Costa, Nuno F. daDaniels, RolfFernandes, Ana I.Pinto, João F.2023-03-162023-03-162022da Costa NF, Daniels R, Fernandes AI, Pinto JF. Downstream Processing of Amorphous and Co-Amorphous Olanzapine Powder Blends. Pharmaceutics. 2022; 14(8):1535. https://doi.org/10.3390/pharmaceutics140815351999-4923http://hdl.handle.net/10400.26/44176This is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)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.engOlanzapine(Co-)amorphousCohesivenessCompressibilityFlowabilityTabletsjournal article10.3390/pharmaceutics14081535