Guidance in the setting of drug particle size specifications to minimize variability in absorption

被引:130
作者
Johnson, KC [1 ]
Swindell, AC [1 ]
机构
[1] QUANTITAT SERV CO,GROTON,CT 06340
关键词
particle size; solubility; absorption rate constant; absorption; dose; simulation;
D O I
10.1023/A:1016068705255
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Purpose. To provide guidance in setting particle size specifications for poorly soluble drugs to minimize variability in absorption. Methods. A previously reported computer method was used to simulate the percent of dose absorbed as a function of solubility, absorption rate constant, dose, and particle size. Results. The simulated percent of dose absorbed was tabulated over a realistic range of solubilities, absorption rate constants, and doses using drug particle sizes that might be typically found in a dosage form. Conclusions. The greatest effect of particle size on absorption was simulated for low dose- low solubility drugs. In general, the sensitivity of absorption to particle size decreased with increasing dose or solubility. At a solubility of 1 mg/mL, particle size had practically no effect on the percent of dose absorbed over the range of doses simulated (1-250 mg).
引用
收藏
页码:1795 / 1798
页数:4
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