Formulation, Characterization and In-Vitro Evaluation of Floating Microspheres of Rasagiline Mesylate

In this work an attempt was made to design a gastro retentive delivery system in the form of floating microspheres for a model anti Parkinson drug rasagiline mesylate. The main objective of the present research work was to enhance bioavailability and duration of action, to increase the residence time of drug in the GIT and to provide controlled release. The use of conventional dosage form may pose major problems due to shorter half-life, maximum absorption in stomach. Therefore, to overcome these drawbacks buoyant polymers can be incorporated in the formulation which increases the drug residence in the stomach. The floating microparticulate drug delivery system control the rate of drug release as well as protect the drug from enzymatic degradation, thereby increasing the residence time in the stomach and provide controlled release of drug. These formulations not only lowers dosing interval but also improves patient compliance and risk of over dosage is low and finally all these factors contribute to increased bioavailability. The scheme of work has been divided into several parts. The collection of theoretical and technical data by extensive literature survey, review of literature and drug profile is presented in chapter 3 and 4 respectively, followed by procurement of materials used in the formulation. The microspheres were prepared by solvent evaporation technique, using rasagiline mesylate as a model drug and guar gum as a polymer, ethyl cellulose was used as gastro retentive and coating material, span-80 was used as emulsifying agent. The floating microspheres were prepared by regular two level factorial design. Drug concentration, volume of acetone and amount of ethyl cellulose were maintained constant. Polymer concentration, stirring speed and concentration of surfactant were the different independent variables. Optimization responses namely particle size, %buoyancy, % entrapment efficiency, % CDR were selected. The optimized batch was evaluated for particle size, SEM, % yield, % buoyancy, % entrapment efficiency, % drug release, in-vitro release kinetics, in-vivo radiographic studies and stability studies. The optimized formulation was selected. Results of FT-IR and DSC revealed that there was no chemical interaction between the drug and the polymer used. The obtained microspheres were spherical in shape, free flowing with ideal particle size for oral delivery. The microspheres exhibited good buoyancy. The kinetic model fitting data showed that the release of drug from microspheres followed first order kinetic model. From the in-vivo radiographic studies of the microspheres in rabbits it can be concluded that the formulation remain in the stomach for duration of 8h. Hence, the gastric residence time of the formulation was found to be increased. The stability studies were carried out for the selected formulations according to ICH guidelines. % DEE, % buoyancy, %CDR and particle size shows that the formulation remained stable at the end of storage period