Development and characterization of long acting parenteral systems of rasagiline for treatment of Parkinsons disease

Abstract

Rasagiline mesylate is neuroprotective MAO-B inhibitor used for treatment of Parkinson s disease which requires daily oral administration due to its short half life. Patients with Parkinson s disease also develop difficulty in swallowing which can be eliminated by parenteral formulation. Present research focussed on preparation and evaluation of sustained release formulations of rasagiline (microspheres and in situ gel forming systems) which can alleviate the problem of daily oral administration by prolonging drug release for one month by single subcutaneous administration. Rasagiline mesylate loaded microspheres were prepared using w/o/w emulsion- solvent evaporation method. Microspheres were evaluated for particle size, percent drug loading and entrapment efficiency. Scanning newlineelectron micrographs revealed spherical non-porous particles with small depressions on surface. Different concentrations of PLGA/Resomer® in situ gel forming systems were prepared and characterized for physical appearance, drug content, syringeability and viscosity. In vitro drug release studies for microspheres and in situ gel forming systems were performed for 45 days. Selected formulations were tested for in vivo efficacy in animals using stereotaxic rotenone model. Selected formulations significantly (plt0.05) improved various behavioural (locomotor activity, grip strength etc.) and biochemical (lipid peroxidation, reduced glutathione etc.) changes. Pharmacokinetic studies in rats showed sustained release of rasagiline from microspheres and in situ gel forming systems for 28 days. With prepared sustained release injectables once a month administration is required making it a favorable approach for the treatment of Parkinson s disease with dysphagia. Prepared systems can be exploited as patient compliant systems for future use.