Structural analysis of pharmaceutical tablets using two-dimensional X-ray absorption fine-structure spectroscopy and its combination with X-ray computed tomography

Abstract

The pharmaceutical properties of a solid formulations depend on their structure. To obtain structural information, such as the density, porosity, crystal forms of drugs, and the three-dimensional distribution of the drug and excipient particles within the formulations, is useful for formulation design and development. In this research, two-dimensional X-ray absorption fine-structure spectroscopy (2D-XAFS) and its combination with X-ray computed tomography (CT) were used for internal-structure analysis of tablets. Tablets containing form-II crystals and/or an amorphous solid dispersion (ASD) of bromhexine hydrochloride (BRH) were prepared and measured at a synchrotron radiation facility. The XAFS spectra of form-II crystals and the ASD of BRH were obtained after properly calibrating the irradiated X-ray energies. Their XAFS spectra showed small but marked differences. Form-II crystals and the ASD could be distinguished and visualized in the 2D-XAFS transmission and CT-XAFS slice images. Both 2D-XAFS and CT-XAFS provided detailed structural information and may be a useful alternative method in the development stage of solid dosage formulations.