The aim of the study is to mechanistically investigate the drug loci, structural integrity, chemical interactions, and absorption behavior of the liquid self-microemulsifying drug delivery system (SMEDDS). The loci of drug molecules in self-forming microemulsions in biorelevant media (fasted state simulated gastric fluid and fed state simulated intestinal fluid) were investigated by ¹H and ¹³C nuclear magnetic resonance (NMR) spectroscopy. Chemical interactions were observed through attenuated total reflectance spectroscopy (ATR). The structural integrity of self-forming microemulsions in biorelevant media was determined by small angle X-ray scattering (SAXS) and fluorescence resonance energy transfer (FRET). Morphological features of self-forming microemulsion were determined by confocal laser scanning microscopy. In vitro, lipid digestion behavior was evaluated for particle size, zeta potential, free fatty acids (FFA), and drug released through standard protocols. In-house characterizations were determined through standard methodologies. ¹H and ¹³C NMR revealed that drug loci were found in a majority in the oily core region in the self-forming microemulsion. The ATR signifies that no inherent chemical was observed in the liquid SMEDDS and drug-loaded self-microemulsions in the biorelevant media. Structural integrity was well maintained during the dispersive and digestive phases in the gastrointestinal lumen during lipolysis in biorelevant conditions, as revealed by SAXS and FRET. An in vitro digestion study in biorelevant conditions depicts no fluctuations in size and zeta potential with a predominant release of FFA and drug, and was to be revealed physiologically acceptable for clinical applications.

中文翻译：

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液体自微乳化给药系统在生物相关介质中的生物力学行为评价

本研究的目的是对液体自微乳化给药系统 (SMEDDS) 的药物位点、结构完整性、化学相互作用和吸收行为进行机械研究。通过¹ H 和¹³研究了生物相关介质（禁食状态模拟胃液和进食状态模拟肠液）中自形成微乳中药物分子的位点C 核磁共振 (NMR) 光谱。通过衰减全反射光谱 (ATR) 观察化学相互作用。自形成微乳液在生物相关介质中的结构完整性由小角 X 射线散射 (SAXS) 和荧光共振能量转移 (FRET) 确定。通过共聚焦激光扫描显微镜确定自形成微乳液的形态特征。在体外，评估了通过标准方案释放的颗粒大小、zeta 电位、游离脂肪酸 (FFA) 和药物的脂质消化行为。内部表征是通过标准方法确定的。¹小时和¹³C NMR显示药物位点大部分位于自形成微乳的油性核心区域。ATR 表示在液体 SMEDDS 和生物相关介质中的载药自微乳液中未观察到固有化学物质。正如 SAXS 和 FRET 所揭示的那样，在生物相关条件下的脂肪分解过程中，在胃肠道腔的分散和消化阶段，结构完整性得到了很好的保持。在生物相关条件下进行的体外消化研究表明，尺寸和 zeta 电位没有波动，主要释放 FFA 和药物，并且在临床应用上显示为生理上可接受的。