Solid-state phase transformations and storage stability of curcumin polymorphs

Abstract

Curcumin crystallizes in three polymorphic forms. Form 1 exists in a monoclinic structure whereas Form 2 and Form 3 exist in orthorhombic structures. The aim of this work was to understand the polymorphic behavior of curcumin and stability of the curcumin forms. Liquid antisolvent precipitation of curcumin in presence of ultrasound and additives results in precipitation of curcumin in orthorhombic forms (Form 2 or Form 3), whereas the raw curcumin and curcumin particles precipitated without ultrasound and without additives exist in monoclinic form. Differential scanning calorimetery (DSC) experiments reveal that both orthorhombic forms (Form 2 and Form 3) precipitated in presence of ultrasound and additives transform to monoclinic form (Form 1) upon heating. The orthorhombic form (Form 3) in particles precipitated in presence of ultrasound only (no additives) transforms directly to monoclinic form (Form 1) upon heating. On the other hand, orthorhombic form (Form 3) in particles precipitated in presence of additives such as HPMC and BSA along with ultrasound, first transforms to Form 2 before finally converting to Form 1 upon heating. All these transformations occur below the melting points of all three forms. These polymorphic transformations also result in a visible change in particle morphology from rice seed like particles or spherical particles to acicular particles. While Form 2 and Form 3 were found to be unstable at higher temperatures, these forms when stored in aqueous suspensions at room temperature (25°C) were found to be stable even after 3 years with no significant change in particle size or particle morphology.