Drug Delivery Systems (DDSs) of known drugs are prominent candidates for new and more effective treatments of various diseases, as they may increase drug solubility, dissolution velocity, and bioavailability. Mitotane (o,p′-dichlorodimethyl dichloroethane [o,p′-DDD]) is used for the treatment of adrenocortical cancer and, occasionally, Cushing’s syndrome. However, the efficacy of mitotane is limited by its low oral bioavailability, caused by its extremely poor aqueous solubility. This research explores the development of a new powder self-emulsifying drug delivery system (P-SEDDS) for mitotane to improve its oral bioavailability. The study focuses on the new concept of a mitotane-loaded P-SEDDS to overcome the challenges associated with its limited solubility and high logP, thereby improving its therapeutic efficacy, reducing off-target toxicity, and avoiding first-pass metabolism. The P-SEDDS formulations were meticulously designed using only α-cyclodextrin and oil, with the goal of achieving a stable and efficient P-SEDDS. The optimized formulation was characterized for pharmaceutical properties, and its pharmacokinetic behavior was examined in rats. The results demonstrated a significant enhancement in the bioavailability of mitotane when delivered through the P-SEDDS, attributed to the increased dissolution velocity and improved absorption of the poorly water-soluble drug. The results suggest that a mitotane-loaded P-SEDDS has distinctly enhanced in vitro and in vivo performance compared with conventional mitotane formulations (Lysodren®), which leads to the conclusion that the P-SEDDS formulation could be a viable and effective strategy for improving the dissolution rate and bioavailability of poorly aqueous-soluble ingredients.

中文翻译：

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米托坦粉末自乳化给药系统：体外和体内评价


已知药物的药物输送系统 (DDS) 是各种疾病的新的、更有效的治疗方法的重要候选者，因为它们可以增加药物的溶解度、溶解速度和生物利用度。米托坦（o,p'-二氯二甲基二氯乙烷 [o,p'-DDD]）用于治疗肾上腺皮质癌，偶尔也用于治疗库欣综合征。然而，米托坦的功效因其水溶性极差而导致其口服生物利用度低而受到限制。本研究探讨了米托坦新型粉末自乳化给药系统（P-SEDDS）的开发，以提高其口服生物利用度。该研究重点关注米托坦负载的P-SEDDS的新概念，以克服其有限溶解度和高logP相关的挑战，从而提高其治疗效果，减少脱靶毒性，并避免首过代谢。 P-SEDDS 配方仅使用 α-环糊精和油精心设计，目标是获得稳定高效的 P-SEDDS。对优化制剂的药物特性进行了表征，并在大鼠中检查了其药代动力学行为。结果表明，通过 P-SEDDS 递送时，米托坦的生物利用度显着增强，这归因于溶解速度的增加和水溶性差的药物的吸收的改善。结果表明，与传统米托坦制剂 (Lysodren®) 相比，负载米托坦的 P-SEDDS 具有明显增强的体外和体内性能，从而得出这样的结论：P-SEDDS 制剂可能是一种可行且有效的改善策略。水溶性差的成分的溶出率和生物利用度。