Preparation of high solubilizable microemulsion of naproxen and its solubilization mechanism

摘要

To improve the skin permeation of naproxen with larger dosage, microemulsion with high content of naproxen was investigated for transdermal delivery and its solubilization mechanism was studied. Naproxen micoremulsions composed of 4% isopropyl myristate, 18% Tween 80, 18% ethanol and water were prepared and phase inversion temperature (PIT) method was used to increase drug content. The using of PIT method resulted in the maximum content of naproxen in microemulsion increased from 1.98 ± 0.13% to 4.12 ± 0.07%, accordingly the permeation rate of naproxen from microemulsion through excised mice skin increased from 135.13 ± 5.50 to 214.46 ± 7.53 μg cm -2 h -1. The analyses of Natural Bond Orbital and interaction energy using the B3LYP and MP2 (fc) methods suggested that the solubilization mechanism of microemulsion for naproxen mainly might be the formation of complex between the hydrogen atom of hydroxyl in Tween 80 and the oxygen atom of carbonyl group in naproxen, as is in accordance with the result from 1H NMR experiments. The change of thermodynamic function with temperature confirmed that, because the complex was easy to be formed in high temperature and that formed at PIT became more stable when the temperature decreased to below PIT, the solubilization ability of microemulsion for naproxen could be improved by the PIT method. The powerful permeation enhancing ability of microemulsion induced by the solubilization of PIT method makes it a promising vehicle for the transdermal delivery of naproxen.