Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin
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Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin. / Beyer, Andreas; Grohganz, Holger; Löbmann, Korbinian; Rades, Thomas; Leopold, Claudia S.
In: Molecules, Vol. 20, No. 10, 2015, p. 19571-87.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin
AU - Beyer, Andreas
AU - Grohganz, Holger
AU - Löbmann, Korbinian
AU - Rades, Thomas
AU - Leopold, Claudia S
PY - 2015
Y1 - 2015
N2 - To benefit from the optimized dissolution properties of active pharmaceutical ingredients in their amorphous forms, co-amorphisation as a viable tool to stabilize these amorphous phases is of both academic and industrial interest. Reports dealing with the physical stability and recrystallization behavior of co-amorphous systems are however limited to qualitative evaluations based on the corresponding X-ray powder diffractograms. Therefore, the objective of the study was to develop a quantification model based on X-ray powder diffractometry (XRPD), followed by a multivariate partial least squares regression approach that enables the simultaneous determination of up to four solid state fractions: crystalline naproxen, γ-indomethacin, α-indomethacin as well as co-amorphous naproxen-indomethacin. For this purpose, a calibration set that covers the whole range of possible combinations of the four components was prepared and analyzed by XRPD. In order to test the model performances, leave-one-out cross validation was performed and revealed root mean square errors of validation between 3.11% and 3.45% for the crystalline molar fractions and 5.57% for the co-amorphous molar fraction. In summary, even four solid state phases, involving one co-amorphous phase, can be quantified with this XRPD data-based approach.
AB - To benefit from the optimized dissolution properties of active pharmaceutical ingredients in their amorphous forms, co-amorphisation as a viable tool to stabilize these amorphous phases is of both academic and industrial interest. Reports dealing with the physical stability and recrystallization behavior of co-amorphous systems are however limited to qualitative evaluations based on the corresponding X-ray powder diffractograms. Therefore, the objective of the study was to develop a quantification model based on X-ray powder diffractometry (XRPD), followed by a multivariate partial least squares regression approach that enables the simultaneous determination of up to four solid state fractions: crystalline naproxen, γ-indomethacin, α-indomethacin as well as co-amorphous naproxen-indomethacin. For this purpose, a calibration set that covers the whole range of possible combinations of the four components was prepared and analyzed by XRPD. In order to test the model performances, leave-one-out cross validation was performed and revealed root mean square errors of validation between 3.11% and 3.45% for the crystalline molar fractions and 5.57% for the co-amorphous molar fraction. In summary, even four solid state phases, involving one co-amorphous phase, can be quantified with this XRPD data-based approach.
U2 - 10.3390/molecules201019571
DO - 10.3390/molecules201019571
M3 - Journal article
C2 - 26516832
VL - 20
SP - 19571
EP - 19587
JO - Molecules
JF - Molecules
SN - 1420-3049
IS - 10
ER -
ID: 161588268