Improvement of Solubility and Oral Bioavailability of Itraconazole by its Oral Solid Dosage Form Fabrication Using Suitable Pharmaceutical Excipients

Abstract

The objective of this study was to develop fast dissolving Itraconazole tablets using suitable excipients to improve solubility and enhance the oral absorption of Itraconazol and match in vitro drug dissolution profile with Sporonax. The combination of the various solubilizer and hydrophilic surfactants like Poloxamer 188, polysorbate 80 and Polyoxyl 35 castor oil (HLB 12-14) were used in the present study. Nine formulations (A1, A2, A3, B1, B2, B3, C1, C2, and C3) were prepared and characterized. Combinations having different HLB values were evaluated, as the major solubility enhancing excipients and surfactants which also facilitate the lymphatic absorption. The formulations were so designed that they form colloidal emulsion on contact with water or GI fluids. This colloidal emulsion also increases the permeability through GI membrane. The optimized tablet formulations were suitably packaged in HDPE and subjected to accelerated stability testing as per the ICH guidelines.
The optimized composition of tablet formulation C3 containing Poloxamer 188 and polysorbate 80, in ratio 2:1 and lactose monohydrate (as the diluents) which was designed in the present study to arrive at a formulation that shows comparable in vitro dissolution rate to Sporonax. Accelerated stability study on the optimized composition in HDPE packaging further demonstrated no adverse changes occur in the formulation when evaluated for parameters such as disintegration time, drug content and in vitro dissolution.   
Keyword: Itraconazol, fast dissolving tablet, Poloxamer 188, polysorbate 80, Polyoxyl 35