TY - JOUR
T1 - Investigation of solid phase composition on tablet surfaces by grazing incidence X-ray diffraction
AU - Koradia, Vishal Shamji
AU - Tenho, Mikko
AU - Diego, Heidi Lopez de
AU - Ringkjøbing-Elma, Michiel
AU - Sonnergaard, Jørn
AU - Salonen, Jamo
AU - Lehto, Vesa-Pekka
AU - Rantanen, Jukka
PY - 2012/1
Y1 - 2012/1
N2 - Purpose: 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.
AB - Purpose: 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.
KW - Former Faculty of Pharmaceutical Sciences
U2 - 10.1007/s11095-011-0520-8
DO - 10.1007/s11095-011-0520-8
M3 - Journal article
C2 - 21744172
SN - 0724-8741
VL - 29
SP - 134
EP - 144
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 1
ER -