rectal administration of drugs Flashcards
where does blood flow in the superior rectal vein
to the liver
where does blood flow to in the middle rectal vein and the inferior rectal vein
to the heart
why should you aim to keep dosage in the lower part of the rectum
because it avoids 1st pass metabolism
what is the structure of the rectum
its a hollow organ with a one cell layer thick epithelium
what does the rectum membrane contain
epithelial, cylindrical and goblet cells (secrete mucous)
is there villi in the rectum
no which means decreased surface area
what is the pH of the rectum
7-8
do the same principles of drug absorption apply to the rectum like they do the GI tract
yes BUT no active transport in the rectum, only diffusion
advantages of rectal drug administration
- absorption not affected by food or gastric emptying
- avoids pH changes in GI tract
- avoids action of gastric juices on drug
- avoids (partially) 1st pass metabolism
- no problems with flavouring
- can be used while vomiting
- can be used in unconsciousness
- can be used for specific patient population eg infants
- quick systemic response
- useful with upper GI disease
disadvantages of rectal drug administration
- patient acceptability (cultural influence)
- irritation of mucus membrane
- small surface area
- less fluid content than small intestine leading got dissolution problems and pain
- drug degradation by rectal bacterial flora
- bowel movements can interupt absorption
what are the rectal formulations
- enema
- foams
- gels
- creams
- ointments
- suppositories
where in the colon do enemas spread to
in a 30ml dose
- 99% in sigmoid colon
in a 100ml dose
66% sigmoid colon
25% descending colon
what is the vehicle on a suppository
the base
what are the characteristics of a suppository vehicle
- fatty
- water soluble, water-miscible vehicle
what are the requirements of a vehicle
- melts, disperses or dissolves at 36 degrees
- rapid solidification and narrow melting range
- easily released from suppository mould
- convenient to handle
- non irritating, non toxic
- physically and chemically stable
- compatible with drug
- have viscosity to prevent over sedimentation of drug but allows flow into mould and also over membranes during application
what is the characteristics of the fatty base of a suppository
- made of theobroma oil (cocoa butter)
- melting point 34.5 degrees
- non-irritant
what are the challenges with the traditional fatty base
polymorphism, theobroma oil exists in different crystal forms
- a-crystal, melts 23 degrees
- y-crystal, melts 19 degrees
- B-crystal, melts 34.5 degrees
what influences the form of the theobroma oil that is used
- degree of heating (up to 36 degrees)
- cooling process (slow)
characteristics of the fatty bases used nowadays in suppository’s
- natural, semi and fully synthetic fat mixtures
- melting point can be titrated
type A way to make gelatin
acid hydrolysis to gelatin cationic
type B way to make gelatin
alkaline hydrolysis to make gelatin anionic
how is gelatin made
purified from skin/bones from hydrolysis
two ways - type A and B
what is the melting point of PEG (polyethylene glycol)
various melting points, approx 50 degrees
why should you dip suppositories with PEG base before insertion
only 3ml of liquid/mucus present in rectum and more water sometimes needed
if not dipped can be osmotic pain
how does PEG bases work
the base disperses in rectal fluid/mucus to release the drug
which base would you choose for
LOW fat and HIGH water solubility
fatty base
which base would you choose for:
HIGH fat and LOW water solubility
aqueous base
which base would you choose for
LOW fat and LOW water solubility
indeterminate
how are suppository moulds calibrated
- they’re filled volumetrically as volume-weight relationship is base dependent
- generate a number of perfectly formed suppositories containing only base
- determine average weight per suppository
does the drug have the same density to the base material
no
what is the displacement of value of a drug
the number of parts by weight of drug which displaces 1 part by weight of the base
what is the displacement value of the base dependent on
the drug
equation for density
density=mass/volume
does the density of the drug need to be the same as the base
yes, as the mould is calibrated by volume
