| Pharmaceutical molecules are capable of forming several different crystallineforms such as polymorphs, hydrates or solvates. The formation of these differentcrystalline forms and their potential to transform to other structures can affectdifferent physical or chemical solid-state properties including stability, solubility,dissolution rate, bioavailability, compactability, and tableting behavior, therefore thesedifferent crystalline forms are very important research targets as well as the discovery,characterization, and physicochemical understanding of the range of crystalline formsthat exist for an active molecule are valuable aspects of pharmaceutical research anddevelopment.Herein in the present study, we found one novel hydrate and five previouslyunknown solvates of clindamycin phosphate through water, MEOH/water,EtOH/water, n-propanol/water, n-butanol/water. These new solid forms werecharacterized by various analytical techniques such as powder X-ray diffraction,single-crystal X-ray diffraction, differential scanning calorimetry, and thermo--gravimetric analysis. Meanwhile the crystal structures of methanol-water solvate andDMSO solvate were resolved by single crystal X-Ray Diffraction (SXRD)，both ofthem crystallized in space group P21but quite different hydrogen bonding networksamong host-host and host-solvent molecules, resulting in different thermal andmoisture stability.In the present work, we studied the desolvation routes upon heating and moistureeffecting. Methanol-water solvate was converted to a polymorph phase upon heatingand desolvation, the desolvation mechanism has two steps, the solvent molecules (onemethanol and two waters) escape, and the solute molecules rearrangement by thelayered structure split thinner, whereas non-desolvation of the DMSO solvate tillmelting point. Upon heating, the solvates in EtOH/water, n-propanol/water,n-butanol/water were similar to methanol-water solvate. The effect of moisture onphase transformation of solvates was monitored by dynamic vapor sorption (DVS)and Powder X-Ray Diffraction (PXRD) analysis. DMSO solvate and the desolvatedproduct of methanol-water solvate were converted to a hydrate form at~43%RH and~98%RH respectively at25oC, but the methanol-water solvate did not transform in allmeasuring humidity range. These different transformation behaviors were rationalized from the distinct hydrogen bonds, which aided in the evaluation of molecularassemblies.Phase transformations of the solid-state forms were established by in-situ Raman,in-situ PVM, slurry conversions at room temperature. These experiments suggest thereversible relationship between solvates from MEOH/water, EtOH/water and hydrateat different composition of organic solutions and water, solvates from MEOH/water,EtOH/water transform to hydrate in water, while hydrate can transform to solvatesfrom MEOH/water, EtOH/water in ethanol/water mixture or methanol/water mixture.During dissolution test in water, it also probably judge that the desolvated productscould transform to hydrate in pure water at room temperature.All the contents above have never been reported at present. |
