Clarke J M, Ramsay L E, Shelton J R, Tidd M J, Murray S, Palmer R F
J Pharm Sci. 1977 Oct;66(10):1429-32. doi: 10.1002/jps.2600661020.
The bioavailability of spironolactone from 10 tablet formulations, selected to provide a wide range of specifications and in vitro dissolution rates, was assessed from the plasma and urinary levels of its major unconjugated metabolite, canrenone, in a study of balanced incomplete block design using 11 healthy subjects. Significant but weak correlations existed between the amount of spironolactone in solution at 40 min in vitro and the area under the plasma concentration-time curve for canrenone and urinary canrenone excretion. The correlations between in vitro dissolution and bioavailability parameters appeared to be weakened by two tablet formulations, one with dibasic calcium phosphate as the principal excipient and the other formulated from micronized spironolactone bulk drug. Measurement of in vitro dissolution of spironolactone tablets is of value for quality control purposes, provided no major alteration is made in the formulation.
在一项采用平衡不完全区组设计的研究中，选取了10种片剂制剂（这些制剂具有广泛的规格和体外溶出速率），通过其主要非共轭代谢物坎利酮的血浆和尿液水平，评估了螺内酯的生物利用度，该研究纳入了11名健康受试者。体外40分钟时溶液中螺内酯的量与坎利酮的血浆浓度-时间曲线下面积以及尿中坎利酮排泄量之间存在显著但较弱的相关性。两种片剂制剂似乎削弱了体外溶出与生物利用度参数之间的相关性，一种以磷酸氢钙作为主要辅料，另一种由微粉化的螺内酯原料药制成。只要制剂没有重大改变，测定螺内酯片的体外溶出度对于质量控制是有价值的。
