Improving the solubility of dexlansoprazole by cocrystallization with isonicotinamide

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• 作者：Jianhui Li^a ; ^b ; Lianyan Wang^b ; Yue Qi Ye^c ; Xue Fu^b ; Qinghua Ren^a ; Hailu Zhang^b ; ^{hlzhang2008@sinano.ac.cn" class="auth_mail" title="E-mail the corresponding author} ; Zongwu Deng^b
• 关键词：Pharmaceutical cocrystal ; Proton-pump inhibitor ; Dexlansoprazole ; Intermolecular interaction ; Solubilization
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2016
• 出版时间：31 March 2016
• 年：2016
• 卷：85
• 期：Complete
• 页码：47-52
• 全文大小：1211 K

文摘

Cocrystallization of an active pharmaceutical ingredient (API) with a cocrystal former (co-former) is widely used to tailor the physicochemical properties of parent APIs. For proton-pump inhibitors (PPIs), the isolation of cocrystals has not been widely investigated. Here, a 1:1 cocrystal of a PPI molecule, dexlansoprazole (DLS), was obtained by solvent crystallization with isonicotinamide (INM). The product was characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), solid-state and liquid NMR, as well as Fourier transform infrared spectroscopy (FTIR) techniques. A two-point R₂²(9) hetero-synthon was proposed to exist in the cocrystal, where intermolecular hydrogen bonding occurs between NH, SO groups of DLS and amide of INM. The dissolution profiles of DLS and DLS–INM in water were also collected, and the results demonstrate the cocrystal exhibits superior apparent maximum solubility relative to the pure drug.