Abstract

The experimental study mainly focused on evaluation of sub-chronic oral toxicity of sustained formulation of metoprolol succinate. After the formulation development of multiparticulate sustained release capsules, there was an urgent need to analyze their in vivo bioavailability in healthy normal human volunteers. Prior to use in human population, a subchronic oral toxicity study was performed on Swiss Albino rats, of the final formulated product to assess the possible therapeutic outcome and related toxicity. The final objective of the study is to find out the pharmacological interaction between the drugs and the excipients that may lead to toxicity to human volunteers. The sustained release formulation of Metoprolol tartrateat was administered in different dose according to the 28 days of study dosing schedule in 48 albino Wistar rats of either sex (24 males and 24 females); periodical safety and efficacy observation were done followed by blood chemistry, hematology and histopathological examination at the end of the study. All the animals were found alive after the study period. No behavioral abnormalities were found in the study animals. Statistical analysis of the results including various parameters like body weight, blood chemistry, hematology and histopathological evaluation did not produce any major differences between control and treated groups. The reformulated sustained release hydroxy propyl methyl cellulose based granules of metoprolol tartrate did not cause any subchronic toxicity to the study animals under experimental conditions.

Key words: Preclinical sub-chronic toxicity study, rats, formulation, metoprolol tartrate.