烯丙孕素固体分散体的制备及其释放度的测定

doi:10.16431/j.cnki.1671-7236.2021.10.008

摘要/Abstract

摘要： 研究旨在提高烯丙孕素（altrenogest，ALT）在水中的分散度及其生物利用率。采用溶剂法（乙基纤维素、羟丙基甲基纤维素、乳糖）和溶剂-熔融法（聚乙二醇6000、单硬脂酸甘油酯、乳糖）制备ALT固体分散体和缓释硅胶栓剂；分别对ALT的线性关系、固体分散体的稳定性、仪器精密度以及加标回收率进行了考察，并用傅里叶变换红外光谱法（FTIR）和显微镜法对其表观形态进行观察鉴定分析，缓释试验测定14 d内ALT缓释度。结果显示，ALT在1~12 μg/mL浓度范围内具有良好的线性关系（R²=0.9996），仪器精密度良好（RSD=0.48%），溶剂法和溶剂-熔融法制备的ALT固体分散体的稳定性考察结果较好，RSD分别为0.57%和0.58%，溶剂法和溶剂-熔融法制备的ALT固体分散体的加标回收率数据之间变异较小，回收率较高；原药和固体分散体的红外光谱图和显微镜成像图均表明形成了ALT固体分散体；溶剂法制备的ALT固体分散体最优组合为ALT∶乙基纤维素∶羟丙基甲基纤维素∶乳糖=1∶0.6∶1∶6；溶剂-熔融法制备ALT固体分散体的最优组合为ALT∶聚乙二醇6000∶单硬脂酸甘油酯∶乳糖=1∶10∶1.5∶6；溶剂法与溶剂-熔融法制备的缓释硅胶栓剂的缓释试验表明，在0~48 h ALT浓度逐步增加，分别于第144和48 h时达到峰值，分别为37.73和30.46 μg/mL，此后分别维持在21和13 μg/mL以上。通过对比，以溶剂法制备的ALT固体分散体缓释效果优于溶剂-熔融法，且该ALT固体分散体的制备方法简单，所用载体原料无毒性，为该固体分散体在体内的进一步应用提供了参考依据。

关键词: 烯丙孕素; 固体分散体制备; 释放度; 傅里叶变换红外光谱法(FTIR); 显微镜成像法

Abstract: The purpose of this study was to improve the dispersion and bioavailability of altrenogest (ALT) in water. The solvent method (ethyl cellulose, hydroxypropyl methyl cellulose, lactose) and solvent-melt method (polyethylene glycol 6000, glycerin monostearate, lactose) were used to preparation the ALT solid dispersions and sustained-release silicone suppository. The linearity, stability of the solid dispersion, precision of the instrument and the recovery rate of the standard were investigated. Fourier transform infrared spectroscopy (FTIR) and microscope were used to observe and analyze its apparent morphology. The sustained-release degree of ALT in 14 d was measured by sustained-release test. The results showed that ALT had a good linear relationship (R²=0.9996) in the concentration range of 1~12 μg/mL, and the instrument precision was good (RSD=0.48%). The stability of ALT solid dispersion prepared by solvent method and solvent-melt method was good, with RSD of 0.57% and 0.58%, respectively. The variation between the spiked recovery data of ALT solid dispersion prepared by solvent method and solvent-melt method was small, and the recovery rate was high. Infrared spectra and microscope images of active agent and solid dispersions showed that ALT solid dispersion was formed. The optimal combination of solvent method to prepare ALT solid dispersion was ethyl cellulose:hydroxypropyl methyl cellulose:lactose=1:0.6:1:6. The optimal combination of solvent-melt method to prepare ALT solid dispersion was PEG6000:glycerol monostearate:lactose=1:10:1.5:6. The sustained-release experiments of the sustained-release silicone suppositorials prepared by solvent method and solvent-melt method showed that the concentration of altrenogest increased gradually from 0-48 h, and reached the peak value of 37.73 and 30.46 μg/mL at 144 and 48 h, respectively, and then remained above 21 and 13 μg/mL, respectively. By comparison, the sustained release effect of the solid dispersion of ALT prepared by solvent method was better than that prepared by solvent-melt method, and the preparation method of the solid dispersion of ALT was simple, and the used carrier materials were non-toxic, which provided a reference basis for the further application of the solid dispersion in vivo.

Key words: altrenogest; preparation of solid dispersion; release degree; Fourier transform infrared spectroscopy (FTIR); microscopic imaging

中图分类号:

S859.7

杨玉帅, 李泽, 杨升. 烯丙孕素固体分散体的制备及其释放度的测定[J]. 中国畜牧兽医, 2021, 48(10): 3575-3584.

YANG Yushuai, LI Ze, YANG Sheng. Preparation and Release Determination of Altrenogest Solid Dispersion[J]. China Animal Husbandry and Veterinary Medicine, 2021, 48(10): 3575-3584.

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