Characterization and stability of ternary solid dispersions with PVP and PHPMA
Characterization and stability of ternary solid dispersions with PVP and PHPMA
复制标题
DOI：
10.1016/j.ijpharm.2011.06.052
复制
发表时间：
2011-10-31
影响因子：
5.8
通讯作者：
Buckton, Graham
中科院分区：
文献类型：
--
作者：
Al-Obaidi, Hisham;Ke, Peng;Buckton, Graham
研究了添加第三种聚合物对不混溶的二元固体分散体的影响。选择模型活性物灰黄霉素（GF）、孕酮（PG）和苯茚二酮（PD）是因为它们具有许多具有至少一个氢键受体部分而不具有任何氢键供体部分的难溶性分子的关键性质。通过喷雾干燥法制备了药物、PVP（聚乙烯吡咯烷酮）（质子受体）和PHPMA（聚[甲基丙烯酸2-羟丙酯]）（质子受体和供体）的三元固体分散体。稳定性研究结果表明，GF和PVP的二元固体分散体（API和PVP）结晶迅速，而PG和PD不可能制备无定形形式。在固体分散体（API、PHPMA和PVP）中掺入PHPMA后，无定形形式延长。在测定药物熔点的基础上，利用Flory-Huggins理论计算了药物与聚合物的混合能。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一致。这些结果表明，向不混溶的二元固体分散体中添加第三聚合物可以显著改善无定形形式的稳定性。(C)2011 Elsevier B. V.保留所有权利。
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. (C) 2011 Elsevier B.V. All rights reserved.