Borrmann Dominik, Danzer Andreas, Sadowski Gabriele
Laboratory of Thermodynamics, Department of Chemical and Biochemical Engineering, TU Dortmund University, Emil-Figge-Str. 70, 44227 Dortmund, Germany.
Pharmaceutics. 2022 May 31;14(6):1181. doi: 10.3390/pharmaceutics14061181.
Water decreases the stability of amorphous solid dispersions (ASDs) and water sorption is, therefore, unwanted during ASD storage. This work suggests a methodology to predict the water-sorption isotherms and the water-sorption kinetics in amorphous pharmaceutical formulations like ASDs. We verified the validity of the proposed methodology by measuring and predicting the water-sorption curves in ASD films of polyvinylpyrrolidone-based polymers and of indomethacin. This way, the extent and the rate of water sorption in ASDs were predicted for drug loads of 0.2 and 0.5 as well as in the humidity range from 0 to 0.9 RH at 25 °C. The water-sorption isotherms and the water-sorption kinetics in the ASDs were predicted only based on the water-sorption isotherms and water-sorption kinetics in the neat polymer on the one hand and in the neat active pharmaceutical ingredient (API) on the other hand. The accurate prediction of water-sorption isotherms was ensured by combining the Perturbed-Chain Statistical Association Theory (PC-SAFT) with the Non-Equilibrium Thermodynamics of Glassy Polymers (NET-GP) approach. Water-sorption kinetics were predicted using Maxwell-Stefan diffusion coefficients of water in the ASDs.
水会降低无定形固体分散体（ASD）的稳定性，因此在ASD储存期间，水分吸附是不希望出现的。这项工作提出了一种方法，用于预测无定形药物制剂（如ASD）中的水吸附等温线和水吸附动力学。我们通过测量和预测基于聚乙烯吡咯烷酮的聚合物和吲哚美辛的ASD薄膜中的水吸附曲线，验证了所提出方法的有效性。通过这种方式，预测了25℃下药物负载量为0.2和0.5以及相对湿度范围为0至0.9时ASD中的水吸附程度和速率。ASD中的水吸附等温线和水吸附动力学仅基于一方面纯聚合物和另一方面纯活性药物成分（API）中的水吸附等温线和水吸附动力学进行预测。通过将扰动链统计缔合理论（PC-SAFT）与玻璃态聚合物的非平衡热力学（NET-GP）方法相结合，确保了水吸附等温线的准确预测。使用ASD中水的麦克斯韦-斯蒂芬扩散系数预测水吸附动力学。
