Improving the skin penetration and antifebrile activity of ibuprofen by preparing nanoparticles using emulsion solvent evaporation method

摘要

Abstract Ibuprofen (IBU) is an effective analgesic, non-steroidal anti-inflammatory drug. Unfortunately, oral IBU can cause adverse gastrointestinal drug reactions, such as bleeding and ulcerations, and increases the risk for stomach or intestinal perforations. In this study, IBU nanoparticles (IBU-NPs) were prepared through emulsion solvent evaporation and freeze-drying to improve their solubility. IBU nanoemulsion and nanosuspension were optimized through a single-factor experiment. IBU-NPs with a mean particle size of 216.9±10.7nm were produced under optimum conditions. These IBU-NPs were characterized by using scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and residual solvent determination to determine their solvent residue, equilibrium solubility, dissolution rate, in vitro transdermal rate, transdermal bioavailability, and antifebrile experiment for febrile rats. The morphological characteristic of IBU-NPs showed porous clusters. Analysis results indicated that the prepared IBU-NPs have low crystallinity. Residual amounts of ethanol and chloroform were 170 and 9.6ppm, respectively, which were less than the ICH limit for class II. Measurement analysis showed that the IBU-NPs were converted underwent amorphous states after preparation, but the chemical structure of the IBU-NPs was unchanged. Transdermal bioavailability of IBU in the IBU-NP group improved significantly compared with oral and transdermal raw IBU. Furthermore, the IBU-NP transdermal gel exhibited a high and stable cooling rate and a long cooling duration in febrile rats. In comparison with the raw oral IBU and raw IBU transdermal gel, the IBU-NP transdermal gel manifested better efficacy at low and mid doses. Basing from the results, we conclude that IBU-NPs can be applied in transdermal delivery formulations and have potential application value for non-oral administration. Graphical abstract Display Omitted