Transcutol® P/Cremophor® EL/Ethyl Oleate-Formulated Microemulsion Loaded into Hyaluronic Acid-Based Hydrogel for Improved Transdermal Delivery and Biosafety of Ibuprofen.

In the present study, a novel transdermal delivery system was developed and its advantages were demonstrated. Ibuprofen is a commonly used anti-inflammatory, antipyretic, and analgesic drug; however, because of its short biological half-life, it must be frequently administered orally and is highly irritating to the digestive tract. To prepare a novel transdermal delivery system for ibuprofen, a microemulsion was used as a drug carrier and dispersed in a hyaluronic acid-based hydrogel (ME/Gel) to increase percutaneous drug absorption while avoiding gastrointestinal tract irritation. The prepared microemulsion had a droplet size of ~ 90 nm, and the microemulsion had good stability in the hydrogel. Rheological tests revealed that the ME/Gel is a pseudoplastic fluid with decreased viscosity and increased shear rate. It displayed a certain viscoelasticity, and the microemulsion distribution displayed minor effects on the rheological characteristics of the hydrogel system. There was no significant difference in the rheology of the ME/Gel at 25°C and 32°C (normal skin surface temperature), which is beneficial for clinical application. Drug transdermal flux was significantly higher than that of the hydrogel and commercial cream groups (p < 0.01). The 24-h cumulative drug permeation amount was 1.42-fold and 2.52-fold higher than that of the hydrogel and cream groups, respectively. By loading into the ME/Gel, the cytotoxicity of the drug to HaCaT cells was reduced. These results indicate that the prepared ME/Gel can effectively improve transdermal ibuprofen delivery and the biosafety of the drug and could therefore have applicability as a drug delivery system.