Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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.
Originalsprog | Engelsk |
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Tidsskrift | Molecules |
Vol/bind | 20 |
Udgave nummer | 10 |
Sider (fra-til) | 19571-87 |
Antal sider | 17 |
ISSN | 1420-3049 |
DOI | |
Status | Udgivet - 2015 |
ID: 161588268