Low Dose, Poorly Extractable Drug in Semi-Solid Dosage Form

Case Study 6: Analytical Method Development for a Low Dose, Poorly Extractable Drug in a Semi-Solid

Formulation of an NME below 10ug/gram for a topical application was requested by the sponsor. The resultant semi-solid dosage form was found to be suitable but difficulty in extracting the NME from the drug product was experienced.

A series of experiments identified one of the components in the drug product was deteriorating the HPLC column and needed to be removed prior to analysis.

An extraction method was developed and included a step to precipitate out the interfering excipient. The supernatant was collected, rinsed, and evaporated before being brought to a total volume of 5 mL. This low total volume was necessary for analysis of related compounds at a very low level.

The recovery of the NME from the drug product is 100% and the method has been validated for use in routine testing of clinical supplies.