Prediction of Anti-Diabetic Alogliptin Stability by Isothermal Studies

Abstract

Alogliptin (ALG) benzoate is an oral hypoglycemic drug that works as a DPP-4 inhibitor to prevent incretin degradation. Forced stability studies use high temperatures to decompose drugs and estimate their behavior at low temperatures. We aimed to evaluate the thermal stability of ALG using two techniques: isothermal thermogravimetry (TGA) and degradation in an oven followed by liquid chromatography (LC-PDA) analysis. ALG was subjected to 150, 155, 160, 165, and 170 °C up to 10% of mass loss in isothermal TGA. In the oven, the drug was submitted to 130, 140, 150, 155, 160, and 170 °C. Kinetic parameters were calculated with the Arrhenius model. ALG followed zero-order kinetics, in which the degradation rate did not depend on reagent concentration. Activation energy ranged from 31.0 to 35.9 kcal mol-1. The degraded drug was less toxic in a cytotoxicity assay in CRIB cells than the undegraded drug. The TGA method is faster and more practical than the oven followed by LC-PDA, and the data present a correlation. Here we described the kinetic parameters of ALG degradation, improving the knowledge about the drug and assisting in developing new formulations from the drug.