Polymorphism and distinct physicochemical properties of the phloretin-nicotinamide cocrystal

The emergence of cocrystals as alternative solid forms for development of novel drug products signifies the relevance of polymorphism studies in cocrystals. We report two novel polymorphs of the cocrystal involving an anti-inflammatory and antioxidative active ingredient, phloretin (PHL), and a pharmaceutically acceptable coformer, nicotinamide (NA). The two polymorphs were structurally characterized. In addition, all the polymorphs and their polymorphic phase transformation were investigated by thermal, slurry and solubility measurements. Form I was identified as the most stable polymorph under ambient conditions. The three polymorphs showed distinct photoluminescence which was rationalized on the basis of pi MIDLINE HORIZONTAL ELLIPSIS pi interactions in their crystal structures. Form I was found to show a higher apparent solubility and dissolution rate which was rationalized on the basis of parameters deduced from molecular dynamics (MD) simulations. The polymorphs of the PHL-NA cocrystal emphasized the impact of polymorphism on the physicochemical properties of cocrystals.

Automated summary

The emergence of cocrystals as alternative solid forms for novel drug product development highlights the importance of polymorphism studies in cocrystals. Two novel polymorphs of a cocrystal involving an anti-inflammatory and antioxidative active ingredient, phloretin (PHL), and a pharmaceutically acceptable coformer, nicotinamide (NA), were structurally characterized. The study of these polymorphs and their phase transformations revealed the impact of polymorphism on the physicochemical properties of cocrystals, with Form I being the most stable under ambient conditions.