Compounding 2: Equipment, Stability & Excipients Flashcards
cautionary note on calibration and materials
calibrate regularly to confirm accuracy
use equipment of material that does not react with compounding ingredients (metal spatulas with metal ion compounds)
measuring volume
use device with measuring capacity equal to or slightly larger than amount being measured for most accurate measurement
measurements made on metric system
cylindrical and conical graduates
graduates measure volume
graduated: same diameter on top and bottom - more accurate than conical or beakers
conical or beakers have wider mouth for easier stirring
wider mouth = lower accuracy
do not use graduate to measure volume <20% of capacity
to read: put on eye level
curve downward = meniscus = bottom of meniscus is center where measurement should be read
syringes for non-sterile
hypodermic (injection) = aka parenteral
syringes most accurate for measuring small volumes
syringes useful for measuring viscous liquids
oral syringe = use for those who need very accurate dose over small dosing cup
syringes for sterile
hypodermic syringes used to transfer drugs/additives into IV bags
syringe package should be wiped with 70% IPA before going into SEC or PEC
sterile syringes must be opened long seal to dec shedding/release of particles into sterile compounding space
needle sticks
recapping can cause needle-sticks = injury, contamination to CSP, infection risk
do not recap syringes in general
preferable use syringes with safety features
leur locks
leur locks make secure, leak-free connections
how to use syringe
do not touch plunger = contamination
IV push: bolus dose into vein directly or through catheter
leur lock: used to connect IV catheter and syringe
syringe types
cannulas = needles
do not use exact size syringe needed to draw up medication bc plunger can be dislodged = use closest size above size needed
do not use two different syringe sizes for dose
oral syringes: used for oral or NG = put “for oral use only”
pipettes
thin, plastic/glass tubes
volumetric pipette: only draws up set volume
Mohr pipette: graduated, can be used to measure different volumes
balances
older balance is Class III torsion balance aka Class A balance = must calculated MWQ
MWQ = SR (typically 6 mg) / acceptable error rate (typically 0.05/5% = typically 120 mg
electronic balance aka analytical balance aka scale = most common; simple and higher sensitivity; must “tare/zero-out” after putting weight boat/glassine paper
do not put material directly on balance - use weight boat or glassine weighing paper
mortars and pestles
compounding pharmacy needs at least 1 glass and 1 Wedgwood or porcelain mortar and pestle
glass: for liquids; things that are oily or can stain
Wedgwood: rough surface; goof for grinding dry crystals/hard powders
Porcelain: smooth; for blending powders and pulverizing gummy consistences
spatulas
mix and transfer
flat part = flatten/grind down ingredients
stainless steel and disposable plastic used commonly
steel: do not use if making mixture with metallic ions
ointment slabs
work surface for other purposes besides making ointments - can be used for forming pills (called a pill tile)
disposable parchment ointment pads can be used if water in mixture will not make paper tear
powder sieves
sifters
sift after powder ground fine to guarantee uniform particle size
electronic mixing
ointment mills, homogenizers, grinders mix ingredients
ointment mill and grinders = dec particle size = inc surface area and rate of absorption
ointment mills
grings and homogenize into uniform
homogenizer
aka electric mortar and pestle = mixes ointments, creams, other semis-solid preparations
hot plate with magnetic stirrer
dissolves and mixes ingredients
has rotating magnet which causes bar to stir
hot plates without bar heats only (can manually mix with glass stirring rod)
heating with hot plates
water bat is helpful when temp needs careful control
put ingredients in container that is put in larger container with water = prevents burning
molds
reusable or disposable
prepare tablets, lozenges/troches, suppositories
in soft such as suppositories, often dispensed in disposable plastic mold; refrigeration helps soft products keep shape
tablets
tablet press is two plastic or metal plates that compress damp powder into tablets
capsules
can be soft gels or hard shells
shells made of gelatin (pork-derived) or hypromellose (plant-based)
capsule sizes: 000 biggest to 5 smallest (can use larger capsule sizes for large animals)
bodies: filled with drug/excipients
cape: put over body by hand or capsule machine
tube sealers
heat and squeeze ends of tubes shut
compounding ingredients
active pharmaceutical ingredients = API
excipients = no therapeutic effect
ingredient quality
ingredients recommended found in USP national formulary (USP-NF) and Food Chemicals Codex = FCC
good to get ingredients from FDA-registered facility
if from non-FDA registered facility - get certificate of Analysis (CoA) to confirm specifications and quality
expiration date
ensure products retains potency and is non-toxic
if ingredient has no expiration date - assign conservative date of no more than 3 years from date of receipt
container label should show date of receipt and assigned expiration date
surfactants
tension = high = separate
surfactant keeps pharmacy from quickly separating = from surface active agent = lowers surface tension/interfacial tension between two ingredients/phases = more miscible (easy to mix)
surfactants are amphiphilic - hydrophilic side and hydrophobic side
surfactants keep consistent dose
includes wetting agents, emulsifiers, suspending agents, levigating agents, foaming agent, glycols/gels
surfactants
tension = high = separate
surfactant keeps pharmacy from quickly separating = from surface active agent = lowers surface tension/interfacial tension between two ingredients/phases = more miscible (easy to mix)
surfactants are amphiphilic - hydrophilic side and hydrophobic side
surfactants keep consistent dose
includes wetting agents, emulsifiers, suspending agents, levigating agents, foaming agent, glycols/gels
wetting agents
reduce surface tension between liquid and solid
put powder with wetting agent before putting into delivery vehicle
levigating agents can be referred to as wetting agents
emulsifiers
added to two or more liquids not able to blend (immiscible emulsion) to keep liquid drops dispersed throughout liquid behicle
suspending agents
solid in liquid = suspension
suspending agent (dispersants/dispersing agents) keeps solid particles from settling
shake to re-disperse solid
can be plasticizer (will make preparation easier to shape/mold)
ora-plus: keeps particles suspended and prevents settling; bland taste
ora-sweet: gives flavor to Ora-Plus
Ora-blend: Ora-plus + ora-sweet
levigating agents
levigation makes particles smaller by grinding
different from trituration in that it needs levigant (glycerin, mineral oil) to aid in grinding
mineral oil common for lipophilic levigating
propylene glycol and glycerin common for aqueous levigating
foaming agent
ant-foaming (simethicone) common in non-sterile compounding
glycols and gels as surfactants and delivery vehicles
PEG and poloxamer (by itself or in PLO gel) are delivery hicles and surfactants
PEG and poloxamer = hydrophilic and hydrophobic parts; eg poloxamer gel good for distributing ingredients into “like phase”
poloxamer: useful for topical drug delivery
hydrophilic-lipophilic balance
surfactant important when putting liquid into liquid for emulsion
select surfactant considering if emulsion is water-in-oil or oil-in-water
if HLB < 10 = use in w/o (lower = lipid soluble)
if HLB >10 = use in o/w (higher = H2O soluble)
HLB <10: glyceryl monostearate; Span 65
HLB >10: PEG 400; Tween 85
stability
throughout storage and use same properties as when it was made
degradation
different based on functional groups reacting
caused by oxidation-reduction, hydrolysis, photolysis
oxidation
compound loses elections = oxidation
gains electrons = reduced
oxidation can be seen with color change (epi bc amber yellow/orangish; others bc pink/reddish)
likely to oxidize: those with hydroxyl -OH group directly on aromatic ring
oxidation examples: sugar caramelizing, alcohol group in sugar is oxidized
alcohol = -OH bound to carbon; water removed when steam evaporates
prevent oxidation control temp to avoid heat and monitor pH/control with buffer; use amber to protect from light; refrigerate; chelate metal ions that have an unshared electron (free radicals) that can catalyze oxidation (chelators = EDTA; EDetic acid); use antioxidants to inhibit free radicals (ascorbic acid/vit C, tocopherols/Vit E)
hydrolysis
water causes cleavage of bond in molecule
desiccants can soak up moisture in container
common hydrolysis: esters, amides, lactams
Ester: carbonyl (C=O) on OR group
amide: carbonyl bonded to nitrogen
lactam: beta-lactam ring
prevent hydrolysis by protecting from moisture; can store drugs as lyophilized (free-dried) powder; hygroscopic salt (salt form of drug that is less hydroscopic = absorbs less water); make prodrug that release active drug by hydrolysis (ASA is hydrolyzed to salicylic acid); control temp; use buffer to maintain pH
binders
stick contents of tablet together
provide strength
diluents and fillers
make something more dilute = diluent
fillers add size to very small dosages
sugars: lactose
starches
Ca salts
cellulose
petrolatum
disintegrants
facilitates breakup s tablet can dissolve and be absorbed
alginates - alginic acid
cellulose
polacrilin potassium
starches
flavorings and color agents
non-caloric, artificial: aspartame, sucralose
glucerin
dextrose
sugar alcohols: mannitol, sorbitol, xylitol
stevia
lubricants
prevent ingredients from sticking
improve powder flowability
magnesium stearate
preservatives
do not use in neonates
chlorhexidine (also surgical scrubs antiseptic)
povidone iodine
sodium benzoate/benzoic acid, benzalkonium chlorid
sorbic acid/potassium sorbate
methyl/ethyl/propyl parabens
EDTA
thimerosal
cetylpyridinium chloride
buffers
ionzed = polar = water-soluble
use Henderson-Hasselbalch equation to determine pH
buffers for acidic pH: hydrochloric acid, acetic acid.sodium acetate; citric acid/sodium citrate
buffers for alkaline pH: sodium hydroxide; boric acid/sodium borate; sodium bicarbonate/sodium carbonate
buffers for neutral pH: sodium bisphosphate/sodium phosphate; potassium phosphate/metaphosphate
water as solvent
purified water has been treated to remove chemicals/contaminants - distillation, deionization, reverse osmosis
distilled water for reconstitution for oral suspension and non-sterile compounds
potable water (tap) is for hand washing and equipment initial cleaning
sterile water as solvent
free of bacterial endotoxicins (pyrogens) from microorganisms that inhabit water
alcohols
have high miscibility with water
can help dissolve solutes that are insoluble in water alone
benzoyl alcohol: also preservative and has fragrance
IPA 70%: disinfectant in sterile compounding
glycols (PEG)
surfactant, solvent, lubricant
water-soluble and water-miscible (mixes well with water into homogenous mixture)
when linked to protein = pegylated = inc 1/2 life
Polybase: suppository base; good emulsifier
oils and fats
mineral oil: from petroleum; in Baby Oil
emmolients/moisturizers
softens and soothes skin
occlusive: petroleum jelly/white petrolatum; theobroma oil/cocoa butter; waxes = protective barrier to prevent water loss
humectants: pull water in from atmosphere; glycerin/glycerol; propylene glycol, PEG
includes ointments, creams, lotions, gels, and suppository bases made of various fats and glycols
ointments
have 0-20% water
best for dry/thick skin
petrolatum
polybase
aquaphor
aquabase
oleaginous = no water; petrolatum/Vaseline
ointments
have 0-20% water
best for dry/thick skin
petrolatum
polybase
aquaphor
aquabase
oleaginous = no water; petrolatum/Vaseline
creams
have >=20% of water
up to 50% oil
good for normal/dry skin
usu water-in-oil or oil-in-water emulsions
lotions
mostly water
best for oily skin
can have alcohol to solubilize ingredients
gels
aqueous solutions of poloxamers are liquid at fridge and gel at room temp
Poloxamer (Pluronic) Lecithin Organogel
Poloxamers have hydrophob chain with two hydrophilic chains
suppository bases, made of various fats and glycols
Polybase
hydrogenated vegetable oils
gelatin
adsorbants
to keep powder dry
magnesium oxide/carbonate
kaolin
anti-foaming agents
simethicone
coatings (regular)
shellac, gelatin, gluten
emulsifiers
type of surfactant
acacia
PEG
enteric-coating
acid-resistant coating to prevent dissolution in stomach by stomach acid destroying drug
cellulose acetate phthalate
gelling/thickening agent
stabilizer
gelatin
cellulose
bentonite
agar
alginates
various gums (guar, xanthan, acacia)
gelatins
bentonite
carbomer
cellulose
starch
poloxamer (pluronic) gels
humectant
prevent preps from becoming dry and brittle
glycerin/glycol
propylene glycol
PEG
