ROLE OF P-GP INHIBITORS ON GUT PERMEATION OF METFORMIN: AN EX-VIVO STUDY

Abstract

Objective: Metformin hydrochloride is a biguanide derivative that is commonly used to treat type 2 diabetes. Metformin has a low oral bioavailability of 50% to 60 %. To overcome these challenges, metformin was used as a Pgp substrate in this research work and used in conjunction with natural P-gp inhibitors. Methods: The study commenced with a chicken non-everted gut sac model that closely resembled in vivo intestinal transport processes. The effect of different P-gp inhibitors on Metformin intestinal permeability was examined in this study to fully recognize the potential significance of Pgp and intestinal metabolism. Results: After evaluating the effectiveness of different P-gp inhibitors at different concentration concentrations i.e. Piperine, Ginger, Drumstick, and Verapamil (standard) at (2 mg/ml, 4 mg/ml, and 6 mg/ml) by non-everted gut sac study. At 2 mg/ml ginger and drumstick could not show any significant improvement. At 4 mg/ml also drumstick could not show any significant improvement in percentage drug permeation. At 6 mg/ml all three natural inhibitors show a significant difference in percentage drug permeation when compared using the f2 similarity index. But piperine was found to be the most potent of all 3 inhibitors because it shows complete release with higher permeation in less time than ginger and drumstick when given in conjunction with Metformin. Then the comparative permeation study of different concentrations (i.e. 2 mg/ml, 4 mg/ml, and 6 mg/ml) of P-gp inhibitors was carried out using the f2 similarity parameter and was that there is no significant difference in the percentage of drug permeation of Metformin in the presence of 2 mg/ml versus 4 mg/ml inhibitors. The same is with 4 mg/ml versus 6 mg/ml of inhibitors. However, when the percentage drug permeation of Metformin in the presence of 2 mg/ml as compared to 6 mg/ml, a significant difference was observed. Conclusion: It was concluded from this research work that Piperine shows significant improvement in % drug permeation when compared using the f2 similarity index and its formulation with metformin may offer a simple and safe approach to enhance the pharmacological profile of metformin for effective anti-diabetic therapy in humans.