DESENVOLVIMENTO DE UM ADESIVO PARA PRÓTESES REMOVÍVEIS CONTENDO MICROPARTÍCULAS POLIMÉRICAS DE NITRATO DE MICONAZOL: SÍNTESE E CARACTERIZAÇÃO
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UEPG |
Texto Completo: | http://tede2.uepg.br/jspui/handle/prefix/1705 |
Resumo: | The combination of well-fitting dentures with topical antifungals is appropriate therapeutic approach for denture stomatitis (EP). It was developed and evaluated an adhesive for removable dentures containing miconazole nitrate (NM) incorporated into mucoadhesive and/or pH dependent polymer microparticles aiming at increasing bioavailability. Initially, microparticles have been developed containing 10% and 20% of NM, spray-drying, using Gantrez MS-955 polymer (G10, G20), Eudragit L-100 (E10, E20) or both (EG10, EG20). An analytical method by high-performance liquid chromatography (HPLC) to quantify NM of the microparticles was validated. Microparticles were characterized by scanning electron microscopy (SEM), x-ray diffraction, Fourier-transformed infrared spectrometry (FTIR), differential scanning calorimetry (DSC), in-vitro release studies (percentage of dissolution / time, and release profiles) and antifungal activity. An experimental denture adhesive formulation (ACT) was developed containing 10% by weight of the microparticles (AE1, AG1, AEG1, AE2, AG2, AEG2) or 2% of pure drug (ANM). For all adhesives it was determined: minimum inhibitory concentration (MIC) for Candida albicans (microdilution and agar dilution); adhesive force (FA among acrylic surfaces after 0.5, 1, 3, or 6 h immersion in water); and toxicity to brine shrimp (24 h and 48 h) by calculating lethal concentration 50 (LC50). The HPLC method was proven specific, linear (r = 0.9992), precise, accurate and robust in the range 5-90 μg.mL-1, with running and retention times of 10.0 and 5.58 minutes, respectively. All microparticles showed acceptable performance (37.22% - 55.36%) and encapsulation (over 89%) values. E10 and E20 microparticles showed spherical and smooth surface, while EG20 had similar shape, but rough surface. G10, G20 and EG20 had depressed craters and morphology. The diameters of the microparticles ranged from 1.9 to 4.3 micrometers. No chemical bond was observed between the MN and the polymers through the FTIR spectra. Microencapsulation contributed to the drug amorphization, according to thermal analysis and X-ray diffraction, reducing the release time. NM and the G10, G20 and EG20 microparticles fitted the biexponential release kinetic model and the microparticles E10, E20 and EG10 fitted to mono-exponential model. The microparticles showed antifungal efficiency similar to pure drug. Extracts of the adhesives containing the microparticles and ANM showed MIC of 1.25 to 5 μg.mL-1 (comparable to Daktarin®, 2.5 μg.mL-1). Significant differences in AF for adhesive formulations evaluated as a function of immersion time in water were observed (p <0.001), with an upward trend between 1 h and 3 h, followed by reduction or stabilization up to 6 h. The incorporation of NM and polymeric microparticles did not affect the FA of the experimental adhesive and AEG20 showed the best results, with high initial values, and holding them for 6 h. All adhesive formulations showed low or no toxicity (LC50 349.53 to 931.00 μg.mL-1). The proposed denture adhesive formulation was proven compatible with the incorporation of polymeric microparticles containing NM. |
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Campanha, Nara HellenCPF:11993069836http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705349Z2Farago, Paulo VitorCPF:02688357999Mima, Ewerton Garcia de OliveiraCPF:29023609832http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4777954P7Morante, Daniel Rodrigo HerrraCPF:01144506921http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4290864J4Paula, Josiane de Fatima Padilha deCPF:49618768953http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4702484Y6Urban, Vanessa MiglioriniCPF:28707998880http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4766953J0CPF:01167831926http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4414725U7Molina, Andrés Felipe Cartagena2017-07-24T19:21:59Z2016-05-162017-07-24T19:21:59Z2016-02-05MOLINA, Andrés Felipe Cartagena. DEVELOPMENT OF REMOVABLE DENTURE ADHESIVE CONTAINING MICONAZOLE NITRATE-POLYMERIC MICROPARTICLES: SYNTHESIS AND CHARACTERIZATION. 2016. 119 f. Tese (Doutorado em Clinica Integrada, Dentística Restauradora e Periodontia) - UNIVERSIDADE ESTADUAL DE PONTA GROSSA, Ponta Grossa, 2016.http://tede2.uepg.br/jspui/handle/prefix/1705The combination of well-fitting dentures with topical antifungals is appropriate therapeutic approach for denture stomatitis (EP). It was developed and evaluated an adhesive for removable dentures containing miconazole nitrate (NM) incorporated into mucoadhesive and/or pH dependent polymer microparticles aiming at increasing bioavailability. Initially, microparticles have been developed containing 10% and 20% of NM, spray-drying, using Gantrez MS-955 polymer (G10, G20), Eudragit L-100 (E10, E20) or both (EG10, EG20). An analytical method by high-performance liquid chromatography (HPLC) to quantify NM of the microparticles was validated. Microparticles were characterized by scanning electron microscopy (SEM), x-ray diffraction, Fourier-transformed infrared spectrometry (FTIR), differential scanning calorimetry (DSC), in-vitro release studies (percentage of dissolution / time, and release profiles) and antifungal activity. An experimental denture adhesive formulation (ACT) was developed containing 10% by weight of the microparticles (AE1, AG1, AEG1, AE2, AG2, AEG2) or 2% of pure drug (ANM). For all adhesives it was determined: minimum inhibitory concentration (MIC) for Candida albicans (microdilution and agar dilution); adhesive force (FA among acrylic surfaces after 0.5, 1, 3, or 6 h immersion in water); and toxicity to brine shrimp (24 h and 48 h) by calculating lethal concentration 50 (LC50). The HPLC method was proven specific, linear (r = 0.9992), precise, accurate and robust in the range 5-90 μg.mL-1, with running and retention times of 10.0 and 5.58 minutes, respectively. All microparticles showed acceptable performance (37.22% - 55.36%) and encapsulation (over 89%) values. E10 and E20 microparticles showed spherical and smooth surface, while EG20 had similar shape, but rough surface. G10, G20 and EG20 had depressed craters and morphology. The diameters of the microparticles ranged from 1.9 to 4.3 micrometers. No chemical bond was observed between the MN and the polymers through the FTIR spectra. Microencapsulation contributed to the drug amorphization, according to thermal analysis and X-ray diffraction, reducing the release time. NM and the G10, G20 and EG20 microparticles fitted the biexponential release kinetic model and the microparticles E10, E20 and EG10 fitted to mono-exponential model. The microparticles showed antifungal efficiency similar to pure drug. Extracts of the adhesives containing the microparticles and ANM showed MIC of 1.25 to 5 μg.mL-1 (comparable to Daktarin®, 2.5 μg.mL-1). Significant differences in AF for adhesive formulations evaluated as a function of immersion time in water were observed (p <0.001), with an upward trend between 1 h and 3 h, followed by reduction or stabilization up to 6 h. The incorporation of NM and polymeric microparticles did not affect the FA of the experimental adhesive and AEG20 showed the best results, with high initial values, and holding them for 6 h. All adhesive formulations showed low or no toxicity (LC50 349.53 to 931.00 μg.mL-1). The proposed denture adhesive formulation was proven compatible with the incorporation of polymeric microparticles containing NM.A associação de próteses bem adaptadas com a presença tópica de antifúngicos é adequada abordagem terapêutica para estomatite protética (EP). Foi desenvolvido e avaliado um adesivo para prótese removível contendo nitrato de miconazol (NM) incorporado a micropartículas poliméricas muco-adesivas e/ou pH dependentes visando aumento de biodisponibilidade. Inicialmente, foram desenvolvidas micropartículas contendo 10% e 20% de NM, por spray-drying, utilizando os polímeros Gantrez MS-955 (G10, G20), Eudragit L-100 (E10, E20) ou ambos (EG10, EG20). Foi validado um método analítico por cromatografia líquida de alta eficiência (CLAE) para se quantificar NM das micropartículas. Estas foram caracterizadas por microscopia eletrônica de varredura (MEV), difração de raios x, espectrometria de infravermelho por transformada em Fourier (FTIR), calorimetria exploratória diferencial (CED), estudos de liberação in-vitro (porcentagem de dissolução/tempo e perfis de liberação) e atividade antifúngica. A seguir foram desenvolvidas formulações de um adesivo experimental para prótese (ACT) acrescido de 10% em peso das micropartículas (AE1, AG1, AEG1, AE2, AG2, AEG2) ou 2% do fármaco puro (AMN). Para todos adesivos determinou-se: concentração inibitória mínima (CMI) em Candida albicans (microdiluição em caldo e diluição em ágar); força adesiva (FA, entre superfícies acrílicas após 0,5, 1, 3, ou 6 h de imersão em água); e toxicidade em Artemia salina (24 h e 48 h), calculando-se concentração letal 50 (CL50). O método de CLAE apresentou-se específico, linear (r = 0,9992), preciso, exato e robusto na faixa de 5 a 90 μg.mL-1, com tempos de corrida e de retenção de 10,0 e 5,58 minutos, respectivamente. Todas as micropartículas mostraram aceitáveis valores de rendimento (37,22% – 55,36%) e de encapsulação (superiores a 89%). As micropartículas E10 e E20 apresentaram forma esférica e superfície lisa, enquanto EG20 possuíam a mesma forma, porém superfície rugosa. As micropartículas G10, G20 e EG20 apresentaram morfologia deprimida e crateras. Os diâmetros das micropartículas variaram entre 1,9 a 4,3 μm. Nenhuma ligação química foi observada entre o NM e os polímeros, através dos espectros de FTIR. A microencapsulação contribuiu para amorfizar o fármaco, segundo as análises térmicas e difração de raios X, reduzindo seu tempo de liberação. Ajustaram-se ao modelo cinético de liberação biexponencial o NM e as micropartículas G10, G20 e EG20, e ao modelo monoexponencial, as micropartículas E10, E20 e EG10. As micropartículas apresentaram eficiência antifúngica similar ao fármaco puro. Extratos dos adesivos contendo micropartículas e a formulação AMN apresentaram CMI entre 1,25 a 5 μg.mL-1 (comparável a Daktarin®, 2,5 μg.mL-1). Foram verificadas diferenças significativas na FA para as formulações de adesivos avaliadas em função do tempo de imersão na água (p<0,001), com tendência de aumento entre 1 h e 3 h, seguido de decréscimo ou estabilização até 6 h. A incorporação do NM e de micropartículas poliméricas não prejudicou a FA do adesivo experimental e AEG20 exibiu os melhores resultados, apresentando elevados valores iniciais, e mantendo-os por 6 h. Todas as formulações de adesivos apresentaram baixa ou nenhuma toxicidade (CL50 de 349,53 a 931,00 μg.mL-1). A formulação de adesivo para prótese removível proposta foi compatível com a incorporação de micropartículas poliméricas contendo NM.Made available in DSpace on 2017-07-24T19:21:59Z (GMT). No. of bitstreams: 1 Andres Felipe.pdf: 3893759 bytes, checksum: fd56d743b750b678334823fb1406f10a (MD5) Previous issue date: 2016-02-05Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUNIVERSIDADE ESTADUAL DE PONTA GROSSAPrograma de Pós-Graduação em OdontologiaUEPGBRClinica Integrada, Dentística Restauradora e Periodontianitrato de miconazolliberação controlada de fármacospreparações farmacêuticas odontológicasadesivos a tecidosestomatite sob próteseCandida albicansmiconazole nitratedrug liberationdental pharmaceutical-preparationstissue adhesivesdenture stomatitisCandida albicansCNPQ::CIENCIAS DA SAUDE::ODONTOLOGIADESENVOLVIMENTO DE UM ADESIVO PARA PRÓTESES REMOVÍVEIS CONTENDO MICROPARTÍCULAS POLIMÉRICAS DE NITRATO DE MICONAZOL: SÍNTESE E CARACTERIZAÇÃODEVELOPMENT OF REMOVABLE DENTURE ADHESIVE CONTAINING MICONAZOLE NITRATE-POLYMERIC MICROPARTICLES: SYNTHESIS AND CHARACTERIZATIONinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UEPGinstname:Universidade Estadual de Ponta Grossa (UEPG)instacron:UEPGORIGINALAndres Felipe.pdfapplication/pdf3893759http://tede2.uepg.br/jspui/bitstream/prefix/1705/1/Andres%20Felipe.pdffd56d743b750b678334823fb1406f10aMD51prefix/17052017-07-24 16:21:59.722oai:tede2.uepg.br:prefix/1705Biblioteca Digital de Teses e Dissertaçõeshttps://tede2.uepg.br/jspui/PUBhttp://tede2.uepg.br/oai/requestbicen@uepg.br||mv_fidelis@yahoo.com.bropendoar:2017-07-24T19:21:59Biblioteca Digital de Teses e Dissertações da UEPG - Universidade Estadual de Ponta Grossa (UEPG)false |
dc.title.por.fl_str_mv |
DESENVOLVIMENTO DE UM ADESIVO PARA PRÓTESES REMOVÍVEIS CONTENDO MICROPARTÍCULAS POLIMÉRICAS DE NITRATO DE MICONAZOL: SÍNTESE E CARACTERIZAÇÃO |
dc.title.alternative.eng.fl_str_mv |
DEVELOPMENT OF REMOVABLE DENTURE ADHESIVE CONTAINING MICONAZOLE NITRATE-POLYMERIC MICROPARTICLES: SYNTHESIS AND CHARACTERIZATION |
title |
DESENVOLVIMENTO DE UM ADESIVO PARA PRÓTESES REMOVÍVEIS CONTENDO MICROPARTÍCULAS POLIMÉRICAS DE NITRATO DE MICONAZOL: SÍNTESE E CARACTERIZAÇÃO |
spellingShingle |
DESENVOLVIMENTO DE UM ADESIVO PARA PRÓTESES REMOVÍVEIS CONTENDO MICROPARTÍCULAS POLIMÉRICAS DE NITRATO DE MICONAZOL: SÍNTESE E CARACTERIZAÇÃO Molina, Andrés Felipe Cartagena nitrato de miconazol liberação controlada de fármacos preparações farmacêuticas odontológicas adesivos a tecidos estomatite sob prótese Candida albicans miconazole nitrate drug liberation dental pharmaceutical-preparations tissue adhesives denture stomatitis Candida albicans CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA |
title_short |
DESENVOLVIMENTO DE UM ADESIVO PARA PRÓTESES REMOVÍVEIS CONTENDO MICROPARTÍCULAS POLIMÉRICAS DE NITRATO DE MICONAZOL: SÍNTESE E CARACTERIZAÇÃO |
title_full |
DESENVOLVIMENTO DE UM ADESIVO PARA PRÓTESES REMOVÍVEIS CONTENDO MICROPARTÍCULAS POLIMÉRICAS DE NITRATO DE MICONAZOL: SÍNTESE E CARACTERIZAÇÃO |
title_fullStr |
DESENVOLVIMENTO DE UM ADESIVO PARA PRÓTESES REMOVÍVEIS CONTENDO MICROPARTÍCULAS POLIMÉRICAS DE NITRATO DE MICONAZOL: SÍNTESE E CARACTERIZAÇÃO |
title_full_unstemmed |
DESENVOLVIMENTO DE UM ADESIVO PARA PRÓTESES REMOVÍVEIS CONTENDO MICROPARTÍCULAS POLIMÉRICAS DE NITRATO DE MICONAZOL: SÍNTESE E CARACTERIZAÇÃO |
title_sort |
DESENVOLVIMENTO DE UM ADESIVO PARA PRÓTESES REMOVÍVEIS CONTENDO MICROPARTÍCULAS POLIMÉRICAS DE NITRATO DE MICONAZOL: SÍNTESE E CARACTERIZAÇÃO |
author |
Molina, Andrés Felipe Cartagena |
author_facet |
Molina, Andrés Felipe Cartagena |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Campanha, Nara Hellen |
dc.contributor.advisor1ID.fl_str_mv |
CPF:11993069836 |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705349Z2 |
dc.contributor.advisor-co1.fl_str_mv |
Farago, Paulo Vitor |
dc.contributor.advisor-co1ID.fl_str_mv |
CPF:02688357999 |
dc.contributor.referee1.fl_str_mv |
Mima, Ewerton Garcia de Oliveira |
dc.contributor.referee1ID.fl_str_mv |
CPF:29023609832 |
dc.contributor.referee1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4777954P7 |
dc.contributor.referee2.fl_str_mv |
Morante, Daniel Rodrigo Herrra |
dc.contributor.referee2ID.fl_str_mv |
CPF:01144506921 |
dc.contributor.referee2Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4290864J4 |
dc.contributor.referee3.fl_str_mv |
Paula, Josiane de Fatima Padilha de |
dc.contributor.referee3ID.fl_str_mv |
CPF:49618768953 |
dc.contributor.referee3Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4702484Y6 |
dc.contributor.referee4.fl_str_mv |
Urban, Vanessa Migliorini |
dc.contributor.referee4ID.fl_str_mv |
CPF:28707998880 |
dc.contributor.referee4Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4766953J0 |
dc.contributor.authorID.fl_str_mv |
CPF:01167831926 |
dc.contributor.authorLattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4414725U7 |
dc.contributor.author.fl_str_mv |
Molina, Andrés Felipe Cartagena |
contributor_str_mv |
Campanha, Nara Hellen Farago, Paulo Vitor Mima, Ewerton Garcia de Oliveira Morante, Daniel Rodrigo Herrra Paula, Josiane de Fatima Padilha de Urban, Vanessa Migliorini |
dc.subject.por.fl_str_mv |
nitrato de miconazol liberação controlada de fármacos preparações farmacêuticas odontológicas adesivos a tecidos estomatite sob prótese Candida albicans |
topic |
nitrato de miconazol liberação controlada de fármacos preparações farmacêuticas odontológicas adesivos a tecidos estomatite sob prótese Candida albicans miconazole nitrate drug liberation dental pharmaceutical-preparations tissue adhesives denture stomatitis Candida albicans CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA |
dc.subject.eng.fl_str_mv |
miconazole nitrate drug liberation dental pharmaceutical-preparations tissue adhesives denture stomatitis Candida albicans |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA |
description |
The combination of well-fitting dentures with topical antifungals is appropriate therapeutic approach for denture stomatitis (EP). It was developed and evaluated an adhesive for removable dentures containing miconazole nitrate (NM) incorporated into mucoadhesive and/or pH dependent polymer microparticles aiming at increasing bioavailability. Initially, microparticles have been developed containing 10% and 20% of NM, spray-drying, using Gantrez MS-955 polymer (G10, G20), Eudragit L-100 (E10, E20) or both (EG10, EG20). An analytical method by high-performance liquid chromatography (HPLC) to quantify NM of the microparticles was validated. Microparticles were characterized by scanning electron microscopy (SEM), x-ray diffraction, Fourier-transformed infrared spectrometry (FTIR), differential scanning calorimetry (DSC), in-vitro release studies (percentage of dissolution / time, and release profiles) and antifungal activity. An experimental denture adhesive formulation (ACT) was developed containing 10% by weight of the microparticles (AE1, AG1, AEG1, AE2, AG2, AEG2) or 2% of pure drug (ANM). For all adhesives it was determined: minimum inhibitory concentration (MIC) for Candida albicans (microdilution and agar dilution); adhesive force (FA among acrylic surfaces after 0.5, 1, 3, or 6 h immersion in water); and toxicity to brine shrimp (24 h and 48 h) by calculating lethal concentration 50 (LC50). The HPLC method was proven specific, linear (r = 0.9992), precise, accurate and robust in the range 5-90 μg.mL-1, with running and retention times of 10.0 and 5.58 minutes, respectively. All microparticles showed acceptable performance (37.22% - 55.36%) and encapsulation (over 89%) values. E10 and E20 microparticles showed spherical and smooth surface, while EG20 had similar shape, but rough surface. G10, G20 and EG20 had depressed craters and morphology. The diameters of the microparticles ranged from 1.9 to 4.3 micrometers. No chemical bond was observed between the MN and the polymers through the FTIR spectra. Microencapsulation contributed to the drug amorphization, according to thermal analysis and X-ray diffraction, reducing the release time. NM and the G10, G20 and EG20 microparticles fitted the biexponential release kinetic model and the microparticles E10, E20 and EG10 fitted to mono-exponential model. The microparticles showed antifungal efficiency similar to pure drug. Extracts of the adhesives containing the microparticles and ANM showed MIC of 1.25 to 5 μg.mL-1 (comparable to Daktarin®, 2.5 μg.mL-1). Significant differences in AF for adhesive formulations evaluated as a function of immersion time in water were observed (p <0.001), with an upward trend between 1 h and 3 h, followed by reduction or stabilization up to 6 h. The incorporation of NM and polymeric microparticles did not affect the FA of the experimental adhesive and AEG20 showed the best results, with high initial values, and holding them for 6 h. All adhesive formulations showed low or no toxicity (LC50 349.53 to 931.00 μg.mL-1). The proposed denture adhesive formulation was proven compatible with the incorporation of polymeric microparticles containing NM. |
publishDate |
2016 |
dc.date.available.fl_str_mv |
2016-05-16 2017-07-24T19:21:59Z |
dc.date.issued.fl_str_mv |
2016-02-05 |
dc.date.accessioned.fl_str_mv |
2017-07-24T19:21:59Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
MOLINA, Andrés Felipe Cartagena. DEVELOPMENT OF REMOVABLE DENTURE ADHESIVE CONTAINING MICONAZOLE NITRATE-POLYMERIC MICROPARTICLES: SYNTHESIS AND CHARACTERIZATION. 2016. 119 f. Tese (Doutorado em Clinica Integrada, Dentística Restauradora e Periodontia) - UNIVERSIDADE ESTADUAL DE PONTA GROSSA, Ponta Grossa, 2016. |
dc.identifier.uri.fl_str_mv |
http://tede2.uepg.br/jspui/handle/prefix/1705 |
identifier_str_mv |
MOLINA, Andrés Felipe Cartagena. DEVELOPMENT OF REMOVABLE DENTURE ADHESIVE CONTAINING MICONAZOLE NITRATE-POLYMERIC MICROPARTICLES: SYNTHESIS AND CHARACTERIZATION. 2016. 119 f. Tese (Doutorado em Clinica Integrada, Dentística Restauradora e Periodontia) - UNIVERSIDADE ESTADUAL DE PONTA GROSSA, Ponta Grossa, 2016. |
url |
http://tede2.uepg.br/jspui/handle/prefix/1705 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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application/pdf |
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UNIVERSIDADE ESTADUAL DE PONTA GROSSA |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Odontologia |
dc.publisher.initials.fl_str_mv |
UEPG |
dc.publisher.country.fl_str_mv |
BR |
dc.publisher.department.fl_str_mv |
Clinica Integrada, Dentística Restauradora e Periodontia |
publisher.none.fl_str_mv |
UNIVERSIDADE ESTADUAL DE PONTA GROSSA |
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