Preparation, characterization, and in vivo evaluation of tanshinone IIA solid dispersions with silica nanoparticles

Yan-rong Jiang,^1,2 Zhen-hai Zhang,¹ Qi-yuan Liu,^1,2 Shao-ying Hu,^1,2 Xiao-yun Chen,^1,2 Xiao-bin Jia<sup>1

1</sup>Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; ²College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China

Abstract: We prepared solid dispersions (SDs) of tanshinone IIA (TSIIA) with silica nanoparticles, which function as dispersing carriers, using a spray-drying method and evaluated their in vitro dissolution and in vivo performance. The extent of TSIIA dissolution in the silica nanoparticles/TSIIA system (weight ratio, 5:1) was approximately 92% higher than that of the pure drug after 60 minutes. However, increasing the content of silica nanoparticles from 5:1 to 7:1 in this system did not significantly increase the rate or extent of TSIIA dissolution. The physicochemical properties of SDs were investigated using scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction, and Fourier transforms infrared spectroscopy. Studying the stability of the SDs of TSIIA revealed that the drug content of the formulation and dissolution behavior was unchanged under the applied storage conditions. In vivo tests showed that SDs of the silica nanoparticles/TSIIA had a significantly larger area under the concentration-time curve, which was 1.27 times more than that of TSIIA (P < 0.01). Additionally, the values of maximum plasma concentration and the time to reach maximum plasma concentration of the SDs were higher than those of TSIIA and the physical mixing system. Based on these results, we conclude that the silica nanoparticle based SDs achieved complete dissolution, increased absorption rate, maintained drug stability, and showed improved oral bioavailability compared to TSIIA alone.

Keywords: tanshinone IIA, solid dispersions, silica nanoparticles, in vitro dissolution, stability, oral bioavailability