Ann Newman - "Analysis of Amorphous and Nanocrystalline Solids from Their X Ray Diffraction Patterns" S. Bates, G. Zografi, D. Engers,  K. Morris, K. Crowley, A. Newman

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      Publication Details (including relevant citation   information):

      Pharm. Res, 2006, 23(10),  2333-2349.


        Purpose  The purpose of     this paper is to provide a physical description of the     amorphous state for pharmaceutical materials and to investigate     the pharmaceutical implications. Techniques to elucidate     structural differences in pharmaceutical solids exhibiting     characteristic X-ray amorphous powder patterns are also     presented.  
        Materials and Methods  The     X-ray amorphous powder diffraction patterns of microcrystalline     cellulose, indomethacin, and piroxicam were measured with     laboratory XRPD instrumentation. Analysis of the data were     carried out using a combination of direct methods, such as pair     distribution functions (PDF), and indirect material modeling     techniques including Rietveld, total scattering, and amorphous     packing.  
        Results  The observation of     X-ray amorphous powder patterns may indicate the presence of     amorphous, glassy or disordered nanocrystalline material in the     sample. Rietveld modeling of microcrystalline cellulose     (Avicel® PH102) indicates that it is predominantly disordered     crystalline cellulose Form Iβ with some amorphous contribution.     The average crystallite size of the disordered nanocrystalline     cellulose was determined to be 10.9 nm. Total scattering     modeling of ground samples of α, γ, and δ crystal forms of     indomethacin in combination with analysis of the PDFs provided     a quantitative picture of the local structure during various     stages of grinding. For all three polymorphs, with increased     grinding time, a two-phase system, consisting of amorphous and     crystalline material, continually transformed to a completely     random close packed (RCP) amorphous structure. The same pattern     of transformation was detected for the Form I polymorph of     piroxicam. However, grinding of Form II of piroxicam initially     produced a disordered phase that maintained the local packing     of Form II but over a very short nanometer length scale. The     initial disordered phase is consistent with continuous random     network (CRN) glass material. This initial disordered phase was     maintained to a critical point when a transition to a     completely amorphous RCP structure occurred.  
        Conclusions  Treating X-ray     amorphous powder patterns with different solid-state models,     ranging from disordered nanocrystalline to glassy and     amorphous, resulted in the assignment of structures in each of     the systems examined. The pharmaceutical implications with     respect to the stability of the solid are discussed.  

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