Drug Delivery Disposition and Dynamics - Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria, 3052, Australia.
Drug Discovery Biology - Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria, 3052, Australia.
Drug Deliv Transl Res. 2015 Dec;5(6):566-74. doi: 10.1007/s13346-015-0253-z.
Lipid-based liquid crystalline (LC) systems have the potential to sustain the oral absorption of poorly water-soluble drugs in vivo, facilitating slow drug release from their complex internal structure. To further evaluate the dynamic relationship between gastric retention and sustained drug absorption for these systems, this study aimed to explore non-invasive X-ray micro-CT imaging as an approach to assess gastric retention. Pharmacokinetic studies were also conducted with cinnarizine-loaded LC formulations to correlate gastric retention of the formulation to drug absorption. The in vivo studies demonstrated the interplay between gastric retention and drug absorption based on the digestibility of the LC structures. An increase in non-digestible phytantriol (PHY) composition in the formulation relative to digestible glyceryl monooleate (GMO) increased the gastric retention, with 68 ± 4 % of formulation intensity remaining at 8 h for 85 % w/w PHY, and 26 ± 9 % for 60 % w/w PHY. Interestingly, it was found that PHY 30 % w/w in GMO provided the highest bioavailability for cinnarizine (CZ) amongst the other combinations, including GMO alone. The studies demonstrated that combining digestible and non-digestible lipids into LC systems allowed for an optimal balance between sustaining drug absorption whilst increasing plasma concentration (C max) over time, leading to enhanced oral bioavailability. The results demonstrate the potential for utilising non-invasive X-ray micro-CT imaging to dynamically assess the GI transit of orally administered liquid crystal-forming formulations.
基于脂质的液晶（LC）系统具有在体内维持难溶性药物口服吸收的潜力，通过其复杂的内部结构来实现药物的缓慢释放。为了进一步评估这些系统的胃滞留与持续药物吸收之间的动态关系，本研究旨在探索非侵入性 X 射线微 CT 成像作为评估胃滞留的方法。还进行了肉桂嗪负载 LC 制剂的药代动力学研究，将制剂的胃滞留与药物吸收相关联。体内研究基于 LC 结构的可消化性，证明了胃滞留与药物吸收之间的相互作用。与可消化的单油酸甘油酯（GMO）相比，制剂中不可消化的植物三醇（PHY）的组成增加会增加胃滞留，85%w/w PHY 的制剂强度在 8 小时时保持 68±4%，而 60%w/w PHY 的制剂强度保持 26±9%。有趣的是，发现 PHY 30%w/w 在 GMO 中为肉桂嗪（CZ）提供了最高的生物利用度，而其他组合，包括单独的 GMO，则不然。这些研究表明，将可消化和不可消化的脂质结合到 LC 系统中，可以在维持药物吸收的同时，随着时间的推移增加血浆浓度（C max），从而提高口服生物利用度，达到最佳平衡。研究结果表明，利用非侵入性 X 射线微 CT 成像技术来动态评估口服给予的形成液晶的制剂在胃肠道中的转运是有潜力的。
