利用冷冻干燥法制备四烯雌酮固体分散体

doi:10.11843/j.issn.0366-6964.2024.09.037

摘要/Abstract

摘要：

本研究旨在制备四烯雌酮(altrenogest, ALT)固体分散体, 提高四烯雌酮的溶解度及其生物利用度, 为其在实际生产中的应用提供参考依据。以聚乙烯吡洛烷酮K30(polyvinyl pyrrolidone k30, PVPK30)为药物载体, 叔丁醇为冻干溶剂, 冷冻干燥法制备四烯雌酮固体分散体。以固体分散体体外溶出度为评价指标对所得ALT固体分散体的质量进行评估, 采用X射线衍射法(X-ray diffraction, XRD)、同步热分析法(simultaneous thermal analysis, TG-DSC)、傅里叶红外光谱法(Fourier transform infrared spectroscopy, FT-IR)、扫描电镜法(scanning electron microscopy, SEM)等方法来描绘其特性, 并研究其在体外的溶出规律。结果显示, 四烯雌酮固体分散体最优制备工艺为药载比1∶8, 叔丁醇浓度为50%, 超声时间80 min。固体分散体在pH为7.4的PBS缓冲液中的平衡溶解度为原料药的5.91倍, 1∶8混合物的3.65倍, 固体分散体6 h体外累积溶出率为89.09%, ALT原料药和物理混合物的累积溶出率为32.94%、28.93%。综上所述, 此方法制备的固体分散体能够有效提高四烯雌酮原料药的溶解度。

关键词: 四烯雌酮, 冷冻干燥法, 固体分散体, 溶解度

Abstract:

The aim of this study was to prepare altrenogest (ALT) solid dispersion, improve the solubility and bioavailability of altrenogest, and provide a reference for its application in actual production. ALT solid dispersion was prepared by freeze-drying method with polyvinyl pyrrolidone k30 (PVPK30) as the drug carrier and tert-butanol as the lyophilized solvent. X-ray diffraction (XRD), simultaneous thermal analysis (TG-DSC), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and other methods were used to characterize the properties. The results showed that the optimal preparation process of tetraene estrone solid dispersion was as follows: drug loading ratio of 1∶8, tert-butanol concentration of 50%, and ultrasonic time of 60 min. The equilibrium solubility of the solid dispersion in pH 5.0 buffer was 5.91 times that of the active pharmaceutical ingredient (API), 3.65 times that of the 1∶8 mixture, the cumulative dissolution rate of the solid dispersion in vitro for 6 h was 89.09%, and the cumulative dissolution rates of the ALT active ingredient and the physical mixture were 32.94% and 28.93%. In summary, the solid dispersion prepared by this method can effectively improve the solubility of altrenogest API.

Key words: ALT, freeze-drying method, solid dispersions, solubility

中图分类号:

S859.79

朱珍珍, 刘大虎, 杨升. 利用冷冻干燥法制备四烯雌酮固体分散体[J]. 畜牧兽医学报, 2024, 55(9): 4131-4140.

Zhenzhen ZHU, Dahu LIU, Sheng YANG. Preparation of Altrenogest Solid Dispersions by Freeze-drying[J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(9): 4131-4140.

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序号 S/N	A	B	C	溶出度/% Dissolution
1	1	3	2	99.211
2	2	1	3	74.929
3	1	1	1	61.101
4	3	1	2	51.960
5	3	2	1	92.237
6	1	2	3	92.370
7	2	2	2	95.744
8	2	3	1	96.560
9	3	3	3	95.820
K1	252.682	187.93	249.898
K2	267.233	280.351	246.915
K3	240.017	291.591	263.119
k1	84.227	62.643	83.299
k2	89.078	93.450	82.305
k3	80.006	97.197	87.706
R	9.072	34.554	5.401	B＞A＞C

因素 Factor	偏差平方和 Sum of squares of deviation	自由度 Degrees of freedom	均方 Mean square	F值 F-value	P
A	123.649	2	61.825	1.140	＞0.05
B	2 154.451	2	1 077.226	19.862	＜0.05
C	49.585	2	24.792	0.457	＞0.05
误差 Error	108.473	2	54.236

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