Elucidating the Molecular Interactions Occurring during Drug Precipitation of Weak Bases from Lipid-Based Formulations: A Case Study with Cinnarizine and a Long Chain Self-Nanoemulsifying Drug Deliver

详细信息    查看全文

• 作者：Philip J. Sassene ; Mette D. Mosgaard ; Korbinian L枚bmann ; Huiling Mu ; Flemming H. Larsen ; Thomas Rades ; Anette M眉llertz
• 刊名：Molecular Pharmaceutics
• 出版年：2015
• 出版时间：November 2, 2015
• 年：2015
• 卷：12
• 期：11
• 页码：4067-4076
• 全文大小：548K
• ISSN：1543-8392

文摘

The aim of this study was to investigate if molecular interactions between the weak base cinnarizine and lipolysis products were affecting the morphology of precipitated drug formed during in vitro lipolysis. In vitro lipolysis studies of a self-nanoemulsifying drug delivery system with or without cinnarizine were conducted. The digestion phases (aqueous phase and pellet phase) were separated by ultracentrifugation, and the pellet was isolated and lyophilized. The lyophilized pellets were examined by X-ray powder diffraction, ¹³C solid-state nuclear magnetic resonance (¹³C NMR), ¹H liquid-state NMR (¹H NMR) spectroscopy and differential scanning calorimetry (DSC). The ¹³C NMR data indicated that the carbonyl groups and aliphatic part of the lipids undergo structural changes when the pellet contains cinnarizine. The ¹H NMR data suggests interactions occurring around the nitrogens on cinnarizine and the carboxylic group of fatty acids. DSC thermograms showed cinnarizine to be homogeneously incorporated into the lipids of the pellet, and no free amorphous cinnarizine was present. The three techniques ¹³C NMR, ¹H NMR, and DSC complement each other and suggest interactions to occur between fatty acids and cinnarizine, which in turn favors amorphous precipitation.