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通过传统溶剂蒸发法和超临界法制备的卡马西平在聚乙烯吡咯烷酮K30中的固体分散体。

Solid dispersion of carbamazepine in PVP K30 by conventional solvent evaporation and supercritical methods.

作者信息

Sethia S, Squillante E

机构信息

College of Pharmacy and Allied Health Professions, St. John's University, 8000 Utopia Parkway, Jamaica, NY 11439, USA.

出版信息

Int J Pharm. 2004 Mar 19;272(1-2):1-10. doi: 10.1016/j.ijpharm.2003.11.025.


DOI:10.1016/j.ijpharm.2003.11.025
PMID:15019063
Abstract

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) was 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.

摘要

本研究比较了通过传统溶剂蒸发法与超临界流体法制备的卡马西平(CBZ)固体分散体的物理化学性质。制备了卡马西平在聚乙烯吡咯烷酮(PVP)K30中与Gelucire 44/14或维生素E TPGS、NF(d-α-生育酚聚乙二醇1000琥珀酸酯)的固体分散体,并通过特性溶解、差示扫描量热法、粉末X射线衍射和傅里叶变换红外光谱对其进行了表征。CBZ/PVP K30和CBZ/PVP K30/TPGS固体分散体的溶解速率有所提高。超临界处理的CBZ/PVP K30获得了最佳的特性溶解速率(IDR),比纯CBZ高四倍。各种固体分散体的热重曲线未显示出CBZ的熔融峰,表明CBZ在载体系统内呈无定形形式。X射线衍射研究进一步证实了这一点。红外光谱研究表明固体分散体中CBZ与PVP K30之间存在相互作用。CBZ的无定形状态以及药物与PVP K30之间相互作用的存在表明,即使有稳定性问题也较少。由于基于超临界的方法制备的固体分散体的IDR优于添加两亲性载体的传统固体分散体,因此与脂质载体相关的稳定性问题不适用,这反过来意味着在现行药品生产质量管理规范下该技术更容易放大生产。

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