Zhang Lingping, Wahlgren Marie, Bergenståhl Björn
Department of Food Technology, Engineering and Nutrition, Lund University, 221 00 Lund, Sweden.
Pharmaceutics. 2022 Apr 20;14(5):896. doi: 10.3390/pharmaceutics14050896.
Oil-based drug delivery systems have been studied in different aspects. The present study proposes a new application for an oil-based delivery system, focusing on controlled release until the drug reaches the later part of the small intestine. Bulk surfactants and interfacial surfactants were added into the oil formulation to provide a better mechanistic understating of the lipolysis. Validation of the modified in vitro method shows the overall conversion from medium-chain triglyceride oil (MCT oil) to free fatty acids (FFA) of 100 ± 4% in five replicates. This fully converted level and high reproducibility are fundamental for the following investigations where any retarding effect can be distinguished from the experimental errors. The results show that viscosity and thermodynamic activity have limited retardation. Furthermore, the former may change the kinetics of lipolysis, while the latter changes the equilibrium level. The gel-forming retarder (ethylcellulose) displayed a strong effect. Whereas the lipolysis was significantly retarded (>50%) when the retarders altered the interfacial composition (poloxamer 407), degradable interfacial surfactants did not have the same effect. However, surface-active, lipolysis-resistant retarders with a high CMC did not show a retarding effect.
油基药物递送系统已在多个方面进行了研究。本研究提出了油基递送系统的一种新应用，重点是实现控释，直至药物到达小肠后半段。将大量表面活性剂和界面表面活性剂添加到油制剂中，以便更好地从机理上理解脂解作用。对改进后的体外方法进行验证表明，在五次重复实验中，中链甘油三酯油（MCT油）向游离脂肪酸（FFA）的总体转化率为100±4%。这种完全转化水平和高重现性对于后续研究至关重要，在后续研究中，可以将任何阻滞效应与实验误差区分开来。结果表明，粘度和热力学活性的阻滞作用有限。此外，前者可能会改变脂解动力学，而后者会改变平衡水平。凝胶形成阻滞剂（乙基纤维素）显示出强烈的作用。当阻滞剂改变界面组成（泊洛沙姆407）时，脂解作用会显著延迟（>50%），而可降解的界面表面活性剂则没有相同的效果。然而，具有高临界胶束浓度的表面活性、抗脂解阻滞剂并未显示出阻滞作用。
