Oral Bioavailability Enhancement of Poorly Soluble Drug by Amorphous Solid Dispersion Using Sucrose Acetate Isobutyrate

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech Pub Date : 2024-09-05 DOI:10.1208/s12249-024-02924-5

Eman M. Mohamed, Sathish Dharani, Tahir Khuroo, Mohammad T. H. Nutan, Phillip Cook, Rajendran Arunagiri, Mansoor A. Khan, Ziyaur Rahman

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Abstract

The focus of the present work was to develop amorphous solid dispersion (ASD) formulation of aprepitant (APT) using sucrose acetate isobutyrate (SAIB) excipient, evaluate for physicochemical attributes, stability, and bioavailability, and compared with hydroxypropyl methylcellulose (HPMC) based formulation. Various formulations of APT were prepared by solvent evaporation method and characterized for physiochemical and in-vivo performance attributes such as dissolution, drug phase, stability, and bioavailability. X-ray powder diffraction indicated crystalline drug conversion into amorphous phase. Dissolution varied as a function of drug:SAIB:excipient proportion. The dissolution was more than 80% in the optimized formulation (F10) and comparable to HPMC based formulation (F13). Stability of F10 and F13 formulations stored at 25 C/60% and 40°C/75% RH for three months were comparable. Both ASD formulations (F10 and F13) were bioequivalent as indicated by the pharmacokinetic parameters C_max and AUC_0-∞. C_max and AUC_0-∞ of F10 and F13 formulations were 2.52 ± 0.39, and 2.74 ± 0.32 μg/ml, and 26.59 ± 0.39, and 24.79 ± 6.02 μg/ml.h, respectively. Furthermore, the bioavailability of ASD formulation was more than twofold of the formulation containing crystalline phase of the drug. In conclusion, stability and oral bioavailability of SAIB based ASD formulation is comparable to HPMC-based formulation of poorly soluble drugs.

Graphical Abstract

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使用异丁酸蔗糖醋酸酯的无定形固体分散体提高难溶性药物的口服生物利用度

本研究的重点是使用蔗糖醋酸异丁酸酯（SAIB）赋形剂开发阿瑞匹坦（APT）的无定形固体分散体（ASD）制剂，评估其理化属性、稳定性和生物利用度，并与基于羟丙基甲基纤维素（HPMC）的制剂进行比较。通过溶剂蒸发法制备了各种 APT 制剂，并对其溶解度、药相、稳定性和生物利用度等理化和体内性能属性进行了表征。X 射线粉末衍射表明结晶药物转化为无定形相。溶解度随药物：SAIB：辅料比例的变化而变化。优化配方（F10）的溶出率超过 80%，与基于 HPMC 的配方（F13）相当。F10 和 F13 制剂在 25°C/60% 和 40°C/75% 相对湿度条件下储存三个月的稳定性相当。根据药代动力学参数 Cmax 和 AUC0-∞，两种 ASD 制剂（F10 和 F13）具有生物等效性。F10 和 F13 制剂的 Cmax 和 AUC0-∞ 分别为 2.52 ± 0.39 和 2.74 ± 0.32 μg/ml，以及 26.59 ± 0.39 和 24.79 ± 6.02 μg/ml.h。此外，ASD 制剂的生物利用度是含结晶相药物制剂的两倍多。总之，基于 SAIB 的 ASD 制剂的稳定性和口服生物利用度与基于 HPMC 的难溶性药物制剂相当。

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来源期刊

AAPS PharmSciTech 医学-药学

CiteScore

6.80

自引率

3.00%

发文量

264

审稿时长

2.4 months

期刊介绍： AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.