In situ measurement of solvent-mediated phase transformations during dissolution testing
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In situ measurement of solvent-mediated phase transformations during dissolution testing. / Aaltonen, Jaakko; Heinänen, Paula; Peltonen, Leena; Kortejärvi, Hanna; Tanninen, Veli Pekka; Christiansen, Leena; Hirvonen, Jouni; Yliruusi, Jouko; Rantanen, Jukka.
In: Journal of Pharmaceutical Sciences, Vol. 95, No. 12, 12.2006, p. 2730-7.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - In situ measurement of solvent-mediated phase transformations during dissolution testing
AU - Aaltonen, Jaakko
AU - Heinänen, Paula
AU - Peltonen, Leena
AU - Kortejärvi, Hanna
AU - Tanninen, Veli Pekka
AU - Christiansen, Leena
AU - Hirvonen, Jouni
AU - Yliruusi, Jouko
AU - Rantanen, Jukka
N1 - (c) 2006 Wiley-Liss, Inc. and the American Pharmacists Association
PY - 2006/12
Y1 - 2006/12
N2 - In this study, solvent-mediated phase transformations of theophylline (TP) and nitrofurantoin (NF) were measured in a channel flow intrinsic dissolution test system. The test set-up comprised simultaneous measurement of drug concentration in the dissolution medium (with UV-Vis spectrophotometry) and measurement of the solid-state form of the dissolving solid (in situ with Raman spectroscopy). The solid phase transformations were also investigated off-line with scanning electron microscopy. TP anhydrate underwent a transformation to TP monohydrate, and NF anhydrate (form beta) to NF monohydrate (form II). Transformation of TP anhydrate to TP monohydrate resulted in a clear decrease in the dissolution rate, while the transformation of NF anhydrate (form beta) to NF monohydrate (form II) could not be linked as clearly to changes in the dissolution rate. The transformation of TP was an order of magnitude faster than that of NF. The presence of a water absorbing excipient, microcrystalline cellulose, was found to delay the onset of the transformation of TP anhydrate. Combining the measurement of drug concentration in the dissolution medium with the solid phase measurement offers a deeper understanding of the solvent-mediated phase transformation phenomena during dissolution.
AB - In this study, solvent-mediated phase transformations of theophylline (TP) and nitrofurantoin (NF) were measured in a channel flow intrinsic dissolution test system. The test set-up comprised simultaneous measurement of drug concentration in the dissolution medium (with UV-Vis spectrophotometry) and measurement of the solid-state form of the dissolving solid (in situ with Raman spectroscopy). The solid phase transformations were also investigated off-line with scanning electron microscopy. TP anhydrate underwent a transformation to TP monohydrate, and NF anhydrate (form beta) to NF monohydrate (form II). Transformation of TP anhydrate to TP monohydrate resulted in a clear decrease in the dissolution rate, while the transformation of NF anhydrate (form beta) to NF monohydrate (form II) could not be linked as clearly to changes in the dissolution rate. The transformation of TP was an order of magnitude faster than that of NF. The presence of a water absorbing excipient, microcrystalline cellulose, was found to delay the onset of the transformation of TP anhydrate. Combining the measurement of drug concentration in the dissolution medium with the solid phase measurement offers a deeper understanding of the solvent-mediated phase transformation phenomena during dissolution.
KW - Microscopy, Electron, Scanning
KW - Nitrofurantoin
KW - Solubility
KW - Spectrophotometry, Ultraviolet
KW - Spectrum Analysis, Raman
KW - Theophylline
KW - Water
KW - X-Ray Diffraction
U2 - 10.1002/jps.20725
DO - 10.1002/jps.20725
M3 - Journal article
C2 - 16892206
VL - 95
SP - 2730
EP - 2737
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
SN - 0022-3549
IS - 12
ER -
ID: 140618537