烯丙孕素-β-环糊精水溶性衍生物包合物的制备及表征

doi:10.16431/j.cnki.1671-7236.2021.11.019

Abstract

Abstract: In order to improve the water solubility of the poorly soluble drug altrenogest(ALT), this experiment used freeze-drying to prepare altrenogest-hydroxypropyl-β-cyclodextrin (ALT-HP-β-CD) and its derivative 2, 6-dimethyl-β-cyclodextrin (DIME-β-CD) inclusion complex drug-carrying system, the linear relationship and specificity of ALT, the precision of the instrument, and the rate and stability of the inclusion complex were measured. Based on the yield of the inclusion complex and the inclusion rate of ALT in the inclusion complex, the orthogonal test design was used to optimize the optimal preparation conditions of the two types of inclusion complexes, and Fourier transform infrared spectroscopy, thermogravimetric analysis and microscopy imaging methods were used to characterize the prepared ALT inclusion complex, and the solubility method was used to determine the solubility of ALT in the inclusion complex. The results showed that:ALT had a good linear relationship in the range of 1~12 μg/mL, and the specificity was good, and the precision of the instrument was good. The average recoveries of ALT-HP-β-CD inclusion complex with 0.1, 0.2 and 0.3 mL ALT standard solution were 97.78%, 99.38% and 99.90%, respectively. The average recoveries of ALT-DIME-β-CD inclusion complex with 0.1, 0.2 and 0.3 mL of ALT standard solution were 93.86%, 97.72% and 94.93%, respectively. The best preparation process for the inclusion complex of ALT-HP-β-CD was at 55 ℃, the molar ratio of ALT to HP-β-CD was 1:7, the inclusion time was 4 h, the pH of the solution was 8, and the amount of solvent water added was 110 mL/g drug. The best preparation process of the inclusion complex of ALT-DIME-β-CD was at 55 ℃, the molar ratio of ALT to DIME-β-CD was 1:4, the inclusion time was 4 h, the pH of the solution was 9, and the amount of solvent water added was 100 mL/g drug. The inclusion complex was characterized by Fourier infrared spectroscopy, thermogravimetric analysis and microscopy imaging methods. The solubility test showed that the solubility of the inclusion complex was about 1 012 times and 1 354 times of the ALT drug, respectively, indicating that the two inclusion complexes could effectively increase the solubility of ALT. The preparation method of the inclusion complex was simple, the conditions were mild, and it was easy to industrialized production.

Key words: altrenogest(ALT); β-cyclodextrin derivative; freeze-drying method; inclusion complex; characterization

CLC Number:

S859.1

YANG Yushuai, LI Ze, JIN Tianming, YANG Sheng. Preparation and Characterization of Altrenogest-β-cyclodextrin Water-soluble Derivative Inclusion Complex[J]. China Animal Husbandry and Veterinary Medicine, 2021, 48(11): 4094-4104.

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Preparation and Characterization of Altrenogest-β-cyclodextrin Water-soluble Derivative Inclusion Complex

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