Compounding 3: Documentation and Preparation Flashcards
master formula record
recipe for compound
what you should do
compounding log or record
log book of all products made at the pharmacy
must have detailed enough documents that another can replicate
what you did
preparation steps
review SDS for each bulk ingredient
garb: minimally clean lab goat and gloves for non-sterile, non-HD
make product according to master formula
reducing particle size
comminution: reduce particle size by grinding, crushing, milling, vibrating
powders must be finely ground and then it will be placed into sieve (sifters; ensure uniform particle size)
once in sieve, brush or plastic spatula is used to force particles through mesh
sieve number = # of holes/in
types of comminution
trituration: “mix thoroughly”; make homogenous; grinding tablets with mortar and pestle; can describe liquids (shaking emulsion)
levigating: triturating powder with mortar and pestle and adding liquid (levigating agent/wetting agent) to help grinding process
spatulation: like levigation but on ointment slab with spatula
pulverization by intervention: for crystalline powders that do not crush easily; crystals are dissolved intervening solvent and mixed until solvent evaporates
geometric dilution
ensure ingredients evenly distributed
small amount of drug is mixed into equal amount of diluent
solution
solute in solvent
homogenous
syrups
elixirs
tinctures
spirits
suspension
solid in liquid
two-phase heterogenous
wetting agent/levigating agent puts insoluble drug into liquid = suspension
particles redisperse easily by shaking
emulsion
liquid dispersed in liquid
two-phase heterogenous
oil-in-water or water-in-oil
emulsifier (surfactant) used to reduce surface tension bt two liquids = emulsion
use HLB number to choose best emulsifier
preciptation/sedimentation
happens in suspensions and emulsion
how to prepare solutions
find if solute will dissolve in solution
dissolution rate = Fick’s First Law of Diffusion
larger surface area, stirring, and heat = inc dissolution rate
buffer system may be needed to resist changes in pH
preservative may be needed
flavorings, sweeteners, coloring agents can be added
how to prepare suspension
wet powder and levigate to form paste
homogenizer can make uniform suspension
preservative may be needed
flavorings, sweeteners can be added
can use surfactants as suspending agents but still need to shake to redisperse before use
how to prepare emulsion
continental/dry gum method:
levigate gym with oil
add water all at once
triturate until cracking heard and looks creamy white
homoginize with homogenizer machine
English/wet gum method:
triturate gum with water to form mucilage
add oil slowly
powders
often include glidant/lubricant to improve flowability (magnesium stearate)
often include surfact to neutralize static change (sodium lauryl sulfate)
how to prepare powders
add inert filler/diluent if very small amount of powder per dose
melting point order
melt ingredient with highest melting point prior to adding ingredients with lower melting points
eutectic mixtures
combo of ingredients will melt at lower temp than any of individual components
can lead to melting and turning into sticky mess
adsorbant can be used - magnesium oxide, magnesium carbonate, kaolin
capsules
soluble shells of gelatin (animal product) or hypromellose (vegetable product)
glycerol and sorbital - plasticizers to make less brittle and more flexible
sizes from larges (000) to smallest (5)
how to prepare capsules
can hand fill or punch method
use hand for small number, machine for larger number
tablets
molded tablet most common in compounding
compressed tablet most common in manufacturing
how to preare molded tablets
alcohol and/or water added to moisten powder
mold pasty mixture into tablets with mold and then dry
lozenges/troches
used for drug that acts in mouth
hard lozenge base: sucrose or syrup
soft lozenge base: PEG
chewable lozenge base: glycerin or gelatin
how to prepare ointment
triturate well with levigating agent
mix powder into ointment base with geometric dilution
some must heat to mix - fusion method
start with ingredient that has highest melting point and then add by decreasing melting point
Gels
pluronic lecithin organogel (PLO gel) can be used for transdermal drug administration
suppository
oil-soluble base: cocoa butter/theobroma oil; hydrogenated vegetable oils
water-soluble base: PEG; gelatin
if prep soften/melts easy, like theobrome oil/cocoa butter - store molds in refrigerator; will melt in hand
to calculate amount of drug displaced, use densitity factor: weight of med per suppository/(weight of suppository blank - weight of medicated suppository + weight of medication per suppository)
how to prepare suppositories
hand molding can be used when only few needed
fusion molding: mixture poured into room temp molds
compression molding: use density factor to find amount of base needed for each suppository, mix with drug, and put into cold compression mold
if using lubricant, must be opposite solubility as suppository base
BUD for nonaqueous formulations
6 months
store at room temp
nonaqueous: white petrolatum, hypromellose capsule,PEG lozenge, oleaginous base, propylene glycol
BUD for water-containing oral
14 days
store at cold temp/refrigerator
BUD for water-containing topical
30 days
store at room temp
aqueous topical: emulsion cream, Verabase lotion, glycerin in 70% IPA, poloxamer gel with leciithin/isopropyl palmitate
BUD for repackaged drugs
expiration date from manufacturer or 6 months from repackaging, whichever is earlier
patient counseling
report ADRs to pharmacy
pharmacy record ADRs in compounding record
physiochemical considerations
sterile preps should be isotonic to human blood and similar osmolarity of ~285 mOsm/L
pH of sterile should be close to neutral
non-PVC bags used for meds with leaching/sorption issues
ampules
filter needle or filter straw needed to remove glass in drug solution after opening ampule
vials with lyophilized or free-dried powder
needs to be reconstituted by adding sterile water
small volume parenteral (SVP)
IV bag or syringe with 100 mL or less
ready-to-use medications (RTU)
prepared IV bags or prefilled syringes
no CSP risk level bc not compounded
ready-to-use vial/bag systems
ADD-Vantage
how to set up items in sterile hood
all work done at least 6 inches into hood to prevent hood and buffer room air from mingling
put items side-by-side
nothing between sterile object and HEPA filter in horizontal airflow hood
do not tear open components
how to transfer solutions and inject into IV bags
use smallest syringe possible for desired amount
swab top of vial or ampule neck with 70% IPA
inject volume of air equal to volume of fluid to be removed UNLESS a HD (negative pressure: put air into syringe and then inject into vial and invert; pull on trigger and drug will go into syringe
puncture bevel up
bring needle straight up to 90 degrees to inject
invert vial with syringe attached after injecting air
measure at point between rubber piston and side of syringe barrel
coring: stopper rubber gets into needle and into solution; look for small cored pieces during visual inspection
if ampule - open by snapping neck away; use filter straw/needle to remove glass then change needle before injecting into IV bag
visual inspection
verify correct volume of product before compounding continues to actually see volume in syringe
“syringe pull-back” = pharmacist verifies empty syringe after compounding done - not recommended
finished CSP. visually inspected for particulates, cored pieces, precipitates, cloudiness; lightly squeeze to check for leaks
terminal sterilization
required for high-risk CSPs
steam sterilization with autoclave
do not use heat on heat-sensitive drugs
bubble-point test and filter integrity
heat-labile drugs (hormones, insulin, other proteins) can be sterilized with filtration with 0.22-micron filter
if filtering - use bubble-point test; tests pressure needed for liquid to bubble out of filter; tests filter integrity
label requirements
names and concentrations of ingredients
BUD
route of admin
storage requirements
HD: label “chemotherapy - dispose of properly” - or similar
auxiliary labels
high-alert meds
pyrogen (bacterial endotoxin) testing
endotoxins ar emade by Gram + and Gram - bacteria/fungi
from Gram - = more potent
pyrogens: can be from using equipment washed with tap water (rinse with steile water and depyrogenated using dry-heat (steam) sterilization with autoclave
sterile preparation and risk
risk of contamination categories by USP (low, medium, and high)
other special categories: low with less than 12 hour BUD and immediate-use - determine appropriate BUD
low-risk sterile compounding
uses 1-3 components supplied as sterile from manufacturer
medium-risk sterile compounding
contamination inc each time bag is entered
if more than 3 components needed = medium risk
eg: parenteral nutrition (many additives); batch of drugs
high-risk sterile compounding
uses non-sterile ingredients and equipment - will need to sterilize end product
includes sterile components outside of ISO 5 air for >1 hr
certain high-risk CSPs and CSPs intended for use beyond recommended BUD need sterility testing (tryptic soy broth or fluid thioglycollate medium; include bacterial endotoxin testing prior to use)
determining BUD based on CSP risk level
determined by USP 797 standards and stability/expiration date of individual ingredients whichever shorter
high CSP risk = shorter BUD
cold temp = longer BUD
sterility testing can see if longer BUD possible
low-risk CSPs with 12-hr or less BUD
ISO 5 PEC or C-PEC in SCA/C-SCA (reconstitute antibiotic single dose vial and transferring to small IV bag in satellite pharmacy not clean room
clean, uncluttered, functionally separate area compounding
for immediate use only
must administer within 1 hr
low CSP risk BUD
room temp: 48 hours
regrigerated BUD: 14 days
frozen BUD: 45 days
medium CSP risk BUD
room temp: 30 hours
refrigerated: 9 days
frozen: 45 days
high risk CSP BUD
room temp: 24 hours
refrigerated: 3 days
frozen: 45 days
low-risk CSP in ISO 5 PEC or C-PEC in SCA or C-SCA (not cleanroom) BUD
room temp: 1 hour
refrigerated/frozen: NA
recalls
high-risk CSPs dispensed before sterility test results require written procedure with daily observation of specimens and immediate recall of dispensed if evidence of microbial growth
osmolarity and tonicity
both express solute concentration in solution
osmolarity includes all solutes
tonicity includes only solutes that do not cross vasculature
osmolarity in IV formulations
hypertonic = >0.9% saline
hypertonic saline (3 or 23.4%) for various acute things like hyponatremia
hypertonic = water out of RBC to dilute; RBCs shriveled and syfunctional
hypertonic saline often restricted to pharmacy and only dispensed for areas where safety can be monitored
solutions with high osmolarity need central line to avoid phlebitis
hypotonic: RBCs absorb fluid nad hemolysis occurs; can be fatal
