Assessment of Dose Proportionality of Rivaroxaban Nanocrystals
| Autor: | Selma Sahin, Tugba Gulsun, Emirhan Nemutlu, Melike Hacer Ozkan, Huriye Demir, Levent Öner |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Cmax
Biological Availability Pharmaceutical Science 02 engineering and technology Aquatic Science 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Rivaroxaban Pharmacokinetics Drug Discovery medicine Animals Particle Size Solubility Ecology Evolution Behavior and Systematics Chromatography Dose-Response Relationship Drug Ecology Chemistry General Medicine Poloxamer 021001 nanoscience & nanotechnology Biopharmaceutics Classification System Bioavailability Nanocrystal Area Under Curve Nanoparticles Rabbits 0210 nano-technology Agronomy and Crop Science Factor Xa Inhibitors medicine.drug |
| Zdroj: | AAPS PharmSciTech. 21 |
| ISSN: | 1530-9932 |
| Popis: | Rivaroxaban (RXB) is a class II drug, according to the Biopharmaceutics Classification System. Since its bioavailability is low at high doses, dose proportionality is not achieved for pharmacokinetic parameters. However, when taken with food, its bioavailability increases at high doses. In this study, nanocrystal technology was used to increase the solubility and, hence, the bioavailability of RXB. Pluronic F127, pharmacoat 603, and PVP K-30 were used as stabilizers to prepare RXB nanosuspension, combining ball mill and high pressure homogenization methods. Particle sizes of RXB in nanosuspension (formulation A:348 nm; formulation B:403 nm) and nanocrystal formulations (formulation A:1167 nm; formulation B:606 nm) were significantly reduced (p < 0.05) compared to those of bulk RXB. In both formulations, 80% of the drug dissolved in 30 min. For dose proportionality evaluation, 3, 10, and 15 mg/kg of RXB nanosuspensions (formulation B) were administered to rabbits. The dose proportionality for AUC andC(max)of RXB nanocrystals was assessed by the power model, variance analysis of pharmacokinetic parameters, linear regression, and equivalence criterion methods. Dose proportionality for AUC was achieved at doses between 10-15 and 3-15 mg/kg. In conclusion, the preparation of a nanocrystal formulation of RXB improved its dissolution rate and pharmacokinetic profile. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink