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Open AccessArticle

Development of a Resveratrol Nanosuspension Using the Antisolvent Precipitation Method without Solvent Removal, Based on a Quality by Design (QbD) Approach

College of Pharmacy, Pusan National University, 63 Busandaehak-ro, Geumjeong-gu, Busan 46241, Korea
Dong-A ST Co. Ltd., Giheung-gu, Yongin, Gyeonggi 446-905, Korea
College of Pharmacy, Kyungsung University, 309, Suyeong-ro, Nam-gu, Busan 48434, Korea
Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA
Department of Pharmaceutical Engineering, Inje University, Gyeongnam 621-749, Korea
College of Pharmacy, Dongguk University, Goyang 410-820, Korea
College of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Korea
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2019, 11(12), 688;
Received: 14 November 2019 / Revised: 11 December 2019 / Accepted: 16 December 2019 / Published: 17 December 2019
The purpose of this study was to develop a resveratrol nanosuspension with enhanced oral bioavailability, based on an understanding of the formulation and process parameters of nanosuspensions and using a quality by design (QbD) approach. Particularly, the antisolvent method, which requires no solvent removal and no heating, is newly applied to prepare resveratrol nanosuspension. To ensure the quality of the resveratrol nanosuspensions, a quality target product profile (QTPP) was defined. The particle size (z-average, d90), zeta potential, and drug content parameters affecting the QTPP were selected as critical quality attributes (CQAs). The optimum composition obtained using a 3-factor, 3-level Box–Behnken design was as follows: polyvinylpyrrolidone vinyl acetate (10 mg/mL), polyvinylpyrrolidone K12 (5 mg/mL), sodium lauryl sulfate (1 mg/mL), and diethylene glycol monoethyl ether (DEGEE, 5% v/v) at a resveratrol concentration of 5 mg/mL. The initial particle size (z-average) was 46.3 nm and the zeta potential was −38.02 mV. The robustness of the antisolvent process using the optimized composition conditions was ensured by a full factorial design. The dissolution rate of the optimized resveratrol nanosuspension was significantly greater than that of the resveratrol raw material. An in vivo pharmacokinetic study in rats showed that the area under the plasma concentration versus time curve (AUC0–12h) and the maximum plasma concentration (Cmax) respectively, than those of the resveratrol raw material. Therefore, the prepara values of the resveratrol nanosuspension were approximately 1.6- and 5.7-fold higher,tion of a resveratrol nanosuspension using the QbD approach may be an effective strategy for the development of a new dosage form of resveratrol, with enhanced oral bioavailability. View Full-Text
Keywords: resveratrol; nanosuspension; quality by design; optimization; bioavailability; dissolution resveratrol; nanosuspension; quality by design; optimization; bioavailability; dissolution
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Kuk, D.-H.; Ha, E.-S.; Ha, D.-H.; Sim, W.-Y.; Lee, S.-K.; Jeong, J.-S.; Kim, J.-S.; Baek, I.-H.; Park, H.; Choi, D.H.; Yoo, J.-W.; Jeong, S.H.; Hwang, S.-J.; Kim, M.-S. Development of a Resveratrol Nanosuspension Using the Antisolvent Precipitation Method without Solvent Removal, Based on a Quality by Design (QbD) Approach. Pharmaceutics 2019, 11, 688.

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