Formulation, in vitro and Bioavailability Assessments of Ranitidine Rectal Suppositories

Abstract

The objective of the current work was to develop and evaluate suppository dosage form in order to improve ranitidine bioavailability as a substitute to the oral administration. Suppocire (different grades), Witepsol W25 and polyethylene glycol (PEG) were used as suppository bases and prepared by molding method. The prepared formulations were examined for hardness, disintegration time, melting point, content uniformity, drug release, stability and bioavailability. The hardness ranged from 3.82 to 12.53 kg and disintegration time from 13.32 to 28.22 min. The melting points of fatty bases had values from 33.94 to 36.82±0.36ºC while PEG based suppositories melting points were directly proportional chain length. Higher content uniformity was observed in PEG based suppositories due to easy incorporation of RT into water soluble base. Release was affected by hydroxyl value and molecular weight (in cases of fatty and PEG bases respectively). All formulations were relatively stable after 12 months. In vivo studies of all formulations exhibited double peak phenomena. PEG based formula (S8) showed significant higher Cmax (10.05±1 μg/ml) and AUC0-12 (58.313±3.9 µg.h/mL) than fatty bases and oral solution. In conclusion, rectal administration of S8 could be prepared as an alternative to the oral dosage form to improve bioavailability and overcome the first-pass metabolism.