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.