Quantifying amorphous content of lactose using parallel beam X-ray powder diffraction and whole pattern fitting.

Abstract

The objective of this study was to demonstrate the applicability of parallel beam X-ray powder diffraction (XRPD) and a new method for whole pattern fitting to the quantification of the residual amount of amorphous content in a pharmaceutical solid using lactose as a model system. Lactose monohydrate, prepared by slurry conversion of anhydrous lactose, was mixed with different amounts of amorphous lactose produced by lyophilization. X-ray powder diffractograms of each mixture were recorded and analyzed by whole pattern fitting using Percentage Crystallinity Determination Software from Kratos Analytical Inc. The polycapillary X-ray optic, which provides a parallel beam of X-radiation, has advantages over Bragg-Brentano Optics with respect to sample height artifacts. Significant shifts in peak position with changes in sample height of lactose monohydrate were observed using Bragg-Brentano Optics while no change was detected for the polycapillary X-ray optic. A technique to normalize all diffractograms to have the same total integrated intensity was necessary to eliminate tube fluctuation effects. After normalization, the amorphous content of lactose in the range of 1-10% was reproducibly predicted (small standard deviation between samplings) using whole pattern fitting. The limit of detection was calculated to be 0.37% amorphous content. The results indicated that parallel beam XRPD and whole pattern fitting can provide accurate analysis of relatively small amounts of amorphous content in pharmaceuticals compared to typical XRPD analysis.