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 microg 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 microm, with equilibrium solubilities spanning from 5 microg/ml (dipyridamole) to 911 microg/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.

Powder dissolution method for estimating rotating disk intrinsic dissolution rates of low solubility drugs.

PURPOSE: The objective was to investigate the applicability and limitations of a novel approach for measuring intrinsic dissolution rates (IDR) of very small quantities of compounds introduced as powders to buffered solutions and comparing these results to disk IDR obtained using the traditional Wood's apparatus. METHODS: The powder dissolution profiles of 13 model drugs were determined at 37 degrees C in USP buffers at pH 1.2, 4.5, and 6.8, stirred at 100 RPM. As little as 0.06 mg of drug were added to 1 mL buffer media. Drug concentration was measured by an in situ fiber optic UV method. The results were converted to rotating disk IDR values by a novel mathematical procedure. RESULTS: The comparison of the powder-based IDR values to those obtained by traditional Wood's apparatus indicated r(2) = 0.97 (n = 26). CONCLUSION: The results demonstrate that using potentially 10,000-fold less drug material does not sacrifice the quality of the measurement, and lends support to an earlier study that the disk IDR measurement may possibly serve as a surrogate for the BCS solubility classification.