The hoof membrane was placed carefully on the Franz diffusion cell of mL capacity, and the surface area available for permeation was 1. Disk diffusion susceptibility method was used to determine the antifungal activity of drug alone and drug-loaded nanoemulgel against T. Both the strains T. Disks containing drug and nanoemulgel were then inserted into inoculated plate by using sterile forceps. The protocol was approved by the Institutional Animal Ethics Committee with approval number Positive control 0.
Undesirable skin changes, i. After a h observation period of skin irritation study, as described in the previous section, rats were sacrificed and excised skin samples from nanoemulgel-treated and negative control no application groups were taken. Five-micrometre thick sections of skin were cut using a microtome and stained with haematoxylin and eosin. Retention time of KCZ was found to be 2. Pseudo-ternary phase diagrams of the nanoemulsion formulations composed of oil phase Labrafac Lipophile WL and S mix Tween 80 and PEG in a ratio of a , b , c and d.
C0 pre-homogenized nanoemulsion crude nanoemulsion , PDI polydispersity index, S. RI refractive index, V viscosity, cP centipoise, t transmittance. Rheogram viscosity vs. The final formulation also contained glycerine as humectant, methyl paraben as a preservative, thioglycolic acid as a penetration enhancer 45 and amino-methyl propanol AMP to maintain the pH 6—6.
NEG 1. Positive control—0. Histopathology of rat skin sections showing the a negative control and b NEG 1 -treated group.
Summary. Discussing existing techniques, ongoing research, new approaches, and basic concepts in the treatment of nail diseases, Topical Nail Products and. Discussing existing techniques, ongoing research, new approaches, and basic concepts in the treatment of nail diseases, Topical Nail Products and Ungual.
For the development of an appropriate nanoemulsion, the selection of a suitable oil, surfactant and co-surfactant is very crucial. Co-surfactant PEG plays a very decisive role during nanoemulsion formulation by decreasing the interfacial stress, leading to interfacial film flexibility. It can be observed that at S mix ratio of Tween 80 used alone without PEG , higher concentration of surfactant was required for the stabilization of minimum amount of oil phase. When the concentration of co-surfactant in the S mix was increased from to NE1; Fig.
The area of nanoemulsion was further increased on increasing the S mix ratio to NE3; Fig. But, on further increasing the S mix ratio to NE4; Fig. Thus, maximum nanoemulsion areas were observed in the S mix ratios of and Nanoemulsions are kinetically stable systems and are formed by using a particular concentration of various components, with no sign of phase separation, creaming or cracking under various stress conditions. The most important feature of nanoemulsions is the mean droplet size, which must be in the nanometric range.
The influence of process variables, i. The results showed that the mean droplet size had an inverse relationship with both the homogenization pressure and number of cycles. The increase in droplet size was observed in NE1, which might be due to the expansion of the interfacial film by the co-surfactant leading to a larger droplet size, whereas decrease in droplet size in NE2 and NE3 might be due to a higher percentage of surfactant in S mix Nanoemulsions developed with non-ionic surfactants were stabilized mainly via steric mechanism, although an electrostatic mechanism cannot be ruled out.
The origin of negative zeta potential of nanoemulsions might be due to preferential adsorption or desorption of electrolyte ions on the surface On increasing the concentration of Tween 80, an increase in negative value of zeta potential might be associated with the presence of impurities, i. Transmission electron microscopy TEM study revealed the droplet morphology of the developed nanoemulsion. Nanoemulsion droplets were observed to be discrete, round in outline and dark in appearance in the photomicrographs. Refractive index RI is the measure of the speed of light through a substance.
The harder it is for light to travel through a medium i. Thus, RI indicates the isotropic nature of the formulation. As the concentration of oil was increased in the formulation, RI was observed to be increased in Table IV The obtained rheogram viscosity vs.
Among different nanoemulgels, NEG 0. Nanoemulgel, NEG 1 , was found to be a creamy and viscous preparation having a smooth homogeneous texture, glossy appearance and no sign of phase separation. Viscosity values of NEG 0. The values of spreadability indicated that the nanoemulgel was easily spreadable by an application of a small amount of shear.
On increasing the concentration of gelling agent, decrease in spreadability was observed 14 , The more the gel is extruded, the better was the extrudability; hence, less amount of force was required to extrude the gel easily. The higher the value of firmness, the thicker is the consistency of a sample. On the basis of the above evaluation parameters, NEG 1 was optimized and selected for further studies.
The three-dimensional rigid structure of NEG 1 showed sustained release of drug as compared to NE3, which released almost all drug within the prescribed period. Cumulative drug permeated from NEG 1 through goat hoof was more than NE3 and drug suspension due to the presence of permeation enhancer thioglycolic acid in the final formulation nanoemulgel , which cleaves the disulphide bonds between the keratin molecules and increases the partitioning of the drug molecule As the drug was poorly aqueous and soluble, we choose DMSO as the solvent for dissolving the drug for determining the antifungal activity in vitro.
DMSO itself possesses antifungal activity. Skin irritation study conducted on rats showed that during the h observation period, no evidence of irritation erythema and edema was observed on visual inspection after the application of nanoemulgel on rat skin. Thus, the developed formulation was non-sensitizing and safe for topical use. In the histopathological analysis of rat skin, the microstructure of normal skin Fig. As stratum corneum plays a major role in preventing the permeation of drugs, its disruption may enhance the permeation of applied formulation through the skin, suitable for its topical delivery Optimized nanoemulsion NE3 was formulated into nanoemulgel NEG 1 with desirable viscosity, spreadability, extrudability, texture and bio-adhesion, as compared to drug suspension for topical application.
In vitro release and ex vivo permeation study of the optimized nanoemulgel NEG 1 showed better efficacies, as compared to drug suspension. The optimized nanoemulgel NEG 1 showed enhanced in vitro antifungal activity on T. Further, skin irritation study showed the safe use of nanoemulgel for topical applications. Thus, nanoemulgel is a safe, effective and promising formulation for the topical treatment of onychomycosis.
We sincerely acknowledge the kind help form Dr.
The authors declare that they have no competing interests and have received no payment for the preparation of this manuscript. Skip to main content Skip to sections. Advertisement Hide. Download PDF. Research Article First Online: 08 February Formulation Development of Nanoemulsion Screening of Components The criterion for screening of components was the solubility of KCZ in different oils, surfactants and co-surfactants Table I.
The supernatant was filtered through a 0. Spreadability was determined by using an apparatus suggested by Mutimer et al. There was a wooden block and a pulley attached to it at one end. S Spreadability M Weight applied to upper slide L Length of glass slide T Time taken to separate the slides completely from each other. It is a test to measure the force required to extrude the gel from the tube. On the application of weight, the amount of gel extruded from the aluminium tube was determined. The nanoemulgel extruded should be at least 0.
The higher the quantity of gel extruded, the better is the extrudability. Tween 80 and PEG were used as the surfactant and co-surfactant, respectively, since they showed the maximum drug solubility, i. Four phase diagrams were prepared with the , , and weight ratios of S mix Tween PEG , as shown in Fig. Oil phase and S mix were then mixed in the weight ratios of to Sixteen different combinations , , , , , , The prepared nanoemulsion formulations were then subjected to stress-stability testing.
After subjecting to heating-cooling cycle, centrifugation and freeze-thaw cycle, those formulations which passed the test Table II , and showed stability, were further characterized. On increasing the number of cycles to 4, no further considerable size reduction was observed. Open image in new window.
C0 crude nanoemulsion It showed that formulations were clear and transparent. After the evaluation of nanoemulsion formulations, optimized formulation NE3 was selected for the stability studies and further formulated into a nanoemulgel. No phase separation and flocculation were observed, proving its stable nature.
The pH values for NEG 0. Viscosities for NEG 0.
Spreadability values for NEG 0. Extrudabilities of NEG 0. Topical nail products and ungual drug delivery.. No portion of this article can be reproduced without the express written permission from the copyright holder. Topics: Books. Capitalist diversity on Europe's periphery. Figure 3. Figure 4. Table 4 Porosity and correlation values for untreated and treated nails.
Figure 5. Figure 6. Figure 7. Example of images of the angle obtained at different times with water and SLS. Figure 8. Figure 9. Figure Patents This work is part of the submitted patent WOA1. Click here for additional data file. Author Contributions E.
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