Understanding stability relationships among three curcumin polymorphs

Abstract

Understanding thermodynamic stability relationship among polymorphs of any active pharmaceutical ingredient (API) is a necessary step for drug formulation development. Knowledge of such relationship enables identification of a stable polymorphic form at the prevalent conditions. Curcumin, a pharmaceutically active ingredient found in herbal spice turmeric, exists in three polymorphic forms; a monoclinic form (Form 1) and two orthorhombic forms (Form 2 and Form 3). However, thermodynamic stability relationships among curcumin polymorphs have not been ascertained yet. This work therefore, was focused on understanding thermodynamic stability relationships among curcumin polymorphs. During purification of curcumin, the pressure applied for vacuum evaporation of organic solvent was found to significantly affect the polymorphic outcome. Form 1 was obtained at pressures ranging from 300 to 400 mbar whereas Form 2 was obtained at pressures ranging from 100 to 200 mbar. Form 3 was obtained by liquid antisolvent precipitation using ultrasound and Bovine Serum Albumin (BSA) as an additive. The obtained polymorphs were characterized by X-ray diffraction (XRD) and Differential Scanning Calorimetry (DSC) techniques. Relative stability of polymorphs was established by conducting solvent mediated transformation studies, thermal analysis through DSC and variable temperature X-ray diffraction studies (VT-XRD). It was observed that Form 2 and Form 3 irreversibly convert to Form 1 upon heating. Further, Form 2 and Form 3 convert to Form 1 in aqueous organic solutions at temperatures ranging from 0 °C to 50 °C. Thus, the curcumin polymorphs were found to be monotropically related to each other with the monoclinic form (Form 1) being the most stable form.