Evogliptin Tartrate

Evogliptin tartrate is a novel dipeptidyl peptidase (DPP-4) inhibitor very recently introduced into the market as an oral hypoglycemic drug.

The literature review has revealed no reports of stability-indicating analytical methods so far for evogliptin tartrate. Thus, the goal of this study was to develop and validate a stability-indicating high-performance thin-layer chromatography (HPTLC) method for evogliptin tartrate in bulk and tablet dosage form.

For the study, precoated plates of silica gel 60F254 were used as stationary phase and acetonitrile–water–formic acid (30:8:2, v/v/v) was used as a developing system. The densitometric scanning was performed at 270 nm, and the method was validated as per International Council for Harmonisation (ICH) guidelines for accuracy, precision, limit of detection (LOD), and limit of quantitation (LOQ). Evogliptin was subjected to forced degradation studies and was exposed to various stress conditions such as acid/base hydrolysis, oxidation, thermal stress, and UV light.

The developed method furnished compact spots of evogliptin (Rf 0.62 ± 0.05) and was linear in the concentration range of 1–5 µg/spot. The lowest detection and quantitation values were found to be 0.331 and 1.003 µg/spot, respectively, and % recovery was found to be 101.09. The low RSD values (below 2%) for intra-day (% RSD 1.86) and inter-day (% RSD 1.43) precision studies demonstrated the preciseness of the developed method.

All the validation parameters were found to be within the acceptable range prescribed by ICH guidelines, indicating that the developed method was accurate, precise, selective, and reproducible. A total of five degradation products were resolved under various stress conditions.

The proposed method has a promising application commercially for identification, routine quantitative determination, and monitoring of stability of the evogliptin tartrate in bulk and tablet dosage forms to guarantee its safety, efficacy, and quality. Moreover, the developed method will also help in formulation development and in determining the appropriate storage conditions.

A fixed dose combination (FDC) bilayer tablet, consisting of high-dose metformin HCl in a sustained release layer and low-dose evogliptin tartrate in an immediate release layer, was developed based on a quality by design (QbD) approach. To implement QbD approach, the bilayer tableting process parameters judged as high risk through risk analysis were optimized by a central composite face-centered design as a design of experiment (DOE) methodology. Using DOE, the optimized conditions of the tableting process for drug products that satisfy the established quality target product profiles were obtained. The content uniformity of low-dose evogliptin tartrate in the optimized bilayer tablet prepared on a large scale was confirmed by at-line transmittance Raman spectroscopy as a process analytical technology. In addition, the in vitro drug release and in vivo pharmacokinetic studies showed that metformin HCl and evogliptin tartrate in the bilayer tablet is bioequivalent to those of the respective reference drugs. Furthermore, the physicochemical stability of the optimized bilayer tablet during storage under long-term and accelerated conditions was also confirmed. Therefore, it can be concluded that the QbD approach is an effective way to develop a new FDC bilayer tablet that is easy to scale up for successful commercialization.