Vippagunta Sudha R, Maul Karin A, Tallavajhala Siva, Grant David J W
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Weaver-Densford Hall, 308 Harvard Street S.E., Minneapolis, MN 55455-0343, USA.
Int J Pharm. 2002 Apr 2;236(1-2):111-23. doi: 10.1016/s0378-5173(02)00019-4.
The purpose of this study is to characterize the nature and solid-state properties of a solid dispersion system of nifedipine (33.3% w/w) in a polymer matrix consisting of Pluronic F68 (33.3% w/w) and Gelucire 50/13 (33.3% w/w). The nature of nifedipine dispersed in the matrix was studied by powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC) and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). The rate and extent of water uptake of the solid dispersion were determined by weight gain. The dissolution rate of nifedipine solid dispersion was determined using Apparatus 2 of USP XXIII (1995). Quantitative PXRD showed that the saturation solubility of nifedipine in the polymer matrix is 2.1-3.0% w/w and indicated an excess of crystalline nifedipine in the solid dispersion. The maximum water uptake by the solid dispersion exposed to 75% RH at 45 degrees C was 3.3 times higher than for the dispersion exposed to 65% RH at 25 degrees C. Over 8 weeks, PXRD and DRIFTS of the nifedipine matrix stored at 25 or 4 degrees C were unchanged, showing constancy of crystallinity and intermolecular interactions. For a given mass of nifedipine (20 mg) and for a given particle size of nifedipine (<850 microm), the initial release rate of nifedipine from the solid dispersion was faster (46.2% of the nifedipine dissolved in 20 min) than that of the pure drug (1.2% of the nifedipine dissolved in 20 min). The results indicate that the nifedipine solid dispersion is physically stable over 8 weeks. Nifedipine is released faster from the solid dispersion than from the pure crystalline drug of the same particle size.
本研究的目的是表征硝苯地平（33.3% w/w）在由普朗尼克F68（33.3% w/w）和Gelucire 50/13（33.3% w/w）组成的聚合物基质中的固体分散体系统的性质和固态性质。通过粉末X射线衍射法（PXRD）、差示扫描量热法（DSC）和漫反射红外傅里叶变换光谱法（DRIFTS）研究了分散在基质中的硝苯地平的性质。通过重量增加测定固体分散体的吸湿速率和程度。使用美国药典XXIII（1995年）的装置2测定硝苯地平固体分散体的溶解速率。定量PXRD表明，硝苯地平在聚合物基质中的饱和溶解度为2.1 - 3.0% w/w，并表明固体分散体中存在过量的结晶硝苯地平。在45℃下暴露于75%相对湿度的固体分散体的最大吸水量比在25℃下暴露于65%相对湿度的分散体高3.3倍。在8周内，储存在25℃或4℃的硝苯地平基质的PXRD和DRIFTS没有变化，表明结晶度和分子间相互作用保持恒定。对于给定质量的硝苯地平（20 mg）和给定粒径的硝苯地平（<850微米），硝苯地平从固体分散体中的初始释放速率更快（20分钟内46.2%的硝苯地平溶解），高于纯药物（20分钟内1.2%的硝苯地平溶解）。结果表明，硝苯地平固体分散体在8周内物理稳定。硝苯地平从固体分散体中的释放比相同粒径的纯结晶药物更快。
