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Miniaturized Rotating Disk Intrinsic Dissolution Rate Measurement: Effects of Buffer Capacity in Comparisons to Traditional Wood’s Apparatus

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Abstract

Purpose

The objective was to investigate the feasibility of using a miniaturized disk intrinsic dissolution rate (IDR) apparatus to determine the Biopharmaceutics Classification System (BCS) solubility class, and to develop an approach where IDR measurements performed in media of different buffer capacity could be compared.

Methods

The disk IDR values of 14 model drugs were determined at 37°C in US Pharmacopeia buffers at pH 1.2, 4.5, and 6.8. As little as 5 mg of drug were compressed in a die, with surface area of 0.071 cm2, with the die assembly rotated at 100 rpm in 10 mL media. Drug concentration was measured by an in situ fiber optic ultraviolet method. The solubilities and pKas were determined, and used to simulate dissolution profiles with a convective-diffusion-with-chemical-reaction model.

Results

The disk IDR values spanned six orders of magnitude (0.00014 to 114 mg min−1 cm−2). The comparison of the miniaturized disk IDR values to published results using traditional dissolution bath apparatus indicated r 2 = 0.99.

Conclusions

The results demonstrate that using 100-fold less drug does not sacrifice the quality of the measurement, and lends support to an earlier study Yu et al. (Int. J. Pharm. 270:221–227, 2004) that the disk IDR measurement may possibly serve as a surrogate for the BCS solubility classification.

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Authors and Affiliations

  1. pION INC, 5 Constitution Way, Woburn, Massachusetts, 01801, USA

    Alex Avdeef & Oksana Tsinman

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  1. Alex Avdeef
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  2. Oksana Tsinman
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Correspondence to Alex Avdeef.

Additional information

Part 4 in the API-Sparing Dissolution Method series from pION. Berger et al. (28) is Part 3 in the series.

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Avdeef, A., Tsinman, O. Miniaturized Rotating Disk Intrinsic Dissolution Rate Measurement: Effects of Buffer Capacity in Comparisons to Traditional Wood’s Apparatus. Pharm Res 25, 2613–2627 (2008). https://doi.org/10.1007/s11095-008-9679-z

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  • DOI: https://doi.org/10.1007/s11095-008-9679-z

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