Laboratorium voor Farmacotechnologie en Biofarmacie, K.U.Leuven, Herestraat 49, bus 921, 3000, Leuven, Belgium.
Pharm Res. 2010 May;27(5):775-85. doi: 10.1007/s11095-010-0069-y. Epub 2010 Mar 2.
The present study aims to determine the drug / polymer miscibility level as a function of the preparation method for an amorphous solid dispersion model system containing itraconazole and eudragit E100. This value was compared to the theoretical crystalline drug solubility in the amorphous polymer and the miscibility of the amorphous drug in the amorphous polymer.
The amorphous solid dispersions were prepared via spray drying and film casting in order to evaluate the influence of the solvent drying rate. The experimental miscibility level was estimated using XRPD, MDSC, FT-IR, HPLC and TGA. The solubility and miscibility were estimated using the Flory-Huggins mixing theory and experimental drug in monomer solubility data.
The experimental miscibility level was found to be 27.5% w/w for spray-dried and 15% for film-casted solid dispersions. FT-IR measurements confirmed the absence of saturable interactions like hydrogen bonds, and analysis of the mixed glass transition temperatures suggested low adhesion forces in the amorphous mixture. The solubility analysis rendered a positive FH interaction parameter, a crystalline solubility of approximately 0.012% w/w and an amorphous drug-polymer miscibility of approximately 7.07% w/w.
The solid dispersions are significantly supersaturated with respect to both crystalline solubility and amorphous miscibility demonstrating the influence of manufacturing methodology.
本研究旨在确定包含伊曲康唑和 Eudragit E100 的无定形固体分散体模型系统的制备方法作为药物/聚合物混溶性的函数。将该值与无定形聚合物中理论结晶药物的溶解度以及无定形药物在无定形聚合物中的混溶性进行比较。
通过喷雾干燥和薄膜铸造制备无定形固体分散体，以评估溶剂干燥速率的影响。使用 X 射线粉末衍射（XRPD）、差示扫描量热法（DSC）、傅里叶变换红外光谱（FT-IR）、高效液相色谱（HPLC）和热重分析（TGA）来估计实验混溶性水平。使用 Flory-Huggins 混合理论和实验药物单体溶解度数据来估计溶解度和混溶性。
喷雾干燥固体分散体的实验混溶性水平为 27.5%w/w，薄膜铸造固体分散体为 15%w/w。FT-IR 测量证实不存在如氢键等饱和相互作用，混合玻璃化转变温度分析表明无定形混合物中粘附力较低。溶解度分析得出了正的 FH 相互作用参数，结晶溶解度约为 0.012%w/w，无定形药物-聚合物混溶性约为 7.07%w/w。
与结晶溶解度和无定形混溶性相比，固体分散体明显过饱和，这表明制造方法的影响。
