Unit 2 - Rectal delivery Flashcards
What mass is a suppository?
Between 1 g (children) and 4 g (adults)
- depends on the density of the suppository base
What property must a suppository have?
Base must melt, soften or dissolve in the mucus secretions of the rectal cavity
What is the drug content of a suppository?
< 0.1% - 4%
- generally 1.5 - 2 times oral dose, but can be equivalent
What are suppositories used to treat?
Local conditions
- haemorrhoids
- fissures
- fistulas
- proctitis
Give three examples of soothing agents used in suppositories
Mild astringents
Vasoconstrictors
Local anaesthetics
Give examples of mild astringents used in suppositories
- bismuth subgallate
- zinc oxide
- hamamelis
Give examples of vasoconstrictors used in suppositories
- adrenaline
- ephedrine
- phenylephrine
Give examples of local anaesthetics used in suppositories
- lignocaine
- benzocaine
- amethocaine
Give examples of corticosteroids that can be used in suppositories
- hydrocortisone
- prednisolone
- betamethasone
Give examples of evacuants that can be used in suppositories
- bisacodyl
- glycerin
Give an example of an antimicrobial that can be used in suppositories
- sulphasalazine
What is an anal polyp caused by?
Protrusion of tissue
What is an internal haemorrhoid caused by?
Dilated superior haemorrhoidal vein
What is an external haemorrhoid caused by?
Dilated inferior haemorrhoidal vein
What is an anal fissure caused by?
Tear in mucus membrane
- caused by a change in bowel habits
What is an anal fistula caused by?
Abnormal passageway
- caused by infection
What are the advantages of rectal delivery?
Can be used to treat systemic conditions where:
- the patient is debilitated/unconscious/unable to swallow
- nausea and vomiting present or likely
- GI disturbance present or likely
- avoidance of biotransformation in GI tract (pH, enzymes)
- unacceptable taste
- partial avoidance of hepatic metabolism
- avoidance of parenteral route in children (e.g. pre-operative)
- drugs of abuse
Give some examples of drugs that can be given rectally
- prochlorperazine
- morphine
- ergotamine
- diclofenac
- indomethacin
- aspirin
- paracetamol
What are the disadvantages of rectal delivery
UK and USA are averse to using suppositories
- accepted in Eastern Europe and parts of Western Europe
Administration issues
Slow and incomplete absorption
Inter- and intra-subject variation
Formulation
How should a rectal suppository be administered?
- If necessary, go to the loo to empty your bowels
- Wash your hands
- Remove any foil or plastic wrapping from the suppository
- Either squat, or lie on your side with one leg straight and the other bent
- Gently but firmly, push the suppository (tapered end first) into the rectum
- push far enough that it does not slip out - Close your left and sit still for a few minutes
- Avoid emptying the bowels for at least one hour
- unless the suppository is a laxative! - Wash your hands again
Why is it sometimes useful to insert a suppository at night rather than during the day?
Once in the rectum the suppository will melt and may leak from the rectum
If you do insert suppositories during the day, be aware that some suppositories can stain your clothes
Where should suppositories be stored?
In a cool dark place
- not in the fridge unless specifically instructed
If they get too warm, they may melt and not be firm enough to insert
What is rectal drug delivery governed by?
Physiological and physiochemical factors
How long is the rectum?
The rectum forms the last 15 to 20 cm of the GI tract
How much mucus does the rectum contain when empty?
2 to 3 ml (per 300 cm2)
How thick is the mucus layer in the rectum?
Approximately 100um thick
Why are water soluble suppositories painful for the patient?
Osmotically attract water to the rectum, increasing the mucus volume
Describe the structure of the rectum
Non-motile
No villi
Abundant vasculature
Why may an evacuant enema be used before administering a suppository?
Greater absorption of drug if the colon or rectum is devoid of faecal matter
What conditions may affect the absorption of a suppository?
- diarrhoea
- colonic obstruction (e.g. tumour)
- tissue dehydration
What percentage of drugs in suppositories avoid hepatic first-pass metabolism?
50 - 70%
Where are drugs in suppositories absorbed into?
Rectal / haemorrhoidal veins
What is the pH of rectal fluids?
pH 7-8
What is the consequence of the rectum not having an effective buffering capacity?
Drugs will not change chemically and will determine the pH of the environment
Which type of drugs are absorbed better in the rectum?
Weaker acids and bases are absorbed better than stronger, highly ionised ones
What physio-chemical factors affect absorption?
- drug solubility
- drug particle size
- base properties
How does the solubility of a drug in a suppository affect its absorption?
- lipid/water coefficient
- lipophilic drugs (especially at low concentration) will be less readily released from a lipophilic base
- hydrophilic drugs should release readily (especially at high concentration
- therefore more water soluble salts (e.g. quinine HCl) preferred in certain formulations
- water soluble bases dissolve in anorectal fluids
- rate of drug absorption cannot be increased above a certain drug concentration
How does the particle size of a drug in a suppository affect the rate of absorption?
Decreased size = increased dissolution = increased rate of absorption
What properties must the suppository base have?
- must be capable of melting, softening or dissolving
- must not be irritating (could initiate a bowel movement)
- compatibility with drug must be ascertained
What are the two stages of absorption of drug from a suppository?
- release of drug from vehicle
- transfer across mucosa
What is the rate limiting step of absorption of a drug from a suppository?
Partitioning of the drug from the melted base
How is the drug in a suppository released from the vehicle?
By melting at body temperature (lipophilic vehicles) or dissolving/dispersing in mucus (hydrophilic vehicles)
What factors affect the release of a drug from a suppository?
- affinity of drug for vehicle
- solubility of drug in rectal fluids
- particle size
- spreading of vehicle
- interactions between drug and vehicle
What factors determine the transfer of a drug in a suppository across the mucosa?
Partitioning and diffusion
How does a drug in a suppository pass into the mucosa of the rectum?
Drug needs to dissolute (slow for poorly soluble drugs) diffuse through mucus layer and then into and through the epithelium of the rectal wall (passive)
What factors affect the transfer of a drug in a suppository into the mucosa?
- lipophilicity (pH dependent for weak acids / bases) - buffer solutions can increase absorption
- site of absorption
Give three examples of absorption enhancers that are included in suppositories
Surfactants
Salicylate derivatives
EDTA
Give examples of surfactants included in suppositories
- cetomacrogols
- tweens and spans
- SDS
How do surfactants work in suppositories?
Lower the surface tension of the vehicle and mucus barrier
- increase membrane permeability by interacting with phospholipids
- phenolics can have decreased absorption
