Rectal and vaginal Flashcards
Why is rectal delivery useful?
Useful when:
The oral route is compromised.
Patient is unable to swallow a tablet, such as an infant.
The drug is not suitable for oral administration.
Unstable at low pH/in gastric enzymes.
Large first pass metabolism.
Unacceptable taste.
Gastric irritation.
High dose required.
Targeted delivery reduces side effects.
Why is rectal delivery good?
The rectal route of drug administration may avoid first-pass metabolism.
3 veins: lower and middle veins drain
into systemic circulation directly.
Smooth walls, no villi.
Region extensively drained by the lymph system.
What are physiological factors affecting absorption?
Absorption occurs through the mucus membrane via passive diffusion, unless a penetration enhancer has been used.
Mucus – 3ml spread over 300cm2.
Little buffer capacity – pH 7.5.
Contents of rectum.
Motility of rectal wall.
Patient-to-patient variation in absorption.
What formulations are for rectal administration?
Suppositories.
Ointments and creams.
Enemas.
Tablets and soft gelatin capsules
Can the rectal route of delivery be used for local and systemic treatment give examples?
The rectal route of delivery can be used for both local and systemic treatment.
Local – Haemorrhoids, laxatives.
Systemic – Pain, asthma, epilepsy
What are disadvantages of rectal delivery?
Drug absorption can be slow, incomplete, unpredictable.
High inter-patient variability.
Inconvenient.
Drug may irritate the rectum.
Large scale production issues.
Acceptability can be an issue.
What problems are there for rectal delivery for around the world?
Suppositories are a popular route for drug administration
in Europe.
In some countries, including the UK and USA, suppositories are less acceptable due to cultural issues.
Suppositories make up less than 1% of the pharmaceutics market in the UK – driven by social attitudes and market response?
Proven to be effective, safe and simple to use, with equivalence to the oral route.
Useful in developing countries, reduction in side effects and little training required compared to IV/IM.
Informing and educating on the benefits.
How are suppositories manufactured?
Drug is uniformly distributed in a vehicle, or ‘base’.
Bases can be fatty or water soluble.
Drug should be insoluble in base used.
Release due to melting or dissolution of suppository depending on base used.
Melting point of suppository should be around 37°C
How do they choose a base for suppositories?
Bland and inert.
Compatible with other ingredients.
Melt, dissolve or disperse at or just below body temperature.
Stable.
Good moulding properties.
Readily release active ingredient.
Easily melted with rapid solidification.
What are the different bases?
Fatty bases – Theobroma oil (cocoa butter), Witepsol.
Water soluble bases – Polyethylene glycol (PEG).
Macrogols
Glycerol-gelatin
How are suppositories manufactured?
Physicochemical properties of drug: balance between water or lipid soluble, particle size (usually 50-100 μm to optimise dissolution and limit aggregation).
Dose: limited to prevent aggregation.
Additives: surfactants to increase wetting, adsorbents, lubricants, preservatives.
What are absorption enhancers used for and give examples?
Potential for peptides & proteins to be administered by rectal route as no peptidases present.
Sodium salicylate can improve the rectal absorption of theophylline - interaction of enhancer with calcium and magnesium ions located in rectal membrane. Calcium ions are needed to preserve tight cell junctions. Interaction of enhancer with calcium may cause temporary change in membrane integrity - increases permeability.
Also polysorbate 80 and sodium lauryl sulphate.
However long term use can lead to irritation and damage to rectum.
How is drug solubility, rate of release, drug particle size and other additives effect formulation of suppositories?
Drug solubility: low water content of rectum.
Rate of release: can be controlled through choice of base.
Drug particle size: agglomeration or precipitation.
Other additives may affect melting point.
How do you calculate suppository calculations?
First step is to calculate the mould calibration value.
Find the displacement value of the drug.
Displacement: the volume or weight of a fluid (as water) displaced by a floating body (as a ship) of equal weight.
Calculate the exact quantities of
drug and base required.
Always calculate for 2 excess per 6 suppositories.
(number of suppositories x mould calibration) x drug strength = total weight of drug.
1/displacement value x total weight of drug = weight of base displaced by drug.
(number of suppositories x mould calibration) – weight of base displaced by drug = actual weight of base required.
What needs tested with suppositories?
Weight, melting point, mechanical strength and dissolution testing.
In vitro release – difficult to correlate
with in vivo situation; dialysis bag or
flow-through method.
