Identification of crystalline form of active ingredient in low strength topical cream
A cream for topical application is formulated using the active ingredient in a concentration of 1 mg/g. The formulation is manufactured using the anhydrous form of the ingredient. The cream contains e.g. water/propylene glycol mixture while it could be expected that the anhydrate could transform to the, in water, thermodynamically more stable monohydrate. Hence it is important to understand how to avoid/minimize this transformation.
The key challenges in the present investigation was to be able to detect the presence of small amounts of the monohydrate form of the API when present in such a low concentration formulation and perform a reproducible sample preparation.
From literature study of the present API it was possible to identify two well separated, but closely located, and intense peaks representing either the anhydrate or the monohydrate form.
By using a specially designed zero background holder with a cavity, filling the cavity and levelling the surface to exactly the correct reference height using a special tool it was possible to obtain relevant sample preparations.
A XRPD method suitable for the peaks identified, the sample preparation developed and with no interference from other ingredients was designed and applied using extremely slow scanning rate for a very limited 2ϴ range. The results proved that it was possible to differentiate between batches and conclude if the 0.1% of active ingredient was present as anydrate, monohydrate or a mixture thereof.