Quantification of Crystallinity in Substantially Amorphous Materials by Synchrotron X-ray Powder Diffractometry

Abstract

Purpose. The aim of this study was to develop a highly sensitive powder X-ray diffraction (XRD) technique for quantification of crystallinity in substantially amorphous pharmaceuticals, utilizing synchrotron radiation and a 2-D area detector. Methods. Diffraction data were acquired at the European Synchrotron Radiation Facility (France) using a 2-D charge-coupled device detector. The crystallization of amorphous sucrose was monitored in situ, isothermally at several temperatures in the range of 90 to 160-C. An algorithm was developed for separation of the crystalline and amorphous intensities from the total diffraction pattern. Results. The synchrotron XRD technique allowed powder diffraction patterns to be recorded with a time resolution of 40 ms. The gradual crystallization of sucrose is analogous to a series of physical mixtures with increasing content of the crystalline component. The in situ crystallization approach circumvented the problem of inhomogeneity in mixingVa potentially serious issue at extreme mixture compositions. The estimated limit of detection of crystalline sucrose in an amorphous matrix was 0.2% w/w, a considerable improvement over the reported value of õ1% w/w with a conventional XRD. Conclusion. High-intensity XRD can discern subtle changes in the lattice order of materials. The first evidence of crystallization can serve as an indicator of the potential physical instability of the product.

Use of Polyvinyl Alcohol as a Solubility-Enhancing Polymer for Poorly Water Soluble Drug Delivery (Part 1)

“…While powder X-ray diffraction (XRD) has been shown to have limits of detection of less than 1% (50). polarized light microscopy (PLM) can serve as a qualitative confirmation of XRD results.…”

Investigation of the Multi-Step Dehydration Reaction of Theophylline Monohydrate Using 2-Dimensional Powder X-ray Diffractometry

“…In XRD employing transmission geometry, the incident Xray beam passes through the sample and the diffraction pattern is acquired using a 2-dimensional area detector positioned on the opposite side of the sample (in relation to the X-ray source) (32,33). The vertical configuration of powder samples was made possible by filling the samples (õ14 mg) in aluminum pans (used generally for differential scanning calorimetry, TA Instruments), and the pans were crimped non-hermetically.…”

“…Calibration was performed using an Al 2 O 3 standard (SRM 764a, NIST). The specific details of the X-ray beam characteristics, the sample chamber, and the data acquisition technique have been described earlier (33).…”

Phase Transitions in Frozen Systems and During Freeze–Drying: Quantification Using Synchrotron X-Ray Diffractometry

“…Synchrotron radiation has already shown promise for in situ monitoring of crystallization and for quantifying the crystallinity in a substantially amorphous matrix (40)(41)(42). In addition to high sensitivity, very rapid data collection is possible (<1 s) enabling time-resolved studies (19,24,(40)(41)(42). An approach based on SXRD could offer numerous advantages.…”