Sucrose acetate isobutyrate (SAIB) and glyceryl monooleate (GMO) hybrid nanoparticles for bioavailability enhancement of rivaroxaban: an optimization study

Abstract

This study aims to improve the RXB bioavailability using hybrid nanoparticles. A modified melt dispersion technique created different formulas with varying GMO-SAIB: RXB and GMO: SAIB ratios, with fixed GMO-SAIB: poloxamer 407 ratios. The PS, PDI, ZP, and EE were measured to determine the optimal formula, which was selected using Design-Expert™ software. The optimized formula was lyophilized and tested for PS, PDI, ZP, and EE. The chosen lyophilized formula (L4) was characterized using FTIR, DSC, PXRD, dissolution studies, and pharmacokinetics studies. The study found correlations between variables and identified how GMO-SAIB concentration affects drug encapsulation. The dissolution parameters were calculated, including % Q5 and % DE). The % Q5 values were 68.4 ± 1.7% and 89.7 ± 3.6% for Xarelto and L4 tablets, respectively. The % DE values were 89.7 ± 0.4% and 97.5 ± 2.1% for Xarelto and L4 tablets, respectively. The AUC values were 2117.0 ng.h/mL (±77.3) and 3919.4 ng.h/mL (±134.8) for Xarelto and L4 tablets, respectively. The Cmax values were 241.3 ng/mL (±21.0) and 521.5 ng/mL (±91.5) for Xarelto and L4 tablets, respectively. In conclusion, the study found that using GMO-SAIB as co-formers effectively enhanced the bioavailability of RXB. The authors recommend using the hybrid nanoparticles technique and suggest further research to enhance its effectiveness for drug delivery.

Graphical Abstract

Keywords:

• Nanonization
• rivaroxaban
• sucrose acetate isobutyrate
• glyceryl monooleate
• bioavailability enhancement

Acknowledgements

We express our gratitude to Sigma Pharmaceutical Industries, Quesna, Egypt for generously providing us with Rivaroxaban, Poloxamer 407, and Mannitol, which were essential components of our research.

Ethical approval

All procedures of animal study were approved and regularly controlled by the Animal Ethics Committee of the Faculty of Pharmacy Cairo University (no. PT2.1.4) and all experiments were performed in accordance with the guidelines and regulations of this committee. All the procedures were also carried out in full accordance with the ARRIVE guidelines 2020 (Percie Du Sert et al. 2020).

Authors’ contributions

Adam A. Al-Shoubki: Conceptualisation, Data curation, Formal analysis, Investigation, Methodology, Validation, Visualisation, Writing - original draft; Mahmoud H. Teaima: Conceptualisation, Resources, Methodology, Project administration, Writing - Review & Editing, Funding acquisition; Rehab Abdelmonem: Conceptualisation, Methodology, Supervision, Visualisation, Writing - Review & Editing; Mohamed A. El-Nabarawi: Conceptualisation, Methodology, Project administration, Supervision, Resources, Visualisation, Writing - Review & Editing, Funding acquisition; Sammar Fathy Elhabal: Data curation, Supervision, Writing - Review & Editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors will provide the raw data that supports their conclusions to any qualified researcher, without any hesitation.

Additional information

Funding

This research received no funding.