Development of rasagiline-containing oral disintegrating tablet formulations, in vitro and in vivo evaluation

Parkinson's disease is a neurodegenerative disease of the nervous system, in which mostly motor movements, speech and other functions are impaired. Because of the role of the MAO-B enzyme in dopamine metabolism, MAO-B inhibitors are important therapeutic advances for Parkinson's patients. There is no commercial ODT form of rasagiline mesylate, which is an effective and more selective MAO-B inhibitor than selegiline. In this thesis, it is aimed to develop orally disintegrating tablet formulations containing rasagiline for use in the treatment of Parkinson's disease. Placebo ODT tablets containing different dispersants/superdispersants were developed and the optimum ODT formulation was determined in line with the results obtained from powder and tablet controls. After adding rasagiline to the optimum ODT formula, powder and tablet controls were made. In addition, Caco-2 cells and intestinal perfusion were performed to determine the intestinal permeability of rasagiline. The hepatic disposition of rasagiline was studied using the in situ liver perfusion method. The disintegration time of the optimum ODT formulation (ODT-9R) was determined as 10.67±1.04 s. Content uniformity is 101.7±4.8. Dissolution studies were performed in three different media (distilled water, 0.1N HCl, pH 6.8 phosphate buffer) and approximately 100% of rasagiline was dissolved in the first 5 minutes. The permeability of the ODT-9R formulation in the Caco-2 cell line (5.624x10-57.88x10-6 cm/s) increased significantly with the effect of excipients (p<0.05). Intestinal permeability values of the ODT-9R formulation increased (3.73x10-4 , 5.89x10-4 , ve 3.27x10-4 cm/s) across jejunum, ileum and colon. Compared with erythrocyte and Evans blue, rasagiline was more widely distributed in the liver, hepatic extraction was determined as 0.404 ± 0.060, and hepatic clearance was determined as 0.101 ± 0.015 mL/s. In line with the findings obtained from the thesis studies, a rasagiline ODT formulation suitable for the targeted purpose was developed. Key words: Orally disintegrating tablet, Intestinal perfusion, Caco-2, Liver perfusion, Rasagiline