Elimination of metformin–croscarmellose sodium interaction by competition

During analytical method development and validation, a strong charge interaction between metformin and croscarmellose sodium was observed when the aqueous solution containing metformin was spiked with croscarmellose sodium. The charge interaction resulted in the retention of metformin in croscarmellose sodium and caused a serious drug recovery problem. The percent recovery of metformin in the solution was much lower than its theoretical values, especially in the low metformin concentration range. To overcome the metformin–croscarmellose interaction, arginine was selected as a competitor for the binding sites on croscarmellose sodium. Because of the competition and stronger interaction between arginine and croscarmellose sodium than metformin and croscarmellose sodium, a complete recovery of metformin in presence of arginine in both low and high concentration ranges was achieved. The effect of arginine on the recovery of metformin and the competition mechanism are discussed in this paper.