Cocrystallization of carbamazepine with amides: Cocrystal and eutectic phases with improved dissolution

Carbamazepine is an anticonvulsant drug which belongs to Biopharmaceutics Classification System (BCS) Class II drugs. In this work, attempts have been made to enhance the dissolution of carbamazepine (CBZ) in aqueous medium by attempting cocrystallization with the coformers such as para-hydroxybenzamide (PHBAD), salicylamide (SAL) and pyrazinamide (PRZ). Binary phase diagrams were constructed by conducting Differential Scanning Calorimetry (DSC) analysis for these CBZ-coformer pairs in order to determine the nature of the solid phase and cocrystal forming zone. CBZ formed a 1:1 cocrystal phase with PHBAD from the eutectic melts at a stoichiometric ratio of 1:1 and 1:2 whereas it formed eutectics with SAL as well as PRZ. Single crystals of CBZ-PHBAD (1:1) cocrystal phase were obtained by solvent evaporation of CBZ-PHBAD eutectic melts in Acetone-Toluene (1:1?vol ratio). Interestingly, recrystallization of eutectic melt of CBZ-PHBAD (1:1) in 1,4-Dioxane produced crystals of para-hydroxybenzamide monohydrate. Crystal structure analysis showed that CBZ-PHBAD (1:1) cocrystal and para-hydroxybenzamide monohydrate crystallized in monoclinic space groups namely P21/c and P21/n respectively. CBZ formed intermolecular interaction with two molecules of PHBAD via O-H�O hydrogen bonding and N-H...O intermolecular interaction which results into a cocrystal. Powder Dissolution (PD) studies were conducted for the CBZ-PHBAD (1:1) cocrystal, CBZ-SAL and CBZ-PRZ eutectic mixtures in Phosphate Buffer Saline (PBS) at 37?�C. Among the three carbamazepine solid forms, CBZ-PHBAD cocrystal exhibited 6.5 times higher dissolution than raw carbamazepine while the CBZ-SAL-SSG-XCBZ-0.5 eutectic and CBZ-PRZ-SSG-XCBZ-0.5 eutectic phases exhibited 2.62 and 3.05 times enhanced dissolution than raw carbamazepine.by Indumathi Sathisaran and Sameer Vishvanath Dalv

Solid-State Phase Transformations and Storage Stability of Curcumin Polymorphs

Curcumin crystallizes in three polymorphic forms. Form 1 exists as a monoclinic structure, whereas Forms 2 and 3 exist as orthorhombic structures. The aim of this work was to understand the polymorphic behavior of curcumin and the stability of the forms of curcumin. Liquid antisolvent precipitation of curcumin in the presence of ultrasound and additives results in the precipitation of curcumin in orthorhombic forms (Form 2 or Form 3), whereas raw curcumin and curcumin particles precipitated without ultrasound and without additives exist in monoclinic form. Differential scanning calorimetery (DSC) experiments reveal that both of the orthorhombic forms (Forms 2 and 3), which precipitated in the presence of ultrasound and additives, transform to a monoclinic form (Form 1) upon heating. The orthorhombic form (Form 3) in particles, which precipitated in the presence of ultrasound only (no additives), transforms directly to a monoclinic form (Form 1) upon heating. On the other hand, the orthorhombic form (Form 3) in particles, which precipitated in the 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 of 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 or spherical to acicular. 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 morphology