Ji Yuanhui, Paus Raphael, Prudic Anke, Lübbert Christian, Sadowski Gabriele
TU Dortmund, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge-Str. 70, 44227, Dortmund, Germany,
Pharm Res. 2015 Aug;32(8):2559-78. doi: 10.1007/s11095-015-1644-z. Epub 2015 Feb 27.
To analyze the dissolution mechanism of solid dispersions of poorly water-soluble active pharmaceutical ingredients (APIs), to predict the dissolution profiles of the APIs and to find appropriate ways to improve their dissolution rate.
The dissolution profiles of indomethacin and naproxen from solid dispersions in PVP K25 were measured in vitro using a rotating-disk system (USP II). A chemical-potential-gradient model combined with the thermodynamic model PC-SAFT was developed to investigate the dissolution mechanism of indomethacin and naproxen from their solid dispersions at different conditions and to predict the dissolution profiles of these APIs.
The results show that the dissolution of the investigated solid dispersions is controlled by dissolution of both, API and PVP K25 as they codissolve according to the initial API loading. Moreover, the dissolution of indomethacin and naproxen was improved by decreasing the API loading in polymer (leading to amorphous solid dispersions) and increasing stirring speed, temperature and pH of the dissolution medium. The dissolution of indomethacin and naproxen from their amorphous solid dispersions is mainly controlled by the surface reaction, which implies that indomethacin and naproxen dissolution can be effectively improved by formulation design and by improving their solvation performance.
The chemical-potential-gradient model combined with PC-SAFT can be used to analyze the dissolution mechanism of solid dispersions and to describe and predict the dissolution profiles of API as function of stirring speed, temperature and pH value of the medium. This work helps to find appropriate ways to improve the dissolution rate of poorly-soluble APIs.
分析难溶性活性药物成分（API）固体分散体的溶出机制，预测API的溶出曲线，并找到提高其溶出速率的合适方法。
采用旋转圆盘系统（USP II）在体外测定吲哚美辛和萘普生在PVP K25固体分散体中的溶出曲线。建立了结合热力学模型PC-SAFT的化学势梯度模型，以研究吲哚美辛和萘普生在不同条件下从其固体分散体中的溶出机制，并预测这些API的溶出曲线。
结果表明，所研究的固体分散体的溶出受API和PVP K25两者的溶出控制，因为它们根据初始API载量共同溶解。此外，通过降低聚合物中的API载量（形成无定形固体分散体）以及提高搅拌速度、温度和溶出介质的pH值，可改善吲哚美辛和萘普生的溶出。吲哚美辛和萘普生从其无定形固体分散体中的溶出主要受表面反应控制，这意味着通过制剂设计和改善其溶剂化性能可有效提高吲哚美辛和萘普生的溶出。
结合PC-SAFT的化学势梯度模型可用于分析固体分散体的溶出机制，并描述和预测API的溶出曲线与搅拌速度、温度和介质pH值的关系。这项工作有助于找到提高难溶性API溶出速率的合适方法。
