Suppository Part 1

Question 1

What are desirable properties of a suppository base?

Answer 1

• can be moulded by pouring or compression
• stable if heated above its melting point
• does not adhere to mould
• releases drug at the desired rate
• keeps its shape when handled and easy to insert
• does not leak out of orifice into which it is inserted
• stable during storage
• non-toxic and non-irritating
• compatible with drug

Question 2

What are the types of bases that can be made with suppositories?

Answer 2

• oleaginous bases
• water-soluble or water-miscible bases
• emulsifying bases

Question 3

What are oleaginous bases and what are some examples of it?

Answer 3

• oleaginous bases are also known as oily or fatty bases

- examples: theobroma oil, hydrogenated fatty acids of vegetable oils, monoglycerides of high MW fatty acids

Question 4

What are some characteristics of theobroma oil?

Answer 4

• composed of triglycerides of mainly oleic, stearic and palmitic acids.
• occurs in three crystalline forms:
  » alpha: unstable; melting point of 22-24 degree celsius
  » beta: stable, melting point of 34-36 degree celsius
  » gamma: unstable, melting point of 18 degree celsius
• use of low heat (40-50 degree celsius) and slow cooling are crucial for direct recrystallisation to the beta-crystals.

Question 5

What are the characteristics of water-soluble or water-miscible bases?

Answer 5

• bases do not melt but dissolve slowly in the biological fluid.
• commonly prepared from glycerinated gelatin or polyethylene glycols.

Question 6

What are the characteristics of glycerinated gelatin?

Answer 6

• USP formula: 20% gelatin + 70% glycerin + 10% water
• Functions of ingredients:
  gelatin –> hardness
  glycerin –> hydrophilicity
• There are two types of gelatin:
  Pharmagel A: cationic and incompatible with anionic compounds
  Pharmagel B: anionic and incompatible with cationic compounds

Question 7

What are some advantages of glycerinated gelatin base?

Answer 7

• more prolonged drug release

- more easily inserted (suitable for urethral administration)

Question 8

What are some disadvantages of glycerinated gelatin bases?

Answer 8

• hygroscopic: dehydrating effect on mucous membrane

- support growth or mould

Question 9

What are polyethylene glycols?

Answer 9

• carbowaxes
• general chemical formula: HOCH2(CH2OCH2)nCH2OH
• combination of PEGs (macrogol) is often employed to obtain a base of desired hardness, melting point and water solubility.

Question 10

What are the examples of macrogol bases?

Answer 10

1. PEG 1000: 96%, PEG 4000: 4% (base is soft and disintegrates rapidly)
2. PEG 1000: 75%, PEG 4000: 25% (base is harder and gives a slower drug release)
3. PEG 1540: 70%, PEG 6000: 30% (base is much harder and can be used for drugs that lower the melting point of the base)
4. PEG 1540: 30%, PEG 6000: 60%, Water: 10% (base includes water and is suitable for water-soluble drugs)

Question 11

What are some of the advantages of PEG bases?

Answer 11

• bases with higher melting point can be formulated
  » convenient storage
  » easy insertion
  » no leakage from orifice
• bases of varying solubilities can be formulated
  » control of drug release

Question 12

What are some disadvantages of PEG bases?

Answer 12

• incompatible with phenols

- hygroscopic (absorb moisture from the air)

Question 13

What are some characteristics and examples of emulsifying bases?

Answer 13

• usually composed of triglycerides with one or more emulsifying agents.
  Examples:
• witepsol: hydrogenated triglycerides of lauric acid with added monoglycerides
• massupol: glyceryl esters, chiefly lauric acid, with added glyceryl monostearate

Question 14

What are some advantages of emulsifying bases?

Answer 14

• not adversely affected by overheating
• solidify rapidly at room temperature
• do not adhere to mould
• non-irritating

Question 15

What are differences in hot and cold processes in the preparation of suppositories?

Answer 15

1. hot process involves fusion or melt moulding, cold process involves hand moulding or compression moulding.
2. hot process employs heat and is unsuitable for thermolabile drug, cold process does not employ heat and is suitable for thermolabile drugs.
3. hot processes are more commonly employed than cold ones.

Question 16

What are the steps for the hot process?

Answer 16

1. base is melted over a hot water-bath.
2. drug is dissolved or dispersed in the molten base
3. molten mixture is poured into lubricated mould and allowed to set in the cold.
4. suppositories formed are removed from the metal moulds or supplied in the disposable moulds.

• mould is either made of metal (reusable) or plastic (disposable).
• condition of the metal mould is important.

Question 17

What are the different types of cold process?

Answer 17

1. Hand moulding
   - slow process that is suitable for small scale production only.
   - base is thoroughly kneaded with the drug, rolled into a thin cylinder of uniform diameter.
   - Then, the cylinder is cut into individual pieces which are hand moulded to the desired shape.
2. Compression moulding
   - partially automated and relatively faster than hand moulding

Question 18

What are the different types of packaging of suppositories?

Answer 18

• partitioned boxes
• screw-capped glass or plastic containers
• aluminium foil wrappings
• disposable plastic moulds