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

Abstract

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

CLC Number:

S859.79

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.

Figures/Tables 12

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References 25

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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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Preparation of Altrenogest Solid Dispersions by Freeze-drying

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水平 Level	药载比(A) Drug-to-carrier ratio(A)	叔丁醇浓度(B)/% Tert-Butanol concentration (B)	超声时间(C)/min Ultrasound time(C)
1	1∶7	30	40
2	1∶8	40	60
3	1∶9	50	80