Enhanced solubility and bioavailability of zanubrutinib nanocrystals: physicochemical and pharmacokinetic evaluation

The present study focuses on the 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 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 studies 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. The ZBR-NCs exhibited 98.67 ± 3.49% release at 10 h, showing an increased ZBR release as compared to free ZBR. Pharmacokinetic evaluation of ZBR-NCs 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 2-month period at refrigerated (2-8 °C) condition, with retention of their physicochemical properties. Collectively, these findings emphasize the potential of ZBR-NCs as a promising strategy to improve solubility and oral absorption of ZBR. HIGHLIGHTSThe ZBR-NCs were prepared using PVPK-30, Poloxamer 407^® and Poloxamer 188^®.The solubility of ZBR was improved 57-fold with NCs.The ZBR-NCs showed higher drug release than free ZBR.The ZBR-NCs achieved a 4.41-fold increase in bioavailability.