Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Feb 9:16:905-924.
doi: 10.2147/IJN.S287665. eCollection 2021.

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

Ravinder Verma  1 , Ajeet Kaushik  2 , Rafa Almeer  3 , Md Habibur Rahman  4 , Mohamed M Abdel-Daim  3   5 , Deepak Kaushik  1
Affiliations

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

Ravinder Verma et al. Int J Nanomedicine. .

Abstract

Purpose: 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 (X1), Tween 20 (X2) and Transcutol P (X3) as independent variables was studied on droplet size (Y1), % cumulative drug release (Y2) and self-emulsification time (Y3) 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.

Keywords: D-optimal mixture design; SNEDDS; in vitro lipolysis; nanotechnology; pharmacodynamic study; rosuvastatin.

PubMed Disclaimer

Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

Figure 1
Figure 1
Solubility of rosuvastatin in different oils and surfactants. Each value shows the mean ± SD (n=3).
Figure 2
Figure 2
Self-emulsification of different oils with selected surfactants (n=3).
Figure 3
Figure 3
Ternary phase diagram of Capmul MCMEP, tween 20 and transcutol P at Smix ratios (A) 1:1, (B) 2:1, (C) 1:2, and (D) 1:3. The colored region (black) represents nano-emulsion formation region.
Figure 4
Figure 4
Various 2-D counter plots for response: (A) globule size, (B) % CDR, and (C) self-emulsification time.
Figure 5
Figure 5
Desirability index for optimized rosuvastatin-loaded SNEDDS.
Figure 6
Figure 6
DSC spectra of (A) pure rosuvastatin, (B) physical mixture of drug and excipients, and (C) optimized SNEDDS formulation.
Figure 7
Figure 7
FT-IR spectrum of (A) pure rosuvastatin, (B) physical mixture of drug and excipients, and (C) optimized SNEDDS formulation.
Figure 8
Figure 8
Transmission electron microscopy (TEM) of optimized SNEDDS formulation.
Figure 9
Figure 9
Dissolution (multi-media) testing of rosuvastatin SNEDDS. Each value represents the mean ± SD (n=3).
Figure 10
Figure 10
Comparative dissolution study (pH 6.6 citrate buffer) of rosuvastatin-loaded SNEDDS, pure drug and marketed tablet. Each value represents the mean ± SD (n=3).
Figure 11
Figure 11
Results of comparative lipid profile testing. Each value represents the mean ± SD (n=6).
See this image and copyright information in PMC

References

    1. Hwang Y-C. Response: comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2019;43:582–9). Diabetes Metab J. 2019;43(6):915–916. doi: 10.4093/dmj.2019.0213 - DOI - PMC - PubMed
    1. Alshora DH, Ibrahim MA, Elzayat E, Almeanazel OT, Alanazi F, Mukherjee A. Rosuvastatin calcium nanoparticles: improving bioavailability by formulation and stabilization codesign. PLoS One. 2018;13(7):e0200218. doi: 10.1371/journal.pone.0200218 - DOI - PMC - PubMed
    1. Lee YJ, Cha SH, Kim H, Choi SE, Cho S, Park Y. Diallyl disulphide-loaded spherical gold nanoparticles and acorn-like silver nanoparticles synthesised using onion extract: catalytic activity and cytotoxicity. Artif Cells Nanomed Biotechnol. 2020;48(1):948–960. doi: 10.1080/21691401.2020.1773485 - DOI - PubMed
    1. Vashist A, Atluri V, Raymond A, et al. Development of multifunctional biopolymeric auto-fluorescent micro- and nanogels as a platform for biomedical applications. Front Bioeng Biotechnol. 2020;8:315. doi: 10.3389/fbioe.2020.00315 - DOI - PMC - PubMed
    1. Nair M, Jayant RD, Kaushik A, Sagar V. Getting into the brain: potential of nanotechnology in the management of NeuroAIDS. Adv Drug Deliv Rev. 2016;103:202–217. doi: 10.1016/j.addr.2016.02.008 - DOI - PMC - PubMed

MeSH terms