An Approach to Enhance the Solubility of an Atypical Antipsychotic Drug, Aripiprazole: Design, Characterization, and Evaluation of Arabinoxylan-Based Nanoparticles.

Abstract

Introduction: Natural polymers have emerged as versatile and sustainable alternatives to synthetic polymers in pharmaceutical and biomedical applications. This study focuses on the extraction of arabinoxylan (AX) from maize husk and its potential as a promising excipient to enhance the solubility and oral bioavailability of Aripiprazole (APZ), a poorly water-soluble antipsychotic drug, offering a robust strategy for overcoming challenges associated with hydrophobic drugs.

Methods: APZ-loaded AX nanoparticles were synthesized using the ionotropic gelation technique. The formulation with the highest encapsulation efficiency designated as FN4 was selected for detailed characterization. Various analytical techniques, including Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD), and Differential Scanning Calorimetry (DSC), were employed to assess the morphological, crystalline, and thermal properties of the nanoparticles. In vitro release studies were conducted on both simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8) to evaluate drug dissolution behaviour. The everted sac method was utilized to assess the permeation and transport of APZ from the AX-based nanoparticles.

Results: The FN4 formulation exhibited an encapsulation efficiency of 88.9% ± 1.77%, with a particle size of 284.4 nm, a polydispersity index (PDI) of 0.346, and a zeta potential of 20.7 mV. SEM analysis revealed a uniform distribution of polyhedral-shaped nanoparticles. XRD and DSC analyses indicated that APZ was in an amorphous state within the nanoparticles. Drug release was more pronounced at pH 6.8, with the AX nanoparticles showing sustained release. The everted sac method demonstrated enhanced permeation of APZ across intestinal membranes, supporting the potential of AX nanoparticles in improving drug absorption.

Discussion: The AX-based nanoparticle formulation significantly improved the solubility, pH-dependent release profile, and sustained release of APZ, offering a promising strategy to enhance the oral bioavailability of poorly soluble drugs. These findings suggest that AX nanoparticles could serve as an effective delivery system for enhancing the therapeutic potential of hydrophobic drugs like APZ.