Research on Metformin Hydrochloride Nitrosamine Impurities and Screen of Hydrophilic Gel Matrix Materials

OBJECTIVE To investigate the correlation between different hydrophilic gel matrix materials and the presence of N-dimethylnitrosamine(NDMA) in metformin hydrochloride(MET) in order to screen the appropriate matrix materials for the preparation of MET sustained-release tablets. METHODS High performance liquid chromatography-triple quadrupole tandem mass spectrometry was used to monitor NDMA. The matrix materials with lower risk of NDMA and similar swelling effect to reference listed drug were firstly determined by compatibility study between raw materials and excipients followed by swelling performance test, then MET sustained-release tablets were prepared with the selected material to investigate its in vitro dissolution behaviors and the risk of alcohol-induced dose dumping. RESULTS It was found that hypromellose(HPMC) was the main cause of the presence of NDMA in MET, and carbopol had similar swelling performance to HPMC. MET sustained-release tablets prepared with carbopol as the matrix material had similar dissolution profiles with reference listed drug, lower risk of dose dumping and better product stability. CONCLUSION Carbopol can be used as an alternative material for HPMC to prepare MET sustained-release tablets.