a syrup | -increase in free water
-microbial growth |
be able to predict free water values in a solution/syrup system: Example if 89.14 g of sucrose in 100 ml of water is saturation how much free water is in syrup usp (85%w/v)? | 4.64 ml. 89.14g/100ml-85g/100ml = 4.14 g/100 ml. how much water is represented by 4.14 g : 4.14 g* 100ml water/89.14 g = 4.64 ml |
Syrup USP | 85% w/v sucrose in water |
Cherry Syrup USP | 80% w/v sucrose, 47.5% v/v cherry juice, 2% v/v EtOH |
know the concept of specific gravity | mass of x / mass of water for equiv volume |
units of specific gravity | unitless |
units of density | g/ml |
convert between specific gravity and dencity | add units g/ml to specific gravity |
utility of alcohol as an ingredient in liquid pharmaceutical dosage forms | preservative, emulsifier, sedative (usually undesired side effect), rarely included for pharmacological effect |
cautions of EtOH in liquid dosage forms | cant have too much in pediatric formulations |
examples of syrup vehicles | simple syrup (50-1005 v/v), Cherry Syrup, Cologel, Sorbitol, glycerin (2-10% v/v) |
USP definition for suspension | liquid preparations that consist of solid particles dispersed throughout a liquid phase in which particles are not completely soluble |
Purpose for suspensions as liquid dosage forms | provide a liquid form of a drug that is otherwise insoluble in water. An alternative to alcohol solutions |
Example when something would be a suspension instead of a solution | when using a capsule or tablet drug source |
Suspending agent | increases the product's viscosity thus decreasing the particle settling rate |
examples of suspending agents | acacia, bentonite, methylcellulose, xanthan gum, tragacanth, carbomer |
micron gauge (hedgeman wedge) | determines the smallest particle diamter size you are able to achieve |
nested sieves | separates particles of different diameters |
Factors that affect sedimentation rate/time | particle size (increase rate), density (increase rate), viscosity (decrease rate) |
relationship between settling rate and settling time | inverse. as settling rate decreases settling time increases |
stokes law | velocity proportional to g * radius * (difference in densities) all over viscosity |
deflocculation | long sedimentation time, but difficult to break up if a cake is formed |
flocculated | short sedimentation time, but redisperses easily |
Know the USP definition for lotions | Not listed, liquid preparation intended for external application |
Know the British pharmacopeia definition for lotions | Liquid or semiliquid preparations which contain one or more active ingredient in a suitable vehicle |
In what set(s) of liquid dosages forms may lotions potentially be found | Suspensions
Emulsions
solutions |
Solutions | liquid preparation containing 1+ chemical substances dissolved(molecularly dispersed) in a suitable solvent or mixture of mutually miscible solvents
Solute dissolved in a solvent |
Suspensions | liquid preparation that consists of solid particles dissolved throughout a liquid phase in which particles are not completely soluble
Pure solvent with solid particles |
Emulsions | two phase system in which one liquid is dispersed throughout another in the form of small droplets
Oil and water |
What are intertriginous areas | ? Where skin touches skin
Gluteal fold, abdominal fold, between breasts. Antifungal agents or lubrication |
What is levigation | Applies to powders which are insoluble in the qs media
The wetting of an insoluble powder agent in a minimal amount of qs media or levigating agent forming a smooth homogenous paste |
What is quantitative transfer | Facilitated transfer of a substance from one vessel to another through a series of repeated washings with the qs media.
Always done prior to qsing
Applies to agents both soluble and insoluble in the qs media |
What is creaming? | Migration of droplets – surfacing or settling |
What is cracking? | Merging of droplets, separation of phases
Usually irreversible |
Be familiar with some common ingredients that could be found in a lotion | Water
Hydrocortisone
calamine |
What does the “internal phase” of an emulsion mean? | The droplets, or micelles |
What does the “external phase” of an emulsion mean? | The suspension medium that the droplets float around in |
What is an oil in water emulsion | Oil droplets in a water phase
Passes conductivity test
When oil added to it, it is not additive
When water added to it, it is additive |
What is an water in oil emulsion | Water droplets in an oil phase
Fails conductivity test
When oil is added to it, it is additive
When water is added to it, it is not additive |
what is an emulsifier? | Promotes the formation of micelles and their charge based separation |
how do emulsifiers work? | They have polar and nonpolar sides that line up at the water and oil interfaces |
Know the definition for emulsification | Added energy through trituration or homogenization creating small droplets of one liquid phase in another and static charge around those droplets |
Know the definition for homogenization | Forcing two immiscible liquids through an orifice under high pressure for the purpose of mixing |
Know some examples of commercially available pharmaceutical emulsions | Lotions, gels, TPN lipid formula, amphotericin-B, propofol |
Know the composition of and the order of incorporation for 4:2:1 emulsions | 4 parts mineral oil
2 parts water
1 part acacia
Refine acacia in mortar, add oil to acacia (2secs) and mix, add water, mix rapidly until viscous |
Know how to use the electrical conductivity test in the analysis of emulsions | Oil in water passes
Water and oil fails
Only a water continuous phase will conduct |
Know how to use the drop dissolution test in the analysis of emulsions | Water will be additive to the oil in water, but not the water in oil
Oil will be additive to the water in oil but not that oil in water |
What factors contribute to the viscosity of an emulsion? | Micelle diameter
Weak hydrogen bonding between micelles |
avogadros number | 6.022 * 10^23 |
When should a substance be incorporated into the internal phase of an emulsion in general? | PO: active ingredients usually in internal phase (mask taste)
Internal use = oil in water (because body is made of water) |
When should a substance be incorporated into the external phase of an emulsion in general? | External: active ingredients usually in external phase (touch skin)
External use = water in oil (want emollient effect) |
Know the composition of lime water | Calcium hydroxide solution 3g/1000ml |
What does HLB stand for? | Hydrophile-lipophile balance |
Soaps | Calcium oleate |
Gums | Acacia
Tragacanth
Xanthan gum |
Surfactants | Tween 80, span 80 |
What range of HLB values tend to form water in oil emulsions | 1 – 9 LOW END = water in oil |
What range of HLB values tend to form oil in water emulsions | 9 – 20 HIGH END = oil in water |
1 pt = x oz | 1 pt = 16 oz |
1 qt = x pts = x ozs | 1 qt = 2 pts = 32 ozs |
1 gallon = x qts = x pts = x ozs | 1 gallon = 4 qts = 8 pts = 128 ozs |
1 apoth oz = x g | 1 apoth oz = 31.10 g |
1 avoir oz = x g | 1 avoir oz = 28.35 g |
1 oz = x ml | 1 oz = 29.57ml |
x gr/g | 15.43 gr/g |
valence of potassium citrate | 3 |
valence of magnesium chloride | 2 |
valence of magnesiumsulfate | 2 |