Polymorphism of crystalline drugs is a common phenomenon. However, the number of reported polymorphic cocrystals is very limited. In this work, the synthesis and solid state characterisation of a polymorphic cocrystal composed of sulfadimidine (SD) and 4-aminosalicylic acid (4-ASA) is reported for the first time. By liquid-assisted milling, the SD:4-ASA 1:1 form I cocrystal, the structure of which has been previously reported, was formed. By spray drying, a new polymorphic form (form II) of the SD:4-ASA 1:1 cocrystal was discovered which could also be obtained by solvent evaporation from ethanol and acetone. Structure determination of the form II cocrystal was calculated using high resolution X-ray powder diffraction. The solubility of the SD:4-ASA 1:1 cocrystal was dependent on the pH and predicted by a model established for a two amphoteric component cocrystal. The form I cocrystal was found to be thermodynamically more stable in aqueous solution than form II, which showed transformation to form I. Dissolution studies revealed that the dissolution rate of SD from both cocrystals was enhanced when compared to a physical equimolar mixture and pure SD.

This study examined the 1:1 cocrystal benzamide: dibenzyl sulfoxide, comprising the poorly water soluble dibenzyl sulfoxide (DBSO) and the more soluble benzamide (BA), to establish if this cocrystal shows advantages in terms of solubility and dissolution in comparison to its pure components and to a physical mixture. Solubility studies were performed by measuring DBSO solubility as a function of BA concentration, and a ternary phase diagram was constructed. Dissolution was examined through intrinsic dissolution studies. Solid-state characterisation was carried out by powder X-ray diffraction (PXRD), energy-dispersive X-ray diffraction (EDX), infra-red spectroscopy (ATR-FTIR) and thermal analysis. DBSO solubility was increased by means of complexation with BA. For the cocrystal, the solubility of both components was decreased in comparison to pure components. The cocrystal was identified as metastable and incongruently saturating. Dissolution studies revealed that dissolution of DBSO from the cocrystal was not enhanced in comparison to the pure compound or a physical mix, while BA release was retarded and followed square root of time kinetics. At the disk surface a layer of DBSO was found. The extent of complexation in solution can change the stability of the complex substantially. Incongruent solubility and dissolution behaviour of a cocrystal can result in no enhancement in the dissolution of the less soluble component and retardation of release of the more soluble component