水溶性烯丙孕素-磺丁基-β-环糊精包合物的制备及表征

旨在提高烯丙孕素原药在水中的溶解度，提高烯丙孕素原药的生物利用度，使用磺丁基-β-环糊精对烯丙孕素原药进行包合。本试验使用冷冻干燥法来制备烯丙孕素-磺丁基-β-环糊精包合物，以此来解决烯丙孕素在临床使用中因其水不溶性而受到限制及其使用后生物利用度低的问题，进而拓宽烯丙孕素的药用途径。通过傅里叶变换红外光谱法、热重分析法和显微镜成像法对所制得的烯丙孕素包合物进行表征，并用溶解度法对包合物进行溶解度测定。以包合物的收率和包合率为评价指标，筛选最优的包合物制备条件。结果显示：经筛选，包合物的最佳制备条件：在55℃，ALT与SBE-β-CD的投料摩尔比为1：6，包合时间为5 h，溶液pH为8，溶剂量为15 mL（当以ALT投药量为0.1 g时计）；以最优制备条件制备所得的包合物中ALT的平均包合率为（90.90±1.80）%（n=3），平均载药量为（4.30±2.30）%（n=3），包合物的收率为（93.19±1.67）%。经傅里叶变换红外光谱法、热重分析法和显微镜成像法对所制得的包合物进行表征，可证实成功制得包合物。溶解度法试验结果表明，形成包合物后，其溶解度较烯丙孕素原药提高了988.86倍，且该包合物稳定性好，可满足不同剂型的要求。磺丁基-β-环糊精对烯丙孕素原药具有较好的增溶作用，达到了增加药物溶解度的目的，且该制备方法简单，条件温和，易于产业化生产，有利于烯丙孕素的进一步开发利用。

Preparation and Characterization of a Water-soluble Inclusion Complex of Altrenogest-sulfobutyl Ether-β-cyclodextrin

To improve the water solubility and bioavailability of altrenogest (ALT), sulfobutyl ether-β-cyclodextrin (SBE-β-CD) was used to encapsulate ALT. In this study, the freeze-drying method was used to prepare the inclusion complex of ALT-SBE-β-CD, to solve the problems of limited clinical use of ALT due to its water insolubility and low bioavailability, so as to broaden the medicinal way of ALT. The inclusion complexes were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis and microscopy, and the solubility of the inclusion complex was determined by the solubility method. Taking the yield and inclusion rate of inclusion complex as evaluation indexes, the optimal preparation conditions of inclusion complex were selected. The optimal preparation conditions were as follows:at 55℃, the molar ratio of ALT to SBE-β-CD was 1:6, the inclusion time was 5 h, the pH value of the solution was 8, and the amount of solvent was 15 mL (when the dosage of ALT was 0.1 g). The average inclusion rate of ALT was (90.90±1.80)% (n=3), the average drug loading was (4.30±2.30)% (n=3), and the yield of the inclusion complex was (93.19±1.67)%. By Fourier transform infrared spectroscopy, thermogravimetric analysis and microscope imaging method for characterizing the inclusion complex was prepared by, verifiable inclusion complex was successful, solubility method, the test results show that the formation of inclusion complex, its solubility is ALT technical increased 988.86 times, and the inclusion complex has good stability, can meet the requirements of different dosage forms. SBE-β-CD has a good solubilization effect on the drug, which can increase the solubility of the ALT. The preparation method is simple, the conditions are mild, and it is easy for industrial production, which is conducive to the further development and utilization of the drug.