Development of a Novel Floating In-situ Gelling System for Stomach Specific Drug Delivery of the Narrow Absorption Window Drug Baclofen

摘要

The present study deals with development of a floating in-situ gel of the narrow absorption window drug baclofen. Sodium alginate-based in-situ gelling systems were prepared by dissolving various concentrations of sodium alginate in deionized water, to which varying concentrations of drug and calcium bicarbonate were added. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) were used to check the presence of any interaction between the drug and the excipients. A 3² full factorial design was used for optimization. The concentrations of sodium alginate (X1) and calcium bicarbonate (X2) were selected as the independent variables. The amount of the drug released after 1 h (Q1) and 10 h (Q10) and the viscosity of the solution were selected as the dependent variables. The gels were studied for their viscosity, in-vitro buoyancy and drug release. Contour plots were drawn for each dependent variable and check-point batches were prepared in order to get desirable release profiles. The drug release profiles were fitted into different kinetic models. The floating lag time and floating time found to be 2 min and 12 h respectively. A decreasing trend in drug release was observed with increasing concentrations of CaCO3. The computed values of Q1 and Q10 for the check-point batch were 25% and 86% respectively, compared to the experimental values of 27.1% and 88.34%. The similarity factor (f2) for the check-point batch being 80.25 showed that the two dissolution profiles were similar. The drug release from the in-situ gel follows the Higuchi model, which indicates a diffusion-controlled release. A stomach specific in-situ gel of baclofen could be prepared using floating mechanism to increase the residence time of the drug in stomach and thereby increase the absorption.