A quick method for the quantitative analysis of mixtures. 1. Powder X-ray diffraction

A method of analyzing mixtures of APIs and excipients using X-ray powder diffraction is described. It uses a simple algorithm based on linear regression in which the pure component phases are fitted to the mixture pattern using linear least squares. Unlike many methods that use only the peaks in the powder pattern, this technique uses all the measured data points in the 2theta scan with minimal data processing. In practice, using 33 different samples on three diffractometers, the method can be shown to work well for mixtures with up to three components, giving mean errors between 1.7% and 3.9% for two-phase mixtures, and 4.0% and 8.6% for three-phase mixtures. These results compare favorably to those given by traditional Rietveld refinement. It is also shown that the Bruker GADDS system, which is designed for high throughput crystallization experiments, is capable of giving results of comparable accuracy to those derived from traditional, single sample diffractometers. It is possible to identify those mixtures for which one or more pure phase X-ray powder patterns are not available with a detection limit around 10%. The techniques are implemented in the PolySNAP computer program. The method requires very little computer time or user interaction.