Poly dispersibility index and zetapotential (ZP)Thepoly dispersibility Indices of SLN dispersions were found to be low in all theSLNs (Table 5).  Concentration of SA andPVA did not show any significant effect on PDI. Zetapotential act as a repulsive factor in the process of emulsion stabilization 33are 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 SLNswere found to be negatively charged due to fatty acids. 34. FT-IR Spectroscopy studiesFT-IR analysis of plain voriconazole, stearic acid,its physical mixture and voriconazole SLN were performed to evaluate thechemical compatibility between voriconazole and stearic acid and represented inFigure 2. Voriconazole showed characteristic peaks of C-N, C-F, and C-Cstretching bands 3200-3000, 1500–1450, and 1600–1450 cm?1,respectively.

Stearic acid has shown significant broadening O-H stretchingvibration peaks between 400-3000 cm-1 representing thecharacteristic peaks of lipids. The same peaks were seen in the spectra offormulation also. In addition, the major peaks observed for voriconazole beforeand after the preparation of solid lipid nanoparticles at 400-3200cm-1were almost superimposable. This suggested the absence of any significantinteractions between voriconazole and stearic acid.Thermal analysisFigure 3 represents the DSC thermograms of purevoriconazole, stearic acid, solid lipid nanoparticles without drug andvoriconazole loaded solid lipid nanoparticles. A sharp endothermic peakcharacterizes thermogram of voriconazole at 132.570 C.

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Thermogram ofstearic acid showed an endothermic peak at 60.220 C. A sharpendothermic peak at 53.990 C was observed in the thermogram of lyophilizedsolid lipid nanoparticles (blank), which appears to be the depressedendothermic peak of stearic acid. A sharp endothermic peak at 54.040Cwas observed in the thermogram of lyophilized voriconazole loaded solid lipidnanoparticles. No endothermic peak of voriconazole was observed in the lyophilizedvoriconazole loaded SLN powder, which could be due to the presence of verysmall quantity of voriconazole in the lyophilized powder.Powder X-ray diffractionFigure 4shows the powder diffraction patterns forvoriconazole, stearic acid, a physical mixture of voriconazole and stearicacid, and voriconazole loaded SLN lyophilized powder.

The presence of sharppeaks in the diffractogram of voriconazole and stearic acid indicated theircrystalline nature. The sharp peaks were observed in the diffractogram ofphysical mixture of voriconazole and stearic acid. The diffractogram ofvoriconazole loaded SLN lyophilized powder showed two characteristic peaks,which appears to be contributions of stearic acid. The characteristic peaks ofvoriconazole are completely attenuated in the diffractogram of lyophilizedpowder of voriconazole-loaded SLN, which seems to be due to the dilution effectexerted by stearic acid.Transmission electron microscopyFigure 5 shows transmission electron micrographs ofvoriconazole SLNs prepared with stearic acid as lipid bases prepared bymelt-emulsion sonication and low temperature-solidification technique. The micrographs showed that theparticles had nanometer- sized spherical shapes.

Transcorneal permeationThe in vitro permeation profile of voriconazole fromSLNs is shown in figure-6. The permeation of voriconazole was evaluated byusing freshly excised goat cornea and using freshly prepared bicarbonate ringersolution (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% and1%w/v PVA solution irrespective of particle size. The higher permeation ofvoriconazole form SLN 7, SLN 8 and SLN 9 could be due to more hydrophilicity ofnanoparticles.

The hydrophilicity might be attributed to the residual PVA atthe surface of nanoparticles formulated with 3% PVA. The existence of residualPVA correlates with the increase of particle size due to PVA concentration. The results of cornealhydration were more than the normal range of 75% to 80% 35indicating slight damage to the corneas. Since the corneal hydration is below83%, the damage appears to be reversible. 36Microbiological studyA clear zone of inhibitionobtained by disc diffusion method was shown in figure 7. Diameter of zone ofinhibition were found to be 27.2 ± 0.95mm and 15.

57±0.43 mm for SLN 7 andsaturated solution of VOZ respectively. The higher zone of inhibition from SLNscould be due to the initial burst release of surface associated drug. A higherpermeation and zone of inhibition against Aspergillusflavus revealed the microbial efficacy of the voriconazole loaded SLNs.CONCLUSIONSStatistical optimization technique was successfully adoptedto predict the composition variables leading to achieve the optimum qualityattribute for VOZ SLNs. This work has shown that voriconazole was successfullyentrapped in stearic acid by the melt-emulsion sonication and lowtemperature-solidification technique for topical ocular delivery.

Concentrationof lipid and surfactant had a great influence on particle size and percent drugloading. Transmission electron microscopy of the SLNs showed sphericalmorphology of the particles. Permeation of voriconazole from SLNs was higherthan saturated drug solution (SSV).The outcomes of in vitro antifungal activity concludes that voriconazoleSLNs was more effective than the tested saturated solution of VOZ. Hence theprepared VOZ SLNs can used to treat ocular fungal infection due to the highpermeation and significant anti-fungal ability.