Physicochemical characterization of dapagliflozin and its solid-state behavior in stress stability test

Abstract

As an active pharmaceutical ingredient, dapagliflozin propanediol monohydrate (D-PD) has been used in the solvated form consisting of dapagliflozin compounded with (S)-propylene glycol and monohydrate at a 1:1:1 ratio. However, dapagliflozin propanediol loses the solvent’s reduced lattice structure at slightly higher temperatures. Due to its sensitive solid-state stability, the temperature and humidity are strictly controlled during the production and storage of dapagliflozin. Thus, crystalline molecular complexes containing pharmaceutical salts, solvates, monohydrates, and cocrystals have recently been developed as alternative strategies. This study investigated the dapagliflozin free base (D-FB), D-PD, and dapagliflozin l-proline cocrystals (D-LP). Their solid-state behavior was also evaluated in stress stability studies. The compounds were analyzed using scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, dynamic vapor sorption (DVS), and powder rheology testing. In addition, Carr’s index, the Hausner ratio, contact angle, and intrinsic dissolution rate were calculated. Dapagliflozin exhibited distinct physical properties depending upon the differences in solid form and also showed significant differences in solid-state behavior in the stress stability test. In conclusion, D-LP was superior to D-FB or D-PD in physicochemical and mechanical properties.

Keywords:

• Dapagliflozin
• stability
• solid-state characterization
• physicochemical property
• cocrystal

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by grants from the National Research Foundation of Korea, funded by the Korean Government [NRF-2018R1A1A1A05023012, NRF-2018R1D1A1B07050538, and 2017R1A5A2015541] and by Chungbuk National University (2019).