Development of Perphenazine-Loaded Solid Lipid Nanoparticles: Statistical Optimization and Cytotoxicity Studies

Abstract

Objective: Perphenazine (PPZ), as a typical antipsychotic medical substance, has the same effectiveness compared to atypical antipsychotic medications for the treatment of schizophrenia. Despite the lipophilic essence, PPZ encounters limited bioavailability caused by the first-pass metabolism following oral administration. In the present study, PPZ-containing solid lipid nanoparticles (PPZ-SLNs) were prepared and optimized based on different factors, including lipid and surfactant amount, to develop appropriate and safe novel oral dosage forms of PPZ.

Methods: The solvent emulsification-evaporation method was utilized to form SLNs by using soybean lecithin, glycerol monostearate (GMS), and Tween 80. Statistical optimization was done by the Box-Behnken design method to achieve formulation with optimized particle size, entrapment efficiency, and zeta potential. Also, transmission electron microscopy, in vitro release behavior, differential scanning calorimetry (DSC), and powder X-ray diffractometry (P-XRD) studies and cytotoxicity studies were assessed.

Results: Optimization exhibited the significant effect of various excipients on SLN characteristics. Our finding indicated that the mean particle size, zeta potential, and entrapment efficiency of optimized PPZ-SLN were, respectively, 104 ± 3.92 nm, -28 ± 2.28 mV, and 83% ± 1.29. Drug release of PPZ-SLN was observed to be greater than 90% for 48 h that emphasized a sustained-release pattern. The DSC and P-XRD studies revealed the amorphous state of PPZ-SLN. FTIR spectra showed no incompatibility between the drug and the lipid. Performing cytotoxicity studies indicated no significant cytotoxicity on HT-29 cell culture.

Conclusion: Our study suggests that PPZ-SLNs can make a promising vehicle for a suitable therapy of schizophrenia for the oral drug delivery system.

Figure 1

3D response surface plot showing the effect of (a) Tween 80 and GMS on size, (b) lecithin and GMS on zeta potential, and (c) Tween 80 and lecithin on EE%.

Figure 2

TEM image of optimized SLN.

Figure 3

In vitro release profile of the optimized PPZ-loaded SLNs and pure PPZ (data shown as mean ± SD, n = 3).

Figure 4

Thermograms of the (a) PPZ, (b) GMS, (c) physical mixture of PPZ and GMS, and (d) PPZ-SLN.

Figure 5

XRD spectra of the (a) PPZ, (b) GMS, (c) physical mixture of PPZ and GMS, and (d) PPZ-SLN.

Figure 6

FTIR spectrum of the (a) PPZ, (b) GMS, (c) physical mixture of the drug and lipid, and (d) PPZ-SLN.

Figure 7

HT-29 cell viability assessed by MTT assay treated with free PPZ solution (24 h postincubation; 48 h post-incubation).