K C Johnson1, A C Swindell. 1. Department of Pharmaceutical Research and Development, Pfizer Central Research, Groton, Connecticut 06340, USA.
Abstract
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).
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).
Authors: Allen R Hilgers; Donald P Smith; John J Biermacher; Jeffrey S Day; Jana L Jensen; Sandra M Sims; Wade J Adams; Janice M Friis; Joe Palandra; John D Hosley; Eric M Shobe; Philip S Burton Journal: Pharm Res Date: 2003-08 Impact factor: 4.200
Authors: Ann F Hubbs; Linda M Sargent; Dale W Porter; Tina M Sager; Bean T Chen; David G Frazer; Vincent Castranova; Krishnan Sriram; Timothy R Nurkiewicz; Steven H Reynolds; Lori A Battelli; Diane Schwegler-Berry; Walter McKinney; Kara L Fluharty; Robert R Mercer Journal: Toxicol Pathol Date: 2013-02-06 Impact factor: 1.902