Solvent-shift strategy to identify suitable polymers to inhibit humidity-induced solid-state crystallization of lacidipine amorphous solid dispersions

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• 作者：Mengchi Sun^a ; Chunnuan Wu^b ; Qiang Fu^a ; Donghua Di^a ; Xiao Kuang^a ; Chao Wang^c ; Zhonggui He^a ; Jian Wang^d ; ^{jianwang@syphu.edu" class="auth_mail" title="E-mail the corresponding author} ; Jin Sun^a ; ^e ; ^{sunjin66@21cn.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：The solvent-shift strategy ; Humidity-induced solid-state crystallization ; Molecular docking ; Drug&ndash ; polymer interactions ; Water uptake
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：30 April 2016
• 年：2016
• 卷：503
• 期：1-2
• 页码：238-246
• 全文大小：1754 K

文摘

The solvent-shift strategy was used to identify appropriate polymers that inhibit humidity-induced solid-state crystallization of amorphous solid dispersions (ASDs). Lacidipine with the polymers, PVP-K30, HPMC-E5 or Soluplus, were combined to form amorphous solid dispersions prepared by solvent evaporation. The formulations were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier-transform infrared spectroscopy (FT-IR) and were subjected to in vitro dissolution testing. The moisture had a significant impact on the amount dissolved for the solid dispersions. Molecular docking studies established that hydrogen bonding was critical for the stabilization of the solid dispersions. The rank order of the binding energy of the drug–polymer association was Soluplus (−6.21 kcal/mol) > HPMC-E5 (−3.21 kcal/mol) > PVP-K30 (−2.31 kcal/mol). PVP-K30 had the highest water uptake among the polymers, as did ASD system of lacidipine-PVP-K30 ASDs. In the Soluplus ASDs, with its strong drug–polymer interactions and low water uptake, moisture-induced solid-state crystallization was not observed.