Phase transformations of amlodipine besylate solid forms.

Hydrate formation and dehydration phenomena are frequently encountered phase transformations during manufacturing and storage of the drug products. It is essential to understand, monitor, and control these transformations to ensure that the quality attributes of the drug product are not affected. In this work, phase transformations of the solid forms of amlodipine besylate (AMB) were studied using Raman and near-infrared (NIR) spectroscopy. AMB exists as anhydrate (AH), monohydrate (MH), dihydrate (DH), and amorphous (AM) form. Solid form quantification models based on multivariate data analysis of the Raman and NIR spectra were developed. The AH, MH, and AM form were transformed to the DH during solubility measurements. The AH to DH transformation also occurred during wet granulation. The transformation kinetics were faster during wet granulation than during the solubility experiments. This was due to the shear forces involved in granulation that can facilitate nucleation and can enhance the overall transformation. The DH form present in the wet granules persisted after drying, and final granules contained a mixture of the AH and DH. The relative importance of the dissolution, nucleation, and growth steps for the transformation was elucidated using optical microscopy experiments. The transformation kinetics were found to be limited by nucleation and growth.