Measurement of the amorphous fraction of olanzapine incorporated in a co-amorphous formulation.

Abstract

Amorphous and co-amorphous formulations have been used to enhance the solubility and bioavailability of poorly water-soluble drugs. However, during handling and/or storage amorphous solids present inherent instability and overtime recrystallize back into their crystalline counterpart. The development of tools capable of quantifying and monitoring the recrystallization of amorphous materials is required to ensure the delivery of solid dosage forms with improved performance. This work describes the development and validation of a computational model for simple measurement of amorphous and co-amorphous olanzapine (OLZ) fractions in tablets. Amorphous OLZ produced by quench cooling and co-amorphous OLZ by solvent evaporation using saccharin (SAC) as a co-former were characterized by calorimetry (DSC), diffractometry (XRPD) and spectroscopy (FTIR and NIR). Spectral differences were used to predict the fraction of amorphous OLZ in samples containing different fractions of powdered amorphous and co-amorphous OLZ:SAC. The models were shown to be linear, accurate and reproducible. Blends of (co)amorphous OLZ and excipients were directly compacted at different pressures and dwell times to impose physical stress on the systems. Data collected from the analysis of the tablets was used in the model to monitor the stability of amorphous and co-amorphous OLZ demonstrating the applicability and validity of the model.