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Eplerenone nanocrystals engineered by controlled crystallization for enhanced oral bioavailability.

ABSTRACT: 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, C_max, and lower T_max 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.

SUBMITTER: Khan MA

PROVIDER: S-EPMC8635601 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Eplerenone nanocrystals engineered by controlled crystallization for enhanced oral bioavailability.

Khan Muhammad Ayub MA Ansari Muhammad Mohsin MM Arif Sadia Tabassam ST Raza Abida A Choi Ho-Ik HI Lim Chang-Wan CW Noh Ha-Yeon HY Noh Jin-Su JS Akram Salman S Nawaz Hafiz Awais HA Ammad Muhammad M Alamro Abir Abdullah AA Alghamdi Amani Ahmed AA Kim Jin-Ki JK Zeb Alam A

Drug delivery 20211201 1

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- ...[more]

PMID: 34842018

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Eplerenone nanocrystals engineered by controlled crystallization for enhanced oral bioavailability.

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Eplerenone nanocrystals engineered by controlled crystallization for enhanced oral bioavailability.

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