Eplerenone nanocrystals engineered by controlled crystallization for enhanced oral bioavailability. (1st January 2021)

• Record Type: Journal Article
• Authors: Khan, Muhammad Ayub; Ansari, Muhammad Mohsin; Arif, Sadia Tabassam; Raza, Abida; Choi, Ho-Ik; Lim, Chang-Wan; Noh, Ha-Yeon; Noh, Jin-Su; Akram, Salman; Nawaz, Hafiz Awais; Ammad, Muhammad; Alamro, Abir Abdullah; Alghamdi, Amani Ahmed; Kim, Jin-Ki; Zeb, Alam
• Is Part Of: Drug delivery. Volume 28:Number 1(2021)
• Page Start: 2510
• Page End: 2524
• Publication Date: 2021-01-01
• Subjects: Eplerenone -- poorly aqueous solubility -- nanocrystals -- controlled crystallization -- dissolution rate and bioavailability -- acute toxicity study; Drug delivery systems -- Periodicals; Drug targeting -- Periodicals; 615.05
• DOI: 10.1080/10717544.2021.2008051
• Languages: English
• ISSNs: 1071-7544

Abstract

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.