Abstract

Poor aqueous solubility is the biggest barriers for new drug candidates emerging from drug discovery programs to enter toxicology studies, let alone clinical trials. Various techniques have been proposed to improve the aqueous solubility of drugs: particle size reduction, solid lipid dispersion, amorphous drug formulations etc are a few such techniques. Mesoporous silica materials (MSM) have attracted the attention of pharmaceutical researchers around the world in last several years as these particles are fully porous amorphous silica particles with highly ordered pore structures with pore size in the range of 2-50 nm. MSMs have shown to effectively increase drug solubility by stabilizing the amorphous state of APIs. In the present study,the mesoporous silica material, MCM- 41 was used as drug carrier for improving the solubility of a poorly water soluble anticancer drug, Dasatanib. Dasatinib is a potent, oral multi targeted kinase inhibitor of BCS Class II drug, approved in 2006 for first line use in patients with chronic myelogenous leukemia and acute lymphoblastic leukemia. DST has very low aqueous solubility. Mesoporous silica nanocarriers (MSNs) were synthesized using an already reported organic template method with some modifications. A DoE based approach was used to achieve the maximum loading of the drug into the mesopores of MCM 41. After successfully loading more than 50% dasatanib into the pores of MSNs, the nanocarriers were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption andzetapotential analysis. The prepared nanocarriers were evaluated for their dissolution behavior in different media. The dissolution profiles thus obtained showed an highly improved release profile for Dasatanib when compared with that of a commercial formulation.