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

摘要

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.