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Comprehensive determination of the solid state stability of bethanechol chloride active pharmaceutical ingredient using combined analytical tools

hal.structure.identifierLaboratoire Physico-Chimie Industrielle du Médicament [LPCIM]
hal.structure.identifierLaboratoire de Contrôle Qualité
dc.contributor.authorROTIVAL, Romain
hal.structure.identifierLaboratoire Physico-Chimie Industrielle du Médicament [LPCIM]
dc.contributor.authorCORVIS, Yohann
hal.structure.identifierSciences et Méthodes Séparatives [SMS]
dc.contributor.authorCARTIGNY, Yohann
hal.structure.identifierLaboratoire Ondes et Matière d'Aquitaine [LOMA]
dc.contributor.authorNÉGRIER, Philippe
hal.structure.identifierLaboratoire de Pharmacochimie
dc.contributor.authorMARCHIVIE, Mathieu
hal.structure.identifierLaboratoire de Pharmacochimie
dc.contributor.authorMASSIP, Stéphane
hal.structure.identifierLaboratoire de Contrôle Qualité
dc.contributor.authorGANA, Inès
hal.structure.identifierLaboratoire de cristallographie et RMN biologiques [LCRB - UMR 8015]
dc.contributor.authorLEMOINE, Pascale
hal.structure.identifierLaboratoire Physico-Chimie Industrielle du Médicament [LPCIM]
dc.contributor.authorESPEAU, Philippe
dc.date.created2013-04-23
dc.date.issued2013
dc.description.abstractEnThe use of an integrative analytical approach allowed us to establish the intrinsic solid state stability of bethanechol chloride (BC), an active pharmaceutical ingredient used in the treatment of urinary retention. First, the crystal structure of the monoclinic form has been described using single crystal X-ray diffraction studies. Second, thermal analyses revealed that the compound degrades upon melting, with an apparent melting temperature estimated to be 231 °C. No transition from the monoclinic to the orthorhombic form has been observed, suggesting that the monoclinic form is the stable one. Third, the two-step melting–decomposition process has been elucidated by liquid chromatography and thermogravimetry coupled to mass spectrometry. The first step corresponds to the sample liquefaction, which consists of the gradual dissolution of bethanechol chloride in its liquid degradant, i.e. betamethylcholine chloride. This step is in agreement with Bawn kinetics and the activation energy of the reaction has been estimated at 35.5 kcal mol−1. The second step occurs with accelerated degradation in the melt. Elucidation of secondary decomposition pathways evidenced autocatalytic properties conferred by the formation of both isocyanic acid and methyl chloride. Finally, dynamic water vapor sorption analysis showed a substantial hygroscopicity of the drug substance. A deliquescent point has been determined at 56% relative humidity at 25 °C.
dc.language.isoen
dc.publisherRoyal Society of Chemistry
dc.rights.urihttp://creativecommons.org/licenses/by-sa/
dc.title.enComprehensive determination of the solid state stability of bethanechol chloride active pharmaceutical ingredient using combined analytical tools
dc.typeArticle de revue
dc.identifier.doi10.1039/C3CE40707A
dc.subject.halChimie/Cristallographie
dc.subject.halChimie/Chimie thérapeutique
bordeaux.journalCrystEngComm
bordeaux.page7970-7980
bordeaux.volume15
bordeaux.issue39
bordeaux.peerReviewedoui
hal.identifierhal-00874391
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-00874391v1
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=CrystEngComm&rft.date=2013&rft.volume=15&rft.issue=39&rft.spage=7970-7980&rft.epage=7970-7980&rft.au=ROTIVAL,%20Romain&CORVIS,%20Yohann&CARTIGNY,%20Yohann&N%C3%89GRIER,%20Philippe&MARCHIVIE,%20Mathieu&rft.genre=article


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