Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin
AbstractTo 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. View Full-Text
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Beyer, A.; Grohganz, H.; Löbmann, K.; Rades, T.; Leopold, C.S. Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin. Molecules 2015, 20, 19571-19587.
Beyer A, Grohganz H, Löbmann K, Rades T, Leopold CS. Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin. Molecules. 2015; 20(10):19571-19587.Chicago/Turabian Style
Beyer, Andreas; Grohganz, Holger; Löbmann, Korbinian; Rades, Thomas; Leopold, Claudia S. 2015. "Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin." Molecules 20, no. 10: 19571-19587.