Molecular state evaluation of active pharmaceutical ingredients in adhesive patches for transdermal drug delivery

In this study, we prepared mock patches consisting of model drug (felbinac) and three types of acrylic polymers with different functional substituent and/or physical properties, and evaluated the correlation of pharmaceutical properties and molecular state of felbinac in these patches. Polarizing microscopic observation, powder X-ray diffraction and Raman spectroscopy were employed and then different propensity was observed in the crystallization behaviour and precipitated crystal form in each patches. In particular, Raman spectra in low frequency region were useful to detect polymorphic change in patches. H-1 NMR was also used to investigate the interaction between felbinac and the polymers. In addition, pharmaceutical properties of mock patches were evaluated by dissolution test and in vitro skin permeation test. From these results, crystallization of felbinac was occurred in the case of weaker interaction between felbinac and the polymer, which has carboxy group as substituent, and resulted in higher drug release and skin permeation. In conclusion, it was essential to consider the compatibility of drug and polymer, which constituted adhesive layer in patches, in molecular level.