title: Detecting phase separation of freeze-dried binary amorphous systems using pair-wise distribution function and multivariate data analysis.
abstract: The purpose of this study is to investigate the use of multivariate data analysis for powder X-ray diffraction-pair-wise distribution function (PXRD-PDF) data to detect phase separation in freeze-dried binary amorphous systems. Polymer-polymer and polymer-sugar binary systems at various ratios were freeze-dried. All samples were analyzed by PXRD, transformed to PDF and analyzed by principal component analysis (PCA). These results were validated by differential scanning calorimetry (DSC) through characterization of glass transition of the maximally freeze-concentrate solute (Tg'). Analysis of PXRD-PDF data using PCA provides a more clear 'miscible' or 'phase separated' interpretation through the distribution pattern of samples on a score plot presentation compared to residual plot method. In a phase separated system, samples were found to be evenly distributed around the theoretical PDF profile. For systems that were miscible, a clear deviation of samples away from the theoretical PDF profile was observed. Moreover, PCA analysis allows simultaneous analysis of replicate samples. Comparatively, the phase behavior analysis from PXRD-PDF-PCA method was in agreement with the DSC results. Overall, the combined PXRD-PDF-PCA approach improves the clarity of the PXRD-PDF results and can be used as an alternative explorative data analytical tool in detecting phase separation in freeze-dried binary amorphous systems.
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark. norman_chieng@imu.edu.my
authors.forename: Norman
authors.initials: N
authors.lastname: Chieng
authors.forename: Hjalte
authors.initials: H
authors.lastname: Trnka
authors.forename: Johan
authors.initials: J
authors.lastname: Boetker
authors.forename: Michael
authors.initials: M
authors.lastname: Pikal
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
authors.forename: Holger
authors.initials: H
authors.lastname: Grohganz
mesh_terms: D002152:Calorimetry, Differential Scanning; D018360:Crystallography, X-Ray; D003911:Dextrans / Q000737:chemistry; D005612:Freeze Drying; D015233:Models, Statistical; D015999:Multivariate Analysis; D044367:Phase Transition; D011142:Polyvinyl Alcohol / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D033362:Powder Diffraction; D025341:Principal Component Analysis; D013678:Technology, Pharmaceutical / Q000379:methods*; D014199:Trehalose / Q000737:chemistry
chemical_list: D003911:Dextrans; D011142:Polyvinyl Alcohol; D014199:Trehalose; D011205:Povidone
keywords: Freeze-drying; Pair-wise distribution function; Phase separation; Powder X-ray diffraction; Principal component analysis