Abstract：
Inclusion complexes require higher concentration of Beta cyclodextrins (βCD) resulting in increased formulation bulk, toxicity, and production costs. This systematic review offers a comprehensive analysis using Quality by design (QbD) as a tool to predict potential applications of Polyvinylpyrrolidone (PVP) as a ternary substance to address issues of inclusion complexes. We reviewed 623 documents from 2013 to 2023 and Eighteen (18) research papers were selected for statistical and meta-analysis using the QbD concept to identify the most critical factors for selecting drugs and effect of PVP on inclusion complexes. The QbD analysis revealed that Molecular weight (MW), Partition coefficient (Log P), and the auxiliary substance ratio directly affected complexation efficiency (CE), thermodynamic stability in terms of Gibbs free energy (ΔG), and percent drug release. However, Stability constant (Ks) remained unaffected by any of these parameters. The results showed that low MW (250), median Log P (6), and a βCD: PVP ratio of 2:3 would result in higher CE, lower G, and improved drug release. PVP improves drug solubility, enhances delivery and therapeutic outcomes, and counteracts increased drug ionization due to decreased pH. In certain cases, its bulky nature and hydrogen bonding with CD molecules can form non-inclusion complexes. The findings of the study shows that there is potential molecular interaction between PVP and β-cyclodextrins, which possibly enhances the stability of inclusion complexes for drug with low MW and log P values less than 9. The systematic review shows a comprehensive methodology based on QbD offers a replicable template for future investigations into drug formulation research.
摘要：
包合物需要更高浓度的β环糊精（βCD），导致制剂体积增加，毒性,和生产成本。本系统综述使用设计质量（QbD）作为预测聚乙烯吡咯烷酮（PVP）作为三元物质解决包合物问题的潜在应用的工具，提供了全面的分析。我们回顾了2013年至2023年的623篇文献，并使用QbD概念选择了18篇研究论文进行统计和荟萃分析，以确定选择药物和PVP对包合物影响的最关键因素。QbD分析显示分子量(MW)，分配系数(LogP),和辅助物质比例直接影响络合效率(CE)，以吉布斯自由能(ΔG)表示的热力学稳定性，和药物释放百分比。然而,稳定常数(Ks)保持不受任何这些参数的影响。结果表明，低MW(250)，中位数对数P（6），βCD：PVP比为2：3会导致更高的CE，较低的G，和改善药物释放。PVP提高药物溶解度，增强分娩和治疗效果，并抵消由于pH降低而导致的药物电离增加。在某些情况下,其庞大的性质和与CD分子的氢键可以形成非包合物。研究结果表明，PVP和β-环糊精之间存在潜在的分子相互作用，这可能增强了低MW和logP值小于9的药物的包合物的稳定性。系统评价表明，基于QbD的综合方法为未来的药物制剂研究提供了可复制的模板。
