Chen Lusi, Zhang Xin, Xie Jiayu, Xiao Tao, Zhong Huiying, He Haibing, Zhang Guoqing, Liu Hongfei
College of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, 330004, China.
School of Food and Biological, Wuyi University, Jiangmen, 529000, China.
AAPS PharmSciTech. 2025 Jan 23;26(1):45. doi: 10.1208/s12249-024-03032-0.
Valsartan (VST) is an angiotensin II receptor antagonist with low oral bioavailability. The present study developed a solid self-nanoemulsifying drug delivery system (S-SNEDDS) to enhance the oral absorption and bioavailability of VST. VST-loaded liquid SNEDDS (VST@L-SNEDDS) was prepared by investigating the solubility of VST and constructing the pseudo-ternary phase diagrams. The formulation of VST@S-SNEDDS was obtained by adsorbing VST@L-SNEDDS onto a solid carrier. In vitro studies including drug dissolution, stability, cytotoxicity, and Caco-2 uptake of VST@S-SNEDDS were assessed. An in vivo pharmacokinetic study of VST@S-SNEDDS was employed to evaluate the oral bioavailability of VST. VST@L-SNEDDS, with an average particle size of 19.90 nm and zeta potential of -20.57 mV, consisted of 12.37% VST (drug loading), 21.91% ethyl oleate, 45.50% RH 40, and 20.22% Transcutol HP. VST@S-SNEDDS was prepared using Neusilin® UFL2 as a solid adsorbent, which contained VST@L-SNEDDS at 2.28 ± 0.15 g/g. The in vitro release study demonstrated that VST@S-SNEDDS exhibited rapid release characteristic without affecting by the pH of the media, and dissolution rates exceeded 90% within 60 min in different media. The long-term stability of VST@S-SNEDDS was better than that of VST@L-SNEDDS. These two formulations increased the Caco-2 uptake significantly. The area under the drug concentration-time curve (AUC) and peak drug concentration in plasma (C) of VST@S-SNEDDS increased by 2.28-fold and 4.86-fold compared to raw VST, respectively. The proposed VST@S-SNEDDS represents a novel approach to enhance the oral absorption and bioavailability of VST, providing a promising avenue for hypertension treatment.
缬沙坦（VST）是一种口服生物利用度较低的血管紧张素II受体拮抗剂。本研究开发了一种固体自纳米乳化药物递送系统（S-SNEDDS），以提高VST的口服吸收和生物利用度。通过研究VST的溶解度并构建伪三元相图，制备了载VST的液体SNEDDS（VST@L-SNEDDS）。通过将VST@L-SNEDDS吸附到固体载体上，得到了VST@S-SNEDDS的制剂。评估了VST@S-SNEDDS的体外研究，包括药物溶解、稳定性、细胞毒性和Caco-2摄取。采用VST@S-SNEDDS的体内药代动力学研究来评估VST的口服生物利用度。VST@L-SNEDDS的平均粒径为19.90nm，ζ电位为-20.57mV，由12.37%的VST（载药量）、21.91%的油酸乙酯、45.50%的RH 40和20.22%的二乙二醇单乙基醚组成。以Neusilin® UFL2作为固体吸附剂制备了VST@S-SNEDDS，其含VST@L-SNEDDS的量为2.28±0.15 g/g。体外释放研究表明，VST@S-SNEDDS表现出快速释放特性，不受介质pH值的影响，在不同介质中60分钟内的溶出率超过90%。VST@S-SNEDDS的长期稳定性优于VST@L-SNEDDS。这两种制剂显著增加了Caco-2摄取。与原料药VST相比，VST@S-SNEDDS的药物浓度-时间曲线下面积（AUC）和血浆中药物峰浓度（C）分别增加了2.28倍和4.86倍。所提出的VST@S-SNEDDS代表了一种提高VST口服吸收和生物利用度的新方法，为高血压治疗提供了一条有前景的途径。
