RESUMEN
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.
RESUMEN
Objective: To perform a preformulation study for the novel antischizophrenic drug DT-195, so as to provide information for its formulation development. Methods: The scanning electron microscopy, X-ray powder diffraction, and the differential scanning calorimetry were used to characterize the appearance and crystalline form of DT-195, and the solubility was tested for DT-195 in different solutions. An HPLC method was established for the preformulation determination of DT-195. The apparent oil/water(O/W) partition coefficient of DT-195 and the equilibrium solubility of the drug under different pH conditions with high and low ion concentrations were determined using the established HPLC method. Results: DT-195 was an off-white crystalline powder, slightly soluble in water, with a good linearity with the peak area within the concentration range of 10-280 μg/ml(r=0.9997)in the HPLC analysis. DT- 195 was stable under acidic conditions and easily degradable under alkaline conditions. The apparent O/W partition coefficient of DT- 195 was 0.23. The solubility of DT-195 in solution decreased with the increase in the solution pH value or ion concentration. Conclusion: The established HPLC method is reliable for the determination of DT-195 and related substances with the high sensitivity, good specificity and the good separation of DT-195 and related substances. The present results have shown that DT-195 is a poorly soluble drug, and thus the improvement of DT-195 solubility in oral preparations will enhance the bioavailability in vivo.