Eudragit L100-coated nintedanib nanocrystals improve oral bioavailability by reducing drug particle size and maintaining drug supersaturation

Jiajing Che; Yu Fu; Yehan Li; Yu Zhang; Tian Yin; Jingxin Gou; Xing Tang; Yanjiao Wang; Haibing He

doi:10.1016/j.ijpharm.2024.124196

Eudragit L100-coated nintedanib nanocrystals improve oral bioavailability by reducing drug particle size and maintaining drug supersaturation

Int J Pharm. 2024 May 3:658:124196. doi: 10.1016/j.ijpharm.2024.124196. Online ahead of print.

Authors

Jiajing Che¹, Yu Fu¹, Yehan Li¹, Yu Zhang¹, Tian Yin², Jingxin Gou¹, Xing Tang¹, Yanjiao Wang¹, Haibing He³

Affiliations

¹ Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
² School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, China.
³ Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address: hhb_emily@126.com.

PMID: 38703933
DOI: 10.1016/j.ijpharm.2024.124196

Abstract

The aim of this study was to prepare nintedanib nanocrystals (BIBF-NCs) to lower the solubility of the drug in the stomach, maintain the supersaturation of the drug in the intestine, and improve the oral absorption of nintedanib (BIBF). In this study, BIBF-NCs were prepared by acid solubilization and alkaline precipitation following nano granding method, with a particle size of 290.80 nm and a zeta potential of -49.13 mV. Subsequently, Nintedanib enteric-coated nanocrystals (BIBF-NCs@L100) were obtained by coating with Eudragit L100. The microscopic morphology, crystalline characteristics, stability, and in vitro dissolution of BIBF-NCs and BIBF-NCs@L100 were also studied. In addition, the in vivo pharmacokinetic behaviors of Samples prepared according to the prescription process of commercially available soft capsules (soft capsules), BIBF-NCs, and BIBF-NCs@L100 were further investigated. The results showed that the oral bioavailability of BIBF-NCs and BIBF-NCs@L100 were increased by 1.43 and 2.58 times, compared with that of the soft capsules. BIBF-NCs@L100 effectively reduced the release of BIBF in the formulation in the stomach, allowing more drug to reach the intestine in the form of nanocrystals, maintaining the supersaturation in the intestine, thereby improving the oral bioavailability of the drug.

Keywords: Nanocrystals; Nintedanib; Oral bioavailability; Supersaturation.