The objective of this study was to explore the benefits of transdermal drug delivery systems as an alternative option for patients who are unable to tolerate oral administration of drugs, such as ibuprofen (IB). To achieve this, nonionic surfactants and three cosolvents were employed to develop new microemulsions (MEs) that contained IB as nanocarriers. The aim was to enhance the solubility and bioavailability of the drug after transdermal administration. The MEs were characterised by droplet size, polydispersity index (PDI), and rheological properties. Furthermore, the flux of IB was evaluated by Franz diffusion cells using excised rat skin and in vivo bioavailability using rats. The results showed that the MEs had ideal viscosity and droplet size below 100 nm. Moreover, using the developed MEs, an improvement in the solubility (170 mg/mL) and flux through the rat skin (94.6 ± 8.0 µg/cm.h) was achieved. In addition, IB demonstrated a maximum plasma level of 0.064 mg/mL after 8 h of transdermal administration in rats using the ME with an increase in the bioavailability of about 1.5 times in comparison to the commercial IB gel. In conclusion, the developed nonionic MEs containing IB can be ideal nanocarriers and promising formulations for the transdermal administration of IB.
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