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

• Published in: International journal of pharmaceutics 2024-06, Vol.658, p.124196-124196, Article 124196
• Main Authors: Che, Jiajing, Fu, Yu, Li, Yehan, Zhang, Yu, Yin, Tian, Gou, Jingxin, Tang, Xing, Wang, Yanjiao, He, Haibing
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Biological Availability; Drug Liberation; Indoles - administration & dosage; Indoles - chemistry; Indoles - pharmacokinetics; Male; Nanocrystals; Nanoparticles - chemistry; Nintedanib; Oral bioavailability; Particle Size; Polymethacrylic Acids - chemistry; Polymethacrylic Acids - pharmacokinetics; Rats, Sprague-Dawley; Solubility; Supersaturation
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2024.124196

[Display omitted] 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.