Eplerenone nanocrystals engineered by controlled crystallization for enhanced oral bioavailability

Poor aqueous solubility of eplerenone (EPL) is a major obstacle to achieve sufficient bioavailability after oral administration. In this study, we aimed to develop and evaluate eplerenone nanocrystals (EPL-NCs) for solubility and dissolution enhancement. D-optimal combined mixture process using Desi...

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Autores principales:	Muhammad Ayub Khan, Muhammad Mohsin Ansari, Sadia Tabassam Arif, Abida Raza, Ho-Ik Choi, Chang-Wan Lim, Ha-Yeon Noh, Jin-Su Noh, Salman Akram, Hafiz Awais Nawaz, Muhammad Ammad, Abir Abdullah Alamro, Amani Ahmed Alghamdi, Jin-Ki Kim, Alam Zeb
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	eplerenone poorly aqueous solubility nanocrystals controlled crystallization dissolution rate and bioavailability acute toxicity study Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/5cc3349ba6b140249dae06910a5a6adb
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spelling	oai:doaj.org-article:5cc3349ba6b140249dae06910a5a6adb2021-12-01T14:40:58ZEplerenone nanocrystals engineered by controlled crystallization for enhanced oral bioavailability1071-75441521-046410.1080/10717544.2021.2008051https://doaj.org/article/5cc3349ba6b140249dae06910a5a6adb2021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/10717544.2021.2008051https://doaj.org/toc/1071-7544https://doaj.org/toc/1521-0464Poor aqueous solubility of eplerenone (EPL) is a major obstacle to achieve sufficient bioavailability after oral administration. In this study, we aimed to develop and evaluate eplerenone nanocrystals (EPL-NCs) for solubility and dissolution enhancement. D-optimal combined mixture process using Design-Expert software was employed to generate different combinations for optimization. EPL-NCs were prepared by a bottom-up, controlled crystallization technique during freeze-drying. The optimized EPL-NCs were evaluated for their size, morphology, thermal behavior, crystalline structure, saturation solubility, dissolution profile, in vivo pharmacokinetics, and acute toxicity. The optimized EPL-NCs showed mean particle size of 46.8 nm. Scanning electron microscopy revealed the formation of elongated parallelepiped shaped NCs. DSC and PXRD analysis confirmed the crystalline structure and the absence of any polymorphic transition in EPL-NCs. Furthermore, EPL-NCs demonstrated a 17-fold prompt increase in the saturation solubility of EPL (8.96 vs. 155.85 µg/mL). The dissolution rate was also significantly higher as indicated by ∼95% dissolution from EPL-NCs in 10 min compared to only 29% from EPL powder. EPL-NCs improved the oral bioavailability as indicated by higher AUC, Cmax, and lower Tmax than EPL powder. Acute oral toxicity study showed that EPL-NCs do not pose any toxicity concern to the blood and vital organs. Consequently, NCs prepared by controlled crystallization technique present a promising strategy to improve solubility profile, dissolution velocity and bioavailability of poorly water-soluble drugs.Muhammad Ayub KhanMuhammad Mohsin AnsariSadia Tabassam ArifAbida RazaHo-Ik ChoiChang-Wan LimHa-Yeon NohJin-Su NohSalman AkramHafiz Awais NawazMuhammad AmmadAbir Abdullah AlamroAmani Ahmed AlghamdiJin-Ki KimAlam ZebTaylor & Francis Grouparticleeplerenonepoorly aqueous solubilitynanocrystalscontrolled crystallizationdissolution rate and bioavailabilityacute toxicity studyTherapeutics. PharmacologyRM1-950ENDrug Delivery, Vol 28, Iss 1, Pp 2510-2524 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	eplerenone poorly aqueous solubility nanocrystals controlled crystallization dissolution rate and bioavailability acute toxicity study Therapeutics. Pharmacology RM1-950
spellingShingle	eplerenone poorly aqueous solubility nanocrystals controlled crystallization dissolution rate and bioavailability acute toxicity study Therapeutics. Pharmacology RM1-950 Muhammad Ayub Khan Muhammad Mohsin Ansari Sadia Tabassam Arif Abida Raza Ho-Ik Choi Chang-Wan Lim Ha-Yeon Noh Jin-Su Noh Salman Akram Hafiz Awais Nawaz Muhammad Ammad Abir Abdullah Alamro Amani Ahmed Alghamdi Jin-Ki Kim Alam Zeb Eplerenone nanocrystals engineered by controlled crystallization for enhanced oral bioavailability
description	Poor aqueous solubility of eplerenone (EPL) is a major obstacle to achieve sufficient bioavailability after oral administration. In this study, we aimed to develop and evaluate eplerenone nanocrystals (EPL-NCs) for solubility and dissolution enhancement. D-optimal combined mixture process using Design-Expert software was employed to generate different combinations for optimization. EPL-NCs were prepared by a bottom-up, controlled crystallization technique during freeze-drying. The optimized EPL-NCs were evaluated for their size, morphology, thermal behavior, crystalline structure, saturation solubility, dissolution profile, in vivo pharmacokinetics, and acute toxicity. The optimized EPL-NCs showed mean particle size of 46.8 nm. Scanning electron microscopy revealed the formation of elongated parallelepiped shaped NCs. DSC and PXRD analysis confirmed the crystalline structure and the absence of any polymorphic transition in EPL-NCs. Furthermore, EPL-NCs demonstrated a 17-fold prompt increase in the saturation solubility of EPL (8.96 vs. 155.85 µg/mL). The dissolution rate was also significantly higher as indicated by ∼95% dissolution from EPL-NCs in 10 min compared to only 29% from EPL powder. EPL-NCs improved the oral bioavailability as indicated by higher AUC, Cmax, and lower Tmax than EPL powder. Acute oral toxicity study showed that EPL-NCs do not pose any toxicity concern to the blood and vital organs. Consequently, NCs prepared by controlled crystallization technique present a promising strategy to improve solubility profile, dissolution velocity and bioavailability of poorly water-soluble drugs.
format	article
author	Muhammad Ayub Khan Muhammad Mohsin Ansari Sadia Tabassam Arif Abida Raza Ho-Ik Choi Chang-Wan Lim Ha-Yeon Noh Jin-Su Noh Salman Akram Hafiz Awais Nawaz Muhammad Ammad Abir Abdullah Alamro Amani Ahmed Alghamdi Jin-Ki Kim Alam Zeb
author_facet	Muhammad Ayub Khan Muhammad Mohsin Ansari Sadia Tabassam Arif Abida Raza Ho-Ik Choi Chang-Wan Lim Ha-Yeon Noh Jin-Su Noh Salman Akram Hafiz Awais Nawaz Muhammad Ammad Abir Abdullah Alamro Amani Ahmed Alghamdi Jin-Ki Kim Alam Zeb
author_sort	Muhammad Ayub Khan
title	Eplerenone nanocrystals engineered by controlled crystallization for enhanced oral bioavailability
title_short	Eplerenone nanocrystals engineered by controlled crystallization for enhanced oral bioavailability
title_full	Eplerenone nanocrystals engineered by controlled crystallization for enhanced oral bioavailability
title_fullStr	Eplerenone nanocrystals engineered by controlled crystallization for enhanced oral bioavailability
title_full_unstemmed	Eplerenone nanocrystals engineered by controlled crystallization for enhanced oral bioavailability
title_sort	eplerenone nanocrystals engineered by controlled crystallization for enhanced oral bioavailability
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/5cc3349ba6b140249dae06910a5a6adb
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Eplerenone nanocrystals engineered by controlled crystallization for enhanced oral bioavailability

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