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

Molecules

Andreas Beyer²  Holger Grohganz¹  Korbinian Lཫmann¹  Thomas Rades¹  Claudia S. Leopold² 

[1] Department of Pharmacy, University of Copenhagen, Copenhagen 2100, Denmark; E-Mails:;Division of Pharmaceutical Technology, University of Hamburg, Hamburg 20146, Germany; E-Mail:

关键词: co-amorphous;    solid state analysis;    composition;    multivariate;    PLS;    XRPD;    recrystallization;    stability;   

DOI  :  10.3390/molecules201019571

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.