Preparation, characterization, and in vivo evaluation of perphenazine-loaded nanostructured lipid carriers for oral bioavailability improvement

Abstract

Objective

The main scope of the present investigation was to improve the bioavailability of perphenazine (PPZ) by incorporating it into the nanostructured lipid carriers (NLCs).

Significance

As a result of lipophilic nature and poor aqueous solubility, as well as extensive hepatic metabolism, PPZ has low systemic bioavailability via the oral route. NLCs have shown potentials to surmount the oral delivery drawbacks of poorly water-soluble drugs.

Methods

The PPZ-NLCs were prepared by the emulsification-solvent evaporation method and subjected for particle size, zeta potential, and entrapment efficiency (EE) analysis. The optimized NLCs were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffractometry (PXRD). Besides, in vitro release behavior, storage stability, and pharmacokinetic studies followed by a single-dose oral administration in rats were performed.

Results

Optimized PPZ-NLCs showed a particle size of less than 180 nm with appropriate EE of more than 95%. Microscopic images captured with SEM and TEM exhibited that NLCs were approximately spherical in shape. DSC and PXRD analysis confirmed reduced crystallinity of PPZ after incorporation in NLCs. FTIR spectra demonstrated no chemical interactions between PPZ and NLC components. In vitro release studies confirmed the extended-release properties of NLC formulations. PPZ-NLCs exhibited good stability at 4 °C within three months. The oral bioavailability of NLC-6 and NLC-12 was enhanced about 3.12- and 2.49-fold, respectively, compared to the plain drug suspension.

Conclusion

NLC can be designated as an effective nanocarrier for oral delivery of PPZ.

Keywords:

• Perphenazine
• schizophrenia
• nanostructured lipid carriers
• oral bioavailability

Acknowledgements

The authors are most grateful to Faranak Faraji for her kind helps in animal testing part of the study. As well as they would like to thank Dr. Masoumeh Kurd for her technical assistance.

Disclosure statement

The authors declare no conflicts of interest.

Additional information

Funding

This work was supported financially [Grant No. 9706063365] by the Hamadan University of Medical Sciences, Hamadan, Iran.