Assessment of the X-ray diffraction-absorption method for quantitative analysis of largely amorphous pharmaceutical composites

Determination of the residual weight fraction of a crystalline drug in a largely amorphous pharmaceutical composite is still a challenging question. None of the quantitative X-ray diffraction (QXRD) methods found in the literature is suitable for these inclusion systems. The composite's diffraction patterns present a structured amorphous halo (arising from the amorphous matrix and drug molecular clusters) in which the crystalline drug peaks rise up. Moreover, the matrix traps a non-negligible quantity of water (which cannot be directly detected by X-ray diffraction) and the crystal structure of the drug may be unknown. In this work, a development of the QXRD analysis based on the diffraction-absorption technique is presented. The method is standardless, avoids the interpretation of the amorphous halo and the knowledge of the crystal structures of the phases, and takes into account the absorbed water. Results are in excellent agreement with those obtained by differential scanning calorimetry (DSC). The general features of the technique open its application to other classes of largely amorphous composite materials, like glass systems generated in the stabilization/solidification of toxic waste.