Potential application of sucrose acetate isobutyrate, and glyceryl monooleate for nanonization and bioavailability enhancement of rivaroxaban tablets

Abstract

This study aimed to investigate the use of Sucrose acetate isobutyrate (SAIB) and Glyceryl monooleate (GMO) as co-formers for creating Cubosomes and SAIB-based nanodispersions of Rivaroxaban (RXB). The process utilized a modified melt dispersion technique with varying polymer: drug ratios (0.5:1, 0.75:1, and 1:1) and a fixed polymer: poloxamer 407 ratio (0.1:1). Particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE) were measured to determine the optimal formulas. The best-lyophilized formulas were then analyzed using Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), dissolution testing, and Pharmacokinetic (PK) studies. The results revealed significant correlations between polymer concentrations and various variables in cubosomal and SAIB-based nanodispersions. An increase in GMO concentration led to a decrease in PS, PDI, and ZP but an increase in EE and yield. Maintaining optimal GMO concentration is crucial for consistent nanoparticle formulations. In contrast, increasing SAIB concentration led to a decrease in PS and PDI but an increase in EE and yield. The drug release rates of different preparations were measured during the dissolution test. The best-lyophilized cubosome (L4) and the best-lyophilized SAIB-based nanodispersions (L8) showed significantly improved drug release compared to XARELTO®. L4 displayed the best dissolution rate, and L8 also had a reasonable rate. A PK study demonstrated that L4 and L8 had significantly better bioavailability than XARELTO®, possibly due to their improved solubility. This study suggests that SAIB and GMO can significantly enhance the solubility and bioavailability of RXB in nano preparations, leading to more efficient drug delivery. This new approach can also reduce the required dosage for the desired therapeutic effect. However, further research is needed to fully understand these polymers' potential benefits and limitations.

Keywords

Nanonization / Rivaroxaban / Sucrose acetate isobutyrate / Glyceryl monooleate / Bioavailability enhancement

Contributions

Adam A. Al-Shoubki: formal analysis, methodology, validation, writing—original draft. Mahmoud H. Teaima: investigation, supervision, writing—review and editing. Rehab Abdelmonem: validation, supervision, writing—review and editing. Mohamed A. El-Nabarawi: conceptualization, investigation, visualization, supervision, study administration. Sammar Fathy Elhabal: investigation, writing—review and editing. All authors have read and approved the final manuscript.

Funding information

This research received no funding.

Ethics approval

All procedures of animal study were approved and regularly controlled by the Animal Ethics Committee of 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 [40].

Declaration of competing interest

We, the authors of this manuscript, declare that there is no conflict of interest between us. We have no financial or personal relationships that could inappropriately influence our work. We have given full disclosure of any potential conflicts of interest to the Journal of Pharmaceutical Science Advances. We are committed to ensuring the integrity and objectivity of our research and writing, and we stand behind the accuracy and validity of our findings.

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.

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