Institute of Pharmaceutical Sciences, King's College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NH, UK.
Int J Pharm. 2011 Oct 31;419(1-2):20-7. doi: 10.1016/j.ijpharm.2011.06.052. Epub 2011 Jul 20.
The effect of adding a third polymer to immiscible binary solid dispersions was investigated. The model actives griseofulvin (GF), progesterone (PG) and phenindione (PD) were selected because they exemplify a key property of many poorly soluble molecules of having at least one hydrogen bonding acceptor moiety while not having any hydrogen bond donating moieties. Ternary solid dispersions of the drug, PVP (polyvinylpyrrolidone) (proton acceptor) and PHPMA (poly[2-hydroxypropyl methacrylate]) (proton acceptor and donor) were prepared by spray drying. Stability results showed that binary solid dispersions (API and PVP) of GF and PVP crystallized quickly while the amorphous form was not possible to prepare for PG and PD. The amorphous form was prolonged upon the incorporation of PHPMA in the solid dispersion (API, PHPMA and PVP). Based on measuring the melting points, the energy of mixing the drug with the polymer was calculated using the Flory-Huggins theory. The results showed that GF had the lowest free energy followed by PG and finally PD which agreed well with the stability results. These results suggest that the addition of a third polymer to immiscible binary solid dispersions can significantly improve the stability of the amorphous form.
研究了向不混溶的二元固体分散体中添加第三种聚合物的效果。选择模型活性物质灰黄霉素 (GF)、孕酮 (PG) 和苯茚二酮 (PD)，是因为它们体现了许多难溶性分子的一个关键特性，即至少有一个氢键接受体部分，而没有任何氢键供体部分。通过喷雾干燥制备了药物、PVP（聚乙烯吡咯烷酮）（质子受体）和 PHPMA（聚[2-羟丙基甲基丙烯酸酯]）（质子受体和供体）的三元固体分散体。稳定性结果表明，GF 和 PVP 的二元固体分散体（API 和 PVP）迅速结晶，而 PG 和 PD 则不可能制备无定形形式。在固体分散体（API、PHPMA 和 PVP）中加入 PHPMA 可延长无定形形式。通过测量熔点，使用 Flory-Huggins 理论计算了药物与聚合物混合的能量。结果表明，GF 的自由能最低，其次是 PG，最后是 PD，这与稳定性结果非常吻合。这些结果表明，向不混溶的二元固体分散体中添加第三种聚合物可以显著提高无定形形式的稳定性。
