Transformations among the New Solid-State Forms of Clindamycin Phosphate

Abstract

An experimental study is undertaken to establish a transformation screen for the solid-state forms of clindamycin phosphate. The experimental study results in six novel crystalline forms: two solvates (with ethanol/water, methanol/water), one hydrate (Form III), and three polymorph forms. Further, all solid-state forms are characterized by various analytical techniques such as X-ray diffraction, differential scanning calorimetry, etc. Two polymorph forms (IV and VI) are selectively prepared by desolvation of the solvates (I and V). The solid-state desolvation results in the appearance of delamination of the 2D layers. Moreover, polymorph IV shows a clear polymorphic transition to a new polymorph form (polymorph II) above 165 °C. Phase transformations of the solid-state forms were also established by slurry conversions at 25 °C. These experiments suggest the reversible relationship between solvate I/V and hydrate Form III at different solvent mixtures. Through the aqueous dissolution test, it is also judged that polymorph II, IV, VI can transform to Form III in water at 25 °C. The conversion relationships among the six solid forms are illustrated