PDF(Pubmed)
Abstract：
This study aimed to enhance the stability of the Rotigotine (ROT) patch using polymers as crystal inhibitors. Three polymers (Poloxamer 188, Soluplus, TPGS) were selected as crystal inhibitors to formulate ROT patches with varying drug loadings (20%, 40%, 60%, and 80%, w/w). SEM and XRD analysis revealed that the Soluplus and Soluplus-TPGS groups with a high concentration (80%, w/w) of ROT could be stored at room temperature for at least 90 days without crystallization. Moreover, the crystallization nucleation time and growth rate were utilized to assess the ability of Poloxamer 188, Soluplus, and TPGS to hinder the formation of ROT crystals and slow down its crystallization rate. Molecular docking results elucidated the intermolecular forces between ROT and different polymers, revealing their mechanisms for crystal inhibition. The ROT-Soluplus-TPGS combination exhibited the lowest binding free energy (-5.3 kcal/mol), indicating the highest binding stability, thereby effectively reducing crystal precipitation. In vitro skin permeation studies demonstrated that ROT patches containing crystal inhibitors exhibited promising transdermal effects. With increasing ROT concentration, the cumulative drug permeation substantially increased, while the lag time was notably reduced. This study offers novel insights for the development of ROT patches.
摘要：
本研究旨在使用聚合物作为晶体抑制剂来增强罗替戈汀(ROT)贴剂的稳定性。三种聚合物（泊洛沙姆188，Soluplus，TPGS）被选为晶体抑制剂，以配制具有不同药物负载的ROT贴剂（20％，40%,60%,80%,w/w）。SEM和XRD分析表明，Soluplus和Soluplus-TPGS基团具有高浓度（80％，w/w）的ROT可以在室温下储存至少90天，而不会结晶。此外，结晶成核时间和生长速率被用来评估泊洛沙姆188，Soluplus，和TPGS阻碍ROT晶体的形成并减慢其结晶速率。分子对接结果阐明了ROT与不同聚合物之间的分子间力,揭示了它们的晶体抑制机制。ROT-Soluplus-TPGS组合表现出最低的结合自由能（-5.3kcal/mol），表示最高的结合稳定性，从而有效地减少晶体沉淀。体外皮肤渗透研究表明，含有晶体抑制剂的ROT贴剂表现出有希望的透皮效果。随着ROT浓度的增加,累积药物渗透大幅增加，而滞后时间明显减少。这项研究为ROT补丁的开发提供了新的见解。
