Preparation, characterization and in vitro dissolution study of Nitrazepam: Cyclodextrin inclusion complex.
Preparation, characterization and in vitro dissolution study of Nitrazepam: Cyclodextrin inclusion complex.
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DOI：
10.4103/0975-7406.94158
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发表时间：
2012-03
影响因子：
0.8
通讯作者：
Patel RP
中科院分区：
文献类型：
--
作者：
Patel JS;Patel RP
制备了硝西泮与羟丙基-β-环糊精（HPβCD）和磺丁基醚-β-环糊精（SBEβCD）的包合物，考察了包合物对非水溶性药物硝西泮溶出度的影响。硝西泮与羟丙基- β-环糊精和磺丁基醚-β-环糊精的相溶解度曲线均为AP型，形成了2：1的包合物。吉布斯自由能值均为负值，表明硝西泮的增溶是自发的，其值随环糊精浓度的增加而减小，表明反应条件随环糊精浓度的增加而变得更有利。采用物理混合、捏合、喷雾干燥、冷冻干燥等方法制备了硝西泮环糊精包合物。通过差示扫描量热法、傅里叶变换红外光谱、扫描电子显微镜和粉末X-射线衍射对配合物进行了表征。这些研究表明，通过冻干制备的复合物成功地将硝西泮分子包合到环糊精空腔中。络合导致硝西泮的溶解性和润湿性的显着改善。在所有样品中，通过冻干法与磺丁基醚β-环糊精制备的复合物对硝西泮的体外溶出速率的改善最大。制备复合物后，硝西泮的平均溶出时间显著缩短。相似因子表明，硝西泮从复合物、物理混合物和纯硝西泮的释放曲线之间存在显著差异。综上所述，与含有硝西泮但不含环糊精的片剂相比，含有用环糊精制备的复合物的片剂在硝西泮的释放曲线方面具有显著改善。
The objectives of this research were to prepare and characterize inclusion complexes of Nitrazepam with Hydroxypropyl-β-cyclodextrin (HPβCD) and Sulfobutyl ether β-cyclodextrin (SBEβCD) to study the effect of complexation on the dissolution rate of Nitrazepam, a water-insoluble drug. The phase solubility profile of Nitrazepam with Hydroxypropyl- β-cyclodextrin and Sulfobutyl ether β-cyclodextrin was an AP-type, indicating the formation of 2:1 stoichiometric inclusion complexes. Gibbs free energy values were all negative, indicating the spontaneous nature Nitrazepam solubilization and their value decreased with increase in the cyclodextrin concentration, demonstrating that the reaction conditions became more favorable as the concentration of cyclodextrins increased. Complexes of Nitrazepam were prepared with cyclodextrin using various methods such as physical mixing, kneading, spray-drying and lyophilization. The complexes were characterized by Differential scanning calorimetry, Fourier-transform infrared, scanning electron microscopy and powder X-ray diffraction studies. These studies indicated that a complex prepared by lyophilization had successful inclusion of the Nitrazepam molecule into the cyclodextrin cavity. Complexation resulted in a marked improvement in the solubility and wettability of Nitrazepam. Among all the samples, a complex prepared with Sulfobutyl ether β-cyclodextrin by lyophilization had the greatest improvement in the in vitro rate of Nitrazepam dissolution. The mean dissolution time for Nitrazepam decreased significantly after preparing complexes. The similarity factor indicated a significant difference between the release profiles of Nitrazepam from complexes, physical mixtures and plain Nitrazepam. To conclude that, the tablets containing complexes prepared with Cyclodextrins had significant improvement in the release profile of Nitrazepam as compared to tablets containing Nitrazepam without cyclodextrin.