Studied by 8 people
Why chose the rectal route?
GI problems
unconsious
very old/young
drug can’t be taken orally (ph, first pass, unaccaptable organoleptic properties)
What are the disadvantages of rectal administration?
people don’t like stuff in their butts
inter/intra subject varition
proctitis (inflammation of rectum- bleeding, pus, mucous)
short shelf life
large scale manufactuse cuks
Is rectal administrtion systemic/ local?
both
What’s the anus
Circular muscle
Describe the rectal wall?
one layer thick
cyckindrical cells
goblet cells
no villi
How much mucus in the rectum
3ml
Whats the surface area of the rectum
300cm
Does the rectum buffer?
Not really
ph 7.5
What are the 3 vessels @ rectum
inferior haemorrhoidal vein
middle haemorrhoidal vein
superior haemorrhoidal vein
where does superior haemorrhoidal vein drain to?
Liver
where do inferior and middle haemorrhoidal veins drain to?
Systemic circulation
Does first pass metabolism happen at the rectal route?
Soemtimes
depends where the drug is absorbed
if high up→ superior haemorrhoidal vein→ liver
Where should the drug be absorbed to avoid FPM?
Lower rectum
Is the 3ml of mucous bad or good for drug absorption?
Bad!
dissolution= rate limiting step
viscosity= barrier
What are the advantageous bits of the rectal physiology?
Motiloty (muscular contractions= spreading of drug=absorbtion)
goood blood supply
no enzymes= no peptidases/esterarses (peptide like drugs??)
What can happen to the suppository base after insertion?
dissolve in rectal fluids
3ml small volume
complete dissolution unlikely
extra water required
painful
melt on the mucus layer at 37C
What will the drug have to do first if its in a vehicle before getting absorbed?
Leave the water immmiscible vehicle (gravity or motility will do that)
What layers does the drug have to pass before getting absorbed?
Mucus layer
Epithelial
What kind of transport will get the drug through the epithelia?
Passive diffusion
Are there active transporters in the rectum?
No
What are the two main classes of suppository bases
Fatty bases (glyceride)
Water soluble bases
What are themelting properties of an ideal base?
Lower range offers better particle seperation which leads to better absorption
Higher range is better for the manufacturing process (won’t melt due to machines)
What are the viscosity properties of an ideal base?
Good flow, diffusion , spreading
Will allow seperation of particles
What are the properties of a base that facilitate easy removal from the mold?
will contract upon solidification
Give examples of water soluble bases for suppositories
polyethylene glycols (macrogols)
glyco-gelatin
Give an example of a fatty base?
Theobroma oil
Semisynth bases
What chemicals is theobroma oil?
it’s cocoa butter
a mixture of triglycerides
2-oleopalmitostearin and 2-oleodistearin
What’s good about cocoa butter?
Will melt
Non-irritating
Solidifies quick
Why isnt theobroma oil used anymore?
polymorphism
insuffient contraction
low softening point
chemical instability
poor water absorbtion
oxidation
leaks from the body
expensive
What are the semi-synth fatty bases now used?
SATURATED FATTY ACIDS
What fatty acids are used now?
C12-C18 fatty acids
mixed triglycerides
Why are the semisynthetic bases now used less prone to oxidation than theobroma oil?
Theobroma oil = unsaturated
Semisynth= saturated (dont get oxidised as easily)
What are the melting point ranges for semi-synth bases?
33-37.5C
Why are semi-synth bases better at absorbing water?
high hydroxyl number
Give examples of semi-synth bases?
Massuppol
Suppocire
What are the disadvantages of semi-synth bases?
brittle if cool quick
less viscous than theobroma oil= sedimentation
If water soluble bases have a melting point higher than body temp, how are the drug particles released?
Suppository breaks up by the rectal fluid
Why are water soluble bases used more rarely ?
the volume of rectal fluid is small , dissolution difficult
What’s the problem that arises with the water soluble bases being hydroscopic?
They draw out water which is painful
What’s in glycerol suppositories BP?
14% gelatin
70% glycerol
List the types of gelatin used in glycerol suppositories
type a
type b
Are type a acidic or basic?
Acidic
Are type b anionic?
yes
(they’re basic, OH- is an anion and a base)
What are the problems with a glycogelatin base?
microbial growth
laxative
irritant
unpredictable dissolution time
hydroscopic
lubricating of moulds is vital
long prep time
What are macrogol bases?
Mixtures of polyethylene glycols of varying m.w.
What is the melting point of macrogols?
50C typically
different m.w. have diff melting points= use a blend to get what you want
What’s the advantage of macrogols over glycogelatin base?
No laxative effect
Why is the contraction of macrgols upon cooling beneficial?
You don’t need to add a lubricant to the base like with glucogelatin bases
Are macogols more or less viscous than theobroma oil?
More viscous= less leakage
What dictates maximum attainable concentration?
Drug solubility in rectal fluids
What will happen if the vehicle to water partition co-eff is high?
Means drug has a high affinity for vehicle
= drug has a low tendency to leave vehicle
What form of base is suitable is the drug is highly soluble in fats?
an aqueous base
What do surface properties determine?
How drug transfers from one phase (base) to another (rectal fluids)
Why is a small particle size important?
less irritation’
less sedimentation
faster dissolution
What is the general thumb of rule for particle size ?
Less than 150 micrometers will prevenent sedimentation
Less than 50 micrometers will prevent irritation
What can happen to really small particles?
Agglomeration (mass or collection)
Describe the suppository quality control test for uniformity of weight
20 samples
2 max can deviate by 5%
none can deviate by over 10%
Describe the suppository quality control test for uniformity of content?
suitable analytical method
10 suppositories
one max can be in 85-115% range
none can be in 75-125% range
When can the uniformity of content test be redone?
If there’s no more than 3 in the 115-85% range
none can be outside 85% -125% range
How to retake the uniformity of content test?
Analise additional 20 samples
What are the methods to measure the melting range of suppositories?
Open capillary tube
u tube
drop point
What should be the melting point for fatty acids?
less than 37C
Describe the suppository quality control test for disintegration
placed in a liquids medium
checked if they disintegrate in an okay time
What is considered as a pass of the disintegration test?
completely dissolve
separated into its components
become soft/disfigured
What are the times for disintegration?
less than 30mins for fatty bases
less than 60mins for aqueous bases
What are rectal capsules?
shell suppositories
lubricating coating
single dose
solid
elongated
smooth
What can be the solvents for rectal solutions?
glycerol/macrogol/ water
What excipients are particularly important in powders and tablets that are used to prepare rectal solutions?
Excipients to prevent aggregation of particles
faciltates dispersion
What monograph do rectal semi-solids go under?
Semi-solids for cutanous use
What monograpgh to rectal foams go under ?
Medicated foams monograpgh
What are rectal tampons?
solid
single dose
INSERTED ONLY FOR A LIMITED TIME
What monograpgh do rectal tampons go under?
Medicated tampons
What materials are used to make medicated tampons?
Celluouse
Collagen
Sillicone
(impregnated w/ api)
Can intravaginal drug delivery be used for systemic effects?
YES
but primarly for local effect
What is the vagina?
Muscular tube
How much fluid produced by the vagina daily?
6ml
How much vaginal secretions present at any given time?
0.5-0.75ml
What’s the pH of the vagina?
4.5
Are enzymes present in the vagina?
Low enzymatic activity
What’s great about the vagina?
vascularised well
prolonged retention
What are the disadvantages of the vagina?
menstrual cycle causes changes
local side effect
variable permeability
Note
Flashcard