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dc.contributor.authorRuiz, Guadalupe N.
dc.contributor.authorRomanini, Michela
dc.contributor.authorBarrio Casado, María del
dc.contributor.authorTamarit Mur, José Luis
dc.contributor.authorPardo Soto, Luis Carlos
dc.contributor.authorMacovez, Roberto
dc.contributor.otherUniversitat Politècnica de Catalunya. Departament de Física
dc.date.accessioned2018-03-09T11:07:43Z
dc.date.available2018-11-06T01:30:29Z
dc.date.issued2017-11-06
dc.identifier.citationRuiz, G., Romanini, M., Del Barrio, M., Tamarit, J. Ll., Pardo, L., Macovez, R. Relaxation dynamics vs crystallization kinetics in the amorphous state: the case of Stiripentol. "Molecular pharmaceutics", 6 Novembre 2017, vol. 14, núm. 11, p. 3636-3643.
dc.identifier.issn1543-8384
dc.identifier.urihttp://hdl.handle.net/2117/114986
dc.description.abstractWith the aim of finding a correlation between the crystallization kinetics and the molecular dynamics of a substance that would allow prediction of its crystallization time as a function of temperature for a given a relaxation time, we have studied stiripentol, an anticonvulsant drug. Stiripentol has been characterized in its supercooled liquid, amorphous (glass), and crystalline states by the concurrent use of broadband dielectric spectroscopy (BDS), differential scanning calorimetry, X-ray diffraction, and optical microscopy. BDS was employed to study both the dipolar molecular dynamics and the kinetics of crystallization from the melt. Three different molecular relaxation dynamics were identified: an a relaxation corresponding to the collective reorientation of the molecules and associated with the glass transition (Tg = 246.2 ± 0.5 K), a Johari Goldstein ß relaxation that can be associated with the single-molecule precursor of the a process, and a ¿ relaxation arising from intramolecular motions. Isothermal crystallization of Stiripentol was studied by means of BDS well above the glass transition (between 273 and 293 K), and it was observed under optical microscope at ambient conditions. Stiripentol did not exhibit any sign of polymorphism at ambient pressure, and it recrystallized from the melt into its stable crystalline form. The crystallization kinetics did not obey the Avrami law. Stiripentol displayed a very low nucleation rate, and drops of liquid stiripentol were observed to crystallize completely from a single nucleus before the appearance of new nuclei, so that the crystallite grew according to the morphology of the liquid domains, a fact that might explain the lack of validity of the Avrami law. Possible correlations between the crystallization kinetics and the molecular dynamics have been analyzed, finding that the crystallization time has a sublinear dependence on the cooperative relaxation time, as is the case in other substances reported in the scientific literature. This could suggest a general correlation of these parameters, at least at temperatures above Tg. The low nucleation rate is an interesting feature in the quest of possible mechanisms that allow enhancing the physical stability of amorphous drugs
dc.format.extent8 p.
dc.language.isoeng
dc.subjectÀrees temàtiques de la UPC::Física
dc.subject.lcshAnticonvulsants
dc.subject.lcshCrystal growth
dc.subject.lcshDielectric Spectroscopy
dc.subject.otheramorphous formulations
dc.subject.otheranticonvulsant drug
dc.subject.othercrystal growth
dc.subject.otherdielectric spectroscopy
dc.subject.othermolecular mobility
dc.subject.otherphysical stability
dc.titleRelaxation dynamics vs crystallization kinetics in the amorphous state: the case of Stiripentol
dc.typeArticle
dc.subject.lemacCristalls -- Creixement
dc.contributor.groupUniversitat Politècnica de Catalunya. GCM - Grup de Caracterització de Materials
dc.identifier.doi10.1021/acs.molpharmaceut.7b00399
dc.description.peerreviewedPeer Reviewed
dc.relation.publisherversionhttp://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.7b00399
dc.rights.accessOpen Access
drac.iddocument21623197
dc.description.versionPostprint (author's final draft)
upcommons.citation.authorRuiz, G.; Romanini, M.; Del Barrio, M.; Tamarit, J. Ll.; Pardo, L.; Macovez, R.
upcommons.citation.publishedtrue
upcommons.citation.publicationNameMolecular pharmaceutics
upcommons.citation.volume14
upcommons.citation.number11
upcommons.citation.startingPage3636
upcommons.citation.endingPage3643


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