Formulation, optimization and full characterization of mirtazapine loaded aquasomes: a new technique to boost antidepressant effects

Abstract

Objective

The development of Mirtazapine (MRT)-loaded aquasomes by co-precipitation sonication technique to boost the antidepressant potential of MRT.

Methodology

MRT-loaded aquasomes formulations were prepared using Box–Behnken design to investigate the effect of independent factors including sonication time (X1), sonication temperature (X2), and sugar concentration (X3) on the dependent variables as particle size and drug loading efficiency. The formulation of the optimized formula was verified by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and X-ray Powder Diffraction (XRPD). Furthermore, the morphology of the formula was evaluated by Transmission Electron Microscopy (TEM). The optimum MRT- loaded aquasomes was assessed for physiochemical properties, in vitro MRT release and in vivo antidepressant effects in mice model.

Results

The results revealed that the optimized formula showed a small particle size of 202.7 ± 3.7 nm and a high loading efficiency of 77.65 ± 2.6%. Thermal DSC and XRPD studies demonstrated the amorphous nature of MRT-loaded aquasomes. The in vitro study demonstrated sustained release of F (opt) 88.16% after 8 h, compared with plain MRT release of 63.06% after 1 h. Mice treated with MRT-loaded aquasomes demonstrated reduced immobility time in behavioral analysis to 37% with MRT-loaded aquasomes, while plain MRT reduced it to 55%.

Conclusion

These results confirmed that the antidepressant effect of MRT was significantly boosted in formulated aquasomes, and thereby they provide a promising carrier nano vesicular system for effective delivery of MRT.

Graphical Abstract

Keywords:

• Aquasomes
• mirtazapine
• depression
• Box–Behnken design
• optimization

Acknowledgments

The authors would like to thank Al-Debeiky © Pharma (DBK) (Cairo, Egypt) Company for the supply of Mirtazapine.

Ethical approval

Measurement of the treatments’ pharmacodynamic parameters conformed to guidelines of Institutional Animal Ethical of Faculty of Pharmacy, Al-Azhar University. The panel test was also carried out according to Al-Azhar University-approved protocol (Approval number: 352).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.