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Nanoemulsions and thermosensitive nanoemulgels of phenytoin and fosphenytoin for intranasal administration: Formulation development and in vitro characterization

2020Journal article Open access
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dc.contributor.authorPires, Patrícia C.
dc.contributor.authorPeixoto, Diana
dc.contributor.authorTeixeira, Isaura
dc.contributor.authorRodrigues, Márcio
dc.contributor.authorAlves, Gilberto
dc.contributor.authorSantos, Adriana O.
dc.date.accessioned2020-07-09T08:41:46Z
dc.date.available2021-01-01T01:30:20Z
dc.date.issued2020
dc.description.abstractPhenytoin is a low solubility anticonvulsant drug. It has, nonetheless, other possible therapeutic indications, such as neuropathic pain, including trigeminal neuralgia, or wound healing. Its use has decreased due to side effects, but nasal/intranasal administration could significantly increase drug safety and efficacy. The aim of this work was to develop and study nanoemulsions and thermosensitive nanoemulgels of phenytoin and fosphenytoin, in combination, for intranasal administration, with immediate and sustained release profiles. Nanoemulsions were prepared by adding the aqueous phase, containing gelling polymers in the case of nanoemulgels, to emulsion preconcentrates, followed, in the optimized procedure, by premix membrane emulsification. Formulation design and optimization was guided by drug strength, rheological behavior, osmolality, mean droplet size and polydispersity. Fosphenytoin interfered significantly with Carbopol but not with Pluronic's gelation, and allowed to achieve drug strengths equivalent to 22 or 27 mg/g of phenytoin in lead nanoemulsions, and 16.7 mg/g of phenytoin in the lead nanoemulgel. The final selected low viscosity nanoemulsions had an immediate or prolonged fosphenytoin release profile, depending of anhydrous phase proportion (10% or 40%, respectively). The thermosensitive nanoemulgel, with 10% anhydrous phase, showed prolonged drug release. Future studies will establish whether they are more suited for topical effects or therapeutic brain delivery.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.ejps.2019.105099pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.6/10338
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationHealth Sciences Research Centre
dc.subjectAdministration Intranasalpt_PT
dc.subjectAnticonvulsantspt_PT
dc.subjectDrug Compoundingpt_PT
dc.subjectDrug Liberationpt_PT
dc.subjectEmulsionspt_PT
dc.subjectGelspt_PT
dc.subjectNanostructurespt_PT
dc.subjectPhenytoinpt_PT
dc.subjectTemperaturept_PT
dc.subjectDrug Delivery Systemspt_PT
dc.titleNanoemulsions and thermosensitive nanoemulgels of phenytoin and fosphenytoin for intranasal administration: Formulation development and in vitro characterizationpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleHealth Sciences Research Centre
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F00709%2F2019/PT
oaire.citation.startPage105099pt_PT
oaire.citation.titleEuropean Journal of Pharmaceutical Sciencespt_PT
oaire.citation.volume141pt_PT
oaire.fundingStream6817 - DCRRNI ID
person.familyNamePires
person.familyNameCastro Peixoto
person.familyNameRodrigues
person.familyNameAlves
person.familyNameOliveira dos Santos
person.givenNamePatrícia
person.givenNameDiana
person.givenNameMárcio José de Abreu Marques
person.givenNameGilberto
person.givenNameAdriana
person.identifierL-8542-2014
person.identifier.ciencia-idDF1D-73CF-6BA4
person.identifier.ciencia-id161A-3EDB-D767
person.identifier.ciencia-id6A1B-B7C8-D70F
person.identifier.ciencia-id891C-417A-1534
person.identifier.orcid0000-0003-0036-4894
person.identifier.orcid0000-0001-9772-4504
person.identifier.orcid0000-0002-7010-0619
person.identifier.orcid0000-0002-4213-0714
person.identifier.orcid0000-0002-1224-9191
person.identifier.ridH-4597-2011
person.identifier.scopus-author-id57211945487
person.identifier.scopus-author-id55513387900
person.identifier.scopus-author-id55663631700
person.identifier.scopus-author-id14049212000
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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