Volume 26, Number 9, 2093-2100, DOI: 10.1007/s11095-009-9921-3

Powder Dissolution Method for Estimating Rotating Disk Intrinsic Dissolution Rates of Low Solubility Drugs

Konstantin Tsinman, Alex Avdeef, Oksana Tsinman and Dmytro Voloboy

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Abstract

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°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 r2 = 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.

Key words  Biopharmaceutics classification system - Low solubility - Powder IDR - Rotating disk intrinsic dissolution rate - Wood’s apparatus

Part 5 in the API-Sparing Dissolution Method series from pION. Avdeef and Tsinman11 is part 4 in the series.

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