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At present, the development of many of the compounds constrained parameters of the physical and chemical properties that they have poor bio-pharmaceutical properties. To avoid consuming a lot of time and money to study these compounds can be screened from the point of view of the biopharmaceutical excellent new chemical entity that is measured physicochemical parameters, such as solubility, oil-water partition coefficient and stability. SX004 for domestic and foreign R \u0026 D for the first time Kayaku 1.1 new chemical entities. Drug widely used in clinical treatment of chronic myeloid leukemia, rapid onset than the first generation of leukemia drug imatinib, gefitinib efficacy of imatinib and second-generation leukemia drug Nile. At present, domestic and not yet reported in the literature. This article from the the SX004's solid-state characterization, liquid characterization and raw materials compatibility be more systematic and in-depth research. HPLC separation system and the establishment of quantitative methodology in accordance with the principle of ternary mobile phase after the first two yuan screening acetonitrile - phosphate binary buffer system, pH of the aqueous phase through a fixed proportion of the organic phase to adjust ratio of 35, according to the indicator of the tailing factor, the detection and separation of the impurities, and the theoretical plate number, selecting the optimal water phase pH = 6.5, then fine-tuning of the proportion of the organic and aqueous phases according to the retention time, to determine the organic phase %. After a ternary system acetonitrile - methanol - phosphate system, but the results are poor, this chapter filter out the best mobile phase: acetonitrile - water (0.5% triethylamine, phosphoric acid to adjust the pH to 6.5) (35 : 65); and its method validation system, which screened for drug prescriptions, the quality of research and Stability of providing accurate, precise, stable detection method. Equilibrium solubility determination in Chapter first measured SX004 solubility in polar solvents, and operate in accordance with the two of the 2010 edition of \solubility greater. Second, in order to further the understanding of the SX004 dissolves in the body, therefore, according to the different pH environment of the gastrointestinal tract, was studied at different pH phosphate buffer SX004 dissolved, and found, SX004 as the pH increases, solubility decreases . In Chapter IV of dissociation constants, depending on the nature of the SX004 free base, the choice of applicable to insoluble compound non-titration method, using the different proportions of methanol - water as a solvent, 0.01mol · L -1 HCl as titrant is titrated. Benet calculated pK b . The results show that the SX004 pK b , free base, 7.743. Chapter V Determination of oil-water partition coefficient, octanol - water simulation system, the the shake flask law-HPLC method, determination of the allocation balance after the drug concentration in the aqueous phase, calculated SX004 Pow. The results showed that when the aqueous phase pH LT; 6.0, the logP LT; 0 and almost unchanged, mainly present in the aqueous phase; when the aqueous phase 6.0 ≤ pH ≤ 7.0, logP is increased with the increase in pH; When the water phase pH GT; 7.0, logP almost unchanged, mainly present in the oil phase. Chapter SX004 hygroscopic test, in order to understand the SX004 hygroscopic, using 25 ℃, relative humidity, respectively RH33.0%, 43.2%, 57.7%, 75.3%, 84.3%, 93.6% conditions determination The SX004 of the absorbent Percentage draw moisture equilibrium curve of CRH geometric calculations. The results show that the SX004's critical relative humidity of 63.33%, extremely hygroscopic. Chapter VII in order to filter out accessories that do not affect the drug stability and, ultimately, to determine the basic prescription drug materials ratio selected raw materials compatibility test, according to accessories type stand for 30 days at 40 ℃, 75%, HPLC determination of content and related substances change. The results show that the SX004 compatible excipients microcrystalline cellulose, low substituted hydroxypropyl cellulose, carboxymethyl cellulose, talc. Chapter VIII the preliminary investigation SX004 stability, the test results of the influencing factors, the SX004 on high humidity sensitive, extremely hygroscopic. Based on the above results, the SX004 aluminum-plastic packaging, placed in 40 ° C, 75% of constant temperature and humidity meter accelerated three-month expedition, the results show that its Appearance, humidifiers, there were no significant changes in content and related substances.
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