Improved solubility of lornoxicam by inclusion into SBA-15: Comparison of loading methods

Abstract

An increasing proportion of new medicinal substances are poorly soluble in water. Adsorption on mesoporous silicas increases their bioavailability when administered orally. Loading method determines adsorption either on the surface in crystalline state or inside the mesopores in amorphus form. The aim of this study was to compare two methods (adsorption equilibrium and solvent evaporation) of lornoxicam adsorption on SBA-15 and APTES-modified SBA-15 in terms of drug adsorption site. Additionally, we investigated the drug release profiles at different pH and cytotoxicity of the analysed mesoporous materials. The materials were characterized by a number of physicochemical techniques including X-ray diffraction, nitrogen adsorption/desorption techniques, differential scanning calorimetry, thermogravimetric analysis, scanning and transmission electron microscopy, infrared spectroscopy and ¹H NMR. Lornoxicam was loaded on the studied materials and released in the media (HCl pH 1.2, phosphate buffers pH 6.8 and 7.4). The cytotoxicity assays of APTES-modified SBA-15 were performed on CaCo-2 human colon cancer cell line. We proved that adsorption equilibrium method is a more advantageous method of loading. It ensures drug adsorption in an amorphous state inside the mesopores. The solvent evaporation method, despite a greater amount of loaded drug, results in drug adsorption in a crystalline state on the silica surface. In drug release studies a greater amount of lornoxicam is released from modified materials compared to crystalline lornoxicam. Cytotoxicity study proved the safety of APTES-modified silica. We concluded that APTES-modified SBA-15 is applicable as an effective and non-toxic carrier for the poorly soluble drug lornoxicam. The adsorption equilibrium method should be the preferred loading method. It enables the adsorption of sparingly soluble substances inside the mesoproes and enhances bioavailability of oral pharmaceutical forms.

Keywords: Dissolution rate; Drug delivery system; Lornoxicam; Mesoporous silica; Physicochemical techniques; SBA-15.