Lecture 7 - Suppositories Flashcards
in suppositories, the drug is incorporated into a base which ___ or ____ at body temp to release the drug
melts or dissolves
TRUE OR FALSE
suppositories are really only used for their systemic effects
FALSE - local or systemic
local irritation, hemorrhoids
systemic hormone delivery or pain relief
vaginal suppositories are also called….
pessaries
an adult rectal suppository weighs around…..
2 grams
what is usually the shape of rectal suppositories vs vaginal
rectal are long and cylindrical with 1 tapered end
vaginal is usually globular oviform or cone shaped
around how much do vaginal suppositories typically weigh
more or less than rectal?
more than rectal - around 5g
uses of vaginal suppositories
hormone delivery
birth control
combat infection
restore vagina lmucosa to normal state
major advantages of suppositories***
NO pH degradation or enzymatic degradation of the drug (like in the gut)
very limited 1st pass effect
drugs that irritate the stomach can be delivered this wat to bypass the stomach
what is the approximate rectal pH and what is the advantage of this***
around 6.8
drugs that are degraded by low pH in the stomach thus won’t be affected by rectal administration
true or false
if a drug is susceptible to degradation in acidic environment, rectal suppositories are not a good chouce
false - they are
rectal pH is close to neutral at 6.8
major issues of suppositories*****
UNPREDICTABLE ABSORPTION - results can vary from patient to patient
can be slow and incomplete absoroption
mucosal irritation
give 3 reasons why absorption from suppositories is unpredictable***
contents of the colon
placement of suppository
GI probelms
which has larger surface area for absorption and what does this mean - GI or rectum***
GI
therefore, absorption may be incomplete and slow when things given rectally
true or false
suppositories do not require special storage requirements
FALSE - they do – this is disadvantage
the rectum is the terminal portion of the_____
large intestine
***volume of the rectal fluid
1-3mL
TRUE OR FALSE
the rectum has high buffer capacity
what is significance
false - low buffer capacity
therefore, the drug inserted must be extremely close to neutral
if basic, can turn fluid alkaline by adding a base which can cause irritation
what position are rectal suppositories supposed to be inserted and why – explainnnn**
in the LOWER AND MIDDLE VEINS
this is bc it drains directly into the inferior vena cava and bypasses the liver and first pass effects to go DIRECTLY into circulation
upper rectal vein drains directly into hepatic portal vein – goes right to liver and subject to hepatic metabolism
blood supply of rectum**
upper, middle, and lower hemorrhoidal veins
what is the MAIN ingredient in a suppository
what is the purpose of it
the base
helps to formulate drug in suppository and allows for drug release and bioavailability
explain how a suppository base should behave at room temp vs at body temp
should remain solid at room temp and melt or dissolve at body temp
name 2 different classifications of suppository bases and give examples
oleaginous/fatty base - COCOA BUTTER
hydrophilic bases – glycerinated gelatin and PEG
we want drugs with ______ partition coefficients to be absorbed through the rectum
HIGH
the rectal membrane is lipophilic - want lipophilic drug
what can you say about the desired particle size of a drug in a suppository
want pretty small to be able to permeate the membrane and leave the base
smaller particles = higher surface area — BETTER DISSOLUTION AND RAPID ABSORPTION
*** a fatty base will release a lipophilic drug quickly or slowly????
SLOWLY – also slower absorption
true or false
a lipophilic drug will have quick drug release from a PEG or glycerinated gelatin suppository base***
TRUE - hydrophilic base and lipophilic drug will allow for quick release
As mentioned, small particle size is desired for drugs incorporated into suppository bases
what is the most common way this is done
trituration
approximate body temp in celsius
approximate room temp in celsius
body - 37
room temp - 22-25
true or false
the suppository base should not interact with the drug
true
aside from causing pain, why must the suppository base not irritate the mucous membrane
may initiate a bowel movement and eliminate chance of drug release and absorption
suppository bases should be _____ viscosity when melted
high
true or false
suppository bases should be physically stable
true
water dispersable suppository base example
cocoa-butter substitutes with surfactans
aside from cocoa butter name other fatty/oleaginous bases
hydrogenated fatty acids of vegetable oils (palm kernal oil, cottonseed oil)
true or false
water soluble/water miscible bases dissolve in the rectum
true
when preparing suppository with cocoa butter, it is VERY IMPORTANT NOT TO EXCEED……
60 degrees celsius
excess heating can form an unstable and low melting point crystalline form — may melt even at low temp
name 2 substances that lower the melting point of cocoa butter and thus should not be used
phenol
chloralhydrate
if worried about cocoa butter melting at room temp, what can we do?
add solidifying agents – cetyl ester wax and beeswax
of the 2 main types of suppository bases, which is mainly used rectally and which is mainly used vaginally
gelatinated glycerin and PEG are typically VAGINAL
cocoa butter typically RECTAL
name 3 COMMERCIAL NAMES of other fatty bases (not cocoa butter)***
all are___
fattibase
wecobee base
witepsol base
triglycerides
glycerinated gelatin is ______ in nature
what does this mean?
hygroscopic
will absorb water from the body fluids to DISSOLVE
if you put in rectum pt will lose fluid and have stinging and laxative effect (may be desired)
*******ratio of glycerinated gelatin
70 glycerin: 20 gelatin: 10 water
true or false
glycerinated gelatin is most frequently used for VAGINAL
true
time range that glycerinated gelatin dissolves vs time that cocoa butter melts
gly. gelatin dissolves SLOWLY - 30-40 mins
cocoa butter melts much faster - 10-15 mins
storage of glycerinated gelatin and why
TIGHT CONTAINERS - it’s hygroscopic!!
explain what should be done before applying suppositories with glyc. gelatin as the base and why
moisten before applying —- reduce initial tendency of the base to draw water from the mucous membrane and cause tissue irritation
glycerinated gelatin bases intended for extended shelf life should have what and why?
PRESERVATIVES like methyl/propyl paraben – bc of water content
PEG ________ and HIGHER are wax like white solids
1000
less than 1000 are liquid at room temp
mix both to get good consistency - achieved by FUSION
with increasing molecular weight of polyethylene glycol bases………
_____increases
____ decreases
hardness increases and water solubility decreases
true or false
for PEG bases, there is no risk of melting so no refrigeration is required
true
true or false
PEG bases take 10-15 mins to dissolve
false 30-40 mins (like glyc. gelatin)
what does PEG interact with and what does this mean
polystyrene (prescription vials)
therefore, can only be dispensed in them if first wrapped in foil
what drug forms a complexation with PEG and what does this mean
Aspirin
THEREFORE, if we use PEG + Aspirin, there will not be quick release
use diff base if we want quick
high concentrations of ________ will soften PEG
salicylic acid
what 3 things will cause crystallization of PEG base
salicylic acid
camphor
sodium barbital
3 methods of suppository preparation
molding (most common) - melt and pour and allow to cool and congeal
compression
hand molding and shaping
when using the molding method for preparing suppositories, the mold should be filled at what temp?
room temp
if cold, could make fractures and fissures in suppositories
______ may be required for some molds and bases
give 2 examples
LUBRICATION
mineral oil and gelatin
not too much - will pool at supp tip
micture should be poured into the mold right before reaching…..
congealing temperature
how much mixture should be poured into the mold
add excessive amounts bc it will shrink when it cools
when a drug is placed into a suppository base, it will…..
displace an amount of base (as a function of its density)
use density factor to determine how much base will be displaced by the drug!!!
weight drug/weight base displaced = density factor
suppositories must be made to _____ before use
come to room temp
counseling for PEG/cocoa butter/vaginal suppositories
PEG - moisten with water before use
cocoa butter - rub with fingers so upper surface melts
vaginal - moisten with water for good lubrication and disintegration
how is strength of API in suppository expressed
amt/suppository
which suppository base interacts with polystyrene
PEG
true or false**
PEG bases may cause stinging and burning when used rectally
true
