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Molecules 2015, 20(10), 19571-19587; doi:10.3390/molecules201019571

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

1
Division of Pharmaceutical Technology, University of Hamburg, Hamburg 20146, Germany
2
Department of Pharmacy, University of Copenhagen, Copenhagen 2100, Denmark
*
Author to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 25 September 2015 / Revised: 19 October 2015 / Accepted: 21 October 2015 / Published: 27 October 2015
(This article belongs to the Collection Poorly Soluble Drugs)
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Abstract

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. View Full-Text
Keywords: co-amorphous; solid state analysis; composition; multivariate; PLS; XRPD; recrystallization; stability co-amorphous; solid state analysis; composition; multivariate; PLS; XRPD; recrystallization; stability
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

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.

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