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解析麦芽糊精掩味能力中的分子力学:为病毒大流行开发奥司他韦的儿科制剂。

Deciphering molecular mechanics in the taste masking ability of Maltodextrin: Developing pediatric formulation of Oseltamivir for viral pandemia.

机构信息

University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India.

Schrodinger Inc., RR Nagar, Bangalore, 560098, India.

出版信息

Carbohydr Polym. 2021 May 15;260:117703. doi: 10.1016/j.carbpol.2021.117703. Epub 2021 Jan 28.

Abstract

Present research work was aimed at masking the bitter taste of anti- viral drug Oseltamivir phosphate (Ost) by complexing it with pea starch maltodextrin- Kleptose Linecaps® (Mld). The Ost groups involved in triggering the bitter sensation were identified by computationally assessing its interaction with human bitter taste receptor hTAS2R 38. A series of exhaustive molecular dynamics (MD) simulation was run using Schrodinger® suite to understand the type of interaction of Ost with Mld. Experimentally, complexes of Ost with Mld were realized by solution method. The complexes were characterized using differential scanning colorimetry (DSC), fourier transform-infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), hot stage microscopy (HSM), scanning electron microscopy (SEM), proton NMR (H-NMR) and Carbon-13 nuclear magnetic resonance (C-NMR). Ost-oral dispersible mini tablets (ODMT) were prepared by direct compression and optimised using mixture designs. Finally, bitter taste perception of Ost-ODMT was evaluated in healthy human volunteers of either sex. Computational assessment, involving interaction of Ost with bitter receptor, predicted the involvement of free amino group of Ost in triggering the bitter response whereas, MD simulation predicted the formation of stable complex between Ost and double helical confirmation of Mld. Different characterization techniques confirmed the findings of MD simulation. Results from the taste assessment in human volunteers revealed a significant reduction in bitter taste of prepared Ost-ODMT.

摘要

本研究旨在通过将抗病毒药物奥司他韦磷酸盐(Ost)与豌豆淀粉麦芽糊精-Kleptose Linecaps®(Mld)复合,掩盖其苦味。通过计算评估其与人苦味受体 hTAS2R38 的相互作用,确定了引发苦味感的 Ost 基团。使用 Schrodinger®套件进行了一系列详尽的分子动力学(MD)模拟,以了解 Ost 与 Mld 的相互作用类型。实验上,通过溶液法实现了 Ost 与 Mld 的复合物。使用差示扫描量热法(DSC)、傅里叶变换-红外光谱(FT-IR)、粉末 X 射线衍射(PXRD)、热台显微镜(HSM)、扫描电子显微镜(SEM)、质子 NMR(H-NMR)和碳-13 核磁共振(C-NMR)对复合物进行了表征。通过直接压缩制备了 Ost-口腔分散片(ODMT),并使用混合设计进行了优化。最后,在健康的男女志愿者中评估了 Ost-ODMT 的苦味感知。涉及 Ost 与苦味受体相互作用的计算评估预测了 Ost 的游离氨基基团参与引发苦味反应,而 MD 模拟预测了 Ost 与双螺旋结构的 Mld 之间形成稳定复合物。不同的特征化技术证实了 MD 模拟的结果。人类志愿者味觉评估的结果表明,制备的 Ost-ODMT 的苦味显著降低。

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