Bibi Hanady Ajine, Holm René, Bauer-Brandl Annette
University of Southern Denmark, Campusvej 55, DK-5230 Odense, Denmark.
Drug Product Development, Janssen Research and Development, Johnson & Johnson, Turnhoutseweg 30, 2340 Beerse, Belgium.
Eur J Pharm Biopharm. 2017 Aug;117:300-307. doi: 10.1016/j.ejpb.2017.05.001. Epub 2017 May 3.
The simultaneous processes of lipid digestion and absorption together determine the oral bioavailability of drugs incorporated into lipid based drug delivery systems (LBDDS). A number of slightly different protocols for in vitro lipolysis are widely accepted; however, the permeation process has so far not been included into the models due to the harsh conditions of lipid digestion compromising permeation barriers. The present study for the first time combines biomimetic permeation and lipolysis of LBDDS. The focus of the current work was on the functional stability of the barrier - Permeapad during lipid digestion. Using calcein as a marker molecule the investigations demonstrated that the barrier was able to maintain its permeation properties in the presence of the SNEDDS (self-emulsifying drug delivery system) formulation, the lipolysis medium, and the lipolysis medium while digesting the SNEDDS. Furthermore, the permeation of cinnarizine (CINN) from SNEDDS was demonstrated to be lower, if the formulation as such was applied as compared to the digested formulation. This support the general perception that meaningful in vitro evaluation of lipid based formulations requires consideration of both, the digestion and absorption, i.e. lipolysis and permeation.
脂质消化和吸收的同步过程共同决定了纳入脂质体药物递送系统（LBDDS）的药物的口服生物利用度。一些略有不同的体外脂解方案已被广泛接受；然而，由于脂质消化的苛刻条件会损害渗透屏障，到目前为止，渗透过程尚未纳入模型中。本研究首次将LBDDS的仿生渗透和脂解结合起来。当前工作重点是脂质消化过程中屏障——Permeapad的功能稳定性。使用钙黄绿素作为标记分子，研究表明，在存在自乳化药物递送系统（SNEDDS）制剂、脂解介质以及消化SNEDDS时的脂解介质的情况下，该屏障能够保持其渗透特性。此外，与消化后的制剂相比，如果直接应用该制剂，西桂利嗪（CINN）从SNEDDS中的渗透被证明较低。这支持了一种普遍观点，即对基于脂质的制剂进行有意义的体外评估需要同时考虑消化和吸收，即脂解和渗透。
