Dahan Arik, Hoffman Amnon
Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA.
J Control Release. 2008 Jul 2;129(1):1-10. doi: 10.1016/j.jconrel.2008.03.021. Epub 2008 Apr 1.
As a consequence of modern drug discovery techniques, there has been a consistent increase in the number of new pharmacologically active lipophilic compounds that are poorly water soluble. A great challenge facing the pharmaceutical scientist is making these molecules into orally administered medications with sufficient bioavailability. One of the most popular approaches to improve the oral bioavailability of these molecules is the utilization of a lipid based drug delivery system. Unfortunately, current development strategies in the area of lipid based delivery systems are mostly empirical. Hence, there is a need for a simplified in vitro method to guide the selection of a suitable lipidic vehicle composition and to rationalize the delivery system design. To address this need, a dynamic in vitro lipolysis model, which provides a very good simulation of the in vivo lipid digestion process, has been developed over the past few years. This model has been extensively used for in vitro assessment of different lipid based delivery systems, leading to enhanced understanding of the suitability of different lipids and surfactants as a delivery system for a given poorly water soluble drug candidate. A key goal in the development of the dynamic in vitro lipolysis model has been correlating the in vitro data of various drug-lipidic delivery system combinations to the resultant in vivo drug profile. In this paper, we discuss and review the need for this model, its underlying theory, practice and limitations, and the available data accumulated in the literature. Overall, the dynamic in vitro lipolysis model seems to provide highly useful initial guidelines in the development process of oral lipid based drug delivery systems for poorly water soluble drugs, and it predicts phenomena that occur in the pre-enterocyte stages of the intestinal absorption cascade.
由于现代药物发现技术的发展，新的具有药理活性的亲脂性化合物数量持续增加，而这些化合物的水溶性很差。制药科学家面临的一大挑战是将这些分子制成具有足够生物利用度的口服药物。提高这些分子口服生物利用度最常用的方法之一是利用基于脂质的药物递送系统。不幸的是，目前基于脂质的递送系统领域的开发策略大多是经验性的。因此，需要一种简化的体外方法来指导合适脂质载体组合物的选择，并使递送系统设计合理化。为满足这一需求，在过去几年中开发了一种动态体外脂解模型，该模型能很好地模拟体内脂质消化过程。该模型已被广泛用于不同基于脂质的递送系统的体外评估，从而加深了对不同脂质和表面活性剂作为给定难溶性候选药物递送系统适用性的理解。动态体外脂解模型开发的一个关键目标是将各种药物 - 脂质递送系统组合的体外数据与体内药物概况相关联。在本文中，我们讨论并综述了该模型的需求、其基础理论、实践和局限性，以及文献中积累的现有数据。总体而言，动态体外脂解模型似乎为难溶性药物的口服脂质基药物递送系统的开发过程提供了非常有用的初步指导，并且它预测了肠道吸收级联中肠上皮细胞前阶段发生的现象。
