Unit 2 - Rectal delivery

Question 1

What mass is a suppository?

Answer 1

Between 1 g (children) and 4 g (adults)

- depends on the density of the suppository base

Question 2

What property must a suppository have?

Answer 2

Base must melt, soften or dissolve in the mucus secretions of the rectal cavity

Question 3

What is the drug content of a suppository?

Answer 3

< 0.1% - 4%

- generally 1.5 - 2 times oral dose, but can be equivalent

Question 4

What are suppositories used to treat?

Answer 4

Local conditions

• haemorrhoids
• fissures
• fistulas
• proctitis

Question 5

Give three examples of soothing agents used in suppositories

Answer 5

Mild astringents
Vasoconstrictors
Local anaesthetics

Question 6

Give examples of mild astringents used in suppositories

Answer 6

• bismuth subgallate
• zinc oxide
• hamamelis

Question 7

Give examples of vasoconstrictors used in suppositories

Answer 7

• adrenaline
• ephedrine
• phenylephrine

Question 8

Give examples of local anaesthetics used in suppositories

Answer 8

• lignocaine
• benzocaine
• amethocaine

Question 9

Give examples of corticosteroids that can be used in suppositories

Answer 9

• hydrocortisone
• prednisolone
• betamethasone

Question 10

Give examples of evacuants that can be used in suppositories

Answer 10

• bisacodyl

- glycerin

Question 11

Give an example of an antimicrobial that can be used in suppositories

Answer 11

• sulphasalazine

Question 12

What is an anal polyp caused by?

Answer 12

Protrusion of tissue

Question 13

What is an internal haemorrhoid caused by?

Answer 13

Dilated superior haemorrhoidal vein

Question 14

What is an external haemorrhoid caused by?

Answer 14

Dilated inferior haemorrhoidal vein

Question 15

What is an anal fissure caused by?

Answer 15

Tear in mucus membrane

- caused by a change in bowel habits

Question 16

What is an anal fistula caused by?

Answer 16

Abnormal passageway

- caused by infection

Question 17

What are the advantages of rectal delivery?

Answer 17

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

Question 18

Give some examples of drugs that can be given rectally

Answer 18

• prochlorperazine
• morphine
• ergotamine
• diclofenac
• indomethacin
• aspirin
• paracetamol

Question 19

What are the disadvantages of rectal delivery

Answer 19

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

Question 20

How should a rectal suppository be administered?

Answer 20

1. If necessary, go to the loo to empty your bowels
2. Wash your hands
3. Remove any foil or plastic wrapping from the suppository
4. Either squat, or lie on your side with one leg straight and the other bent
5. Gently but firmly, push the suppository (tapered end first) into the rectum
   - push far enough that it does not slip out
6. Close your left and sit still for a few minutes
7. Avoid emptying the bowels for at least one hour
   - unless the suppository is a laxative!
8. Wash your hands again

Question 21

Why is it sometimes useful to insert a suppository at night rather than during the day?

Answer 21

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

Question 22

Where should suppositories be stored?

Answer 22

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

Question 23

What is rectal drug delivery governed by?

Answer 23

Physiological and physiochemical factors

Question 24

How long is the rectum?

Answer 24

The rectum forms the last 15 to 20 cm of the GI tract

Question 25

How much mucus does the rectum contain when empty?

Answer 25

2 to 3 ml (per 300 cm2)

Question 26

How thick is the mucus layer in the rectum?

Answer 26

Approximately 100um thick

Question 27

Why are water soluble suppositories painful for the patient?

Answer 27

Osmotically attract water to the rectum, increasing the mucus volume

Question 28

Describe the structure of the rectum

Answer 28

Non-motile No villi Abundant vasculature

Question 29

Why may an evacuant enema be used before administering a suppository?

Answer 29

Greater absorption of drug if the colon or rectum is devoid of faecal matter

Question 30

What conditions may affect the absorption of a suppository?

Answer 30

- diarrhoea - colonic obstruction (e.g. tumour) - tissue dehydration

Question 31

What percentage of drugs in suppositories avoid hepatic first-pass metabolism?

Answer 31

50 - 70%

Question 32

Where are drugs in suppositories absorbed into?

Answer 32

Rectal / haemorrhoidal veins

Question 33

What is the pH of rectal fluids?

Answer 33

pH 7-8

Question 34

What is the consequence of the rectum not having an effective buffering capacity?

Answer 34

Drugs will not change chemically and will determine the pH of the environment

Question 35

Which type of drugs are absorbed better in the rectum?

Answer 35

Weaker acids and bases are absorbed better than stronger, highly ionised ones

Question 36

What physio-chemical factors affect absorption?

Answer 36

- drug solubility - drug particle size - base properties

Question 37

How does the solubility of a drug in a suppository affect its absorption?

Answer 37

- 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

Question 38

How does the particle size of a drug in a suppository affect the rate of absorption?

Answer 38

Decreased size = increased dissolution = increased rate of absorption

Question 39

What properties must the suppository base have?

Answer 39

- must be capable of melting, softening or dissolving - must not be irritating (could initiate a bowel movement) - compatibility with drug must be ascertained

Question 40

What are the two stages of absorption of drug from a suppository?

Answer 40

- release of drug from vehicle | - transfer across mucosa

Question 41

What is the rate limiting step of absorption of a drug from a suppository?

Answer 41

Partitioning of the drug from the melted base

Question 42

How is the drug in a suppository released from the vehicle?

Answer 42

By melting at body temperature (lipophilic vehicles) or dissolving/dispersing in mucus (hydrophilic vehicles)

Question 43

What factors affect the release of a drug from a suppository?

Answer 43

- affinity of drug for vehicle - solubility of drug in rectal fluids - particle size - spreading of vehicle - interactions between drug and vehicle

Question 44

What factors determine the transfer of a drug in a suppository across the mucosa?

Answer 44

Partitioning and diffusion

Question 45

How does a drug in a suppository pass into the mucosa of the rectum?

Answer 45

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)

Question 46

What factors affect the transfer of a drug in a suppository into the mucosa?

Answer 46

- lipophilicity (pH dependent for weak acids / bases) - buffer solutions can increase absorption - site of absorption

Question 47

Give three examples of absorption enhancers that are included in suppositories

Answer 47

Surfactants Salicylate derivatives EDTA

Question 48

Give examples of surfactants included in suppositories

Answer 48

- cetomacrogols - tweens and spans - SDS

Question 49

How do surfactants work in suppositories?

Answer 49

Lower the surface tension of the vehicle and mucus barrier - increase membrane permeability by interacting with phospholipids - phenolics can have decreased absorption