AAPS PharmSciTech

, Volume 19, Issue 3, pp 1205–1218 | Cite as

ω-3 Fatty Acid Synergized Novel Nanoemulsifying System for Rosuvastatin Delivery: In Vitro and In Vivo Evaluation

  • Chandra Bhushan Tripathi
  • Neha Gupta
  • Pranesh Kumar
  • Ashok Kumar Singh
  • Vinit Raj
  • Poonam Parashar
  • Mahendra Singh
  • Jovita Kanoujia
  • Malti Arya
  • Shubhini A Saraf
  • Sudipta Saha
Research Article


The present study was undertaken to improve rosuvastatin (RSV) bioavailability and pharmacological response through formation of SNES using Perilla frutescens oil as lipid carrier. The composition of oil was estimated by fatty acid methyl ester (FAME) analysis using gas chromatography. Solubility of RSV in Perilla frutescens oil and Cremophor EL was 25.0 ± 3.0 and 60.0 ± 5.0 mg/mL, respectively. Later, nanophasic maps and a central composite design were employed to determine the maximum nanoemulsion region and further optimize SNES in this study. Finally, the optimized formulation was evaluated in vitro and in vivo. FAME analysis revealed that PUFA content was 70.3% of total fatty acid. Optimized SNES formulation demonstrated particle size of 17.90 nm, dissolution 98.80%, cloud point 45°C, emulsification time 2 min, and viscosity 241.41 ± 5.52 cP. The hypolipidemic property of SNES was further explored using Triton X-100-induced hyperlipidemic rat model, and there were reductions of serum cholesterol, triglyceride, and LDL and VLDL levels in the SNES-treated group as compared to the toxic control. Pharmacokinetic study of SNES revealed significantly higher C max (60.13 ± 25.43 ng/mL) and AUC0–∞ (6195 ± 42.38 ng h/mL) vis-à-vis marketed tablet (284.80 ± 13.44 ng/mL, 3131.72 ± 51.93 ng h/mL, respectively). RSV was successfully incorporated into ω-3 fatty acid-based SNES with improved pharmacokinetic parameters (~ 2-fold improved bioavailability) and better hypolipidemic properties, owing to the synergistic effects of hepatic lipid regulation itself. The results clearly explicated that ω-3 fatty acid-based SNES effectively enhanced bioavailability and pharmacological responses of RSV, suggesting that these formulations may be useful as alternative for hyperlipidemia treatment in future drug design perspective.


rosuvustatin self-nanoemulsifying system ω-3 fatty acid hypolipidemic action Perilla frutescens oil 



The authors acknowledge the kind support of M/s IPCA Pharmaceuticals Pvt. Ltd., Mumbai and M/s BASF, Germany, for providing the ex gratis samples. The authors also acknowledge the SAIF Department, Babasaheb Bhimrao Ambedkar University for providing some evaluation facilities for this research work.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12249_2017_933_MOESM1_ESM.jpg (25 kb)
Suppl. Fig. 1A FTIR Spectrum of Rosuvastatin (JPEG 24 kb)
12249_2017_933_MOESM2_ESM.jpg (23 kb)
Suppl. Fig. 1B FTIR Spectrum of Cremophor EL (JPEG 22 kb)
12249_2017_933_MOESM3_ESM.jpg (33 kb)
Suppl. Fig. 1C FTIR Spectra of Perilla frutescens oil (JPEG 33 kb)
12249_2017_933_MOESM4_ESM.jpg (12 kb)
Suppl. Fig. 1D FTIR Spectra of rosuvastatin loaded SNES (JPEG 11 kb)
12249_2017_933_MOESM5_ESM.jpg (147 kb)
Suppl. Fig. 2 Standard HPLC chromatogram of Rosuvastatin with internal standard (Atorvastatin 100 ng/ml) in rat plasma (JPEG 147 kb)


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Copyright information

© American Association of Pharmaceutical Scientists 2017

Authors and Affiliations

  • Chandra Bhushan Tripathi
    • 1
  • Neha Gupta
    • 1
  • Pranesh Kumar
    • 1
  • Ashok Kumar Singh
    • 1
  • Vinit Raj
    • 1
  • Poonam Parashar
    • 1
  • Mahendra Singh
    • 1
  • Jovita Kanoujia
    • 1
  • Malti Arya
    • 1
  • Shubhini A Saraf
    • 1
  • Sudipta Saha
    • 1
  1. 1.Department of Pharmaceutical SciencesBabasaheb Bhimrao Ambedkar UniversityLucknowIndia

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