title: Influence of chitosan and carboxymethylchitosan on the polymorphism and solubilisation of diflunisal.
abstract: The interactions of diflunisal (DF) with chitosans (CS) of different molecular weights and carboxymethylchitosan (CMCS), a water-soluble derivative, have been investigated. The interactions in solution have been studied by solubility assays in which the highest solubilisation (13-fold) was obtained with CMCS. Solid dispersions were prepared by coevaporation and kneading methods. Solid state characterisation was performed by X-ray diffraction analysis, scanning electron microscopy, thermomicroscopy, differential thermal analysis and infrared spectroscopy. Drug-polymer electrostatic interactions and hydrogen bonds are the main binding forces in these systems. The kneading method gave rise to amorphous systems regardless of the polymer employed. However, coevaporation resulted in the formation of different polymorphs of diflunisal (form II or III) depending on the type of polymer used. Therefore, it seems that drug-polymer interactions determine the crystallization pattern of the drug. Finally, diflunisal release from these systems improved markedly with CMCS and significantly in the presence of low molecular weight CS.
authors.affiliation: Departamento de Química y Edafología, Facultad de Ciencias, University of Navarra, Irunlarrea s/n, Pamplona 31080, Navarra, Spain. Electronic address: dlucio@alumni.unav.es.
authors.forename: David
authors.initials: D
authors.lastname: Lucio
authors.affiliation: Departamento de Química y Edafología, Facultad de Ciencias, University of Navarra, Irunlarrea s/n, Pamplona 31080, Navarra, Spain. Electronic address: azornoza@unav.es.
authors.forename: Arantza
authors.initials: A
authors.lastname: Zornoza
authors.affiliation: Departamento de Química y Edafología, Facultad de Ciencias, University of Navarra, Irunlarrea s/n, Pamplona 31080, Navarra, Spain. Electronic address: moharriz@unav.es.
authors.forename: María Cristina
authors.initials: MC
authors.lastname: Martínez-Ohárriz
mesh_terms: D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D003460:Crystallization; D018360:Crystallography, X-Ray; D004055:Differential Thermal Analysis; D004061:Diflunisal / Q000737:chemistry*; D004337:Drug Carriers; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D008956:Models, Chemical; D008970:Molecular Weight; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D004337:Drug Carriers; C514968:carboxymethyl-chitosan; D004061:Diflunisal; D048271:Chitosan
keywords: Carboxymethylchitosan; Chitosan; Diflunisal; Drug release; Polymorphism