Influence of hydrophilic additives on the supersaturation and bioavailability of dutasteride-loaded hydroxypropyl- β-cyclodextrin nanostructures

Influence of hydrophilic additives on the supersaturation and bioavailability of dutasteride-loaded hydroxypropyl- β-cyclodextrin nanostructures

Min-Soo KimDepartment of Pharmaceutical Engineering, Inje University, Gimhae, Gyeongnam, Republic of KoreaAbstract: The objectives of this study were to develop a novel solid dutasteride formulation with improved physicochemical properties and oral bioavailability, and to examine the correlation bet...

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Autor principal: Kim MS
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2013
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Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/f544b1dd6d65482eb136ed2d242037c4
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spelling oai:doaj.org-article:f544b1dd6d65482eb136ed2d242037c42021-12-02T04:25:22ZInfluence of hydrophilic additives on the supersaturation and bioavailability of dutasteride-loaded hydroxypropyl- β-cyclodextrin nanostructures1176-91141178-2013https://doaj.org/article/f544b1dd6d65482eb136ed2d242037c42013-05-01T00:00:00Zhttp://www.dovepress.com/influence-of-hydrophilic-additives-on-the-supersaturation-and-bioavail-a13095https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Min-Soo KimDepartment of Pharmaceutical Engineering, Inje University, Gimhae, Gyeongnam, Republic of KoreaAbstract: The objectives of this study were to develop a novel solid dutasteride formulation with improved physicochemical properties and oral bioavailability, and to examine the correlation between its in vitro dissolution and in vivo pharmacokinetic parameters. Hydroxypropyl-β-cyclodextrin (HP-β-CD) nanostructures with or without hydrophilic additives were manufactured using the supercritical antisolvent process. The dutasteride-loaded HP-β-CD nanoparticles formed aggregates with a mean particle size of less than 160 nm and a specific surface area greater than 100 m2/g. Increases in the supersaturation and dissolution rate for dutasteride were dependent on the type of additive; increases in maximum solubility and extended supersaturation were observed in dutasteride-loaded HP-β-CD nanostructures with hydroxypropylmethyl cellulose, whereas the dissolution rate was the highest for nanostructures containing d-α-tocopheryl polyethylene glycol 1000 succinate. In rats, the oral bioavailability of dutasteride increased with the supersaturation induced by the HP-β-CD nanostructures. In addition, compared with the in vitro drug release rate, the in vivo pharmacokinetic parameters were more closely correlated with in vitro parameters related to supersaturation (solubility). Further, the bioavailability of the dutasteride-loaded HP-β-CD nanostructures with hydroxypropylmethyl cellulose was similar to that of the commercially available soft gelatin capsule (Avodart®). In conclusion, preparation of dutasteride-loaded HP-β-CD nanostructures using the supercritical antisolvent process affords a viable alternative solid dosage form for dutasteride.Keywords: solubility, bioavailability, dutasteride, nanostructure, supercritical antisolventKim MSDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 2029-2039 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Kim MS
Influence of hydrophilic additives on the supersaturation and bioavailability of dutasteride-loaded hydroxypropyl- β-cyclodextrin nanostructures
description Min-Soo KimDepartment of Pharmaceutical Engineering, Inje University, Gimhae, Gyeongnam, Republic of KoreaAbstract: The objectives of this study were to develop a novel solid dutasteride formulation with improved physicochemical properties and oral bioavailability, and to examine the correlation between its in vitro dissolution and in vivo pharmacokinetic parameters. Hydroxypropyl-β-cyclodextrin (HP-β-CD) nanostructures with or without hydrophilic additives were manufactured using the supercritical antisolvent process. The dutasteride-loaded HP-β-CD nanoparticles formed aggregates with a mean particle size of less than 160 nm and a specific surface area greater than 100 m2/g. Increases in the supersaturation and dissolution rate for dutasteride were dependent on the type of additive; increases in maximum solubility and extended supersaturation were observed in dutasteride-loaded HP-β-CD nanostructures with hydroxypropylmethyl cellulose, whereas the dissolution rate was the highest for nanostructures containing d-α-tocopheryl polyethylene glycol 1000 succinate. In rats, the oral bioavailability of dutasteride increased with the supersaturation induced by the HP-β-CD nanostructures. In addition, compared with the in vitro drug release rate, the in vivo pharmacokinetic parameters were more closely correlated with in vitro parameters related to supersaturation (solubility). Further, the bioavailability of the dutasteride-loaded HP-β-CD nanostructures with hydroxypropylmethyl cellulose was similar to that of the commercially available soft gelatin capsule (Avodart®). In conclusion, preparation of dutasteride-loaded HP-β-CD nanostructures using the supercritical antisolvent process affords a viable alternative solid dosage form for dutasteride.Keywords: solubility, bioavailability, dutasteride, nanostructure, supercritical antisolvent
format article
author Kim MS
author_facet Kim MS
author_sort Kim MS
title Influence of hydrophilic additives on the supersaturation and bioavailability of dutasteride-loaded hydroxypropyl- β-cyclodextrin nanostructures
title_short Influence of hydrophilic additives on the supersaturation and bioavailability of dutasteride-loaded hydroxypropyl- β-cyclodextrin nanostructures
title_full Influence of hydrophilic additives on the supersaturation and bioavailability of dutasteride-loaded hydroxypropyl- β-cyclodextrin nanostructures
title_fullStr Influence of hydrophilic additives on the supersaturation and bioavailability of dutasteride-loaded hydroxypropyl- β-cyclodextrin nanostructures
title_full_unstemmed Influence of hydrophilic additives on the supersaturation and bioavailability of dutasteride-loaded hydroxypropyl- β-cyclodextrin nanostructures
title_sort influence of hydrophilic additives on the supersaturation and bioavailability of dutasteride-loaded hydroxypropyl- β-cyclodextrin nanostructures
publisher Dove Medical Press
publishDate 2013
url https://doaj.org/article/f544b1dd6d65482eb136ed2d242037c4
work_keys_str_mv AT kimms influenceofhydrophilicadditivesonthesupersaturationandbioavailabilityofdutasterideloadedhydroxypropylbetacyclodextrinnanostructures
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