Effect of particle size on oral absorption of carvedilol nanosuspensions: in vitro and in vivo evaluation

Dandan Liu,1 Hao Pan,2 Fengwei He,1 Xiaoyu Wang,3 Jinyu Li,3 Xinggang Yang,3 Weisan Pan31Department of Pharmaceutical Engineering, School of Biomedical and Chemical Engineering, Liaoning Institute of Science and Technology, Benxi, People’s Republic of China; 2School of Pharmacy, Queen&...

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Autores principales: Liu DD, Pan H, He FW, Wang XY, Li JY, Yang XG, Pan WS
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Publicado: Dove Medical Press 2015
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spelling oai:doaj.org-article:12e33e01419c41c982922718c6ff9f832021-12-02T01:34:06ZEffect of particle size on oral absorption of carvedilol nanosuspensions: in vitro and in vivo evaluation1178-2013https://doaj.org/article/12e33e01419c41c982922718c6ff9f832015-10-01T00:00:00Zhttps://www.dovepress.com/effect-of-particle-size-on-oral-absorption-of-carvedilol-nanosuspensio-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Dandan Liu,1 Hao Pan,2 Fengwei He,1 Xiaoyu Wang,3 Jinyu Li,3 Xinggang Yang,3 Weisan Pan31Department of Pharmaceutical Engineering, School of Biomedical and Chemical Engineering, Liaoning Institute of Science and Technology, Benxi, People’s Republic of China; 2School of Pharmacy, Queen’s University Belfast, Belfast, Northern Ireland, UK; 3Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China Abstract: The purpose of this work was to explore the particle size reduction effect of carvedilol on dissolution and absorption. Three suspensions containing different sized particles were prepared by antisolvent precipitation method or in combination with an ultrasonication process. The suspensions were characterized for particle size, surface morphology, and crystalline state. The crystalline form of carvedilol was changed into amorphous form after antisolvent precipitation. The dissolution rate of carvedilol was significantly accelerated by a reduction in particle size. The intestinal absorption of carvedilol nanosuspensions was greatly improved in comparison with microsuspensions and solution in the in situ single-pass perfusion experiment. The in vivo evaluation demonstrated that carvedilol nanosuspensions and microsuspensions exhibited markedly increased Cmax (2.09- and 1.48-fold) and AUC0–t (2.11- and 1.51-fold), and decreased Tmax (0.34- and 0.48-fold) in contrast with carvedilol coarse suspensions. Moreover, carvedilol nanosuspensions showed good biocompatibility with the rat gastric mucosa in in vivo gastrointestinal irritation test. The entire results implicated that the dissolution rate and the oral absorption of carvedilol were significantly affected by the particle size. Particle size reduction to form nanosized particles was found to be an efficient method for improving the oral bioavailability of carvedilol. Keywords: carvedilol, nanosuspensions, intestinal absorption, oral bioavailability, gastrointestinal irritationLiu DDPan HHe FWWang XYLi JYYang XGPan WSDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 6425-6434 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Liu DD
Pan H
He FW
Wang XY
Li JY
Yang XG
Pan WS
Effect of particle size on oral absorption of carvedilol nanosuspensions: in vitro and in vivo evaluation
description Dandan Liu,1 Hao Pan,2 Fengwei He,1 Xiaoyu Wang,3 Jinyu Li,3 Xinggang Yang,3 Weisan Pan31Department of Pharmaceutical Engineering, School of Biomedical and Chemical Engineering, Liaoning Institute of Science and Technology, Benxi, People’s Republic of China; 2School of Pharmacy, Queen’s University Belfast, Belfast, Northern Ireland, UK; 3Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China Abstract: The purpose of this work was to explore the particle size reduction effect of carvedilol on dissolution and absorption. Three suspensions containing different sized particles were prepared by antisolvent precipitation method or in combination with an ultrasonication process. The suspensions were characterized for particle size, surface morphology, and crystalline state. The crystalline form of carvedilol was changed into amorphous form after antisolvent precipitation. The dissolution rate of carvedilol was significantly accelerated by a reduction in particle size. The intestinal absorption of carvedilol nanosuspensions was greatly improved in comparison with microsuspensions and solution in the in situ single-pass perfusion experiment. The in vivo evaluation demonstrated that carvedilol nanosuspensions and microsuspensions exhibited markedly increased Cmax (2.09- and 1.48-fold) and AUC0–t (2.11- and 1.51-fold), and decreased Tmax (0.34- and 0.48-fold) in contrast with carvedilol coarse suspensions. Moreover, carvedilol nanosuspensions showed good biocompatibility with the rat gastric mucosa in in vivo gastrointestinal irritation test. The entire results implicated that the dissolution rate and the oral absorption of carvedilol were significantly affected by the particle size. Particle size reduction to form nanosized particles was found to be an efficient method for improving the oral bioavailability of carvedilol. Keywords: carvedilol, nanosuspensions, intestinal absorption, oral bioavailability, gastrointestinal irritation
format article
author Liu DD
Pan H
He FW
Wang XY
Li JY
Yang XG
Pan WS
author_facet Liu DD
Pan H
He FW
Wang XY
Li JY
Yang XG
Pan WS
author_sort Liu DD
title Effect of particle size on oral absorption of carvedilol nanosuspensions: in vitro and in vivo evaluation
title_short Effect of particle size on oral absorption of carvedilol nanosuspensions: in vitro and in vivo evaluation
title_full Effect of particle size on oral absorption of carvedilol nanosuspensions: in vitro and in vivo evaluation
title_fullStr Effect of particle size on oral absorption of carvedilol nanosuspensions: in vitro and in vivo evaluation
title_full_unstemmed Effect of particle size on oral absorption of carvedilol nanosuspensions: in vitro and in vivo evaluation
title_sort effect of particle size on oral absorption of carvedilol nanosuspensions: in vitro and in vivo evaluation
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/12e33e01419c41c982922718c6ff9f83
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