Preparation and evaluation of miconazole nitrate-loaded solid lipid nanoparticles for topical delivery

Abstract

The purpose of this study was to prepare miconazole nitrate (MN) loaded solid lipid nanoparticles (MN-SLN) effective for topical delivery of miconazole nitrate. Compritol 888 ATO as lipid, propylene glycol (PG) to increase drug solubility in lipid, tween 80, and glyceryl monostearate were used as the surfactants to stabilize SLN dispersion in the SLN preparation using hot homogenization method. SLN dispersions exhibited average size between 244 and 766 nm. All the dispersions had high entrapment efficiency ranging from 80% to 100%. The MN-SLN dispersion which showed good stability for a period of 1 month was selected. This MN-SLN was characterized for particle size, entrapment efficiency, and X-ray diffraction. The penetration of miconazole nitrate from the gel formulated using selected MN-SLN dispersion as into cadaver skins was evaluated ex-vivo using franz diffusion cell. The results of differential scanning calorimetry (DSC) showed that MN was dispersed in SLN in an amorphous state. The MN-SLN formulations could significantly increase the accumulative uptake of MN in skin over the marketed gel and showed a significantly enhanced skin targeting effect. These results indicate that the studied MN-SLN formulation with skin targeting may be a promising carrier for topical delivery of miconazole nitrate.

Fig. 1

Particle size distribution curve of sample A

Fig. 2

Differential scanning thermograms of bulk material of miconazole nitrate (a), compritol 888 ATO (b), and MN-SLNs (c)

Fig. 3

X-ray diffractograms of bulk material of miconazole nitrate (a), compritol 888 ATO (b), and MN-SLNs (c)

Fig. 4

Fourier transform infrared spectrums: (a) bulk material of miconazole nitrate, (b) MN-loaded lipid nanoparticles, and (c) Bulk material of compritol 888 ATO

Fig. 5

Thixotropic behavior of gels containing MN-SLNs (a) at 5°C, (b) at 25°C, and (c) at 40°C

Fig. 6

Ex-vivo release of miconazole nitrate from marketed and SLN gels of 2% miconazole nitrate

Fig. 7

Comparison of the drug levels from ex-vivo skin penetration studies: (a) receptor compartment, (b) remained on the skin, and (c) penetrated in the skin