Solid dispersion of carbamazepine in PVPK30 by conventional solvent evaporation and supercritical methods
Solid dispersion of carbamazepine in PVPK30 by conventional solvent evaporation and supercritical methods
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DOI：
10.1016/j.ijpharm.2003.11.025
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发表时间：
2004-03-19
影响因子：
5.8
通讯作者：
Squillante, E
中科院分区：
文献类型：
--
作者：
Sethia, S;Squillante, E
本研究比较了传统溶剂挥发法制备卡马西平固体分散体和超临界流体法制备卡马西平固体分散体的理化性质。制备了卡马西平在聚乙烯吡咯烷酮(PVP)K30中的固体分散体，并用本征溶出度、差示扫描量热法、粉末X-射线衍射法和傅立叶变换红外光谱对其进行了表征。CBZ/PVP K30和CBZ/PVP K30/TPGS固体分散体具有较高的溶出度。超临界处理的CBZ/PVP K30的最佳本征溶出度(IDR)Wm是纯CBZ的4倍。不同固体分散体的热图没有显示CBZ的熔融峰，说明CBZ在载体体系中是无定形的。X射线衍射研究进一步证实了这一点。红外光谱研究表明，CBZ与PVP K30在固体分散体中存在相互作用。CBZ的无定形状态，再加上药物和PVP K30之间的相互作用，表明稳定性问题较少。由于超临界工艺生产的固体分散体的IDR比添加了两亲性载体的传统固体分散体更好，因此不存在与脂质载体相关的稳定性问题，这反过来又意味着在当前该技术的良好制造规范下更容易扩大规模。(C)2003爱思唯尔B.V.保留所有权利。
This study compares the physicochemical properties of carbamazepine (CBZ) solid dispersions prepared by either a conventional solvent evaporation versus a supercritical fluid process. Solid dispersions of carbamazepine in polyvinylpyrrolidone (PVP) K30 with either Gelucire 44/14 or Vitamin E TPGS, NF (D-alpha-tocopheryl polyethylene glycol 1000 succinate) were prepared and characterized by intrinsic dissolution, differential scanning calorimetry, powder X-ray diffraction and Fourier transform infrared spectroscopy. CBZ/PVP K30 and CBZ/PVP K30/TPGS solid dispersions showed increased dissolution rate. The best intrinsic dissolution rate (IDR) wm obtained for supercritically processed CBZ/PVP K30 that was four-fold higher than pure CBZ. Thermograms of various solid dispersions did not show the melting peak of CBZ, indicating that CBZ was in amorphous form inside the carrier system. This was further confirmed by X-ray diffraction studies. Infrared spectroscopic studies showed interaction between CBZ and PVP K30 in solid dispersions. The amorphous state of CBZ coupled with presence of interaction between drug and PVP K30 suggests fewer, if any, stability problems. Because the supercritical-based process produced solid dispersions with IDR better than conventional solid dispersions augmented with amphiphilic carriers, stability issues associated with lipid carriers do not apply, which, in turn, implies easier scale up under current Good Manufacturing Practice for this technique. (C) 2003 Elsevier B.V. All rights reserved.