Self Nanoelmusifying Drug Delivery System of Rosuvastatin: Bioavailability Evaluation and In vitro - In vivo Correlation.

Abstract

Background: Rosuvastatin, most commonly used in the form of calcium salt, belongs to the statin groups of synthetic antihyperlipidemic agents. Rosuvastatin possesses high permeability, however, its aqueous solubility is poor, causing a slow dissolution rate in water. Consequently, this dissolution rate has a decisive role in the release and absorption of rosuvastatin in the gastrointestinal tube.

Objective: The aims of this study were to evaluate the absorption of the drug from the self-nano emulsifying drug delivery system of rosuvastatin (Ros SNEDDS) compared to rosuvastatin substance and to develop a level-A in vitro-in vivo correlation (IVIVC) for Ros SNEDDS.

Methods: An in-house developed LC-MS/MS method was used to determine the concentrations of rosuvastatin in dog plasma. Six beagle dogs received an intravenous dose, Ros SNEDDS, rosuvastatin substance. In vitro dissolution of the Ros SNEDDS was carried out with different conditions. Correlation models were developed from the dissolution and absorption results of Ros SNEDDS.

Results: The results showed a 1.7-fold enhanced oral bioavailability and 2.1-time increase of rosuvastatin C_max in Ros SNEDDS form, compared to the rosuvastatin substance. A 900 ml dissolution medium of pH of 6.6 has demonstrated its suitability, the in vitro dissolution model was studied and supported by the Weibull equation with a weighting factor of 1/y² as it presented the lowest values of AIC.

Conclusion: Ros SNEDDS demonstrated higher bioavailability of rosuvastatin in comparison to rosuvastatin substance and established a level A IVIVC used in future bioequivalence trials.