Co-polymer mixed micelles enhanced transdermal transport of Lornoxicam: in vitro characterization, and in vivo assessment of anti-inflammatory effect and antinociceptive activity

The objective of this study was to develop mixed micelles of Lornoxicam, using a Pluronic (R) mixture of L121 and P123. The technique used for the preparation was thin-film hydration according to a Box Behnken design with three central points for each formula. The independent variables studied were Pluronic (R): drug ratio, Pluronic (R) L121: Pluronic (R) P123 ratio and amount of soya-bean lecithin. The studied dependent variables were: percent entrapment efficiency (% EE), particle size (PS), poly-dispersity index (PDI), zeta potential (ZP) and in vitro LX released (after 2, 10 h). Numerical optimization was used to statistically optimize the formulae using Design-Expert (R) software. Choosing the best formula was in terms of maximizing % EE, ZP (as absolute value) and in vitro release, while minimizing PS and PDI. Characterization of best formula was performed by Transmission electron microscopy, Differential scanning calorimetry, Fourier transform infrared spectroscopy, stability testing, ex vivo permeation and skin deposition studies using rat skin. The in vivo pharmacodynamics activities of the optimized formula were examined on male rats and mice and related to that of the oral commercial product. The optimized formula demonstrated to be non-irritant, with considerably improved anti-inflammatory and analgesic activities. Higher in vivo skin permeation was confirmed using confocal laser scanning microscopy. In conclusion, the obtained results proved that mixed micelles could be promising method for transdermal drug delivery.