Preformulation study on novel antischizophrenic drug DT-195 / 国际药学研究杂志

ABSTRACT

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.