Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
AAPS PharmSciTech. 2020 Apr 21;21(4):118. doi: 10.1208/s12249-020-01644-w.
Pentoxifylline (PTX), an anti-hemorrhage drug used in the treatment of intermittent claudication, is extensively metabolized by the liver resulting in a reduction of the therapeutic levels within a short duration of time. Self-nano-emulsifying drug delivery system (SNEDDS) is well reported to enhance the bio-absorption of drugs by forming nano-sized globules upon contact with the biological fluids after oral administration. The present study aimed to formulate, characterize, and improve the oral bioavailability of PTX using SNEDDS. The formulated SNEDDS consisted of palm oil, Capmul® MCM, and Tween® 80 as oil, surfactant, and co-surfactant, respectively. The mixture design module under the umbrella of the design of experiments was used for the optimization of SNEDDS. The dynamic light-scattering technique was used to confirm the formation of nanoemulsion based on the globule size, in addition to the turbidity measurements. In vivo bioavailability studies were carried out on male Wistar rats. The pharmacokinetic parameters upon oral administration were calculated using the GastroPlus software. The optimized SNEDDS had a mean globule size of 165 nm with minimal turbidity in an aqueous medium. Bioavailability of PTX increased 1.5-folds (AUC = 1013.30 ng h/mL) as SNEDDS than the pure drug with an AUC of 673.10 ng h/mL. In conclusion, SNEDDS was seen to enhance the bioavailability of PTX and can be explored to effectively control the incidents of intermittent claudication.
己酮可可碱（PTX）是一种用于间歇性跛行治疗的抗出血药物，在短时间内大量代谢，导致治疗水平降低。自微乳给药系统（SNEDDS）通过在口服后与生物体液接触时形成纳米大小的球体，广泛报道可增强药物的生物吸收。本研究旨在通过 SNEDDS 来配方、表征和提高 PTX 的口服生物利用度。所配制的 SNEDDS 由棕榈油、Capmul® MCM 和 Tween® 80 分别作为油、表面活性剂和助表面活性剂组成。在实验设计的伞形下使用混合设计模块对 SNEDDS 进行优化。动态光散射技术用于基于球体大小确认纳米乳液的形成，除了浊度测量。在雄性 Wistar 大鼠上进行了体内生物利用度研究。使用 GastroPlus 软件计算口服给药后的药代动力学参数。优化的 SNEDDS 在水介质中具有 165nm 的平均球体大小和最小浊度。与 AUC 为 673.10ng h/mL 的纯药物相比，SNEDDS 使 PTX 的生物利用度增加了 1.5 倍（AUC=1013.30ng h/mL）。总之，SNEDDS 被认为可以提高 PTX 的生物利用度，可以探索其有效地控制间歇性跛行的发生。
