Abstract

The markedly low oral bioavailability of domperidone (anti-emetic drug) is associated with rapid first-pass metabolism in the intestine and liver. To counteract such affects, there is a need to devise a strategy to enhance absorption and subsequently bioavailability. Thus, the current study was aimed at synthesizing phytosomes consisting of phosphatidylcholine and piperine (a P-glycoprotein inhibitor). Phytosomes were prepared by salting-out method. The developed phytosomes were extensively characterized for size, zeta potential, polydispersity index, entrapment efficiency (EE %), infra-red spectroscopy, X-ray diffraction, in vitro drug release, ex vivo permeation, in vivo pharmacokinetic and toxicity. The engineered formulations of phytosomes with piperine exhibited a significant improvement in oral bioavailability of domperidone (79.5%) in comparison with the pure drug suspension under the same conditions. Pharmacokinetic parameters such as maximal plasma concentration (C_max) and the plasma concentration (estimated from area under the curve; AUC) of domperidone have been greatly increased relative to drug alone. The improved drug absorption was attributed to inhibition of P-glycoprotein transporter. The findings of current research work suggest that the optimized phytosomes based drug delivery containing phytochemicals as bioenhancers have the potential to improve bioavailability of poorly bioavailable drugs that are substrate to P-glycoprotein.

摘要

多潘立酮（止吐药）的显着低口服生物利用度与肠道和肝脏中快速的首过代谢有关。为了抵消这种影响，需要设计一种策略来增强吸收和随后的生物利用度。因此，目前的研究旨在合成由磷脂酰胆碱和胡椒碱（一种 P-糖蛋白抑制剂）组成的植物体。采用盐析法制备植物体。开发的植物体在大小、zeta 电位、多分散指数、包封率 (EE%)、红外光谱、X 射线衍射、体外药物释放、离体渗透、体内药代动力学和毒性。与相同条件下的纯药物混悬液相比，含有胡椒碱的植物体工程制剂在多潘立酮的口服生物利用度（79.5%）方面表现出显着提高。与单独使用药物相比，多潘立酮的药代动力学参数，例如最大血浆浓度 (C _max ) 和血浆浓度（根据曲线下面积估计；AUC）已大大增加。药物吸收的改善归因于对 P-糖蛋白转运蛋白的抑制。当前研究工作的结果表明，优化的基于植物体的药物递送含有植物化学物质作为生物增强剂，有可能提高作为 P-糖蛋白底物的低生物利用度药物的生物利用度。