Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin

作者：Beyer Andreas; Grohganz Holger; Lobmann Korbinian; Rades Thomas; Leopold Claudia S^*

来源：Molecules, 2015, 20(10): 19571-19587.

DOI：10.3390/molecules201019571

• co-amorphous
• solid state analysis
• composition
• multivariate
• PLS
• XRPD
• recrystallization
• stability

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, -indomethacin, -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.

• 出版日期2015-10