Determination of average crystallite shape by X-ray diffraction and computational methods.
The objective of this work was to develop a method to estimate the average shape and habit of organic crystalline material using X-ray powder diffraction (XRPD), the single-crystal structure, and computational methods. It is proposed that the relative intensities of the peaks in an XRPD pattern from a sample exhibiting a "standard" preferred orientation correlates with the shape of the crystallites present. Models were developed to yield a quantitative "enhancement" factor for each face. The combined simple-forms morphology (CSM) of the material was then produced by indexing the observed faces and modifying the simulated Bravais-Friedel-Donnay-Harker (BFDH) morphology. The average shape of crystallites can be estimated from the CSM by multiplying each face by its enhancement factor. Acetaminophen crystals in two different habits and ibuprofen crystallized from toluene were used. The predicted shapes closely resembled the average shapes observed with microscopy. Results suggested the average shapes of the organic crystalline materials can be estimated by XRPD and the computational simulation. The current limitations are the need to "index" the faces, the size of the crystallites, and the unknown impact of a polydisperse size distribution on the calculation. The method must be used within the limits described; however, it is the only method found that may be adapted to large, more representative sample sizes. The determination of the average morphology is often a "bottle neck" in elucidating other important behaviors of large quantities of crystalline powders used in pharmaceutical development and processing.