Abstract
The aim of the present study was to investigate the potential of nanoemulsion formulations for transdermal delivery of indomethacin (IND). Nanoemulsions formulations with different Surfactant: co surfactant ratios (S mix); F1-F6 (1:1, 2:2, 3:1, 4:1, 1:2 and 3:2) were prepared by the spontaneous emulsification method, and characterized for morphology using transmission electron microscopy (TEM), droplet size, and rheological characteristics. The ex vivo skin permeation studies were performed using Franz diffusion cell with rabbit skin as permeation membrane. A significant increase in the permeability parameters such as steady-state flux (Jss), permeability coefficient (Kp), and enhancement ratio (Er) was observed in nanoemulsion formulations compared with the conventional IND gel. The anti-inflammatory effects of nanoemulsion formulations showed a significant increase in percent inhibition value after 4 hours when compared with conventional IND gel on carrageenan-induced paw edema in rats. Significant increase in permeability parameters was observed in nanoemulsion formulations (P< 0.05). The steady-state flux (Jss) and permeability coefficient (Kp) for optimized nanoemulsion formulation (F1, 1:1 S mix were found to be 22.61±3.45 μg/ cm2/h and 0.22x10− 2 ±0.0003 cm/h, respectively), which were significant compared with conventional IND gel and (P< 0.001). Enhancement ratio (Er) was found to be 8.939 in optimized formulation F1 compared with IND gel. These results suggested that nanoemulsions can be used as potential vehicles for improved transdermal delivery of indomethacin as an approach to eliminate the side effect of the oral dose.
Highlights
Nanoemulsions (NE) have received a growing attention as colloidal drug carriers for pharmaceutical applications
Previous reports indicated that the superior dermal flux appeared mainly due to the large solubilizing capacity of the nanoemulsions, which led to larger concentration gradient towards the skin [24]
Isopropyl myristate (IPM) was an excellent enhancer in transdermal delivery as previously reported [28] and it was selected as the oil phase
Summary
Nanoemulsions (NE) have received a growing attention as colloidal drug carriers for pharmaceutical applications. Nanoemulsions have several advantages such as enhanced drug solubility, good thermodynamic stability, enhancing effect on transdermal ability over conventional formulation [18,26,41] nanoemulsions can accommodate both hydrophilic and lipophilic drugs [19,25,53]. Indomethacin, (IND) is a potent non-steroidal anti-inflammatory drug with analgesic and antipyretic properties. Like other NSAIDs, the most common side effect of indomethacin in oral dosage forms is gastrointestinal irritation. Alternative routes of administration for these drugs are being currently investigated. More attention has focused on nanoemulsions for transdermal delivery of drugs [11,16,27,31]
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