Preparation, characterization and in vitro evaluation of atorvastatin nanosuspensions
Yaman Ahmad Akour, Ahmad Aljaberi, Saja H. Hamed, Alaa Altaher, Eman M. Migdadi
Abstract
Poorly water-soluble drugs present a significant challenge for pharmaceutical development, particularly affecting the pharmacokinetics of orally administered drugs due to their poor dissolution. This study aimed to enhance the dissolution of a low water solubility drug atorvastatin using nanosuspension technology. Antisolvent technique was utilized to prepare atorvastatin calcium nanosuspensions. Different stabilizers were used including Cremophor, HPMC, pluronics (F127, F108, and F68), PEG400, PEG600, PEG 1k, PEG8k, PVA, PVP k30, PVP k10, PVP 44k, SLS, sodium alginate, Tween 20, and Tween 80.
Introduction
The pharmaceutical industry struggles with poor aqueous solubility of drugs and thus, their limited bioavailability [1] (reference). Solubility is crucial in pharmaceuticals, with 75–90% of drug candidates under development, and up to 40% of marketed products are poorly soluble [1]. This results in low bioavailability, reduced therapeutic effects, and dosage escalation that necessitate careful consideration in product design and manufacturing. To date, various strategies regarding low solubility problem have been studied include micronization, solid dispersion and supercritical fluid (SCF).
Materials and method
2.1. Materials
Atorvastatin calcium was gifted from RAM Pharmaceuticals Ind. Co., Amman, Jordan. Acetonitrile was purchased from Scharlau, Barcelona, Spain. Hydroxypropyl methylcellulose (HPMC) was obtained from Ashland Industries Europe GmbH, Switzerland. Mannitol and Trehalose were supplied by GenoChem, Valencia, Spain. Methanol ≥ 99.9% was provided by Honeywell, France. Pluronic® F108, F68, and F127 were purchased from BIOSYNTH Carbosynth, California, USA.
Results
3.1. Characterization of nanosuspensions
After preparation of the atorvastatin calcium nanosuspensions, they were characterized for the average particle size analysis, PDI, and zeta potential, in which each trial consisted of three runs (n = 3). Any measure above 3000 nm was considered aggregate since the instrument could not measure values above this number. The nanosuspensions with a particle size range between 50–400 nm were chosen and lyophilized and further characterized for the average particle size, PDI, and zeta potential after reconstitution. Each analysis consists of three runs (n = 3).
Discussion
The pharmaceutical industry faces many problems with poor aqueous solubility of drugs and thus, their limited bioavailability [1]. Several techniques have been used in literature to enhance the solubility or the dissolution of these drugs [1]. Nanosuspension was shown to be a promising and efficient strategy for enhancing the dissolution of poorly soluble drugs [1]. Atorvastatin calcium, a lipid-lowering drug falls within the BCS class-II category, characterized by low solubility and high permeability.
Acknowledgments
The authors acknowledge the Applied Science Private University, Amman, Jordan.
Citation: Akour YA, Aljaberi A, Hamed SH, Altaher A, Migdadi EM (2025) Preparation, characterization and in vitro evaluation of atorvastatin nanosuspensions. PLoS One 20(10): e0335024. https://doi.org/10.1371/journal.pone.0335024
Editor: Taher Hatahet, Queen's University Belfast, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND
Received: May 5, 2025; Accepted: October 6, 2025; Published: October 21, 2025
Copyright: © 2025 Akour et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: This research was funded by the Applied Science Private University, Amman, Jordan, Grant number: DRGS-2020-2021-1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
