Predicting process design spaces for spray drying amorphous solid dispersions

International Journal of Pharmaceutics: X

Gabriele Sadowski¹  Samuel O. Kyeremateng¹  Matthias Degenhardt²  Kristin Lehmkemper²  Stefanie Dohrn³  Christian Luebbert³  Pranay Rawal³ 

[1] Co. KG, Global Pharmaceutical R&D, Knollstraße, D-67061 Ludwigshafen am Rhein, Germany;;AbbVie Deutschland GmbH &TU Dortmund University, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge-Str. 70, D-44227 Dortmund, Germany;

关键词: Amorphous solid dispersion;    Residual solvent;    Spray drying;    Solvent selection;    PC-SAFT;    Process design space;   

DOI  :  

来源: DOAJ

【 摘 要 】

Amorphous solid dispersions (ASDs) are commonly manufactured using spray-drying processes. The product quality can be decisively influenced by the choice of process parameters. Following the quality-by-design approach, the identification of the spray-drying process design space is thus an integral task in drug product development. Aiming a solvent-free and homogeneous ASD, API crystallization and amorphous phase separation needs to be avoided during drying. This publication provides a predictive approach for determining spray-drying process conditions via considering thermodynamic driving forces for solvent drying as well as ASD-specific API/polymer/solvent interactions and glass transitions. The ternary API/polymer/solvent phase behavior was calculated using the Perturbed-Chain Statistical Associating Theory (PC-SAFT) and combined with mass and energy balances to find appropriate spray-drying conditions. A process design space was identified for the ASDs of ritonavir and naproxen with either poly(vinylpyrrolidone) or poly(vinylpyrrolidone-co-vinylacetate) spray dried from the solvents acetone, dichloromethane, or ethanol.

【 授权许可】

Unknown