Formulation and evaluation of ibrutinib-loaded glycyrrhizic acid conjugated ovalbumin nanoparticles and ibrutinib-glycyrrhizic acid complex for improved oral bioavailability

Abstract

The study aimed at enhancing the oral bioavailability of the BCS class 2 drug Ibrutinib (IBR), which exhibits low solubility (0.002 mg/mL) and high permeability (3.9% oral bioavailability). This was achieved through the formulation and evaluation of Ibrutinib-loaded Glycyrrhizic acid conjugated egg ovalbumin nanoparticles (IBR-GA-EA NPs) and Ibrutinib-Glycyrrhizic acid complex (IBR-GA-COMP). The formulation of Ibrutinib-Glycyrrhizic acid complex aimed to enhance the oral bioavailability of Ibrutinib. Lyophilized Ibrutinib-Glycyrrhizic acid complex was prepared and characterized through various studies including DSC, FTIR, in vitro release, and in vivo pharmacokinetics studies. DSC and FTIR confirmed successful formulation development. The nanoparticles exhibited spherical morphology with favourable characteristics: particle size of 194.10 nm, PDI of 0.22, and zeta potential of -33.96 mV. Encapsulation efficiency was 82.88%. In vitro release study displayed major improvement in drug release pattern compared to the free drug suspension. In vivo pharmacokinetic studies demonstrated 3.21-fold and 3.41-fold increase in the oral bioavailability of IBR-GA-EA NPs and IBR-GA-COMP, respectively, compared to IBR suspension alone. The formulated IBR-GA-EA NPs and IBR-GA-COMP are promising drug delivery methods as they successfully improve the solubility and oral bioavailability of Ibrutinib.

Keywords: Ibrutinib; complexes; conjugated nanoparticles; oral bioavailability enhancement; solubility enhancement.