title: Investigation of solid phase composition on tablet surfaces by grazing incidence X-ray diffraction.
abstract: OBJECTIVE
  To investigate solid state transformations of drug substances during compaction using grazing incidence X-ray diffraction (GIXD).
  
  
  METHODS
  The solid forms of three model drugs-theophylline (TP), nitrofurantoin (NF) and amlodipine besylate (AMB)-were compacted at different pressures (from 100 to 1000 MPa); prepared tablets were measured using GIXD. After the initial measurements of freshly compacted tablets, tablets were subjected to suitable recrystallization treatment, and analogous measurements were performed.
  
  
  RESULTS
  Solid forms of TP, NF and AMB showed partial amorphization as well as crystal disordering during compaction; the extent of these effects generally increased as a function of pressure. The changes were most pronounced at the outer surface region. The different solid forms showed difference in the formation of amorphicity/crystal disordering. Dehydration due to compaction was observed for the TP monohydrate, whereas hydrates of NF and AMB were stable towards dehydration.
  
  
  CONCLUSIONS
  With GIXD measurements, it was possible to probe the solid form composition at the different depths of the tablet surfaces and to obtain depth-dependent information on the compaction-induced amorphization, crystal disordering and dehydration.
authors: Department of Pharmaceutics and Analytical Chemistry Faculty of Pharmaceutical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.
authors: Vishal
authors: V
authors: Koradia
authors: Mikko
authors: M
authors: Tenho
authors: Heidi
authors: H
authors: Lopez de Diego
authors: Michiel
authors: M
authors: Ringkjøbing-Elema
authors: Jørn
authors: J
authors: Møller-Sonnergaard
authors: Jarno
authors: J
authors: Salonen
authors: Vesa-Pekka
authors: VP
authors: Lehto
authors: Jukka
authors: J
authors: Rantanen
mesh_terms: D017311:Amlodipine / Q000737:chemistry; D019245:Compressive Strength; D003460:Crystallization; D009582:Nitrofurantoin / Q000737:chemistry; D011312:Pressure; D013499:Surface Properties; D013607:Tablets / Q000737:chemistry*; D013806:Theophylline / Q000737:chemistry; D014961:X-Ray Diffraction / Q000379:methods*
chemical_list: D013607:Tablets; D017311:Amlodipine; D009582:Nitrofurantoin; D013806:Theophylline