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Patients diagnosed with diabetes are prescribed a large number of medications for appropriate therapy, increasing risk of side effects or drug interactions. Metformin, a guanidine derivative is commonly used as a drug of choice for the treatment of non insulin dependent diabetes mellitus. There are a number of interactions reported for metformin. On the other hand, NSAIDs are generally used for the treatment of pain, fever and inflammation, particularly arthritis. Since the former drug is used in long term therapy, it may be co-administered with other drugs. In the present paper, we investigated the in-vitro availability of metformin in presence of commonly used NSAIDs, like diclofenic sodium, flurbiprofen, ibuprofen, mefenamic acid, meloxicam and tiaprofenic acid. These studies were carried out using modified BP 2007 dissolution test apparatus in simulated body environments at 37oC. These drug interactions were analyzed by UV/ VIS spectroscopy and the effect on the availability of both metformin and NSAIDs in presence of each other was calculated by applying simultaneous equation which was derived by modifying Beers law. The interactions were further studied by RP-HPLC with mobile phase consisting of methanol and water (80:20 v/v) maintained at a flow rate of 1 mLmin -1 at isobestic point 241 nm (metformin, diclofenac sodium, flurbiprofen, tiaprofenic acid, ibuprofen, meloxicam and mefenamic acid) respectively. The results showed that the in vitro availability of NSAIDs and metformin owing to interaction was depressed through the formation of charge transfer complexes which was found to be associated with inter- and intra-molecular rearrangement of the electronic cloud of the interacting drugs. Hence it is envisaged that concurrent administration of metformin and NSAIDs could alter the bio-availability and impair the clinical efficacy of both drugs. Effect of pH is also studied on these drug-drug interactions.

journal of the chilean chemical society

IN VITRO STUDIES OF INTERACTION BETWEEN METFORMIN AND NSAIDS (NON STEROIDAL ANTI-INFLAMATORY DRUGS) USING SPECTROPHOTOMETRY AND RP-HIGH PERFORMANCE LIQUID CHROMATOGRAPHY