Early stages of drug crystallization from amorphous solid dispersion via fractal analysis based on chemical imaging

dc.accessRightsAnonymous
dc.audienceScience
dc.contributor.authorKuentz, Martin
dc.contributor.authorAbreu-Villela, Renata
dc.contributor.authorSchönenberger, Monica
dc.contributor.authorCaraballo, Isidoro
dc.date.accessioned2018-12-14T15:42:37Z
dc.date.available2018-12-14T15:42:37Z
dc.date.issued2018-12
dc.description.abstractEarly stages of crystallization from amorphous solid dispersion (ASD) are typically not detected by means of standard methods like powder X-ray diffraction (XRPD). The aim of this study is therefore to evaluate if fractal analysis based on energy dispersive X-ray imaging can provide the means to identify early signs of physical instability. ASDs of the poorly water-soluble compound, felodipine (FEL) were prepared by solvent evaporation using different grades of HPMCAS, at 50 wt% drug loading. Samples were stored at accelerated conditions of 40 °C. Scanning electron microscopy equipped with an energy-dispersive X-ray spectroscopy (SEM-EDS) was used for elemental mapping of tablet surfaces. Comparative data were generated with a standard XRPD and with more sensitive methods for detection of early instability, i.e. laser scanning confocal microscopy (LSM) and atomic force microscopy (AFM). The SEM-EDS identified changes of drug-rich domains that were confirmed by LSM and AFM. Early changes in drug clusters were also revealed by a multifractal analysis that indicated a beginning phase separation and drug crystallization. Therefore, the presented fractal cluster analysis based on chemical imaging bears much promise as a new method to detect early signs of physical instability in ASD, which is of great relevance for pharmaceutical development.
dc.identifier.doihttps://doi.org/10.1016/j.ejpb.2018.10.007
dc.identifier.issn0939-6411
dc.identifier.issn1873-3441
dc.identifier.urihttp://hdl.handle.net/11654/26982
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofEuropean Journal of Pharmaceutics and Biopharmaceuticsen_US
dc.subjectSolid dispersion
dc.subjectAmorphous drug
dc.subjectPhase separation
dc.subjectCrystallization
dc.subjectChemical imaging
dc.subjectMultifractal analysis
dc.titleEarly stages of drug crystallization from amorphous solid dispersion via fractal analysis based on chemical imaging
dc.type01A - Beitrag in wissenschaftlicher Zeitschrift
dc.volume133
dspace.entity.typePublication
fhnw.InventedHereYes
fhnw.IsStudentsWorkno
fhnw.PublishedSwitzerlandNo
fhnw.ReviewTypeAnonymous ex ante peer review of a complete publication
fhnw.affiliation.hochschuleHochschule für Life Sciencesde_CH
fhnw.affiliation.institutInstitut für Pharma Technologyde_CH
fhnw.pagination122-130
fhnw.publicationOnlineJa
fhnw.publicationStatePublished
relation.isAuthorOfPublication68819448-8611-488b-87bc-1b1cf9a6a1b4
relation.isAuthorOfPublication.latestForDiscovery68819448-8611-488b-87bc-1b1cf9a6a1b4
Dateien