Process optimization and evaluation of novel baicalin solid nanocrystals

Abstract

Peng-Fei Yue,1,2 Yu Li,1 Jing Wan,1 Yong Wang,1 Ming Yang,1 Wei-Feng Zhu,1 Chang-Hong Wang,2 Hai-Long Yuan31Key Lab of Modern Preparation of TCM, Jiangxi University of Traditional Chinese Medicine, Nanchang, 2Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 3302 Hospital of PLA Institute of Chinese Materia Medica, Beijing, People's Republic of ChinaAbstract: The objective of this study was to prepare baicalin solid nanocrystals (BCN-SNS) to enhance oral bioavailability of baicalin. A Box–Behnken design approach was used for process optimization. The physicochemical properties and pharmacokinetics of the optimal BCN-SNS were investigated. Multiple linear regression analysis for process optimization revealed that the fine BCN-SNS was obtained wherein the optimal values of homogenization pressure (bar), homogenization cycles (cycles), amount of TPGS to drug (w/w), and amount of MCCS to drug (w/w) were 850 bar, 25 cycles, 10%, and 10%, respectively. Transmission electron microscopy and scanning electron microscopy results indicated that no significant aggregation or crystal growth could be observed in the redispersed freeze-dried BCN-SNS. Differential scanning calorimetry and X-ray diffraction results showed that BCN remained in a crystalline state. Dissolution velocity of the freeze-dried BCN-SNS powder was distinctly superior compared to those of the crude powder and physical mixture. The bioavailability of BCN in rats was increased remarkably after oral administration of BCN-SNS (P < 0.05), compared with those of BCN or the physical mixture. The SNS might be a good choice for oral administration of poorly soluble BCN, due to an improvement of the bioavailability and dissolution velocity of BCN-SNS.Keywords: baicalin, solid nanocrystals, optimization, in vivo/vitro evaluation