Multivariate quantification of the solid state phase composition of co-amorphous naproxen-indomethacin

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Autor/in:
Erscheinungsjahr:
2015
Medientyp:
Text
Schlagworte:
  • co-amorphous
  • solid state analysis
  • composition
  • multivariate
  • PLS
  • XRPD
  • recrystallization
  • stability
Beschreibung:
  • 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.
Lizenz:
  • info:eu-repo/semantics/openAccess
Quellsystem:
Forschungsinformationssystem der UHH

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oai:www.edit.fis.uni-hamburg.de:publications/77a646f5-a8db-4571-927f-291487e55d07