Formulation, In-vitro Release and Bioavailability Study of Domperidone Rectal Suppositories

Domperidone is practically insoluble prokinetic drug; the systemic bioavailability of the drug following oral administration is only 13-17% because of extensive presystemic metabolism in the gut wall and liver. The applicability of the solid dispersion technique as a method for enhancing absorption of the drug through achieving better dissolution characteristics and better bioavailability for domperidone had been utilized. Solid dispersions of domperidone were prepared using Pluronic F-127, Myrj 52, PEG 4000 and PEG 6000 as carriers, at different drug to carrier ratios. The spectroscopic infra-red (IR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and powder X-ray diffractometry (PXRD) studies were performed to characterize the role of these carriers in increasing bioavailability through decreasing the crystallinity of domperidone. Selected solid dispersion of the drug with these carriers was used to formulate domperidone suppositories. It was found that, the release of pure domperidone from the hydrophilic bases was remarkably higher than that from the lipophilic ones. Domperidone solid dispersion with Pluronic F-127 formulated into suppository, showed enhanced release reaching about 33.188  5.655% in 45min from PEG suppository base, compared to drug alone 15.834  1.538%. Addition of 4 %w/w cetrimide as a release enhancer increased the release to 82.997  1.306 % in 30 min. Bioavailability of domperidone formulated as suppositories containing solid dispersion with Pluronic F-127 (F-18) was studied in rabbits. The results were promising with significant increase in both maximum plasma concentration and the area under the plasma concentration time curve compared with the marketed domperidone rectal suppository Motinorm®. So we can conclude that inclusion of the drug in this form into suppositories enhanced bioavailability and avoids the presystemic metabolism.