Formulation and optimization of drug-loaded mesoporous silica nanoparticle-based tablets to improve the dissolution rate of the poorly water-soluble drug silymarin

Abstract

Porous carriers have been put forward as a promising alternative for stabilizing the amorphous state of loaded drugs, and thus significantly improving the dissolution rate of poorly soluble compounds. The purpose of this study was to enhance the saturation solubility, dissolution rate and drug loading of the poorly water-soluble drug silymarin via incorporation into mesoporous silica nanospheres within a lyophilized tablet to obtain a unique formulation. 32 full factorial design was applied to study the effect of both independent variables, polyvinyl alcohol (PVA) as stabilizer and binder and sucrose as cryoprotectant and disintegrant; and on the dependent variables that included the mean particle size (Y1), disintegration time (Y2), tablet strength (Y3) and % of drug release after 2 min, R2min,Y4. The drug-loaded mesoporous silica nanospheres and the optimized formula was evaluated by different characterization methods: scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry, X-ray diffractometry and Fourier transform infrared spectroscopy; as well as drug content, saturation solubility and moisture content. The evaluation demonstrated that the loaded mesoporous silica nanospheres and the optimized formula are in amorphous state without any chemical interaction with the silica matrix or the stabilizer. Moreover, the drug was stably maintained in nanosize range with narrow particle size distribution. Furthermore, the optimized lyophilized tablets had highly porous structure, low friability (less than 1%), fast disintegration (less than 30 s), high tablet strength, low moisture content (less than 1%), remarkably increased dissolution rate and noticeable improvement in saturation solubility.