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 diffract ion (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 quanti tative "enhancement" factor for each face. The combined simple-forms morpho logy (CSM) of the material was then produced by indexing the observed faces and modifying the simulated Bravais-Friedel-Donnay-Harker (BFDH) morpholog y. The average shape of crystallites can be estimated from the CSM by multi plying each face by its enhancement factor. Acetaminophen crystals in two d ifferent habits and ibuprofen crystallized from toluene were used. The pred icted 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 limi tations are the need to "index" the faces, the size of the crystallites, an d the unknown impact of a polydisperse size distribution on the calculation . The method must be used within the limits described; however, it is the o nly method found that may be adapted to large, more representative sample s izes. 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. (C) 2000 Wiley- Liss, Inc. and the American Pharmaceutical Association.