从超饱和脂质的药物递送系统中探索沉淀抑制剂改善Cinnarizine的体内吸收

越来越多地探讨过饱和的脂质的药物递送系统作为生物能力的配方方法，特别是在较低水溶性药物的临床前评价中。在通过热诱导的过饱和增加药物负荷导致某些药物的体内暴露中产生增强，对于其他药物，例如Cinnarizine，未发现过饱和的基于脂质的系统，没有有利于增加体内生物利用度。我们假设掺入沉淀抑制剂以减少药物沉淀可能解决这一限制。因此，比较了具有或不含沉淀抑制剂的诱导型基于基于脂质的药物递送系统的诱导型诱导物的药代动力学谱。选择五种沉淀抑制剂，用于基于二十一赋料的高通量筛选进行研究。In vivo results showed that addition of 5% precipitation inhibitors to long chain monoglyceride (LCM) or medium chain monoglyceride (MCM) formulations showed a general trend of increases in cinnarizine bioavailability, albeit only statistically significantly increased for Poloxamer 407 + LCM system (i.e. 2.7-fold increase in AUC0-24h compared to LCM without precipitation inhibitors). It appeared that precipitation inhibitors mitigated the risk of in vivo precipitation of cinnarizine from sLBDDS and overall, bioavailability was comparable to that previously reported for cinnarizine after dosing of non-supersaturated lipid systems. In summary, for drugs which are prone to precipitation in supersaturated lipid-based drug delivery systems, such as cinnarizine, inclusion of precipitation inhibitors mitigates this risk and provides the opportunity to maximize exposure which is ideally suited in early efficacy and toxicology evaluation.继续阅读如何从超饱和脂质的药物递送系统中改善Cinnarizine的体内吸收

关键词：超饱和脂质的药物递送系统，沉淀抑制剂，高通量筛选，生物能力配方，药代动力学谱，soluplus.那维生素E-TPGS