Dissolution Profiles for Finely Divided Drug Suspensions

Abstract

□ A suspension of micronized prednisolone acetate was separated into four fractions by the technique of centrifugal elutriation. Data showed that each fraction had a narrow particle size. The dissolution experiments were carried out under sink conditions (<10% of saturation concentration) in a dissolution apparatus with a rotating filter assembly and a continuous circulation of filtered fluid samples through a recording spectrophotometer. The dissolution profile was highly reproducible and substantially different for each fraction. As expected, fractions with the smallest and largest particles showed the fastest and slowest dissolution, respectively. Almost the entire dissolution profiles for four small particle size fractions can be satisfactorily described by the Higuchi–Hiestand model with the dissolution rate constant, K, in the range of 1.5–2.0 × 10–9cm2/sec. This is ~3.5 times greater than the value for K calculated on the basis of reported reasonable values for diffusion coefficient, density, and solubility.