Physicochemical Understanding of Polymorphism and Solid-State Dehydration/Rehydration Processes for the Pharmaceutical Material Acrinol, by Ab Initio Powder X-ray Diffraction Analysis and Other Techniques

The extensively used antibacterial agent acrinol is known to form a monohydrate phase (<b>H</b>) on crystallization from water. We demonstrate here that acrinol also forms two anhydrous polymorphs, denoted form I (<b>AI</b>) and form II (<b>AII</b>). Polymorph <b>AI</b> is obtained directly on heating <b>H</b>, by a solid-state dehydration process, and polymorph <b>AII</b> is obtained subsequently from <b>AI</b>, by a polymorphic transformation. The crystal structures of <b>AI</b> and <b>AII</b> have been determined directly from powder X-ray diffraction data, employing the direct-space genetic algorithm technique for structure solution, followed by Rietveld refinement. From the structural properties of <b>AI</b> and <b>AII</b>, mechanistic aspects of the dehydration process and the polymorphic transformation have been established. From measurements of initial dissolution rates and enthalpies of dissolution, <b>AII</b> is assigned as the thermodynamically stable polymorph, with a monotropic relationship between <b>AI</b> and <b>AII</b>. The hydration properties of <b>AI</b> and <b>AII</b> differ significantly, with hydration of <b>AI</b> occurring at substantially lower relative humidity than <b>AII</b>.