期刊
MOLECULAR PHARMACEUTICS
卷 12, 期 4, 页码 1040-1049出版社
AMER CHEMICAL SOC
DOI: 10.1021/mp500510m
关键词
solid dispersions; quantum mechanics; molecular modeling; miscibility; drug-polymer interactions
资金
- Engineering and Physical Sciences Research Council [EP/L000253/1, EP/M022609/1, EP/J003921/1] Funding Source: researchfish
- EPSRC [EP/M022609/1, EP/J003921/1, EP/L000253/1] Funding Source: UKRI
In this study molecular modeling is introduced as a novel approach for the development of pharmaceutical solid dispersions. A computational model based on quantum mechanical (QM) calculations was used to predict the miscibility of various drugs in various polymers by predicting the binding strength between the drug and dimeric form of the polymer. The drug/polymer miscibility was also estimated by using traditional approaches such as Van Krevelen/Hoftyzer and Bagley solubility parameters or FloryHuggins interaction parameter in comparison to the molecular modeling approach. The molecular modeling studies predicted successfully the drugpolymer binding energies and the preferable site of interaction between the functional groups. The drugpolymer miscibility and the physical state of bulk materials, physical mixtures, and solid dispersions were determined by thermal analysis (DSC/MTDSC) and X-ray diffraction. The produced solid dispersions were analyzed by X-ray photoelectron spectroscopy (XPS), which confirmed not only the exact type of the intermolecular interactions between the drugpolymer functional groups but also the binding strength by estimating the N coefficient values. The findings demonstrate that QM-based molecular modeling is a powerful tool to predict the strength and type of intermolecular interactions in a range of drug/polymeric systems for the development of solid dispersions.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据