The optimisation of extemporaneous compounding of low-dose nifedipine capsules

Extemporaneous compounding is often necessary when a suitable drug product is not on the market (eg, when the patient is a child). The medication of children often differs from adults as there are several excipients which are generally recognised as safe but which nevertheless are unsuitable ingredients for paediatric medication. Extemporaneous compounding is the only manufacturing method to tailor the final drug product with specific needs. However, the disadvantage is the lack of standardised instructions. The situation is even more difficult if the active pharmaceutical ingredient is light sensitive.

The aim of the study was to optimise the extemporaneous compounding of low-dose nifedipine (NIF) capsules size 3 (0.3 mL) and 4 (0.21 mL) by comparing the volumetric and gravimetric methods. The suitability of several fillers-lactose (LAC), mannitol (MAN) and microcrystalline cellulose (MCC)-for capsule compounding was evaluated.

The powder properties of NIF, LAC, MAN and MCC were characterised. The volumetric and gravimetric methods (12 batches) were evaluated by the European Pharmacopoeia (Ph. Eur.). The light degradation of NIF was studied with a UV-Vis spectrophotometer.

All manufactured capsules met the Ph. Eur. requirements on uniformity of mass (2.9.5.). With regard to uniformity of content (2.9.6.), nine of the 12 batches met the Ph. Eur.

However, deviation from the average content was greater with LAC than with MAN and MCC. According to the uniformity of dosage units (Ph. Eur. 2.9.40.), eight of the 12 batches met the requirements, with LAC being slightly poorer than MAN and MCC.

Both volumetric and gravimetric methods were suitable for low-dose NIF capsule compounding. The powder loss during preparation was greater with the gravimetric method, even though it produced better quality capsules. MAN and MCC were slightly better than LAC as capsule fillers. Solid NIF degraded slowly when exposed to artificial light whereas dissolved NIF degraded in less than an hour.