Complementary near-infrared and Raman chemical imaging of pharmaceutical thin films.

Complementary near-infrared (NIR) and Raman mapping techniques have been used to study the distribution of drug particles suspended in a polymeric film. The film configuration was used with the goal of maintaining a drug with a particle size of less than 10 µm in a nonagglomerated form and to satisfy two commonly encountered pharmaceutical needs: enhanced dissolution rate of poorly soluble drugs and the content uniformity of drugs administered in low doses. A total of four film batches were prepared for this study using hydroxypropyl methylcellulose (HPMC) with griseofulvin as the active pharmaceutical ingredient. The NIR method analyzed a film area of 3 × 2.6 mm, whereas Raman mapping analyzed an area of 10 × 10 µm, and every sample was analyzed by the two methods. The second derivative transform removed baseline variations in the NIR spectra and provided differentiation between the two components. NIR chemical imaging did not identify clusters larger than 0.05 mm. Raman analysis identified areas rich in griseofulvin or HPMC, which were used to develop a partial least squares discriminant analysis method to determine drug or polymer distribution throughout the film.