Forced degradation studies of vildagliptin raw material alone and in the presence of excipients using HPLC-UV analysis.

Abstract

The chemical stability of a drug formulation can change the potency and safety of the finished medicinal product. A forced degradation study can be a good method to examine the stability of a drug molecule and formulation. An RP-HPLC method was developed with a gradient elution for the optimum separation of vildagliptin and related degradants in the raw material and in the presence of several common excipients under normal and severe conditions. Under acidic and basic conditions, one major degradant at relative retention time (RRT) 1.3 and three major degradants at RRTs 0.4, 0.7 and 1.2 were observed, respectively. By oxidative degradation, five major degradants at RRTs 0.5, 0.6, 0.7, 0.8 and 1.2 were detected. Neutral hydrolysis of vildagliptin produced one major degradant at RRT 0.7 while under thermal and UV conditions no significant degradants were noticeable. The presence of a mixture of excipients together with vildagliptin decreased the percentage of vildagliptin degradation. Individual excipients, including microcrystalline cellulose, magnesium stearate, povidone, sodium starch glycolate, sucrose and lactose when mixed with vildagliptin, decreased the percent of degradation depending on their chemical nature. The presence of excipients decreased the number of degradant products, or affects the formation percentage of these degradants.