羟基酪醇丁酸酯的处方前研究

Objective: To determine the apparent oil/water(O/W)partition coefficient of hydroxytyrosol butyrate(HT-Bu), and investigate the solubility, dissolution tendency and stability of HT-Bu in different buffers, so as to provide theoretical basis for the preparation research of HT-Bu. Methods: The appearance and solubility of HT-Bu were investigated, and a high performance liquid chromatography(HPLC)method was established for the quantitative determination of HT-Bu. The solubility and O/W partition coefficient of HT-Bu in different pH buffer solutions were determined by the shakeing flask method. Results: HT-Bu was slightly yellow-colored, viscous, odorless and tasteless oily liquid. The quantitative HPLC method for the HT-Bu determination showed a good linearity within the concentration range of 5-50 μg/ml(r=0.9998). The apparent O/W partition coefficient of HT-Bu was 1.0. In the acetonitrilewater(60:40, V/V) solution, HT-Bu was stable within 12 hours at room temperature. In the different pH buffer solutions(pH 2.0-9.0), the solubility of HT-Bu increased at first and then decreased with the increase of the solution pH. HT-Bu was unstable at pH 5.5, with a large amount decomposed after kept in the solution for 6 h. HT-Bu was stable at pH 8, 0 giving a little amount decomposed after 12 h in the solution, and stable at pH 7.4 showing no significant decomposition after 12 h keeping in the solution. Conclusion: HT-Bu showed a good water solubility, which is unstable in acidic and alkaline solutions.