title: A structural investigation into the compaction behavior of pharmaceutical composites using powder X-ray diffraction and total scattering analysis.
abstract: OBJECTIVE
  To use advanced powder X-ray diffraction (PXRD) to characterize the structure of anhydrous theophylline following compaction, alone, and as part of a binary mixture with either alpha-lactose monohydrate or microcrystalline cellulose.
  
  
  METHODS
  Compacts formed from (1) pure theophylline and (2) each type of binary mixture were analyzed intact using PXRD. A novel mathematical technique was used to accurately separate multi-component diffraction patterns. The pair distribution function (PDF) of isolated theophylline diffraction data was employed to assess structural differences induced by consolidation and evaluated by principal components analysis (PCA).
  
  
  RESULTS
  Changes induced in PXRD patterns by increasing compaction pressure were amplified by the PDF. Simulated data suggest PDF dampening is attributable to molecular deviations from average crystalline position. Samples compacted at different pressures were identified and differentiated using PCA. Samples compacted at common pressures exhibited similar inter-atomic correlations, where excipient concentration factored in the analyses involving lactose.
  
  
  CONCLUSIONS
  Practical real-space structural analysis of PXRD data by PDF was accomplished for intact, compacted crystalline drug with and without excipient. PCA was used to compare multiple PDFs and successfully differentiated pattern changes consistent with compaction-induced disordering of theophylline as a single component and in the presence of another material.
authors.affiliation: Duquesne University, Pittsburgh, Pennsylvania, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Moore
authors.forename: Alison M
authors.initials: AM
authors.lastname: Steinbach
authors.forename: Ira S
authors.initials: IS
authors.lastname: Buckner
authors.forename: Peter L D
authors.initials: PL
authors.lastname: Wildfong
mesh_terms: D002482:Cellulose / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D044367:Phase Transition; D011208:Powders / Q000737:chemistry; D025341:Principal Component Analysis; D013806:Theophylline / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods*
chemical_list: D011208:Powders; D002482:Cellulose; D013806:Theophylline; C109691:microcrystalline cellulose