Pharmaceutical Research

, Volume 23, Issue 10, pp 2333–2349

Analysis of Amorphous and Nanocrystalline Solids from Their X-Ray Diffraction Patterns

  • Simon Bates
  • George Zografi
  • David Engers
  • Kenneth Morris
  • Kieran Crowley
  • Ann Newman
Special Issue

Abstract

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.

Key Words

amorphous CRN disorder disordered nanocrystalline glass pair distribution function (PDF) RCP Rietveld total scattering X-ray powder diffraction (XRPD) 

Abbreviations

API

active pharmaceutical ingredient

CRN

continuous random network

NN

nearest neighbor

NNN

next nearest neighbor

NNNN

next next nearest neighbor

LRO

long-range order

MCC

microcrystalline cellulose

MRO

medium-range order

PDF

pair distribution function

RCP

random close packed

SRO

short-range order

XRPD

X-ray powder diffraction

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Simon Bates
    • 1
  • George Zografi
    • 2
  • David Engers
    • 3
  • Kenneth Morris
    • 3
  • Kieran Crowley
    • 4
  • Ann Newman
    • 1
  1. 1.SSCI, IncWest LafayetteUSA
  2. 2.University of WisconsinMadisonUSA
  3. 3.Industrial and Physical PharmacyPurdue UniversityWest LafayetteUSA
  4. 4.Cardinal HealthSomersetUSA

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