MDM: Rectal and Vaginal route Flashcards
When is the rectal route use/ why is it useful?
- Patient unable to swallow tablet
- oral route compromised
- Targeted delivery reduces side effects
- Drug not stable for oral administration: unstable at low pH, large first pass metabolism, unacceptable taste, gastric irritant, high doses required
Describe rectal delivery
- Avoids first pass metabolism
- 3 veins: lower and middle veins drain into the systemic circulation directly
- Smooth walls, no villi
- Region extensively drained by the lympathic system
How is a rectal drug normally absorbed?
by passive diffusion across the mucus membrane unless a penentration enhancer has been used
What are physiological factors effecting absorption via the rectal route?
- Rectal motility
- patient to patient varriation in absorption
- contents of the rectum
- little buffer capacity (pH7.5)
- Mucus - 3ml spreads over 300cm3
What are rectal drug formulations?
- suppositries
- ointments and creams
- tablets and soft gelatine capsules
- enemas (when liquid/ gas injected into the rectum ti expell its contents)
Does the rectal route have a systemic or local effect?
Both
local - haemorrhoids, laxatives
systemic - pain, asthma, epilepsy
What are disadvantages of the rectal route?
- inconvient
- drug may irritate the rectum
- high inter-patient variabilty
- drug absorption can be slow, incomplete, unpredictable
- patient compliance/ acceptability
- large scale production issues
What countries is patient compliance good and bad? where would suppositries be useful? why?
- European countries good compliance. UK and US poor compliance
- Developing countries - reduced side effects and little training required compared to IV/IM
- effective, simple, safe to use
Describe requirements for a supositry during manufacture
- Drug is uniformly distributed in vehicle/ base
- bases can be water sol or fatty sol
- drugs should be insoluble in base used
- release of dug on melting or dissolution of the suppository depending on base used
- melting point of suppository should be around 37 degrees
When choosing a base what requirements are there?
- Bland and inert
- compatable with other materials
- melt, dissolve or disperse below body temperature
- stable
- good moulding properties
- readily release AI
- Easily melted with rapid solidification
What types of bases is there?
- Fatty bases - theobroma oil/ witepsol
- water soluble bases - PEG
- Glycerol - gelatin
- macrogols
- What should the physiochemical properties of the suppository be?
- What addatives should be added?
- What should the dose be?
- Balance between lipid and water soluble. Particle size 50-100um to optomise dissolution and limit aggregation
- preseratives, adsorbents, lubricants, surfactants to increase wetting (PALS)
- low to prevent aggregation
What absorption enhancers are used and how do these effect absorption of drugs?
what is the limitations?
- Sodium salicylate can improve rectal absorption of theophylline. Sodium salicylate interacts with Ca2+ and Mg2+ ions located in the rectal membrane. Ca2+ ions are needed to preserve tight cell junctions. Interaction with Ca2+ causes a tempory change in membrane integtity increasing permability
- Polysorbate 80 and sodium lauryl sulphate
Long term use can lead to irritation and damage to the rectum
How do you do supository calculations?
- Calculate nould calibration (given in exam)
- Find displacement value of drug (given in exan)
- Calculate exact quantities of drug and base required
What is the displacement value?
The volume or weight of a fluid displaced by a floating body of equal weight
The displacement value of a drug is the number of parts by weight of drug which displaces 1 part by weight of the base, e.g. 1.4g Chloral hydrate displaces 1g of base
