Downstream Processing of Amorphous and Co-Amorphous Olanzapine Powder Blends

The work evaluates the stability of amorphous and co-amorphous olanzapine (OLZ) in tablets manufactured by direct compression. The flowability and the compressibility of amorphous and co-amorphous OLZ with saccharin (SAC) and the properties of the tablets obtained were measured and compared to those of tablets made with crystalline OLZ. The flowability of the amorphous and mostly of the co-amorphous OLZ powders decreased in comparison with the crystalline OLZ due to the higher cohesiveness of the former materials. The stability of the amorphous and co-amorphous OLZ prior to and after tableting was monitored by XRPD, FTIR, and NIR spectroscopies. Tablets presented long-lasting amorphous OLZ with enhanced water solubility, but the release rate of the drug decreased in comparison with tablets containing crystalline OLZ. In physical mixtures made of crystalline OLZ and SAC, an extent of amorphization of approximately 20% was accomplished through the application of compaction pressures and dwell times of 155 MPa and 5 min, respectively. The work highlighted the stability of amorphous and co-amorphous OLZ during tableting and the positive effect of compaction pressure on the formation of co-amorphous OLZ, providing an expedited amorphization technique, given that the process development-associated hurdles were overcome.

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Materials

OLZ was a gift from Rampex Labs Pvt. Ltd. (Telangana, India). SAC (Sigma-Aldrich, Steinheim, Germany) was used as the co-former and dichloromethane (Biochem Chemopharma, Cosne sur Loire, France) as the solvent for the preparation of OLZ-CAM. Liquid nitrogen (Air Liquide, Lisbon, Portugal) was used to prepare amorphous OLZ. Tablets were manufactured from blends of OLZ and SAC, dibasic calcium phosphate anhydrous (DI-CAFOS^® A60, a gift from Budenheim, Budenheim, Germany), microcrystalline cellulose (Avicel PH-101, FMC Corp., Cork, Ireland), polyvinylpyrrolidone (K25, BASF, Ludwigshafen, Germany) and croscarmellose sodium (JRS Pharma, Rosenberg, Germany). Demineralized water (Destillo 2, Herco, Freiberg am Neckar, Germany), sodium hydroxide (Eka, Marietta, GA, USA), and potassium phosphate monobasic (Carlo Erba Reagents, Val de Reuil, France) were used to prepare the phosphate buffer (pH 8.0) for the dissolution studies. Marketed tablets of OLZ (15 mg, Generis Farmacêutica, S.A., Amadora, Portugal) were used as controls in the dissolution studies. A desiccator containing magnesium nitrate (53% RH, ThermoFisher GmbH, Kandel, Germany) was used to store amorphous OLZ and OLZ-CAM.

da Costa, N.F.; Daniels, R.; Fernandes, A.I.; Pinto, J.F. Downstream Processing of Amorphous and Co-Amorphous Olanzapine Powder Blends. Pharmaceutics 2022, 14, 1535. https://doi.org/10.3390/pharmaceutics14081535