Rectal dosage forms

Question 1

Physiological Factors Affecting Absorption from the Rectum (4)

Answer 1

1. Quantity of Fluid available
2. Properties of rectal mucus
3. Contents of the Rectum
4. Motility of the Rectal Wall

Question 2

Properties of ideal suppository base (15)

Answer 2

1. Innocuous (not harmful/offesnsive)
2. Devoid of physiological activity.
3. No local irritation.
4. Not absorbed through rectal mucosa.
5. Neutral (no interaction with actives).
6. Rapid/complete fusion, disintegration and dissolution.
7. Time interval between fusion and solidification of final mixture should be sufficiently long to allow filling of mould without difficulty.
8. Time interval between fusion and solidification should also be short enough to prevent sedimentation of suspended solids.
9. Fats used as suppository bases melt within a 3ºC range. Narrow melting range important in controlling melting time after insertion as well as for maintaining shape under various ambient T°.
10. Onset of melting too low: cannot remove from package.
11. Onset above 37ºC: little drug release.
12. Formulation: should be adaptable for manufacture by either fusion or compaction.
13. High-speed manufacture: contraction on cooling should be sufficient to allow easy release from mould without the need for a mould lubricant.
14. Final product should be odourless and opaque with a uniform surface.
15. It should retain its hardness and fusion point over the range of temperatures at which it is likely to be stored.

Question 3

What is the weight of a base given by

Answer 3

number x mass of suppository - (mass of Ing’t)/DV of Ing’t

Question 4

What is theobroma oil (4)

Answer 4

1. Solid fat expressed from roasted seeds of Theobroma cacao Linn. (Sterculaceae).
2. Defined in most pharmacopoeias.
3. 73% mono-oleo-disaturated glycerides (mainly oleo-palmitostearin, linoleic acid).
4. Small amounts of saturated acids + traces of sterols.

Question 5

what is the importance of adhesion to moulds (3)

Answer 5

1. Only slight contraction on cooling, thus theobroma oil prone to mould adhesion.
2. Moulds must therefore be lubricated with: spirit soap, mineral oil, silicone spray or hydro-alcoholic spray.
3. MAIN REASON FOR USING SYNTHETIC BASES FOR INDUSTRIAL MANUFACTURE

Question 6

what are the physical characteristics of hard fats (3)

Answer 6

1. Mono-, di- or triglycerides of saturated straight-chain fatty acids (C10 to C18).
2. White or pale yellow, brittle, almost odourless and tasteless solid, oily to touch.
3. Hydroxyl value indicates hydrophilicity.

Question 7

What are the different grades and melting points of hard fats (5)

Answer 7

1. A 35-36.5℃
2. B 36-37.5℃
3. C 38-40℃
4. D 42-45℃
5. Grade D is useful if drug forms eutectic mixture (two or more solid components that melts at a lower temperature than the individual components) - available with and without surfactant

Question 8

What are the uses/melting points of grade H, W, S & E hard fats

Answer 8

H - mass production, but brittle if fast cooled. Low hydroxyl range (32-33.5℃)

W - large or small scale, fast cooling without brittleness. Medium hydroxyl range

S - good dispensing categories for drugs. High hydroxyl range
E - melt above 37℃. Useful for raising low melting point

Question 9

What are macrogols (5)

Answer 9

1. Polyethylene glycols (PEG) permitted if soluble in water and body fluids.
2. Dissolve completely within 60 min.
3. Useful for penicillin, digitalis, morphine and sulphathiazole.
4. Slightly irritant.
5. Variable drug release (rectal fluid volume).

Question 10

What is Glycogelatin (gelatin + glycerin) (3)

Answer 10

1. Mild local irritant used as a bowel evacuant (soap occasionally added to enhance effect.
2. Better drug release properties than fats.
3. Unsuitable for high-speed manufacture.

Question 11

what is the distinct purpose of retention enemas (2)

Answer 11

1. Local-acting liquids intended to be used as bowel evacuants (purgatives - used pre-operatively).
2. Retention enemas from which systemic drug absorption is intended.

Question 12

What are the advantages of rectal enemas (3)

Answer 12

1. Useful alternative to suppositories and may enable controlled-release of drugs (e.g. by using ion-exchange resins.
2. May enhance drug absorption because liquid is applied over a larger area of mucosa cf.. suppositories.
3. Thickening agents (e.g. starches and cellulose ethers) aid retention and may render formulation bioadhesive.

Question 13

What are uses of enemas (2)

Answer 13

1. antibacterial lavage (Sodium phthalylsulphathiazole)
2. removal of threadworms (quassia infusion).

Question 14

What are disadvantages of enemas (3)

Answer 14

1. Inconvenience.
2. Unpleasantness.
3. Increased risk of loss by involuntary expulsion - particularly by debilitated and young patients.