Rectal Route Flashcards
What action can rectal route be used for?
Local + systemic
What can rectal route be used locally for?
Pain + itch
What can be given to locally treat rectum?
Antiseptics, local anaesthetics + anti-inflammatory
Can all drugs given for oral administration be given via the rectal route?
YES
What can given to treat systemically?
Rectum
Anti-inflammatories, analgesics + anti-asthmatics
How is the drug rectally absorbed?
Passive diffusion
What is the rate + extent of rectal absorption compared to oral + why?
Lower = small SA
Describe what happens after absorption in rectum
Drug enters haemorrhoidal vein, after absorption
Blood in lower + middle haemorrhoidal veins drain systemic circulatory directly
Blood from upper vein enters portal vein, which flows into liver = 1st-pass metabolism
What physiological factors affect rectal absorption?
Quantity of rectal fluid
Properties of rectal fluid
Contents of rectum
Motility of rectal wall
Why does quality of rectal fluid affect absorption?
Limited fluid in a thin layer
= dissolution poorly for H2O-soluble drugs = rate limiting step in absorption process
Why does properties of rectal fluid affect absorption?
Neutral pH, minimal buffering capacity = inability to control degree of drug ionisation
= salt form used to control ionisation to provide local/systemic absorption
What does it mean if there is no esterase or peptidases in rectal fluid?
Greater stability of peptide-like drugs
Why does content of the rectum affect absorption?
Presence of faeces affects dissolution = effects absorption
What are the rectal advantages?
Possible to remove dose
Suitable for drugs liable to degrade in GI tract
Suitable for elderly, terminally ill, paediatric or unable to swallow
Immediate-release or modified-release
What does the rectal route also surpass?
1st-pass metabolism
What are the rectal disadvantages?
Compliance poor Upward movement of dosage Specialist required Drug absorption slower than oral Local side effects Manufacture of suppositories more difficult
Why is upward movement of dose a rectal disadvantage?
Increases 1st-pass metabolism
What are the rectal dosage forms?
Suppositories = most common Foams Solutions Suspension Emulsions Rectal capsules Tampons
Describe suppositories
Single dose preparations
Formulated in different size + shapes
Tapered at one end
Excipients may be added
Why are suppositories tapered at one end?
Aid insertion
= wider in middle (aid retention)
What is the drug content of suppositories?
0.1% w/w to 40% w/w
Describe the drug-release mechanism
Melting or spreading
Sedimentation
Wetting
Dissolution
What should the suppository base be?
Solid at RT BUT soften at 37 degrees Non-irritant to rectal mucosa Physically + chemically stable over shelf-life Compatible with drug High viscosity
Why must the suppository base have a high viscosity?
To minimise leakage
What are the 2 types of suppository base?
Glyceride - fatty bases
H2O-soluble bases
What is an example of a glyceride suppository base?
Witepsol
What is an example of a H2O-soluble suppository base?
Glycerol-gelatin
Describe fatty suppository bases
Semi or fully synthetic fatty acids
Mixed triglycerides with C12-C18 saturated fatty acid
What is the typical melting range for fatty suppository base?
33-37 degrees
Describe glycerol-gelatin hydrophilic suppository base
Mix of gelatin, glycerol + H2O
Higher gelatin proportion
Hygroscopic
Why is there a higher gelatin content in glycerol-gelatin hydrophilic suppository base?
More rigid + longer-acting
Describe polyethylene glycol suppository base
Mix of different molecular weight of polyethylene glycols
PEG above 4000
What are lower molecular weights of polyethylene glycol?
Liquids
Why do polyethylene glycol suppository bases have a PEG of above 4000?
Waxy solids
What are the issues with hydrophilic suppository bases?
Small amount of liquid already in rectum = base could withdraw H2O from rectal epithelium
= dehydration + pain
Many drugs incompatible
Drug release slow
What excipients may be used?
Surface-active agents
Hygroscopicity reducing agents
Melting point controlling agents
Other excipients
Why are surface-active agents used?
To enhance wetting properties of base with rectal fluid = enhance drug release
What is an example of surface-active agent?
Sorbitan esters
What are surface-active agents added to?
Fatty base or lipophilic drug
Why are hygroscopicity reducing agents used?
Added in fatty bases to reduce uptake of H2O from atmosphere storage
What is an example of a hygroscopicity reducing agents?
Colloidal silicon dioxide
Why are melting point controlling agents used?
To increase or decrease melting point of fatty base
What are examples of melting point controlling agents?
Beeswax = increase melting point
Glyceryl monostearate = decrease melting point
What other excipients are used?
Diluents Adsorbents Lubricants Preservatives Colouring
What drugs are normally unsuitable for rectal route + why?
Hydrophilic compounds = limited H2O in rectum
What does drug solubility in rectal fluid determine?
Rate + extent of absorption
What happens when a drug has a high base-to-H2O partition coefficient?
Likely to be in solution
= lower tendency to leave dosage form
What would be the 1st choice of drug for rectal route?
H2O-soluble drug dispersed in fatty base
