Compounding is the process where a pharmacist or other registered person prepares, mixes, combines, packages or labels a medicine for an individual patient.
Medicines compounded, or prepared “extemporaneously”, are unlicensed medicines and not subject to Medicines Regulatory Authority oversight. Thus, assumptions cannot be made regarding quality and stability of these compounded products relative to licensed medicines.
In terms of Section 22C(5) of the Medicines and Related Substances Act, 1965 (Act No. 101 of 1965), “No person shall compound or dispense a medicine unless he or she is authorised thereto in terms of the Pharmacy Act, 1974, is a veterinarian or is the holder of a licence as contemplated in subsection (1) (a).” This license may be granted by the Director-General to a medical practitioner, dentist, practitioner, veterinarian, nurse or other person registered under the Health Professions Act, 1974 (Act No. 56 of 1974).
Pharmacists or other registered persons should only engage in extemporaneous preparation when all routes of timely procurement have been exhausted (medicine cannot be sourced locally or globally; suitable therapeutic alternatives are not available or the medicine is not available from an authorised specialised compounding facility), or if the appropriate formulation or strength of the medicine is no readily available.
Extemporaneous preparations should be compounded by a pharmacist or other registered person in accordance with the Medicines and Related Substances Act, 1965 (Act No. 101 of 1965), as amended (adhering to minimum standards relating to premises, facilities and equipment) and at a facility that is licenced according to the Pharmacy Act.
Section 3 of the General Regulations to the Medicines and Related Substances Act, 2017, provides the conditions for compounding a medicine. In terms of Section 3(1) of the Regulations:
“A pharmacist or other person licensed in terms of section 22C(1)(a) of the Act to compound a medicine for sale in terms of section 14(4) of the Act, shall only compound a quantity that is intended to be used by a patient for no more than 30 consecutive days from the date of compounding: Provided that the date of compounding and the statement “Use within 30 days” are clearly indicated on the label.”
Standard operating procedures will assist to minimise risk regarding calculation errors, inappropriate validation of the preparation, microbial contamination, stability and storage of the compounded product, labelling errors, patient acceptability and the health and safety of personnel involved in compounding – appropriately aligned with Good Pharmacy Practice regulations.
Labelling should contain batch number, date of preparation, expiry date, the statement “Use within 30 days”, and all relevant labelling specific to the preparation. Relevant record-keeping should be maintained.
Standardised formulas have been provided for the following essential medicines that have supply constraints:
MORPHINE, ORAL SOLUTION
- Morphine, oral solution:
- 1 mg/mL (0.1%)
- 5 mg/mL (0.5%)
- 20 mg/mL (2%)
Declaration:
Active ingredient: Morphine hydrochloride/sulphate 1 mg/mL; 5 mg/mL; 20 mg/mL
Dosage form: Oral solution
Excipients: Benzoic acid, propylene glycol, sorbitol, purified water
Formula:
| 1 mg/mL | 5 mg/mL | 20 mg/mL | |
|---|---|---|---|
|
Morphine hydrochloride/sulphate |
50 g | 250 g | 1000 g |
|
Benzoic acid solution 5%* |
100 mL | 100 mL | 100 mL |
|
Sorbitol 70% |
1500 mL | 1500 mL | 1500 mL |
|
Sterile water, add to |
5000 mL | 5000 mL | 5000 mL |
(Smaller volumes can be formulated - calculate proportions).
Preparation:
Dissolve the morphine in approximately 2000 mL of the purified water. Dissolve the benzoic acid solution 5% in this solution. Add the 70% sorbitol solution and a sufficient quantity of purified water to a volume of 5000 ml and mix well.
Quality requirements
Identity: as stated under the section "Declaration", above.
Content of morphine hydrochloride: 90–110% of the declared amount, calculated as the pure substance.
pH: ≤ 4
Appearance: The solution is clear and almost free of visible particles.
Storage: Glass amber bottle, below 25 °C with an expiry date of 1 month.
*To make the benzoic acid 5% solution: Dissolve the benzoic acid in the propylene glycol, adding the hot purified water to a volume of 1000 mL.
|
Benzoic acid |
50 g |
|
Propylene glycol |
750 mL |
|
Sterile water, heated to ±60oC, add to |
1000 mL |
Storage: Glass amber bottle, below 25 °C with an expiry date of 1 month.
Note: Commercial preparation of methyl parahydroxybenzoate, propyl hydroxybenzoate, alcohol and purified water[1] could be considered as the diluent for morphine, oral solution, if available.
PODOPHYLLIN, TOPICAL SOLUTION
- Podophyllin 20% in compound benzoin tincture BP, 100 mL.
Active ingredient: Podophyllin 200 mg/mL
Dosage form: Topical solution
Excipients: Compound Benzoin Tincture BP
Formula
Podophyllin resin BP 20 g
Compound benzoin tincture BP, add to 100 mL
Preparation
- Weigh out the podophyllin resin, and place in 100 mL amber glass bottle (previously dried out with a few drops of 70% alcohol).
- Add compound benzoin tincture to 100 mL and mix well.
- Decant 10 mL in an amber glass bottle for a treatment course and label appropriately.
Storage: Glass amber bottle, below 25 °C with an expiry date of 6 months.
Quality requirements
Identity: as stated under the section "Declaration", above.
Content of podophyllin: 90–110% of the declared amount, calculated as the pure substance.
Appearance: The solution is clear and almost free of visible particles.
Label: Appropriately labelled for external use only.
References
[1] Commercial preparation formulated in accordance with the World Health Organisation. Model formulary: Morphine formulations on the Essential Medicines List for Children.
http://www.who.int/selection_medicines/committees/expert/19/applications/Morphine_2_2_C_NF.pdf