Enhanced solubility and bioavailability of zanubrutinib nanocrystals: Physicochemical and Pharmacokinetic evaluation

The present study focuses on development of zanubrutinib nanocrystals (ZBR-NCs) to enhance its solubility, dissolution rate and oral bioavailability. The ZBR-NCs were successfully prepared by antisolvent precipitation method and subjected to physicochemical and pharmacokinetic evaluations. The resulting nanocrystals exhibited a particle size of 258.8 ± 12.56 nm, a polydispersity index value of 0.24 ± 0.02, a zeta potential of -18.4 ± 1.40 mV, and a drug content of 93.56 ± 2.5%. The solubility studies revealed a 57-fold increase in ZBR solubility as compared to the pure drug. The solid-state characterization confirmed reduced crystallinity of the ZBR within the nanocrystals and its compatibility with Poloxamer 188® as a stabilizing agent. The spherical shape of ZBR-NCs was demonstrated by high-resolution transmission electron microscopy study. ZBR-NCs exhibited 98.67 ± 3.49% release at 10 hours, showing an increased release as compared to free ZBR. Pharmacokinetic evaluation of ZBR-NC after oral administration displayed a 4.41-fold increase (p < 0.001) in bioavailability. The stability study of ZBR-NCs showed good stability over a two-month period at refrigerated (2-8 °C) condition, with retention of their physicochemical properties. Collectively, these findings underscore the potential of ZBR-NCs as a promising strategy to improve solubility and oral absorption of ZBR.