Miniaturization of Powder Dissolution Measurement and Estimation of Particle Size

The objective was to investigate the applicability and limitations of an approach for estimating particle size from powder dissolution measurement using as little as 50 μg of sample in 1 ml of buffer solutions. The powder dissolution profiles of five sparingly‐soluble drugs (hydrochlorothiazide, phenazopyridine hydrochloride, 2‐naphthoic acid, indomethacin, and dipyridamole) were evaluated with a novel biexponential spherical particle equation and also the Wang–Flanagan spherical particle non‐sink equation. The results were compared to particle sizing based on measured specific surface area by the Brunauer–Emmett–Teller (BET) method, and also based on Coulter counting. With the exception of hydrochlorothiazide, the model compounds indicated some agglomeration in the dissolution media. The dry‐state specific surface area was larger than expected from either the Coulter method or the powder‐dissolution data, especially for phenazopyridine hydrochloride. The particle radii estimated by the powder dissolution method ranged from 10 to 68 μm, with equilibrium solubilities spanning from 5 μg/ml (dipyridamole) to 911 μg/ml (hydrochlorothiazide). Powder dissolution data collected with the miniaturized apparatus can be used to determine particle size, with estimated values agreeing reasonably with those measured by the Coulter counter method.