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目的:测定醋酸氯地孕酮(CA)的平衡溶解度及表观油水分配系数,为CA新剂型的体外评价进行处方前研究。方法:采用高效液相色谱法测定CA在水及不同pH(1·2、2·0、3·0、4·5、5·5、6·8、7·4、8·0)介质及常用9种有机溶剂(包括甲醇、乙醇等)中的平衡溶解度;采用摇瓶法测定其在正辛醇与水及各pH介质组成的体系中的表观油水分配系数(P)。结果:37℃时,CA在水及9种pH值介质中的平衡溶解度依次为0·473、0·533、0·423、0·056、0·309、0·428、0·447、0·428、0·448μg·mL-1,在甲醇、乙醇等中的平衡溶解度为7320·61～344248·70μg·mL-1;CA在水中的lgP值为4·05,不同pH条件下的lgP值差别不大(4·11～4·25)。结论:CA不溶于水,易溶于有机溶剂,在弱酸环境下有一定程度的降解;且其lgP值较大,提示在制剂研究中需采用适当的增溶手段。
OBJECTIVE: To determine the equilibrium solubility and apparent oil-water partition coefficient of chlormadinone acetate (CA) for pre-prescription study in vitro. Methods: The content of CA in water and different pH (1 · 2,2 · 0,3 · 0,4 · 5,5 · 5,6 · 8,7 · 4,8 · 0) media and The equilibrium solubility of 9 organic solvents (including methanol, ethanol, etc.) was used. The apparent water-oil partition coefficient (P) was determined by shaking flask method in a system composed of n-octanol and water and each pH medium. Results: At 37 ℃, the equilibrium solubility of CA in water and nine pH media were 0 473, 0 533, 0 423, 0 056, 0 309, 428 0, 447 0 · 428,0 · 448μg · mL-1, the equilibrium solubility in methanol, ethanol and so on was 7320 · 61 ~ 344248 · 70μg · mL-1; the lgP value of CA in water was 4.05, the lgP The difference is not significant (4.11 ~ 4.25). CONCLUSION: CA is insoluble in water, soluble in organic solvents and degraded to a certain degree under weak acid environment. And its lgP value is large, suggesting that suitable solubilization means should be used in the formulation research.