Improved Pharmacodynamic Potential of Rosuvastatin by Self-Nanoemulsifying Drug Delivery System: An in vitro and in vivo Evaluation

Abstract

The purpose of this proposed research was to investigate a nano-formulation developed using self-nanoemulsifying drug delivery system (SNEDDS) to improve the pharmacodynamic potential of rosuvastatin by assisting its transportation through lymphatic circulation. Methods: The utilized lipids, surfactants, and co-surfactants for SNEDDS were selected on the basis of solubility studies. The SNEDDS formulation was optimized by implementing a D-optimal mixture design, wherein the effect of concentration of Capmul MCM EP (X 1), Tween 20 (X 2) and Transcutol P (X 3) as independent variables was studied on droplet size (Y 1), % cumulative drug release (Y 2) and self-emulsification time (Y 3) as dependent variables. The optimized formulation was evaluated via in vitro parameters and in vivo pharmacodynamic potential in Wistar rats. Results: The D-optimal mixture design and subsequent ANOVA application resulted in the assortment of the optimized SNEDDS formulation that exhibited a droplet size of nano range (14.91nm), in vitro drug release of >90% within 30 minutes, and self-emulsification time of 16 seconds. The in vivo pharmacodynamic study carried out using Wistar rats confirmed the better antihyperlipidemic potential of developed formulation in normalizing the lipidic level of serum in contrast to pure drug and marketed tablets. Conclusion: This research reports the application of D-optimal mixture design for successful and systematic development of rosuvastatin-loaded SNEDDS with distinctly enhanced in vitro and in vivo performance in comparison to marketed formulation. Eventually, improved anti-hyperlipidemic efficacy was envisaged which might be attributed to increased drug solubility and absorption. Overall, this study shows the utility of SNEDDS for improving the dissolution rate and bioavailability of poor aqueous-soluble drugs. The present SNEDDS formulation could be a promising approach and alternative to conventional dosage form.

Development of Piperine-Loaded Solid Self-Nanoemulsifying Drug Delivery System: Optimization, In-Vitro, Ex-Vivo, and In-Vivo Evaluation

“…The appropriate quantity of selected components was mixed into a glass vial to form a uniform homogeneous mixture. The calculated amount of PE (20 mg) was added in the SNEDDS (F1-F17) followed by vortexing to obtain a homogeneous mixture of PE-SNEDDS [21,22]. PE-SNEDDS was preserved at ambient temperature for further study.…”

Evaluation of in vitro Dissolution Profile and Physicochemical Characterization of Polymer Based Formulations of Sparingly Soluble Rosuvastatin

“…Prominent peaks of the untreated active ingredient were found at 3417.86 (alcohol group), 2927.94 (O-H stretching carboxylic acid), 1550.77 (carbonyl group), 1151.50 (sulfone group) and 964.41 (aromatic C-H bending) cm -1 (Figure 3A). 47,48 Additionally, in physical mixtures of KIR and KF90 with pure RVT, prominent peaks of RVT were found at almost the same position (KIR: 3429.43, 2926.01, 1548.84 cm -1 ; KF90: 3427.51, 2936.52, 1548.84 cm -1 ) which ensure pure drug remained unchanged and no interaction with the polymers occurred in the physical mixture formulations (Figures 3D, 3E). The spectra of the solid dispersion systems, RVT-KIR, RVT-KF90 solid dispersion system also maintained consistency with the pure RVT spectrum (KIR: 3427.51, 2924.09 cm -1 ; KF90: 3429.33, 2926.01, 1548.91 cm -1 ; Figures 3F, 3G).…”

“…DSC thermogram of PM formulations displayed different sharp endothermic peaks from the pure RVT which is due to the crystallinity form change of this drug. 47 In case of SD formulations, the melting point was in between pure RVT and KIR for RVT-KIR SD formulations, and a decrease in melting point was observed for the RVT-KF90 SD formulations (Figure 4F, 4G). The peaks of the pure RVT were disappeared in the DSC curve of SD formulations due to the conversion of RVT crystal structure to the amorphous state.…”

“…The peaks of the pure RVT were disappeared in the DSC curve of SD formulations due to the conversion of RVT crystal structure to the amorphous state. 47 Scanning electron microscopic (SEM) analysis. Surface morphology of the pure RVT, PMs and SDs have been inspected by performing SEM analysis.…”

Multidrug Resistance of Cancer Cells and the Vital Role of P-Glycoprotein

“…Third-generation inhibitors: Third-generation inhibitors are often created to alleviate the issues associated with first-and second-generation inhibitors. The key advantage of utilizing third-generation inhibitors is that they are less toxic than the previous two generations of inhibitors, and they are more selective and effective against P-gp [70]. They have no pharmacological interactions with chemotherapeutic drugs and have been discovered to be 200 times more powerful than the previous two generations of inhibitors.…”