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.
KEY WORDS Biopharmaceutics Classification System - buffer capacity - low solubility - rotating disk intrinsic dissolution rate - Wood’s apparatus
Part 4 in the API-Sparing Dissolution Method series from pION. Berger et al. (28) is Part 3 in the series.