Extemporaneous Preparations
Standard Treatment Guidelines and Essential Medicines List for South Africa, Hospital Level, Adults 2019 Edition
Podophylline, topical solution
EXTEMPORANEOUS COMPOUNDING
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 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 FORMULATION GUIDE
Different concentrations of morphine can be compounded to make the oral solution. However, it is recommended that a standard concentration (mg/mL) is used per ward/facility to prevent dosing errors. The following standard concentrations should be used:
- 1 mg/mL
- 5 mg/mL
- 10 mg/mL
Lower concentrations (e.g., 1mg/mL) are used for children and frail care patients where lower doses are usually required. Dosing for adult patients is generally commenced using concentrations of 5mg/mL or 10mg/mL. Higher strengths (20mg/mL) may be required in patients with complex pain (e.g. oncology centres and specialist care, opioid tolerant patients).
The volume compounded is dependent on individual patient requirements. Any remaining unused solution must be discarded 30 days from the day of compounding, in keeping with legislation and the expected stability of oral morphine solutions. Therefore, in order to prevent wastage, compound a volume in line with expected usage in a 30-day period. Compounding is usually done for individual patients, but can be done in anticipation of demand, with due regard to the limited stability of oral morphine solutions. Large volumes cannot be prepared for bulk stock and kept in stock awaiting prescriptions. The same approach should be applied to stock prepared for use on hospital wards.
Tables 1 and 2 below show the amount (in grams) of morphine hydrochloride/sulphate required to make 100 mL and 500 mL morphine oral solutions, respectively, at concentrations of 1 mg/mL, 5 mg/mL or 10 mg/mL, using nipastat 0.15% solution (procured commercially as a premade solution) as diluent. Varying volumes of nipastat 0.15% are combined with each fixed amount of morphine powder, in order to produce the final volume required. Please refer below for instructions for Neonates, infants and young children (under the age of 6 years old).
Table 1: Amount (in grams) of morphine hydrochloride/sulphate required to make a 100 mL oral morphine solution at concentrations of 1 mg/mL, 5 mg/mL or 10 mg/mL
Formula:
| Final morphine concentration | 1 mg/mL | 5 mg/mL | 10 mg/mL |
| Morphine hydrochloride/sulphate | 0.1 g | 0.5 g | 1 g |
| Nipastat 0.15% Solution*, make up to | To 100 mL | To 100 mL | To 100 mL |
*Nipastat 0.15% Solution (2.5 L) procured as a pre-made solution contains methylhydroxybenzoate (2.5 g), propylhydroxybenzoate (1.25 g), alcohol 99% (125 mL), purified water to 2.5L
Table 2: Amount (in grams) of morphine hydrochloride/sulphate required to make a 500mL oral morphine solution at concentrations of 1 mg/mL, 5 mg/mL or 10 mg/mL
Formula:
| Final morphine concentration | 1 mg/mL | 5 mg/mL | 10 mg/mL |
| Morphine hydrochloride/sulphate | 0.5 g | 2.5 g | 5 g |
| Nipastat 0.15% Solution*, make up to | To 500 mL | To 500 mL | To 500 mL |
*Nipastat 0.15% Solution (2.5 L) procured as a pre-made solution contains methylhydroxybenzoate (2.5 g), propylhydroxybenzoate (1.25 g), alcohol 99% (125 mL), purified water to 2.5 L
Neonates, infants and young children (under the age of 6 years old)
While the use of nipastat could be considered in children under the age of 6 years old; the high percentage of alcohol in this formulation is of concern in this group of patients. There is a lack of robust data on extemporaneous formulations for neonates, infants and younger children with available excipients and formulations. It is thus recommended that for this group of patients:
- A diluted morphine intravenous formulation be used orally (in consultation with specialists in units and your pharmacy department) e.g. Add 1ml of 10mg/ml IV solution to 9ml normal saline (preservative-free), to make 1mg/ml concentration. (To be stored in fridge for no longer than 7 days).
- Alternative morphine extemporaneous formulations excluding the use of alcohol for example:
Formula:
Declaration:
Active ingredient: Morphine hydrochloride/sulphate 1 mg/mL
Dosage form: Oral solution
Excipients: Benzoic acid, propylene glycol, sorbitol, purified water
| 1 mg/mL | |
| Morphine hydrochloride/sulphate | 0.1 g |
| Benzoic acid solution 5%* | 2 mL |
| Sorbitol 70% | 30 mL |
| Sterile water, add to | 100 mL |
| (Smaller volumes can be formulated - calculate proportions) | |
Preparation:
Dissolve the morphine in approximately 40 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 100 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 100mL.
| Benzoic acid | 5 g |
| Propylene glycol | 75 mL |
| Sterile water, heated to ±60ºC, add to | 100 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 water1 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:
1. Weigh out the podophyllin resin, and place in 100 mL amber glass bottle (previously dried out with a few drops of 70% alcohol).
2. Add compound benzoin tincture to 100 mL and mix well.
3. 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.
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
Standard Treatment Guidelines and Essential Medicines List for South Africa, Hospital Level, Adults 2019 Edition
Updated as per Erratum 2024/10/03/EDP/01