Parin Chokshi*, Rajashree Mashru, Preeti Jadeja and Apeksha Kadam

Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, 390001, Vadodara, Gujarat, India

*Corresponding Author: Parin Chokshi, Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, 390001, Vadodara, Gujarat, India.

Received: November 14, 2025; Published: November 28, 2025

Abstract

The study aimed to improve the oral bioavailability of nintedanib (NTB), a poorly soluble and extensively metabolized drug used for idiopathic pulmonary fibrosis. NTB’s low bioavailability (~4.7%) results from limited solubility (BCS Class IV) and rapid UGT-mediated metabolism. To address both challenges, NTB was formulated as nanocrystals combined with a natural bioenhancer that inhibits UGT. Four candidates-naringenin, piperine, quercetin, and curcumin-were screened using human liver microsomes. Naringenin showed the strongest inhibition, retaining 73% NTB and reducing UGT activity by over 82%. The optimized NTB nanocrystals with naringenin (NTB-NC with NGN) had a particle size of 144.43 nm, a PDI of 0.14, and a zeta potential of −17.3 mV. This formulation achieved a 6.31-fold increase in solubility and more than 93% drug release within 15 minutes. In mice, NTB-NC with NGN produced 1.43-fold higher Cmax than raw NTB, and a 1.3-fold higher AUC than NTB nanocrystals alone, confirming naringenin’s metabolic inhibition. The dual strategy of nanocrystal formulation with UGT enzymes bio-enhancement offers a significant improvement in NTB’s bioavailability, potentially allowing lower doses and reduced side effects for better therapeutic outcomes in IPF patients.

Keywords: Nintedanib; Naringenin; Bioavailability Enhancement; Human Liver Microsomes; UGT enzyme Inhibition; Nanocrystals; Idiopathic Pulmonary Fibrosis; Pharmacokinetics

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Citation

Citation: Parin Chokshi.,et al. “Novel Synergistic Approach: Enhancing the Oral Bioavailability of Nintedanib via Nanocrystal Technology using Naringenin as a Potent UGT Enzyme Inhibitor Identified Through Human Liver Microsome Studies". Acta Scientific Pharmaceutical Sciences 9.12 (2025): 36-47.

Copyright

Copyright: © 2025 Parin Chokshi., 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.