Powder Dissolution Method for Estimating Rotating Disk Intrinsic Dissolution Rates of Low Solubility Drugs
- 1.4k Downloads
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.
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.
The comparison of the powder-based IDR values to those obtained by traditional Wood’s apparatus indicated r2 = 0.97 (n = 26).
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 wordsBiopharmaceutics classification system Low solubility Powder IDR Rotating disk intrinsic dissolution rate Wood’s apparatus
We thank Christel Bergström and Per Artursson of Uppsala University and Per Nielsen of pION for helpful discussions and suggestions regarding the API-sparing dissolution methodology.
- 1.Guidance for Industry. Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System. Washington, D.C., USA: FDA; 2000.Google Scholar
- 9.The United States Pharmacopeia (USP 32). United States Pharmacopeial Convention, Inc., Rockville, MD, 2009.Google Scholar
- 12.Avdeef A, Tsinman K, Tsinman O, Sun N, Voloboy D. Miniaturization of Powder Dissolution Measurement and Estimation of Particle Size. Chem. Biodiv. 2009. In press.Google Scholar
- 13.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.Google Scholar
- 14.Bijlani V, Yuonaye D, Katpally S, Chukwumezie BN, Adeyeye MC. Monitoring ibuprofen release from multiparticulates: in situ fiber-optic technique versus the HPLC method. AAPS Pharm.Sci.Tech. 2007, 8, Article 52 (http://www.aapspharmscitech.org).
- 16.Carstensen JT, Advanced Pharmaceutical Solids. Marcel Dekker, New York, 2001, pp. 51–88, 191–208.Google Scholar
- 21.Nernst W. Theorie der reaktionsgeschwindigkeit in heterogenen systemen. Z Phys Chem. 1904;47:52–55.Google Scholar
- 22.Brünner E. Reaktionsgeschwindigkeit in heterogenen systemen. Z Phys Chem. 1904;47:56–102.Google Scholar
- 29.Levich VG. Physiochemical Hydrodynamics. Englewood Cliffs, N. J: Prentice-Hall; 1962. p. 39–72.Google Scholar
- 30.Avdeef A, Absorption and Drug Development. Wiley-Interscience. NJ: Hoboken; 2003.Google Scholar