Solid dispersions with hydrogenated castor oil increase solubility, dissolution rate and intestinal absorption of praziquantel

Detalhes bibliográficos
Autor(a) principal: Chaud, Marco Vinicius
Data de Publicação: 2010
Outros Autores: Tamascia, Pollyanna, de Lima, Andrea Cristina [UNESP], Paganelli, Maria Ondina, Gremião, Maria Palmira Daflon [UNESP], de Freitas, Osvaldo
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1590/S1984-82502010000300010
http://hdl.handle.net/11449/7828
Resumo: The solubility behavior of drugs remains one of the most challenging aspects in formulation development. Solid Dispersion (SD) has tremendous potential for improving drug solubility. Although praziquantel (PZQ) is the first drug of choice in the treatment of schistosomiasis, its poor solubility has restricted its delivery oral route. In spite of its poor solubility, PZQ is well absorbed in the gastrointestinal tract, but large doses are required to achieve adequate concentration at the target sites. The aim of this study was to improve the solubility and dissolution rate of PZQ and to evaluate its intestinal absorption. SDs were formulated with PEG-60 castor oil hydrogenated (CR-60) using a fusion and evaporation method. Pure PZQ and physical mixtures (PM) and PZQ-CR-60 (2:1; 1:1; 1:2 ratios) were compared as regards their solubility, dissolution and intestinal absorption. The experimental results demonstrated the improvement in the solubility, dissolution rate and intestinal absorption. In addition, the solubility behavior showed pH dependency and that the solubility of PZQ was slower in acidic medium than in neutral and basic mediums. The increase in PZQ solubility of the SD with the CR-60 could be attributed to several factors such as improved wettability, local solubilization, drug particle size reduction and crystalline or, interstitial solid solution reduction.
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spelling Solid dispersions with hydrogenated castor oil increase solubility, dissolution rate and intestinal absorption of praziquantelSolid dispersionPraziquantel/dissolution ratesPraziquantel/solubilityPraziquantel/intestinal absorptionThe solubility behavior of drugs remains one of the most challenging aspects in formulation development. Solid Dispersion (SD) has tremendous potential for improving drug solubility. Although praziquantel (PZQ) is the first drug of choice in the treatment of schistosomiasis, its poor solubility has restricted its delivery oral route. In spite of its poor solubility, PZQ is well absorbed in the gastrointestinal tract, but large doses are required to achieve adequate concentration at the target sites. The aim of this study was to improve the solubility and dissolution rate of PZQ and to evaluate its intestinal absorption. SDs were formulated with PEG-60 castor oil hydrogenated (CR-60) using a fusion and evaporation method. Pure PZQ and physical mixtures (PM) and PZQ-CR-60 (2:1; 1:1; 1:2 ratios) were compared as regards their solubility, dissolution and intestinal absorption. The experimental results demonstrated the improvement in the solubility, dissolution rate and intestinal absorption. In addition, the solubility behavior showed pH dependency and that the solubility of PZQ was slower in acidic medium than in neutral and basic mediums. The increase in PZQ solubility of the SD with the CR-60 could be attributed to several factors such as improved wettability, local solubilization, drug particle size reduction and crystalline or, interstitial solid solution reduction.A solubilidade de fármacos ainda é um dos principais desafios no desenvolvimento de formulações farmacêuticas. As dispersões sólidas (DS) apresentam grande potencial para melhorar a solubilidade de fármacos. O praziquantel é o fármaco de primeira escolha no tratamento da esquistossomose, contudo a baixa solubilidade em água restringe seu uso à administração pela via oral. Apesar da baixa solubilidade, o PZQ é bem absorvido através do trato gastrintestinal, mas doses orais elevadas são requeridas para garantir concentrações suficientes de fármaco para o tecido alvo. O objetivo deste estudo foi melhorar a solubilidade, a dissolução e avaliar a absorção do PZQ. As DS foram formuladas com óleo de castor hidrogenado - PEG 60 (CR-60), pelo uso dos métodos de fusão e evaporação do solvente. PZQ puro, mistura física (MF) e DS de CR-60-PZQ (1:2; 1:1; 2:1) foram comparados quanto à solubilidade, dissolução e absorção intestinal. Os resultados experimentais mostraram aumento na solubilidade, na taxa de dissolução e na absorção intestinal do PZQ nas DS. A solubilidade do PZQ foi maior em meio ácido, mostrando uma dependência do pH. O aumento na solubilidade do PZQ nas DS com CR-60 foi atribuída a fatores como aumento da molhabilidade, solubilização local, redução granulométrica e redução da cristalinidade ou, ainda, a ocorrência de uma solução sólida intersticial.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Sorocaba, Curso Farm, Dept Pharmaceut Sci, BR-18023000 Sorocaba, SP, BrazilUniv Metodista Piracicaba, Fac Hlth Sci, Dept Pharm, Piracicaba, BrazilSão Paulo State Univ Julio de Mesquita Filho, Fac Pharmaceut Sci Araraquara, Dept Drugs & Pharmaceut, São Paulo, BrazilUniv São Paulo, Dept Pharmaceut Sci Ribeirao Preto, BR-05508 São Paulo, BrazilSão Paulo State Univ Julio de Mesquita Filho, Fac Pharmaceut Sci Araraquara, Dept Drugs & Pharmaceut, São Paulo, BrazilUniversidade de São Paulo (USP), Conjunto QuimicasUniv SorocabaUniv Metodista PiracicabaUniversidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)Chaud, Marco ViniciusTamascia, Pollyannade Lima, Andrea Cristina [UNESP]Paganelli, Maria OndinaGremião, Maria Palmira Daflon [UNESP]de Freitas, Osvaldo2014-05-20T13:24:52Z2014-05-20T13:24:52Z2010-07-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article473-481application/pdfhttp://dx.doi.org/10.1590/S1984-82502010000300010Brazilian Journal of Pharmaceutical Sciences. São Paulo: Univ São Paulo, Conjunto Quimicas, v. 46, n. 3, p. 473-481, 2010.1984-8250http://hdl.handle.net/11449/7828S1984-82502010000300010WOS:000286701000010S1984-82502010000300010-en.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBrazilian Journal of Pharmaceutical Sciences0.4830,214info:eu-repo/semantics/openAccess2024-06-24T13:45:38Zoai:repositorio.unesp.br:11449/7828Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T17:08:11.068200Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Solid dispersions with hydrogenated castor oil increase solubility, dissolution rate and intestinal absorption of praziquantel
title Solid dispersions with hydrogenated castor oil increase solubility, dissolution rate and intestinal absorption of praziquantel
spellingShingle Solid dispersions with hydrogenated castor oil increase solubility, dissolution rate and intestinal absorption of praziquantel
Chaud, Marco Vinicius
Solid dispersion
Praziquantel/dissolution rates
Praziquantel/solubility
Praziquantel/intestinal absorption
title_short Solid dispersions with hydrogenated castor oil increase solubility, dissolution rate and intestinal absorption of praziquantel
title_full Solid dispersions with hydrogenated castor oil increase solubility, dissolution rate and intestinal absorption of praziquantel
title_fullStr Solid dispersions with hydrogenated castor oil increase solubility, dissolution rate and intestinal absorption of praziquantel
title_full_unstemmed Solid dispersions with hydrogenated castor oil increase solubility, dissolution rate and intestinal absorption of praziquantel
title_sort Solid dispersions with hydrogenated castor oil increase solubility, dissolution rate and intestinal absorption of praziquantel
author Chaud, Marco Vinicius
author_facet Chaud, Marco Vinicius
Tamascia, Pollyanna
de Lima, Andrea Cristina [UNESP]
Paganelli, Maria Ondina
Gremião, Maria Palmira Daflon [UNESP]
de Freitas, Osvaldo
author_role author
author2 Tamascia, Pollyanna
de Lima, Andrea Cristina [UNESP]
Paganelli, Maria Ondina
Gremião, Maria Palmira Daflon [UNESP]
de Freitas, Osvaldo
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Univ Sorocaba
Univ Metodista Piracicaba
Universidade Estadual Paulista (Unesp)
Universidade de São Paulo (USP)
dc.contributor.author.fl_str_mv Chaud, Marco Vinicius
Tamascia, Pollyanna
de Lima, Andrea Cristina [UNESP]
Paganelli, Maria Ondina
Gremião, Maria Palmira Daflon [UNESP]
de Freitas, Osvaldo
dc.subject.por.fl_str_mv Solid dispersion
Praziquantel/dissolution rates
Praziquantel/solubility
Praziquantel/intestinal absorption
topic Solid dispersion
Praziquantel/dissolution rates
Praziquantel/solubility
Praziquantel/intestinal absorption
description The solubility behavior of drugs remains one of the most challenging aspects in formulation development. Solid Dispersion (SD) has tremendous potential for improving drug solubility. Although praziquantel (PZQ) is the first drug of choice in the treatment of schistosomiasis, its poor solubility has restricted its delivery oral route. In spite of its poor solubility, PZQ is well absorbed in the gastrointestinal tract, but large doses are required to achieve adequate concentration at the target sites. The aim of this study was to improve the solubility and dissolution rate of PZQ and to evaluate its intestinal absorption. SDs were formulated with PEG-60 castor oil hydrogenated (CR-60) using a fusion and evaporation method. Pure PZQ and physical mixtures (PM) and PZQ-CR-60 (2:1; 1:1; 1:2 ratios) were compared as regards their solubility, dissolution and intestinal absorption. The experimental results demonstrated the improvement in the solubility, dissolution rate and intestinal absorption. In addition, the solubility behavior showed pH dependency and that the solubility of PZQ was slower in acidic medium than in neutral and basic mediums. The increase in PZQ solubility of the SD with the CR-60 could be attributed to several factors such as improved wettability, local solubilization, drug particle size reduction and crystalline or, interstitial solid solution reduction.
publishDate 2010
dc.date.none.fl_str_mv 2010-07-01
2014-05-20T13:24:52Z
2014-05-20T13:24:52Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1590/S1984-82502010000300010
Brazilian Journal of Pharmaceutical Sciences. São Paulo: Univ São Paulo, Conjunto Quimicas, v. 46, n. 3, p. 473-481, 2010.
1984-8250
http://hdl.handle.net/11449/7828
S1984-82502010000300010
WOS:000286701000010
S1984-82502010000300010-en.pdf
url http://dx.doi.org/10.1590/S1984-82502010000300010
http://hdl.handle.net/11449/7828
identifier_str_mv Brazilian Journal of Pharmaceutical Sciences. São Paulo: Univ São Paulo, Conjunto Quimicas, v. 46, n. 3, p. 473-481, 2010.
1984-8250
S1984-82502010000300010
WOS:000286701000010
S1984-82502010000300010-en.pdf
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Brazilian Journal of Pharmaceutical Sciences
0.483
0,214
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 473-481
application/pdf
dc.publisher.none.fl_str_mv Universidade de São Paulo (USP), Conjunto Quimicas
publisher.none.fl_str_mv Universidade de São Paulo (USP), Conjunto Quimicas
dc.source.none.fl_str_mv Web of Science
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
_version_ 1808128759300096000

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