Patel R, Patel M
Department of Pharmaceutics, S. K. Patel College of Pharmaceutical Education and Research, Ganpat University, Kherva, Gujarat, India.
Drug Discov Ther. 2010 Dec;4(6):442-52.
The objectives of this research were to prepare and characterize inclusion complexes of lorazepam with hydroxypropyl-β-cyclodextrin and to study the effect of complexation on the dissolution rate of lorazepam, a water-insoluble drug. The phase solubility profile of lorazepam with hydroxypropyl-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 of lorazepam solubilization, and they decreased with an increase in the cyclodextrin concentration, demonstrating that the reaction conditions became more favorable as the concentration of cyclodextrins increased. Complexes of lorazepam 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 lorazepam molecule into the cyclodextrin cavity. Complexation resulted in a marked improvement in the solubility and wettability of lorazepam. Among all the samples, a complex prepared with hydroxypropyl-β-cyclodextrin by lyophilization had the greatest improvement in the in vitro rate of lorazepam dissolution. The mean dissolution time for lorazepam decreased significantly after preparing complexes and physical mixtures of lorazepam with cyclodextrin. The similarity factor indicated a significant difference between the release profiles of lorazepam from complexes and physical mixtures and from plain lorazepam. Tablets containing complexes prepared with cyclodextrins had significant improvement in the release profile of lorazepam as compared to tablets containing lorazepam without cyclodextrin.
本研究的目的是制备并表征劳拉西泮与羟丙基-β-环糊精的包合物，并研究包合作用对水不溶性药物劳拉西泮溶出速率的影响。劳拉西泮与羟丙基-β-环糊精的相溶解度曲线为AP型，表明形成了化学计量比为2:1的包合物。吉布斯自由能值均为负值，表明劳拉西泮增溶过程具有自发性，且随着环糊精浓度的增加而降低，这表明随着环糊精浓度的增加，反应条件变得更加有利。采用物理混合、捏合、喷雾干燥和冻干等多种方法，用环糊精制备了劳拉西泮包合物。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射线衍射研究对包合物进行了表征。这些研究表明，冻干法制备的包合物成功地将劳拉西泮分子包合到环糊精腔内。包合作用使劳拉西泮的溶解度和润湿性显著提高。在所有样品中，用羟丙基-β-环糊精通过冻干法制备的包合物对劳拉西泮体外溶出速率的改善最大。制备劳拉西泮与环糊精的包合物和物理混合物后，劳拉西泮的平均溶出时间显著缩短。相似因子表明，劳拉西泮从包合物和物理混合物中的释放曲线与纯劳拉西泮的释放曲线之间存在显著差异。与不含环糊精的劳拉西泮片剂相比，含环糊精制备的包合物的片剂在劳拉西泮释放曲线方面有显著改善。
