Suppositories Calculations 5f5

8 Suppository calculations

By the end of this chapter you should be able to: ● calculate quantities of base and drug required for the preparation of theobroma oil and glycerol-gelatin medicated suppositories.

Suppositories Suppositories are dosage forms prepared for drug delivery via the rectum. They consist of an active medicament dispersed throughout an inactive base. The bases used in these products can be broadly classified into two groups: ■ Fatty bases. These may be of natural origin, such as theobroma oil (cocoa butter), or synthetic fats such as Witepsol. ■ Hydrophilic bases. The most commonly used hydrophilic base is composed of a solid glycerol/gelatin mixture.

Displacement values Suppositories are prepared by dissolving or dispersing an active medicament in a molten base and pouring the mixture into a suppository mould. Suppository moulds are normally available in 1 g, 2 g and 4 g sizes – the approximate weights of theobroma oil suppositories that are produced from them – although the volume of the suppository mould will be constant. However, because the density of the medicament may vary considerably from that of the base, the weight of the base required to make a suppository will vary depending on the medicament used. For example, 2 g of a medicament with twice the density of theobroma oil would occupy approximately the same volume as 1 g of the suppository base. The displacement values (DVs) of medicaments are required when calculating the weight of suppository base required to prepare medicated suppositories (see Example 8.1). The displacement value of a medicament is the number of parts, by weight, of a medicament that will displace one part of suppository base (normally theobroma oil). Displacement values for various medicaments are given in the Pharmaceutical Codex.

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94 PRACTICAL PHARMACEUTICAL CALCULATIONS

(Note: The following examples take no of preparation losses and it is normal practice to prepare for an excess quantity of suppositories.)

Example 8.1

Calculate the quantities required to make 10 theobroma oil suppositories (2 g mould) each containing 400 mg of zinc oxide (Displacement value = 4.7)

Solution steps 1 Calculate the total weight of zinc oxide required. 2 Calculate what weight of base would be required to prepare 10 unmedicated suppositories. 3 Determine what weight of base would be displaced by the medicament. 4 Calculate, therefore, the weight of base required to prepare the medicated suppositories. Total weight of zinc oxide required = 400 mg × 10 = 4 g Weight of base required for unmedicated suppositories = 2 g × 10 = 20 g As the displacement value of zinc oxide = 4.7 This means that 4.7 g of zinc oxide would displace 1 g of theobroma oil 1 g of zinc oxide would displace 1 ÷ 4.7 g of theobroma oil So, 4 g of zinc oxide will displace (4 × 1) ÷ 4.7 g of theobroma oil = 0.85 g Therefore, the weight of base required to make medicated suppositories = 20 – 0.85 g = 19.15 g Answer: 19.15 grams

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Note that for theobroma oil suppositories you can calculate the amount of base displaced by the active ingredient by dividing the amount of active ingredient by the displacement value, e.g. 200 mg of a drug with a DV of 4 will displace 200/4 mg or 50 mg of base in each mould. Glycero-gelatin base has a density 1.2 times greater than theobroma oil. Therefore, a 1 g suppository mould will produce a 1 g theobroma oil suppository, but a 1.2 g glycero-gelatin suppository. This factor must be taken into in displacement value calculations.

Example 8.2

Calculate the quantities required to make six glycerogelatin suppositories (4 g mould), each containing 100 mg aminophylline (Displacement value = 1.3)

Solution steps 1 Calculate the total weight of aminophylline required. 2 Calculate what weight of glycero-gelatin base would be required to prepare 10 unmedicated suppositories. 3 Determine what weight of base would be displaced by the medicament. 4 Calculate, therefore, the weight of base required to prepare the medicated suppositories. Total weight of aminophylline required = 100 mg × 6 = 600 mg or 0.6 g Weight of base required for unmedicated suppositories = 4 g × 6 × 1.2 (to take of the greater density of this base) = 28.8 g As the displacement value of aminophylline = 1.3 This means that 1.3 g of aminophylline displaces 1 g of theobroma oil So, 1 g of aminophylline displaces 1 ÷ 1.3 g of theobroma oil 0.6 g of aminophylline displace (1 × 0.6) ÷ 1.3 g of theobroma oil = 0.46 g of theobroma oil

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This means that the aminophylline would displace 0.46 g × 1.2 of the glycero-gelatin base = 0.55 g Therefore, the weight of base required to make medicated suppositories = 28.8 g – 0.55 g = 28.25 g Answer: 28.25 grams

Medicaments included as a percentage w/w If a medicament is present in a suppository as a percentage w/w, then its displacement value is not required when calculating the respective amounts of medicament and base required to prepare the suppository.

Example 8.3

What quantities are required to prepare eight theobroma oil suppositories, in a 4 g mould, containing 1% w/w lignocaine hydrochloride?

Solution steps 1 Calculate the total weight of the medicated suppositories. 2 Calculate, therefore, the weight of the drug required (1% of the total weight). 3 Subtract the weight of the drug from the total weight of the suppositories to find the weight of the base required. Total weight of the suppositories = 32 g Weight of drug required (1% w/w) = (32 × 1) ÷ 100 g = 0.32 g Therefore, weight of base required = 32 g – 0.32 g = 31.68 g Answer: 31.68 grams

Again, if a glycero-gelatin base is used, the appropriate correction factor must be used as a 1 g mould for a theobroma oil suppository will actually hold 1.2 g of glycero-gelatin base.

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Example 8.4

Prepare 12 glycero-gelatin suppositories, containing 0.5% w/w cinchocaine hydrochloride. Use a 2 g mould

Solution steps 1 Calculate the total weight of the medicated suppositories, allowing for the greater density of the glycero-gelatin base. 2 Calculate the weight of the drug required. 3 Subtract the weight of the drug from the total weight of the suppositories to determine the weight of the base required. Total weight of the suppositories = 12 × 2 g × 1.2 = 28.8 g Weight of drug required = (28.8 g × 0.5) ÷ 100 = 0.144 g (or 144 mg) Therefore weight of base required = 28.8 g – 0.144 g = 28.66 g Answer: 28.66 grams

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SELF-ASSESSMENT Now try the self-assessment questions to ensure you have understood this chapter.

Questions 1 How would you prepare 10 theobroma oil suppositories (1 g mould) containing 2.5% w/w bismuth subgallate? 2 How would you prepare six theobroma oil suppositories (2 g mould) containing 10% w/w zinc oxide? 3 Six theobroma oil suppositories (2 g), each containing 125 mg of paracetamol, are to be prepared. The displacement value of paracetamol is 1.5. What quantities of base and medicament are required? 4 You are asked to prepare 11 theobroma oil suppositories (2 g mould) each containing 100 mg of aspirin (DV = 1.1). What weights of base and medicament are required? 5 Prepare 10 theobroma oil suppositories, each containing 50 mg of bismuth subgallate (DV = 2.5). If a 2 g mould is used, what quantities of base and medicament are required? 6 A prescriber requests five glycero-gelatin suppositories be made, containing 1% w/w hydrocortisone acetate. If a 4 g mould is used, what quantities of base and medicament are needed? 7 Prepare eight glycero-gelatin suppositories (in a 2 g mould) each containing 20 mg of morphine hydrochloride (DV = 1.6). 8 Ten glycero-gelatin suppositories, each containing 30 mg phenobarbitone sodium (DV = 1.2), are to be prepared using a 1 g mould. What quantities of base and medicament are required? 9 Prepare 12 glycero-gelatin suppositories, in a 2 g mould, each containing 50 mg of diphenhydramine hydrochloride (DV = 1.2).

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10 You are required to prepare 10 theobroma oil suppositories (2 g). Each suppository must contain 50 mg of bismuth subgallate (DV = 2.5) and 10 mg of hydrocortisone acetate (DV = 1.5). Calculate the weight of each medicament and of theobroma oil required to prepare the suppositories. (Hint: Calculate the weight of base displaced by each medicament and subtract both these from the weight of the unmedicated suppositories.)