分子模拟技术对布洛芬固体分散体稳定性分子机制的预测

发布时间：2018-05-29 03:30

本文选题：布洛芬 + 固体分散体　；参考：《沈阳药科大学学报》2017年05期

【摘要】：目的采用分子对接技术预测聚合物诱导的布洛芬固体分散体超饱和分子机制,并采用试验进行验证,为选择合理的辅料将布洛芬制成固体分散体提供依据。方法以PVP-K30、Soluplus、PVP-VA、HPMC-E5和HPMC-AS共5种常见制备固体分散体的载体为研究对象,首先,采用分子对接技术将布洛芬分别与5种载体进行分子对接,预测药物与载体分子间的相互作用;其次,将预测得到且与药物结合比较稳定的载体用来制备固体分散体,并采用差示扫描量热分析法和红外光谱法对固体分散体进行表征,进一步采用溶出度试验对方法的可行性进行验证,从而阐明固体分散体稳定性的机制。结果采用分子对接方法得到了5种辅料和药物的结合能值,其中布洛芬分别与PVP-K30和Soluplus结合的能量较低,其结合能ΔG值分别为(-28.38±0.67)k J·mol-1和(-10.93±0.25)k J·mol-1,得出PVP-K30与布洛芬的结合能强于Soluplus。除此之外,溶出度验证试验结果显示:不仅在p H值为1.2的溶出介质中,以PVP-K30为载体的布洛芬固体分散体较Soluplus易溶出,而且在p H值为7.4的溶出介质中,两种布洛芬固体分散体在30 min时累积溶出量均达到85%,随着试验时间的推移,Soluplus组累积释放度降低,而PVP-K30组累积释放度几乎无变化,表明PVP-K30与布洛芬结合的稳定性较Soluplus好,此验证结果与分子对接预测结果一致。结论通过分子模拟技术可以对固体分散体稳定性分子机制进行预测,并筛选出PVP-K30作为制备布洛芬固体分散体的最佳辅料,为难溶性药物选择合适的辅料制成固体分散体提供了参考依据。
[Abstract]:Objective to predict the suprasaturation molecular mechanism of polymer induced ibuprofen solid dispersion by molecular docking technique, and to verify it by experiments, and to provide the basis for selecting reasonable excipients to prepare ibuprofen into solid dispersion. Methods five kinds of solid dispersion carriers, PVP-K30Soluplusus PVP-VAAHPMC-E5 and HPMC-AS, were used to prepare solid dispersions. Firstly, ibuprofen was docked with five carriers by molecular docking technique to predict the interaction between drug and carrier molecules. The solid dispersion was prepared by using the predicted carrier, which was stable in combination with the drug, and characterized by differential scanning calorimetry (DSC) and infrared spectroscopy (IR). The feasibility of the method was verified by dissolution test to clarify the mechanism of solid dispersion stability. Results the binding energies of five kinds of excipients and drugs were obtained by molecular docking method. The binding energies of ibuprofen to PVP-K30 and Soluplus were lower, and their binding energy 螖 G values were -28.38 卤0.67kJ mol-1 and 10.93 卤0.25kJ mol -1, respectively. The binding energy of ibuprofen and ibuprofen was higher than that of Soluplus. In addition, the results of dissolution verification test showed that ibuprofen solid dispersion with PVP-K30 as carrier was easier to dissolve than Soluplus, not only in dissolution medium with pH value of 1.2, but also in solvent with pH value 7.4. The cumulative dissolution of two ibuprofen solid dispersions at 30 min reached 850.The cumulative release rate of Soluplus group decreased with the passage of experimental time, but the cumulative release rate of PVP-K30 group was almost no change, indicating that the stability of the combination of PVP-K30 and ibuprofen was better than that of Soluplus. The results are in agreement with the predicted results of molecular docking. Conclusion the molecular mechanism of the stability of solid dispersion can be predicted by molecular simulation, and PVP-K30 is selected as the best adjunct for the preparation of ibuprofen solid dispersion. It provides a reference for the preparation of solid dispersions by choosing suitable excipients for dissolving drugs.
【作者单位】：沈阳药科大学药学院;沈阳药科大学制药工程学院;
【分类号】：R943

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