Experimental observations and dissipative particle dynamic simulations on microstructures of pH-sensitive polymer containing amorphous solid dispersions

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• 作者：Mengchi Sun^a ; Bingyu Li^b ; Yanchun Li^b ; Yangdan Liu^c ; Qi Liu^d ; Hailun Jiang^e ; Zhonggui He^a ; Yongshan Zhao^f ; ^{zhao09081@163.com} ; Jin Sun^a ; ^{sunjin66@21cn.com}
• 关键词：Amorphous solid dispersion ; Molecular basis ; Microstructures ; Dissipative particle dynamics
• 刊名：International Journal of Pharmaceutics
• 出版年：2017
• 出版时间：30 January 2017
• 年：2017
• 卷：517
• 期：1-2
• 页码：185-195
• 全文大小：2946 K
• 卷排序：517

文摘

Amorphous solid dispersion (ASD) technique is an effective strategy to increase the dissolution rate of poorly soluble drugs. However, it is inherently unstable, and the molecular basis for achieving kinetic stability is not well understood. In this study, lacidipine-Eudragit_E_100 solid dispersions with 20% drug loading were prepared using the solvent evaporation. Dissolution tested showed that ASD had a significantly high rate, which was dependent on the pH of the medium. Based on time-dependent measurement of supersaturation and particle size, inhibition of crystal growth by Eudragit_E_100 differed at pH 1.2 and 6.8 to a great extent. Dissipative particle dynamic (DPD) simulation revealed that at pH 1.2, the swollen microstructures of the particles were associated with rapid drug release. At pH 6.8, a compacted microstructure of small amorphous particle-aggregated large particles was associated with slow dissolution. The DPD simulation provides insight into the structural basis for experimental observations, and thus is a useful tool to investigate the microstructures of ASD.