Rectal delivery

Question 1

What are the problems with oral drug delivery?

Answer 1

patient could have problems with their GIT, could be nauseous or be postoperative

patient could be unconscious = cannot cooperate

patient could be very old, young or mentally disturbed

Question 2

What is the rectum?

Answer 2

the rectum is part of the colon
- forms the final 150-200 mm of GIT

consists of the

• anal canal
• ampulla (80%) = expanded section where faeces are stored

is a hollow organ with smooth surface because of the absence of villi
only has three folds representing rectal valves.

rectal wall is composed of one thick epithelium layers containing cylindrical cells and goblet cells secretes mucus.

separated from the outside world by a circular muscle
- anus.

Question 3

Where are drugs absorbed through in the rectum?

Answer 3

there are 3 main veins

inferior and middle haemorrhoidal = lower part of rectum

• passes to the inferior vena cava
• takes drugs straight into blood circulation

superior haemorroidal = upper part of rectum

• passes to the portal vein
• passes to the liver where it is metabolised (primary site of metabolism)

bioavailability from upper part will be low because of first pass elimination

Question 4

What is the difference between shallow and deep suppository insertion into the rectum?

Answer 4

shallow suppository insertion

• taken up by the inferior and middle haemorroidal vein
• taken straight into systemic circulation (blood) by the inferior vena cava

deep suppository insertion

• taken up by the superior haemorroidal vein
• taken into the liver to be metabolised by the portal vein

Question 5

How are drugs released from the rectal dosage forms?

Answer 5

after insertion of the dosage form (suppository)
- it will either melt or dissolve in the rectal fluid

volume of the rectal fluid is small and the suppository vehicle will attract water by osmosis from the surrounding (unpleasant sensation) to get dissolved

drug will leave the vehicle by the rectum movement and then dissolve in rectal fluid.

Question 6

What are the physiological factors affecting rectal absorption? What are drug related factors affecting rectl absorption?

Answer 6

physiological factors

• quantity of fluid available = in the rectum
• properties of rectal mucus = viscosity
• contents of rectum
• motility of rectal wall = may cause leakage depending on motility

drug related factors
- solubility in water and vehicle = not suitable for very hydrophilic (unpleasant sensation by osmosis) or very low-water soluble drugs (poor dissolution)
= higher solubility means greater dissolution
= tamoxifen

• particle size = 50-100μm
• pKa

Question 7

What drugs are suitable for rectal delivery?

Answer 7

suitable for peptide-like drugs
- the absence of esterase and peptidase enzymes enhance the stability of these peptides

compared to oral delivery where they had poor suitability

Question 8

What are the uses of rectal drug delivery?

local
systemic

Answer 8

local

• treatment of haemorrhoids and relief of its symptoms (itching and pain)
• active ingredients include = vasoconstrictors, local anaestheics, astringents and anti-inflammatory
• treatment of constipation = active ingredients include bisacodyl, glycerin

systemic
- analgesic drugs
= most common use
= various opioids (morphine) have been used rectally to treat cancer pain but only 30-40% bioavailable when taken orally

• anti-asthmatics
• anti-inflammatory drugs = paracetamol
• anti epileptic drugs = diazepam rectubes®

Question 9

What are the advantages of rectal delivery?

Answer 9

suitable for drugs liable to degradation in GIT
= peptides and esters

partially avoid hepatic first pass elimination
= if taken by the inferior and middle haemorroidal veins to the inferior vena cava

can accommodate small and large doses

suitable for children who are unable to tolerate oral doses

suitable for vomiting and nauseous patients

Question 10

What are the disadvantages of rectal delivery?

Answer 10

patient compliance is poor
- especially in long term treatment

upward movement of drug increases first pass effect
- depends on shallow or deep insertion

drug absorption is slower
- lower SA

suppositories can leak
- due to rectal motility

Question 11

What are suppositories?

Answer 11

suppositories are the most commonly used rectal dosage forms

• are single dose preparations with a shape, volume and consistency appropriate for rectal administration
• come of different shapes and sizes = 1-4 g

Question 12

What are the requirements of an ideal suppository base/vehicle?

Answer 12

suppository vehicle should melt or disperse at body temperature = below 37 degrees Celsius

should be non-irritating

physically and chemically stable

pharmacologically inert

compatible with range of drugs

convenient to handling during manufacturing and storage

have good viscosity (as it affect flow into the moulds during manufacturing and spreading into the interface with the rectal fluid for release and absorbance).

Question 13

What are the types of suppository vehicles?

Answer 13

fatty vehicle

water-soluble vehicle

Question 14

What are fatty vehicles? What are the types? What are their properties?

Answer 14

semi-or fully synthetic
= Cocoa butter (theobroma oil) is a very commonly used base but not anymore because\

• has polymorphic behaviour = has different crystalline forms with different melting points
• low softening point
• chemical instability
• poor water-absorptive power (less decomposition)
• expensive

new fatty bases have become available (Witepsol, Fattibase, Cotmar)
- mixtures of natural and synthetic vegetable oils

consists of mixed trigylcerides, waxes and fatty alcohol

Question 15

What is glycerinated gelatin? What is its properties?

Answer 15

glycerinated gelatin = glycerol-gelatin
- is a mixture of gelatin, glycerol and water

when mixed they form
- translucent, gelatinous mixtures which disperse in rectum

ratio of mixing these components affect the dispersion time and hence the duration of action
- higher content of gelatin makes the formulation more rigid and longer acting)

needs to be stored in a closed container as they are hygroscopic
- absorb moisture from the air

Question 16

What is polyethylene glycol? What is its properties? What are the disadvantages?

Answer 16

polyethylene glycol (PEG) = macrogol

Versatile polymers
- mixtures of polyethylene glycol at different molecular weight

PEGs are miscible with rectal fluids and hence drug released by dispersion
examples = PEG 600 (liquid), PEG1000 (semisolid), PEG4000 (solid)

disadvantages

• can develop peroxides on storage
• hygroscopic = adsorb water from rectum and resulting in uncomfortable sensation

Question 17

What are the types of rectal dosage forms?

Answer 17

There are several rectal preparations such as

• suppositories
• rectal capsules
• rectal tablets
• rectal foams
• tampons
• enemas and microenemas = solutions, suspensions, emulsions

Question 18

What are enemas?

Answer 18

liquid preparations
- rectal solutions, emulsions and suspensions

used for systemic, local actions and diagnostic purposes

large volume enemas up to 100 mL

might contain vehicles only (arachisoil enema) or other excipients such as viscosity and pH modifiers.

Question 19

What are microenemas?

Answer 19

solution or dispersion of drugs in small volumes = ~ 3mL
- water or vegetable oil

limited use because of:

• high cost compared to suppositories
• difficult to be administrated by patient themselves.

Question 20

What are rectal capsules?

Answer 20

shell suppositories are solid single dose preparations

elongated in shape and have smooth external appearance that is lubricated

used for systemic circulations and are filled with

• solution
• suspension of drugs in vegetable oil or liquid paraffin.

Question 21

What are rectal tablets?

Answer 21

not ideal because they needs high amount of water for disintegration which is not available in rectum.