Investigation of solid phase composition on tablet surfaces by grazing incidence X-ray diffraction.

Vishal Koradia, Mikko Tenho, Heidi Lopez de Diego, Michiel Ringkjøbing-Elema, Jørn Møller-Sonnergaard, Jarno Salonen, Vesa-Pekka Lehto, Jukka Rantanen

Department of Pharmaceutics and Analytical Chemistry Faculty of Pharmaceutical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.

Pharmaceutical research 2012 Jan

filter terms:

To investigate solid state transformations of drug substances during compaction using grazing incidence X-ray diffraction (GIXD). 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. 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. 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.

Citation

Vishal Koradia, Mikko Tenho, Heidi Lopez de Diego, Michiel Ringkjøbing-Elema, Jørn Møller-Sonnergaard, Jarno Salonen, Vesa-Pekka Lehto, Jukka Rantanen. Investigation of solid phase composition on tablet surfaces by grazing incidence X-ray diffraction. Pharmaceutical research. 2012 Jan;29(1):134-44