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Comparison of the Disk Instrinsic Dissolution Rate Measurements using Traditional USP (900 mL, 500 mg: Yu et al. 2004) and Miniaturized (15 mL, 5 mg) Dissolution Apparatus, and its Relationship to the Biopharmaceutics Classification System

Alex Avdeef, pION INC, 5 Constitution Way, Woburn, MA 01801 USA

Measurement of intrinsic dissolution rate (IDR) profiles and/or solubility of sparingly soluble compounds at different pH values, as well as with presence of solubilizing/complexing excipients, by in situ fiber optic UV monitoring of the concentration of model drugs (without separation of precipitate from the solution) will be described. Also, comparisons between the literature values of IDR1 and values obtained on a new miniaturized system will be described. The FDA have shown interest to investigate whether IDR can be a substitute method for solubility class assessment in the Biopharmaceutic Classification System (BCS).¹

A novel method and instruments (µDISS Profiler and Mini-IDR)^2-4 were used to collect dissolution profiles in 2 15 mL of buffered media at different pH values with or without the presence of excipients for the low soluble compounds carbamazepine and griseofulvin (as powders and as compressed miniaturized pellets, using 5 mg of compound). The UV absorbance was corrected for background distortion and light scattering due to precipitation in the solution. It allowed in situ monitoring of the concentration of studied compounds in their saturated solutions as function of time, overcoming a longstanding problem in solubility measurement. This means no filtration or centrifugation was required.

The study demonstrated that in situ UV monitoring is highly versatile technique allowing to measure intrinsic dissolution profiles and/or equilibrium solubility of compounds while monitoring all kinetic peculiarities of dissolution/precipitation solution.

1 Yu LX, Carlin AS, Amidon GL, Hussain AS. Feasibility studies of utilizing disk intrinsic dissolution rate to classify drugs. Int. J. Pharm. 2004, 270, 221-227.
2 Avdeef A et al. Dissolution and Solubility. In: Testa, B., van de Waterbeemd, H. (Eds.). Comprehensive Medicinal Chemistry II, Vol. 5 ADME-TOX Approaches. Elsevier: Oxford, UK, 2007, pp. 399-423.
3 Avdeef A. Solubility of sparingly-soluble drugs. Dressman, J.; Reppas, C. (Eds., special issue: The Importance of Drug Solubility). Adv. Drug Deliv. Rev. 2007, 59, 568-590.
4 Avdeef A et al. Solubility–Excipient Classification Gradient Maps. Pharm. Res. 2007, 24, 530-545.

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Last modified: 28 April 2008