Process optimization and evaluation of novel baicalin solid nanocrystals

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 Yuan<sup>3

1</sup>Key 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 China

Abstract: 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