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Third-generation solid dispersion combining Soluplus and poloxamer 407 enhances the oral bioavailability of resveratrol.
Int J Pharm. 2021 Feb 15; 595:120245.IJ

Abstract

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® and Tween® 80. The former was selected as a carrier at the ratio of resveratrol: Soluplus® (1:2). Then, third-generation solid dispersions were developed with Gelucire® and poloxamer 407 at 5 and 15% to resveratrol: Soluplus® (1:2). All formulations enhanced solubility around 2-fold when compared to resveratrol: Soluplus® (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®: 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.

Authors+Show Affiliations

BIAL-Portela & Cª, S.A., Avenida da Siderugia Nacional, 4745-457 Trofa, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal.Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas de Araraquara, Drugs and Pharmaceuticals, Brazil.BIAL-Portela & Cª, S.A., Avenida da Siderugia Nacional, 4745-457 Trofa, Portugal.BIAL-Portela & Cª, S.A., Avenida da Siderugia Nacional, 4745-457 Trofa, Portugal.BIAL-Portela & Cª, S.A., Avenida da Siderugia Nacional, 4745-457 Trofa, Portugal.ICBAS - Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; CIBIO/InBIO-UP-Research Centre in Biodiversity and Genetic Resources, University of Porto, Rua Padre Armando Quintas, 7, 4485-661 Vairão, Portugal.INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; CESPU - Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde and Instituto Universitário de Ciências da Saúde, Rua Central de Gandra 1317, 4585-116, Gandra, Portugal. Electronic address: bruno.sarmento@ineb.up.pt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33484925

Citation

Vasconcelos, Teófilo, et al. "Third-generation Solid Dispersion Combining Soluplus and Poloxamer 407 Enhances the Oral Bioavailability of Resveratrol." International Journal of Pharmaceutics, vol. 595, 2021, p. 120245.
Vasconcelos T, Prezotti F, Araújo F, et al. Third-generation solid dispersion combining Soluplus and poloxamer 407 enhances the oral bioavailability of resveratrol. Int J Pharm. 2021;595:120245.
Vasconcelos, T., Prezotti, F., Araújo, F., Lopes, C., Loureiro, A., Marques, S., & Sarmento, B. (2021). Third-generation solid dispersion combining Soluplus and poloxamer 407 enhances the oral bioavailability of resveratrol. International Journal of Pharmaceutics, 595, 120245. https://doi.org/10.1016/j.ijpharm.2021.120245
Vasconcelos T, et al. Third-generation Solid Dispersion Combining Soluplus and Poloxamer 407 Enhances the Oral Bioavailability of Resveratrol. Int J Pharm. 2021 Feb 15;595:120245. PubMed PMID: 33484925.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Third-generation solid dispersion combining Soluplus and poloxamer 407 enhances the oral bioavailability of resveratrol. AU - Vasconcelos,Teófilo, AU - Prezotti,Fabíola, AU - Araújo,Francisca, AU - Lopes,Carlos, AU - Loureiro,Ana, AU - Marques,Sara, AU - Sarmento,Bruno, Y1 - 2021/01/21/ PY - 2020/11/16/received PY - 2020/12/21/revised PY - 2020/12/22/accepted PY - 2021/1/24/pubmed PY - 2021/3/2/medline PY - 2021/1/23/entrez KW - Amorphous KW - Bioavailability KW - Metabolism inhibitor KW - Permeability enhancer KW - Resveratrol KW - Solid dispersions SP - 120245 EP - 120245 JF - International journal of pharmaceutics JO - Int J Pharm VL - 595 N2 - 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® and Tween® 80. The former was selected as a carrier at the ratio of resveratrol: Soluplus® (1:2). Then, third-generation solid dispersions were developed with Gelucire® and poloxamer 407 at 5 and 15% to resveratrol: Soluplus® (1:2). All formulations enhanced solubility around 2-fold when compared to resveratrol: Soluplus® (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®: 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. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/33484925/Third_generation_solid_dispersion_combining_Soluplus_and_poloxamer_407_enhances_the_oral_bioavailability_of_resveratrol_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(21)00049-1 DB - PRIME DP - Unbound Medicine ER -