Concurrent Use of Thermal Analysis and X-ray Powder Diffraction to Characterize Hydration States

摘要

A challenge faced during early pharmaceutical drug development is a rapid, primary understanding of a material's solid state. Pharmaceutical drug development candidates often present as both multiple solid and hydration states. Characterization of the hydration states, which may exhibit important differences in solubility, dissolution rate and stability, is critical in selection of the optimal form for development. Rapid identification and characterization of the hydration states of an anti-infective candidate, PG-532969, was accomplished through the coordinated use of thermal and x-ray powder diffraction analysis. Although the hydration state ultimately selected had acceptable solubility, it exhibited variable hydration characteristic of a "channel" structure (Ref. 1), requiring careful characterization to avoid potential development and manufacturing issues. Correlation of thermal and x-ray data generated a basic description of the crystal lattice behavior as a function of hydration level, leading to clear description of boundary conditions for the manufacturing process. Coupling results from these two techniques also demonstrated the existence of additional hydration states and provided information relating to phase transformations.