In vitro and in vivo evaluation of pioglitazone hydrochloride/metformin hydrochloride sustained-release tablets

Objective:To prepare pioglitazone hydrochloride(PH)/metformin hydrochloride(MH) sustained-release tablets,and evaluate their release behaviors in vitro and in vivo.Methods:The MH sustained-release part was prepared by hydrophilic matrix combined with sustained release film coating technology.The HPMC K100M and EudragitNE 30D were used as hydrophilic matrix and film coating.The PH immediate-release part was prepared by coating technology.The release/dissolution behaviors were evaluated in different dissolution media[hydrochloric acid(pH 2.0),acetic acid buffer solution(pH 4.5),purified water,and phosphate buffer solution(pH 6 8) ].The in vivo pharmacokinetics of the tablets was investigated in Beagle dogs.Results:The release characteristics of MH in different media were similar with that of reference tablets.Higuchi model was optimal for the description of drug release profile.The dissolution characteristic of PH in pH 2.0 was similar with reference tablets,but higher than reference tablets in other PH dissolution media.The results of pharmacokinetics in Beagle dogs showed that relative bioavailability of MH and PH was(93.38 ± 10.72) % and(100.72 ± 19.28) %,respectively.Conclusion:The obtained tablets were bioequivalent to reference tablets.The MH release from sustained-release part showed good in vitro-in vivo correlations.