Singh Gurinder, Pai Roopa S
a Department of Pharmaceutics, Faculty of Pharmacy , Al-Ameen College of Pharmacy , Bangalore , Karnataka , India.
Drug Deliv. 2016;23(2):532-9. doi: 10.3109/10717544.2014.930760. Epub 2014 Jun 25.
Atazanavir (ATV) is a HIV protease inhibitor. Due to its intense lipophilicity, the oral delivery of ATV encounters several problems such as poor aqueous solubility, pH-dependent dissolution, rapid first-pass metabolism in liver by CYP3A5, which result in low bioavailability. To overcome afore mentioned limitations, ATV-loaded Eudragit RL100 nanoparticles (ATV NPs) were prepared to enhance oral bioavailability. ATV NPs were prepared by nanoprecipitation method. The ATV NPs were systematically optimized (OPT) using 3(2) central composite design (CCD) and the OPT formulation located using overlay plot. The pharmacokinetic study of OPT formulation was investigated in male Wistar rats, and in-vitro/in-vivo correlation level was established. Intestinal permeability of OPT formulation was determined using in situ single pass perfusion (SPIP) technique. Transmission electron microscopy studies on OPT formulation demonstrated uniform shape and size of particles. Augmentation in the values of Ka (2.35-fold) and AUC0-24 (2.91-fold) indicated significant enhancement in the rate and extent of bioavailability by the OPT formulation compared to pure drug. Successful establishment of in vitro/in vivo correlation (IVIVC) Level A substantiated the judicious choice of the in vitro dissolution milieu for simulating the in vivo conditions. In situ SPIP studies ascribed the significant enhancement in absorptivity and permeability parameters of OPT formulation transport through the Peyer's patches. The studies, therefore, indicate the successful formulation development of NPs with distinctly improved bioavailability potential and can be used as drug carrier for sustained or prolonged drug release.
阿扎那韦（ATV）是一种HIV蛋白酶抑制剂。由于其极强的亲脂性，ATV的口服给药面临几个问题，如在水中溶解度差、pH依赖性溶解、在肝脏中被CYP3A5快速首过代谢，这些导致其生物利用度低。为克服上述局限性，制备了载阿扎那韦的Eudragit RL100纳米颗粒（ATV NPs）以提高口服生物利用度。ATV NPs通过纳米沉淀法制备。使用3（2）中心复合设计（CCD）对ATV NPs进行系统优化（OPT），并使用叠加图定位OPT配方。在雄性Wistar大鼠中研究了OPT配方的药代动力学，并建立了体外/体内相关性水平。使用原位单通道灌注（SPIP）技术测定OPT配方的肠道通透性。对OPT配方的透射电子显微镜研究表明颗粒形状和大小均匀。与纯药物相比，OPT配方的Ka值（2.35倍）和AUC0-24（2.91倍）增加表明其生物利用度的速率和程度有显著提高。成功建立体外/体内相关性（IVIVC）A级证实了为模拟体内条件而明智选择体外溶出介质。原位SPIP研究表明OPT配方通过派伊尔结转运的吸收性和通透性参数显著提高。因此，这些研究表明成功开发了具有明显提高的生物利用度潜力的纳米颗粒配方，可作为药物载体用于持续或延长药物释放。
