Effect of binary combinations of solvent systems on permeability profiling of pure agomelatine across rat skin: a comparative study with statistically optimized polymeric nanoparticles

Abstract

Objective: Agomelatine (AGM), an antidepressant drug has low biological half-life coupled with extensive hepatic first-pass metabolism. For effective treatment of depression, daily medication is required but irregular dose intake occurs due to psychological illness which can be overcome by development of transdermal drug delivery system. But for effective transdermal delivery permeation of AGM through stratum corneum is a crucial step. Thus present study was intended to formulate and optimize polymeric nanoparticles of agomelatine and to compare the effect of binary combinations of solvent system on permeability profiling of pure agomelatine with statistically optimized polymeric nanoparticles.

Methods: Polymeric agomelatine nanoparticles (AGM-PNPs) were prepared by nano-precipitation method which was further optimized by experimental design and characterized by FTIR, DSC, XRD and SEM study while ex-vivo study was performed on adult male wistar rats.

Results: The optimized formulation has particle size in nano range (107.64 nm) with low PDI (0.209), stable zeta potential (−15 mV) and high entrapment efficiency (81.91%). Ex-vivo analysis of optimized nanoparticles suggests that nanoparticles permeate faster compared to plain AGM, while, permeation profile of AGM was enhanced when combination of solvent systems were used. It was observed that among various solvent system 33% PG-ethanol showed maximum flux (148.48 ± 3.24 µg/cm²/h) and least lag time (4.04 ± 0.12 h). The flux was further enhanced (180.98 ± 2.54 µg/cm²/h) when 5%v/v transcutol-HP was added as penetration enhancer.

Conclusion: The above observations concluded that binary combination of 33% PG-ethanol with 5 %v/v transcutol-HP can serve as a solvent system of choice for effective transdermal delivery of agomelatine via nanoparticulate system.

Keywords:

• Agomelatine
• polymeric nanoparticles
• penetration enhancers
• solvent system
• flux
• lag time

Ethical approval

The study was conducted after receiving approval from Institutional Animal Ethics Committee of UDPS, R.T.M. Nagpur University, Nagpur (protocol approval no. IAEC/UDPS/2018/40).

Acknowledgements

The authors express sincere thanks to Mehta API Pvt. Ltd. Mumbai, Evonik Degussa Pvt. Ltd. Mumbai, Himedia Mumbai, Mohini Organics Pvt. Ltd. Mumbai, and Gattefosse, France for providing gratis sample of agomelatine, PLGA, Pluronic F-68, PVA, Iso propyl myristate, and Transcutol HP, respectively, for research work.

Disclosure statement

The authors have no declaration of interest.

Additional information

Funding

The present research was funded by University Research Promotion Scheme Dev/RTMNURP/AH/1672(3), R.T.M. Nagpur University, Nagpur.