Rectal and Vaginal Delivery Flashcards
what must you do with diazepam suppositories
make sure green shows and dose is locked in place
therapeutic effects of suppositories can be
local and systemic
which population is best for suppositories
children
elderly
uncooperative
what limits suppository use
tradition and culture
local effects of suppositories
pain control
infection
inflammation
constipation
systemic effects of systemic effects
asthma
fever control
RA
drug factors of absorption
solubility - must be solubilized to be absorbed
pKa
partition coefficient - not too high so doesnt stay in base but high enough to cross
formulation factors for absorption
base type and amount
formulation disintegration
drug dissolution
physiological factors of absorption
pH
water amount
where is there direct systemic absorption
lower and middle veins
where is there absorption that passes the liver
upper vein
whats critical to how drug is released and absorbed
application
what is the ph of the rectum and what determine the final ph
7.5 wiht little buffer capacity (will change based on drug)
not able to maintain its ph so drug solution will determine the ph
amount of water in the rectum
3ML
main absorption mechanism in rectal
passive
drug release
melts and spreads
sedimentation
wetting
dissolution
what are the major parameters of suppository
partition coeffecient
pka
particle size
surfactants
partition coefficient limits what
rate limiting from vehicle to body fluid
pka limits what
rate limiting rom body fluid into blood
want non ionized
what particle size is preferred in suppositories
50-100um
what do surfactants in suppositories do
promote wetting, partition and permeation
components of an ideal base
non toxic non irritating no metastable form s wetting and emulsifying properties high water number stability over storage east manufacturing properties
whats a metastable form
heating causes it to change forms and then change the melting point temperature
advantages of cocoa butter
nonreactive
nontoxic
versatile
why isnt cocoa butter used anymore as a vehile
polymorphism
low softening point
cost
what is used as a vehicle now
semisynthetic fatty triglycerides
hydrophilic vehicle properties
higher melting point - not intended to melt release by dissolution
slower drug dissolution
hygroscopic
drug instability
molding mehtods for suppositories
hand molding compression molding pour molding automatic molding in package molding
4 things for quality control
weight
disintigration
melting behavious
softening time
why is water as a solvent avoided
accelerates vehicle oxidation precipitates dissolved substances instability in presence of water growth of bacteria and fungus little impact on drug absorption
physics problems
hygroscopicity of gelatin and PEG
viscosity
volume contraction
whats contraction hole formation
when pour in mold it contracts as it cools so have to overfill the mold to compensate
how should suppositories be stored
some refridgerated
avoid temp fluctuation
avoid from light and oxygen
completely closed
good and bad of enema
easy drug absorption
application in convenience
how do effervecent tables work in the rectum
dissolve and realease co2 to stimulate defecation
limited use becuase not enough water
intravaginal products used for
STI
contraception
cancer
hormone replacement
vaginal mucosa
epithelium
laminar propria
blood vessels
muscularis
arteries the the vagina
iliac artery
vaginal venous plexus
vaginal artery and vein
epithelium thickness changes during menstruation affecting what
drug absorption
amount and ph of vaginal fluid
.5-10ml
3.5-4.9
cervial mucus can act as a what
barrier
what can the drug be degraded by
cervicovaginal fluid
contians enzymes and nucleases
what are synthetic epithelial tissues used for
in vitro irritation models
siRNA mechanism
rna corresponds with specific target and drug properties are incorporated into it
crosses the cell membrane and use RNAi mechanism for gene slicing that exhibits therapeutic effect
factors affecting siRNA delivery
pH nucleases infections lower pH menstruation alters microflora and endothelial thickness mucosal entrapment vaginal fluid volume
advantage of vag gel
doesnt require HCP
discrete
portable
disadvantage of vag gel
messy have to apply before intercourse requires time to disperse dose may not be accurate short lasting
advantage of vag film and tablet/supp
doesnt require HCP
portable
discreet
not messy
disavantage of vag film and tablet/supp
require insertion before intercourse
time to melt
short acting
possibly limited use in hihg temperature climates
advantage of vag ring
doesnt require insertion by HCP doesnt have to be inserted before intercourse discreet not messy long lasting
disadvantage of vag ring
siRNA cant withstand high processing temps
advantage of foam
not that messy
doesnt require HCP
disadvantage of foam
time to disperse
has to be inserted before intercouse
short acting
4 things in and ideal vaginal delivery system
non irritating
doesnt get trapped in mucosal layer
resist degradation but nucleases
resist inactivation in low pH
