Yuhan Research Institute, Yuhan Corporation, Yongin 17084, Republic of Korea; School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
Korea Institute of Toxicology, Jinju 52584, Republic of Korea.
Int J Pharm. 2020 Dec 15;591:119998. doi: 10.1016/j.ijpharm.2020.119998. Epub 2020 Oct 22.
The purpose of this study was to develop an oral dosage form of orlistat for the treatment of obesity with reduced adverse effects, for example, fatty and oily stool that have been reported to be associated with the mechanism of action of orlistat. Based on the in vitro results obtained in this study, xanthan gum was selected as an oil-entrapping agent. Thus, the co-administration of mini-tablets containing orlistat and mini-tablets containing xanthan gum was proposed as the optimized dosage form for orlistat. The prepared mini-tablets showed an equivalent drug release profile with a similarity factor value, f, more than 50 to that of commercially marketed orlistat immediate-release capsules, Xenical® capsules. In addition, the optimized formulation also showed the in vivo anti-obesity effects similar to those of Xenical® capsules. In particular, the analysis of feces excreted by Sprague-Dawley rats revealed that the optimized formulation resulted in significantly less oily stool, steatorrhea, than Xenical® capsules (P < 0.05). Consequently, the proposed formulation, the co-administration of mini-tablets containing orlistat and mini-tablets containing xanthan gum, may be considered as a promising anti-obesity treatment with reduced adverse effects related to orlistat.
本研究旨在开发一种奥利司他口服剂型，用于治疗肥胖症，并减少不良反应，例如油性粪便和油性腹泻，这些不良反应与奥利司他的作用机制有关。基于本研究中获得的体外结果，选择黄原胶作为包埋油的制剂。因此，建议将含有奥利司他的迷你片剂和含有黄原胶的迷你片剂共同给药作为奥利司他的优化剂型。所制备的迷你片剂显示出与市售奥利司他速释胶囊（Xenical®胶囊）相当的药物释放特征，相似因子值 f 大于 50。此外，优化配方还显示出与 Xenical®胶囊相似的体内抗肥胖效果。特别是，对 Sprague-Dawley 大鼠粪便的分析表明，与 Xenical®胶囊相比，优化配方导致油性粪便和脂肪泻明显减少（P < 0.05）。因此，所提出的配方，即含有奥利司他的迷你片剂和含有黄原胶的迷你片剂的共同给药，可能被认为是一种有前途的抗肥胖治疗方法，可减少与奥利司他相关的不良反应。
