NDLI: Development of self-nanoemulsifying drug delivery system for oral bioavailability enhancement of valsartan in beagle dogs

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Development of self-nanoemulsifying drug delivery system for oral bioavailability enhancement of valsartan in beagle dogs

Content Provider	Springer Nature Link
Author	Li, Zhenbao Zhang, Wenjuan Gao, Yan Xiang, Rongwu Liu, Yan Hu, Mingming Zhou, Mei Liu, Xiaohong Wang, Yongjun He, Zhonggui Sun, Yinghua Sun, Jin
Copyright Year	2016
Abstract	Valsartan, an angiotensin II receptor antagonist, is widely used to treat high blood pressure in the clinical setting. However, its poor water solubility results in the low oral bioavailability. The aim of this study was to improve dissolution rate and oral bioavailability by developing a self-nanoemulsifying drug delivery system. Saturation solubility of valsartan in various oils, surfactants, and cosurfactants was investigated, and the optimized formulation was determined by central composite design-response surface methodology. The shape of resultant VAL-SNEDDS was spherical with an average diameter of about 27 nm. And the drug loading efficiency is approximately 14 wt%. Differential scanning calorimetry and XRD studies disclosed the molecular or amorphous state of valsartan in VAL-SNEDDS. The dissolution study indicated that the self-nanoemulsifying drug delivery systems (SNEDDS) exhibited significantly enhanced dissolution compared with market capsules (Diovan®) in various media. Furthermore, the stability of formulation revealed that valsartan SNEDDS was stable under low temperature and accelerated test condition. Furthermore, the pharmacokinetics demonstrated that C $_{max}$ and AUC$_{(0-∞)}$ of SNEDDS capsules were about three- and twofold higher than Diovan® in beagle dogs, respectively. Meanwhile, the safety evaluation implied that VAL-SNEDDS was innocuous to beagle dogs during 15 days of continuous administration. Our results suggested that VAL-SNEDDS was a potential and safe delivery system with enhanced dissolution rate and oral bioavailability, as well as offered a strategy for the engineering of poorly water-soluble drugs in the clinical setting.
Starting Page	100
Ending Page	110
Page Count	11
File Format	PDF
ISSN	2190393X
Journal	Drug Delivery and Translational Research
Volume Number	7
Issue Number	1
e-ISSN	21903948
Language	English
Publisher	Springer US
Publisher Date	2016-11-03
Publisher Institution	Controlled Release Society
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Valsartan SNEDDS Central composite design Dissolution study Bioavailability Pharmaceutical Sciences/Technology
Content Type	Text
Resource Type	Article
Subject	Pharmaceutical Science

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