FORMULATION, CHARACTERIZATION AND PHARMACOKINETIC EVALUATION OF RIVAROXABAN-CITRIC ACID COCRYSTALS WITH ENHANCED SOLUBILITY, STABILITY AND BIOAVAILABILITY
DOI:
https://doi.org/10.22159/ijap.2026v18i2.57537Keywords:
Rivaroxaban, Citric acid, Cocrystals, Solubility, Dissolution, BioavailabilityAbstract
Objective: The attempt was made to improve solubility, flow properties, stability and bioavailability of rivaroxaban (RRB) by cocrystal formation.
Methods: The attempt was made to fabricate microwave assisted cocrystals of RRB using 10 different solid carboxylic acids as a cocrystal formers in 1:1 and 1:2 stoichiometric ratio. All the drug-coformer combinations were subjected to solubility analysis. Rivaroxaban-citric acid (RRB-CA)was further subjected to characterizations like Fourier transform infrared (FTIR), differential scanning colorimetry (DSC) and x-ray diffraction (XRD) to confirm the formation cocrystals as it shown highest solubility sediment delivery model (SeDeM) analysis was implemented to estimate comparative compressibility of pure drug and cocrystals. Cocrystals were further formulated into an immediate-release tablet and subjected to dissolution analysis in comparison with pure drug tablet. The comparative pharmacokinetic analysis was performed using wistar rats to. The comparative stability and shelf-life analysis was performed.
Results: Solubility analysis showed highest solubility with RRB-CA combination. The characterizations like FTIR, DSC and XRD confirmed the formation cocrystals. SeDeM (Sediment Delivery Model) analysis showed improved flowability and compressibility after cocrystal formation. The comparative dissolution study performed with pure RRB tablet and RRB-CA cocrystals showed improved dissolution after cocrystallizaion. The pure drug showed % drug release60.02±3.80% while RRB-CA cocrystals showed the drug release of 99.20±2.89%. Pharmacokinetic analysis performed using wistar rats demonstrated the improved bioavailability of RRB when administered as cocrystal. The pharmacokinetic parameters like peak plasma concentration (Cmax), AUC0-t(area under curve 0-t) and AUC0–∞(area under curve 0-∞)were significantly improved with cocrystallization. The peak plasma concentration of RRB pure drug was14.3389±1.4116µg/ml while for RRB-CA cocrystal it was 23.9644±1.5870 µg/ml. In shelf-life analysis, RRB showed the shelf life of 15.45 mo while cocrystal tablet showed the shelf life of 26.25 mo.
Conclusion: The cocrystallization of RRB with CA resulted in improved solubility by 5.80 folds while powdered dissolution showed the improvement by 1.65 folds. The results of kinetic study also demonstrated the improvement Cmax by 1.67 folds and AUC by 1.55 folds. Overall, the cocrystallization resulted in improved solubility, dissolution, bioavailability and stability.
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