Poly dispersibility index and zeta
poly dispersibility Indices of SLN dispersions were found to be low in all the
SLNs (Table 5). Concentration of SA and
PVA did not show any significant effect on PDI.
potential act as a repulsive factor in the process of emulsion stabilization 33
are shown in Table 5. The values ranged from -22.8±0.54 to -26.5±0.06for all formulations.
The result could be due to the higher shielding effect of PVA. All the SLNs
were found to be negatively charged due to fatty acids. 34.
FT-IR Spectroscopy studies
FT-IR analysis of plain voriconazole, stearic acid,
its physical mixture and voriconazole SLN were performed to evaluate the
chemical compatibility between voriconazole and stearic acid and represented in
Figure 2. Voriconazole showed characteristic peaks of C-N, C-F, and C-C
stretching bands 3200-3000, 1500–1450, and 1600–1450 cm?1,
respectively. Stearic acid has shown significant broadening O-H stretching
vibration peaks between 400-3000 cm-1 representing the
characteristic peaks of lipids. The same peaks were seen in the spectra of
formulation also. In addition, the major peaks observed for voriconazole before
and after the preparation of solid lipid nanoparticles at 400-3200cm-1
were almost superimposable. This suggested the absence of any significant
interactions between voriconazole and stearic acid.
Figure 3 represents the DSC thermograms of pure
voriconazole, stearic acid, solid lipid nanoparticles without drug and
voriconazole loaded solid lipid nanoparticles. A sharp endothermic peak
characterizes thermogram of voriconazole at 132.570 C. Thermogram of
stearic acid showed an endothermic peak at 60.220 C. A sharp
endothermic peak at 53.990 C was observed in the thermogram of lyophilized
solid lipid nanoparticles (blank), which appears to be the depressed
endothermic peak of stearic acid. A sharp endothermic peak at 54.040C
was observed in the thermogram of lyophilized voriconazole loaded solid lipid
nanoparticles. No endothermic peak of voriconazole was observed in the lyophilized
voriconazole loaded SLN powder, which could be due to the presence of very
small quantity of voriconazole in the lyophilized powder.
Powder X-ray diffraction
Figure 4shows the powder diffraction patterns for
voriconazole, stearic acid, a physical mixture of voriconazole and stearic
acid, and voriconazole loaded SLN lyophilized powder. The presence of sharp
peaks in the diffractogram of voriconazole and stearic acid indicated their
crystalline nature. The sharp peaks were observed in the diffractogram of
physical mixture of voriconazole and stearic acid. The diffractogram of
voriconazole loaded SLN lyophilized powder showed two characteristic peaks,
which appears to be contributions of stearic acid. The characteristic peaks of
voriconazole are completely attenuated in the diffractogram of lyophilized
powder of voriconazole-loaded SLN, which seems to be due to the dilution effect
exerted by stearic acid.
Transmission electron microscopy
Figure 5 shows transmission electron micrographs of
voriconazole SLNs prepared with stearic acid as lipid bases prepared by
melt-emulsion sonication and low temperature-solidification technique. The micrographs showed that the
particles had nanometer- sized spherical shapes.
The in vitro permeation profile of voriconazole from
SLNs is shown in figure-6. The permeation of voriconazole was evaluated by
using freshly excised goat cornea and using freshly prepared bicarbonate ringer
solution (pH 7.4) as the releasing medium for 4 hours. SLNs prepared with 3%
w/v PVA solution showing maximum Papp followed by SLNs prepared with 2% and
1%w/v PVA solution irrespective of particle size. The higher permeation of
voriconazole form SLN 7, SLN 8 and SLN 9 could be due to more hydrophilicity of
nanoparticles. The hydrophilicity might be attributed to the residual PVA at
the surface of nanoparticles formulated with 3% PVA. The existence of residual
PVA correlates with the increase of particle size due to PVA concentration.
The results of corneal
hydration were more than the normal range of 75% to 80% 35
indicating slight damage to the corneas. Since the corneal hydration is below
83%, the damage appears to be reversible. 36
A clear zone of inhibition
obtained by disc diffusion method was shown in figure 7. Diameter of zone of
inhibition were found to be 27.2 ± 0.95mm and 15.57±0.43 mm for SLN 7 and
saturated solution of VOZ respectively. The higher zone of inhibition from SLNs
could be due to the initial burst release of surface associated drug. A higher
permeation and zone of inhibition against Aspergillus
flavus revealed the microbial efficacy of the voriconazole loaded SLNs.
Statistical optimization technique was successfully adopted
to predict the composition variables leading to achieve the optimum quality
attribute for VOZ SLNs. This work has shown that voriconazole was successfully
entrapped in stearic acid by the melt-emulsion sonication and low
temperature-solidification technique for topical ocular delivery. Concentration
of lipid and surfactant had a great influence on particle size and percent drug
loading. Transmission electron microscopy of the SLNs showed spherical
morphology of the particles. Permeation of voriconazole from SLNs was higher
than saturated drug solution (SSV).The outcomes of in vitro antifungal activity concludes that voriconazole
SLNs was more effective than the tested saturated solution of VOZ. Hence the
prepared VOZ SLNs can used to treat ocular fungal infection due to the high
permeation and significant anti-fungal ability.