Autor(es): Vasconcelos, Teofilo ; Prezotti, Fabiola [UNESP] ; Araujo, Francisca ; Lopes, Carlos ; Loureiro, Ana ; Marques, Sara ; Sarmento, Bruno
Data: 2021
Identificador Persistente: http://hdl.handle.net/11449/209193
Origem: Oasisbr
Assunto(s): Solid dispersions; Bioavailability; Amorphous; Permeability enhancer; Metabolism inhibitor; Resveratrol
Made available in DSpace on 2021-06-25T11:51:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-02-15
FEDER - Fundo Europeu de Desenvolvimento Regional
Portuguese funds through FCT - Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior
Resveratrol is a very promising anti-oxidant drug candidate with low oral bioavailability due to its intrinsic poor water solubility, intestinal efflux and metabolization mechanisms. Resveratrol solubility high-throughput screening with different carriers was performed showing an enhancement above 2000-fold with Soluplus (R) and Tween (R) 80. The former was selected as a carrier at the ratio of resveratrol: Soluplus (R) (1:2). Then, third-generation solid dispersions were developed with Gelucire (R) and poloxamer 407 at 5 and 15% to resveratrol: Soluplus (R) (1:2). All formulations enhanced solubility around 2-fold when compared to resveratrol: Soluplus (R) (1:2) solid dispersion. Caco-2 cells permeability studies showed that both surfactants increased drug permeability and the fraction recovered (2-fold) suggesting that these could reduce efflux mechanism and metabolism. Formulation with 15% poloxamer 407 demonstrated most promising results and was selected for further studies. In in vivo studies, resveratrol:Soluplus (R): poloxamer 407 (1:2-15%) third generation solid dispersion presented an AUCo-t of 279 +/- 54 ng.h/mL and a Cmax of 134 +/- 78 ng/mL, 2.5 fold higher than solid dispersion without poloxamer 407. This work reports the development of third-generation solid dispersion that significantly improved resveratrol bioavailability. This was accomplished by an increased solubility and most probably by reducing intestinal efflux and metabolism mechanisms.
BIAL Portela & Ca SA, Ave Siderugia Nacl, P-4745457 Trofa, Portugal
Univ Porto, ICBAS Inst Ciencias Biomed Abel Salazar, Rua Jorge Viterbo Ferreira 228, P-4050313 Porto, Portugal
Univ Porto, INEB Inst Engn Biomed, Rua Alfredo Allen 208, P-4200135 Porto, Portugal
Univ Porto, i3S Inst Invest & Inovacao Saude, Rua Alfredo Allen 208, P-4200135 Porto, Portugal
Univ Estadual Paulista, Fac Ciencias Farmaceut Araraquara Drugs & Pharmac, Sao Paulo, SP, Brazil
Univ Porto, CIBIO InBIO UP Res Ctr Biodivers & Genet Resource, Rua Padre Armando Quintas 7, P-4485661 Vairao, Portugal
CESPU Inst Invest & Formacao Avancada Ciencias &, Rua Cent Gandra 1317, P-4585116 Gandra, Portugal
Inst Univ Ciencias Saude, Rua Cent Gandra 1317, P-4585116 Gandra, Portugal
Univ Estadual Paulista, Fac Ciencias Farmaceut Araraquara Drugs & Pharmac, Sao Paulo, SP, Brazil
Portuguese funds through FCT - Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior: UID/BIM/04293/2019
Portuguese funds through FCT - Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior: POCI-01-0145-FEDER-016385
