期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 595, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2021.120245
关键词
Solid dispersions; Bioavailability; Amorphous; Permeability enhancer; Metabolism inhibitor; Resveratrol
资金
- FEDER - Fundo Europeu de Desenvolvimento Regional
- Portuguese funds through FCT - Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior [UID/BIM/04293/2019, POCI-01-0145-FEDER-016385]
Resveratrol, a promising anti-oxidant drug candidate, was formulated into third-generation solid dispersions using Soluplus and Tween 80 as carriers, significantly enhancing its solubility. In vivo studies showed that formulations containing 15% poloxamer 407 demonstrated the most promising results, with a 2.5 fold increase in bioavailability compared to formulations without poloxamer 407.
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.
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