(586s) Characterization of Solid-State Forms and Phase Transformations of Clindamycin Phosphate

Two previously unknown solvates (ethanol-water solvate I and methanol-water solvate V), one new hydrate, Form III, and three novel polymorph forms (polymorph II, IV, VI) of clindamycin phosphate are discovered and characterized by various analytical techniques such as powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. Solvate V is structurally characterized by single-crystal X-ray diffraction. The combined experimental and computational study was undertaken to understand the relationship among the discovered solid-state forms. Polymorph VI is obtained by the desolvation of solvate V, the desolvation mechanism has two steps, the solvent molecules (one methanol and two water) escape, and the solute molecules rearrangement by the layered structure split thinner. Base on the study, the desolvation of solvate I to polymorph IV may resemble solvate V. Upon heating, polymorph IV transform to polymorph II by solid-state transition. By suspension transition and solubility determination experiment, solvate I, V, polymorph II, IV, VI can transform to Form III in a pure water solution. Meanwhile, Form III also can convert to solvate I, V in a mix ethanol-water or a mix methanol-water solution respectively. The conversion relationships among the six solid forms have been illustrated.