DSM Resolve, Geleen, The Netherlands.
Mol Pharm. 2012 Oct 1;9(10):2924-32. doi: 10.1021/mp300280k. Epub 2012 Sep 6.
The use of hot-melt extrusion for preparing homogeneous API-excipient mixtures is studied for miconazole-PEG-g-PVA [poly(ethylene glycol)-poly(vinyl alcohol) graft copolymer] solid dispersions with a 5 cm(3) table-top, twin-screw corotating microcompounder (DSM Xplore). Phase behavior of PEG-g-PVA, miscibility of miconazole in PEG-g-PVA and the partitioning of miconazole between PEG and PVA amorphous phases are characterized using a combination of modulated DSC, XRPD, and solid-state (1)H and (13)C NMR methods. The (1)H NMR transverse magnetization relaxation (T(2) relaxation) method is used to analyze the phase composition and molecular mobility of the copolymer. The T(2) relaxation decay of pure PEG-g-PVA can be described by four T(2) relaxation components in the temperature range studied. PVA crystallinity is not largely affected by hot-melt extrusion and the presence of the drug. Miconazole preferably resides in the PEG amorphous phase, and its molecules are well dispersed in the PEG-g-PVA matrix using hot-melt extrusion mixing. Miconazole forms amorphous nanoclusters whose average size equals approximately 1.6 nm, indicating solid solution formation (molecular level dispersion) of the drug in the polymer.
研究了使用热熔挤出法制备米康唑-PEG-g-PVA[聚(乙二醇)-聚(乙烯醇)接枝共聚物]固体分散体的均匀 API-赋形剂混合物，使用 5 cm(3) 台式、双螺杆同向旋转微型混合器（DSM Xplore）。采用调制差示扫描量热法、X 射线粉末衍射、固态（1）H 和（13）C NMR 方法相结合，研究了 PEG-g-PVA 的相行为、米康唑在 PEG-g-PVA 中的混溶性以及米康唑在 PEG 和 PVA 无定形相之间的分配。（1）H 磁共振横向磁化弛豫（T（2）弛豫）法用于分析共聚物的相组成和分子迁移率。在所研究的温度范围内，纯 PEG-g-PVA 的 T（2）弛豫衰减可以用四个 T（2）弛豫分量来描述。PVA 结晶度受热熔挤出和药物存在的影响不大。米康唑优先位于 PEG 无定形相中，并且其分子在热熔挤出混合过程中在 PEG-g-PVA 基质中得到良好分散。米康唑形成无定形纳米簇，其平均尺寸约为 1.6nm，表明药物在聚合物中形成无定形固溶体（分子水平分散）。
