Investigation of the Effect of Co-crystal Habit on Dissolution, Flowability and Tabletability

D. R. Serrano Lopez, P. O'Connell, A. M. Healy Trinity College Dublin Purpose Sulfadimide (SDM) is a poorly-soluble anti-infective agent. Co-crystallization with suitable coformers, such as 4aminosalicylic acid (4ASA), combined with changes in the crystal habit, can favourably alter its physicochemical properties. The aim was to engineer SDM: 4ASA cocrystals with different habits and investigate the effect on dissolution flow and tableting properties. Methods SDM: 4ASA cocrystals were prepared in a 1:1 molar ratio. Polymorph one (P1) was obtained by liquid-assisted ball milli Polymorph two (P2) was prepared by: solvent evaporation technique using ethanol (habit I) or acetone (habit II) as solven solvent evaporation followed by grinding (habit III) and spray drying (habit IV). Solid products were analysed by PXRD, SEM and DSC. Flow-through cell dissolution studies in deionised water were performed. Carr’s compressibility index wa calculated. Biconvex tablets were compressed using a Natoli NPRD10 tablet press. Hardness testing was performed. Results DSC results showed that the melting point of both polymorphs was between those of SDM and 4ASA. P1 and P2 exhibite characteristic diffraction peaks which differ from those of the single components. Bragg peak positions for P2 was the sam in all the samples, however the peak intensity varied, indicating different preferred crystal orientation (Fig 1). SEM micrographs showed the difference in the crystal habits: small prismatic crystals (P1), large prismatic crystals (P2-habit I) large plate-like crystals (P2-habit II), microspheres (P2-habit III) and small cube like-crystals (P2-habit IV) (Fig 2). P1 an P2-habit IV exhibited the fastest dissolution rate. However, P2-habit IV was transformed to P1 during dissolution. P2-hab exhibited the highest Carr’s compressibility index (43.9%) indicating poor flowability. P2-habit I and II exhibited the low hardness. Spray drying and milling resulted in powders with improved tabletability. Conclusion Physicochemical properties of a drug can be affected by the crystal habit. Even for cocrystals with poor pharmaceutical characteristics, a habit may be engineered which results in better dissolution, flowability and tableting behavior. Acknowledgements: this publication has emanated from research conducted with the financial support of Science Founda Ireland under Grant Number SFI/12/RC/2275. ,