Development of a Solid Supersaturable Micelle of Revaprazan for Improved Dissolution and Oral Bioavailability Using Box-Behnken Design

Yoon Tae Goo,1,* Cheol-Ki Sa,1,* Ji Yeh Choi,2 Min Song Kim,1 Chang Hyun Kim,1 Hyeon Kyun Kim,1 Young Wook Choi1 1College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea; 2Department of Psychology, York University, Toronto, Ontario, Canada*These authors contributed equally to this workCo...

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Autores principales:	Goo YT, Sa CK, Choi JY, Kim MS, Kim CH, Kim HK, Choi YW
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	revaprazan supersaturation solid micelle box-behnken design dissolution oral bioavailability Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b755269784fd4dbf9c4473e647f0f5f2
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spelling	oai:doaj.org-article:b755269784fd4dbf9c4473e647f0f5f22021-12-02T14:40:57ZDevelopment of a Solid Supersaturable Micelle of Revaprazan for Improved Dissolution and Oral Bioavailability Using Box-Behnken Design1178-2013https://doaj.org/article/b755269784fd4dbf9c4473e647f0f5f22021-02-01T00:00:00Zhttps://www.dovepress.com/development-of-a-solid-supersaturable-micelle-of-revaprazan-for-improv-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yoon Tae Goo,1,* Cheol-Ki Sa,1,* Ji Yeh Choi,2 Min Song Kim,1 Chang Hyun Kim,1 Hyeon Kyun Kim,1 Young Wook Choi1 1College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea; 2Department of Psychology, York University, Toronto, Ontario, Canada*These authors contributed equally to this workCorrespondence: Young Wook ChoiCollege of Pharmacy, Chung-Ang University, 84 Heuksuk-Ro, Dongjak-Gu, Seoul, 06974, KoreaTel +82 2 820 5609Email ywchoi@cau.ac.krPurpose: To enhance the oral bioavailability of revaprazan (RVP), a novel solid, supersaturable micelle (SSuM) was developed.Methods: Surfactants and solid carriers were screened based on a solubility and a flowability test, respectively. Supersaturating agents, including Poloxamer 407 (P407), were screened. The SSuM was optimized using a Box-Behnken design with three independent variables, including Gelucire 44/14:Brij L4 (G44/BL4; X1) and the amounts of Florite PS-10 (FLO; X2) and Vivapur 105 (VP105; X3), and three response variables, ie, dissolution efficiency at 30 min (Y1), dissolution enhancing capacity (Y2), and Carr’s index (Y3). The solid state property was evaluated, and a dissolution test was conducted. RVP, Revanex®, solid micelle (P407-free from the composition of SSuM), and SSuM were orally administrated to rats (RVP 20 mg equivalent/kg) for in vivo pharmacokinetic study.Results: G44 and BL4 showed great solubility, with a critical micelle concentration range of 119.2– 333.0 μg/mL. P407 had an excellent supersaturating effect. FLO and VP105 were selected as solid carriers, with a critical solidifying ratio (g/mL) of 0.30 and 0.91, respectively. With optimized values of X1 (– 0.41), X2 (0.31), and X3 (– 0.78), RVP (200 mg)-containing SSuM consisting of G44 (253.8 mg), BL4 (106.2 mg), FLO (99.3 mg), VP105 (199.8 mg), and P407 (40 mg) was developed, resulting in Y1 (40.3%), Y2 (0.008), and Y3 (12.3%). RVP existed in an amorphous state in the optimized SSuM, and the SSuM formed a nanosized dispersion in the aqueous phase, with approximately 71.7% dissolution at 2 h. The optimized SSuM improved the relative bioavailability of RVP in rats by approximately 478%, 276%, and 161% compared to raw RVP, Revanex®, and solid micelle, respectively.Conclusion: The optimized SSuM has great potential for the development of solidified formulations of poorly water-soluble drugs with improved oral absorption.Keywords: revaprazan, supersaturation, solid micelle, Box-Behnken design, dissolution, oral bioavailabilityGoo YTSa CKChoi JYKim MSKim CHKim HKChoi YWDove Medical Pressarticlerevaprazansupersaturationsolid micellebox-behnken designdissolutionoral bioavailabilityMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 1245-1259 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	revaprazan supersaturation solid micelle box-behnken design dissolution oral bioavailability Medicine (General) R5-920
spellingShingle	revaprazan supersaturation solid micelle box-behnken design dissolution oral bioavailability Medicine (General) R5-920 Goo YT Sa CK Choi JY Kim MS Kim CH Kim HK Choi YW Development of a Solid Supersaturable Micelle of Revaprazan for Improved Dissolution and Oral Bioavailability Using Box-Behnken Design
description	Yoon Tae Goo,1,* Cheol-Ki Sa,1,* Ji Yeh Choi,2 Min Song Kim,1 Chang Hyun Kim,1 Hyeon Kyun Kim,1 Young Wook Choi1 1College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea; 2Department of Psychology, York University, Toronto, Ontario, Canada*These authors contributed equally to this workCorrespondence: Young Wook ChoiCollege of Pharmacy, Chung-Ang University, 84 Heuksuk-Ro, Dongjak-Gu, Seoul, 06974, KoreaTel +82 2 820 5609Email ywchoi@cau.ac.krPurpose: To enhance the oral bioavailability of revaprazan (RVP), a novel solid, supersaturable micelle (SSuM) was developed.Methods: Surfactants and solid carriers were screened based on a solubility and a flowability test, respectively. Supersaturating agents, including Poloxamer 407 (P407), were screened. The SSuM was optimized using a Box-Behnken design with three independent variables, including Gelucire 44/14:Brij L4 (G44/BL4; X1) and the amounts of Florite PS-10 (FLO; X2) and Vivapur 105 (VP105; X3), and three response variables, ie, dissolution efficiency at 30 min (Y1), dissolution enhancing capacity (Y2), and Carr’s index (Y3). The solid state property was evaluated, and a dissolution test was conducted. RVP, Revanex®, solid micelle (P407-free from the composition of SSuM), and SSuM were orally administrated to rats (RVP 20 mg equivalent/kg) for in vivo pharmacokinetic study.Results: G44 and BL4 showed great solubility, with a critical micelle concentration range of 119.2– 333.0 μg/mL. P407 had an excellent supersaturating effect. FLO and VP105 were selected as solid carriers, with a critical solidifying ratio (g/mL) of 0.30 and 0.91, respectively. With optimized values of X1 (– 0.41), X2 (0.31), and X3 (– 0.78), RVP (200 mg)-containing SSuM consisting of G44 (253.8 mg), BL4 (106.2 mg), FLO (99.3 mg), VP105 (199.8 mg), and P407 (40 mg) was developed, resulting in Y1 (40.3%), Y2 (0.008), and Y3 (12.3%). RVP existed in an amorphous state in the optimized SSuM, and the SSuM formed a nanosized dispersion in the aqueous phase, with approximately 71.7% dissolution at 2 h. The optimized SSuM improved the relative bioavailability of RVP in rats by approximately 478%, 276%, and 161% compared to raw RVP, Revanex®, and solid micelle, respectively.Conclusion: The optimized SSuM has great potential for the development of solidified formulations of poorly water-soluble drugs with improved oral absorption.Keywords: revaprazan, supersaturation, solid micelle, Box-Behnken design, dissolution, oral bioavailability
format	article
author	Goo YT Sa CK Choi JY Kim MS Kim CH Kim HK Choi YW
author_facet	Goo YT Sa CK Choi JY Kim MS Kim CH Kim HK Choi YW
author_sort	Goo YT
title	Development of a Solid Supersaturable Micelle of Revaprazan for Improved Dissolution and Oral Bioavailability Using Box-Behnken Design
title_short	Development of a Solid Supersaturable Micelle of Revaprazan for Improved Dissolution and Oral Bioavailability Using Box-Behnken Design
title_full	Development of a Solid Supersaturable Micelle of Revaprazan for Improved Dissolution and Oral Bioavailability Using Box-Behnken Design
title_fullStr	Development of a Solid Supersaturable Micelle of Revaprazan for Improved Dissolution and Oral Bioavailability Using Box-Behnken Design
title_full_unstemmed	Development of a Solid Supersaturable Micelle of Revaprazan for Improved Dissolution and Oral Bioavailability Using Box-Behnken Design
title_sort	development of a solid supersaturable micelle of revaprazan for improved dissolution and oral bioavailability using box-behnken design
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/b755269784fd4dbf9c4473e647f0f5f2
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Development of a Solid Supersaturable Micelle of Revaprazan for Improved Dissolution and Oral Bioavailability Using Box-Behnken Design

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