Effects of Alcohol on Release Characteristics of Metformin Hydrochloride Extended-Release Tablets in Vitro and in Vivo / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the effects of alcohol on release characteristics of metformin hydrochloride extended-release tablets in vitro and in vivo. METHODS: The release behaviors and swelling of self-made metformin hydrochloride extended-release tablets and commercial products Glucophage XR in different release media including water, 5% alcohol, 20% alcohol and 40% alcohol were investigated and similar factor method was used to evaluate the similarity of release. Based on results in vitro, water and the alcoholic medium with significant differences were selected for Beagle dogs experiments to investigate further the effects of alcohol on release characteristics of metformin hydrochloride extended-release tablets in vivo. RESULTS: Along with the increase of the alcohol concentration in the release media, both formation rate of the gel layer became slower and the penetration of the solvents became less in the swelling process, only dissolving a small amount of drug, so the release of self-made tablets and Glucophage XR gradually decreased in vitro. Both release in 40% alcohol produced a significant difference compared with that in water (f2<50), but the release of self-made tablets was greatly similar to Glucophage XR in the same media.In vivo studies of Beagle dogs revealed that an initial low release of both preparations was observed in 40% alcohol which was consistent with the vitro, while a certain increase was observed later, but the overall release was not statistically different from that of the water supply group. Moreover,the main pharmacokinetic parameters of the self-made tablets and Glucophage XR between the water-supply group and the 40% alcohol-supply group had no statistical difference. CONCLUSION: Alcohol has the same effects on the release characteristics of self-made metformin hydrochloride extended-release tablets and Glucophage XR in vitro and in vivo. High concentration of alcohol has a significant effect on the release characteristics in vitro, but it has no significant effect on the overall release in vivo.