Optimizing ibrutinib bioavailability: Formulation and assessment of hydroxypropyl-β-cyclodextrin-based nanosponge delivery systems

Q2 Agricultural and Biological Sciences

Current Research in Pharmacology and Drug Discovery Pub Date : 2025-01-01 DOI:10.1016/j.crphar.2025.100213

Sunitha Sampathi , Nitiraj Kulkarni , D.V.R.N. Bhikshapathi , Jagadish V. Tawade , Nainaru Tarakaramu , Rzgar Farooq Rashid , Aziz Kubaev

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Abstract

Background

The current research aims to improve the oral bioavailability of ibrutinib (IBR), a class II drug with low solubility, through the formulation of nanosponges (NSPs) that incorporate IBR, utilizing Hydroxypropyl β-cyclodextrin (HPβCD) and 1,1′-carbonyldiimidazole (CDI) as cross-linking agent.

Methods

IBR-loaded HPβCD-NSPs were formulated by optimizing the molar proportion of HPβCD to CDI, as well as stirring rate and duration using a design-based methodology. The synthesized nanoparticles (NSPs) were examined for size, potential, and entrapment of drug. Characterization was performed by X-ray diffraction analysis, Fourier Transform Infrared Spectroscopy (FT-IR), and Differential Scanning Calorimetry (DSC), to assess compatibility. Permeability studies were conducted, followed by in vitro and in vivo assessments.

Results

The optimized IBR-loaded HPβCD NSPs demonstrated a mean particle size of 145.6 ± 6.8 nm, a PDI of 0.170 ± 0.036, and an EE of 71.04 ± 2.40%. Further validation through zeta sizing, microscopic and spectral analysis, release studies, and pharmacokinetic assessments confirmed the optimization. The HPβCD NSPs demonstrated 14.96 times higher AUC0-t (area under the curve) with a Cmax increase of 6.45 times compared to the free drug, indicating a substantial improvement in bioavailability.