Chromatographic Behaviour and Analytical Method Development for Metformin HCl: Application to Permeation Studies through Caco-2 Cells
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Metformin HCl (Mtf) is a polar compound with low bioavailability. Counter ions have been shown to improve the bioavailability of polar ionizable drugs. The goal of this work was to develop an HPLC method that is capable of separating and quantifying Mtf from a group of selected organic anions: diclofenac sodium (DS), citric acid (CA), hydroxyl cinnamic acid (HCA), 8-anilinonaphthalene-1-sulfonic acid (ANS),and trisodium phosphate (TSP). Thus, the effect of the mixture of anions on the transport of Mtf through Caco-2 cells could be studied. During the development of the method, interesting chromatographic behaviors of Mtf were observed using a polar stationary phase (Hypersil® SAS, C1). The developed method was validated and found to be linear in the range 2-100 µg/mL with good accuracy and precision. The method was applied for transport experiments of Mtf across Caco-2 cells in the presence and absence of organic anions. Apparent permeability coefficients (Papp) were calculated. The Papp of Mtf was increased in the presence of CA and DS from 3.37×10-6 cm/s to 5.08×10-6 and 4.25×10-6 cm/s respectively, while it was decreased to 1.9×10-6 cm/s (p-value 0.01) in the presence of HCA. Interestingly, the Papp for Mtf increased more than four-fold when present with both calcium and CA together, which might lead to significant improvement in the bioavailability of the drug.
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