PDF(Pubmed)
Abstract：
The pharmaceutical industry faces a significant challenge from the low water solubility of nearly 90% of newly developed Active Pharmaceutical Ingredients (APIs). Despite extensive efforts to improve solubility, approximately 40% of these APIs encounter commercialization hurdles, impacting drug efficacy. In this context, a promising strategy will be introduced in which nanosuspensions, particularly polyvinyl alcohol (PVA) as a stabilizer, are applied to increase drug solubility. In this work using molecular dynamics simulations, the nanosuspension of four poorly water-soluble drugs (flurbiprofen, bezafibrate, miconazole, and phenytoin) stabilized with PVA is investigated. The simulation data showed van der Waals energies between polyvinyl alcohol with flurbiprofen and bezafibrate are - 101.12 and - 58.42 kJ/mol, respectively. The results indicate that PVA is an effective stabilizer for these drugs, and superior interactions are obtained with flurbiprofen and bezafibrate. The study also explores the impact of PVA on water molecule diffusion, providing insights into the stability of nanosuspensions. Obtained results also provide valuable insights into hydrogen bond formation, diffusion coefficients, and nanosuspension stability, contributing to the rational design and optimization of pharmaceutical formulations.
摘要：
制药行业面临着近90%新开发的活性药物成分(API)的低水溶性的重大挑战。尽管广泛的努力来提高溶解度，这些原料药中约有40%遇到商业化障碍，影响药物疗效。在这种情况下，一个有前途的战略将被引入，其中纳米悬浮液，特别是聚乙烯醇（PVA）作为稳定剂，用于增加药物溶解度。在这项使用分子动力学模拟的工作中，四种水溶性差的药物(氟比洛芬，苯扎贝特,咪康唑,研究了用PVA稳定的苯妥英）。模拟数据显示聚乙烯醇与氟比洛芬和苯扎贝特之间的范德华能量为-101.12和-58.42kJ/mol，分别。结果表明，PVA是这些药物的有效稳定剂，并且与氟比洛芬和苯扎贝特获得了优异的相互作用。该研究还探讨了PVA对水分子扩散的影响，提供对纳米悬浮液稳定性的见解。获得的结果也为氢键形成提供了有价值的见解，扩散系数，和纳米悬浮稳定性，有助于合理设计和优化药物制剂。
