Skip to main content
Log in

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

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  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 

  2. Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12:413–420.

    Article  PubMed  CAS  Google Scholar 

  3. Kostewicz ES, Wunderlich M, Brauns U, Becker R, Bock T, Dressman JB. Predicting the precipitation of poorly soluble weak bases upon entry in the small intestine. J Pharm Pharmacol. 2004;56:43–51.

    Article  PubMed  CAS  Google Scholar 

  4. 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.

    Article  PubMed  CAS  Google Scholar 

  5. Dressman JB, Amidon GL, Reppas C, Shah VP. Dissolution testing as a prognostic tool for oral drug absorption: immediate release dosage forms. Pharm Res. 1998;15:11–22.

    Article  PubMed  CAS  Google Scholar 

  6. Wood JH, Syarto JE, Letterman H. Improved holder for disk intrinsic dissolution rate studies. J Pharm Sci. 1965;54:1068.

    Article  PubMed  CAS  Google Scholar 

  7. Serajuddin ATM, Jarowski CI. Effect of diffusion layer pH and solubility on the dissolution rate of pharmaceutical bases and their hydrochloride salts I: phenazopyridine. J Pharm Sci. 1985;74:142–147.

    Article  PubMed  CAS  Google Scholar 

  8. Jinno J, Oh D-M, Crison JR, Amidon GL. Dissolution of ionizable water-insoluble drugs: the combined effect of pH and surfactant J. Pharm Sci. 2000;89:268–274.

    Article  CAS  Google Scholar 

  9. The United States Pharmacopeia (USP 32). United States Pharmacopeial Convention, Inc., Rockville, MD, 2009.

  10. Noyes AS, Whitney WR. The rate of solution of solid substances in their own solutions. J Amer Chem Soc. 1897;19:930–934.

    Article  Google Scholar 

  11. Avdeef A, Tsinman O. Miniaturized rotating disk intrinsic dissolution rate measurement: effects of buffer capacity in comparisons to traditional Wood’s apparatus. Pharm. Res. 2008;25:2613–2627.

    Article  PubMed  CAS  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.

  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).

  15. Pedersen PV, Brown KF. Theoretical isotropic dissolution of nonspherical particles. J Pharm Sci. 1976;85:1437–1442.

    Article  Google Scholar 

  16. Carstensen JT, Advanced Pharmaceutical Solids. Marcel Dekker, New York, 2001, pp. 51–88, 191–208.

  17. Mosharraf M, Nyström C. The effect of particle size and shape on the surface specific dissolution rate of micronized practically insoluble drugs. Int J Pharm. 1995;122:35–47.

    Article  CAS  Google Scholar 

  18. Galli C. Experimental determination of the diffusion boundary layer with micron and submicron particles. Int J Pharm. 2006;313:114–122.

    Article  PubMed  CAS  Google Scholar 

  19. Jashnani RN, Byron PR, Dalby RN. Validation of an improved Wood’s rotating disk dissolution apparatus. J. Pharm. Sci. 1993;82:670–671.

    Article  PubMed  CAS  Google Scholar 

  20. Dokoumetzidis A, Macheras P. A century of dissolution research: from Noyes and Whitney to the Biopharmaceutics Classification System. Int J Pharm. 2006;321:1–11.

    Article  PubMed  CAS  Google Scholar 

  21. Nernst W. Theorie der reaktionsgeschwindigkeit in heterogenen systemen. Z Phys Chem. 1904;47:52–55.

    CAS  Google Scholar 

  22. Brünner E. Reaktionsgeschwindigkeit in heterogenen systemen. Z Phys Chem. 1904;47:56–102.

    Google Scholar 

  23. Hixson A, Crowell J. Dependence of reaction velocity upon surface and agitation. I. Theoretical considerations. Ind Eng Chem. 1931;23:923–931.

    Article  CAS  Google Scholar 

  24. Higuchi WI, Hiestand EN. Dissoluiton rates of finely divided powders I. Effect of particle sizes in a diffusion process. J Pharm Sci. 1963;52:67–71.

    Article  PubMed  CAS  Google Scholar 

  25. Pedersen PV, Brown KF. General class of multiparticulate dissolution models. J Pharm Sci. 1975;64:1435–1438.

    Article  Google Scholar 

  26. Lu AT, Frisella ME, Johnson KC. Dissolution modelling: factors affecting the dissolution rates of polydisperse powders. Pharm Res. 1993;10:1308–1314.

    Article  PubMed  CAS  Google Scholar 

  27. Tinke AP, Vanhoutte K, De Maesschalck R, Verheyen S, De Winter H. A new approach in the prediction of the dissolution behaviour of suspended particles by means of the particle size distribution. J Pharm Biomed Anal. 2005;39:900–907.

    Article  PubMed  CAS  Google Scholar 

  28. Okazaki A, Mano T, Sugano K. The theoretical model of poly-disperse drug particles in biorelevant media. J Pharm Sci. 2008;97:1843–1852.

    Article  PubMed  CAS  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 

  31. Sheng JJ, Kasim NA, Chandrasekharan R, Amidon GL. Solubilization and dissolution of insoluble weak acid, ketoprofen: effect of pH combined with surfactant. Eur J Pharm Sci. 2006;29:306–314.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alex Avdeef.

Additional information

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

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tsinman, K., Avdeef, A., Tsinman, O. et al. Powder Dissolution Method for Estimating Rotating Disk Intrinsic Dissolution Rates of Low Solubility Drugs. Pharm Res 26, 2093–2100 (2009). https://doi.org/10.1007/s11095-009-9921-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-009-9921-3

Key words

Navigation