Role of P-GP inhibitors on gut permeation of metformin: an ex-vivo study
- Vol.14(10)
- M P Innovare Academic Sciences Pvt Ltd 2022
- 18-23p.
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 thecomparative 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/mlversus 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.