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Pharmaceutical Research

, Volume 21, Issue 12, pp 2300–2306 | Cite as

Reexamination of Convective Diffusion/Drug Dissolution in a Laminar Flow Channel: Accurate Prediction of Dissolution Rate

  • Paul J. Missel
  • Larry E. Stevens
  • John W. Mauger
Article

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Purpose.

The convective diffusion/dissolution theory applied to flow-through dissolution in a laminar channel was reexamined to evaluate how closely it can predict release rate for a model compound on an absolute basis—a comparsion that was lacking from the original literature observations reported from this technique.

Methods.

The theory was extended to allow for a finite flux of dissolving material, replacing the fixed concentration by a flux condition on the dissolving surface. The derivation introduces a new parameter, ks, an area-independent analog of the dissolution rate constant defined in the USP intrinsic dissolution procedure.

Results.

The release rate for ethyl-p-aminobenzoate originally observed fell within 10% of the absolute prediction assuming a solubility limited situation, and deviated from this prediction in a manner possibly consistent with a finite flux-limited condition, with ks ≈ 10−4 M s−1. For materials exhibiting lower ks values, the derivation suggests that at high flow rates, a limit occurs where dissolution rate becomes independent of shear rate and merely a function of solubility and surface area.

Conclusions.

The new parameter ks may be deduced from any set of geometric and flow conditions, provided the fluid velocity can be determined everywhere in the domain.

Key words:

convective diffusion dissolution dissolution rate intrinsic dissolution rate flow-through dissolution 

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References

  1. 1.
    1. USP 26 section <711> Dissolution, pp. 2155–2156.Google Scholar
  2. 2.
    2. USP 26 section <1087> Intrinsic Dissolution, pp. 2333–2334.Google Scholar
  3. 3.
    3. USP 26 section <724> Drug Release, pp. 2157–2165.Google Scholar
  4. 4.
    4. The Anecortave Acetate Clinical Study Group. Anecortave acetate as monotherapy for treatment of subfoveal neovascularization in age-related macular degeneration (AMD): 12 month clinical outcomes. Ophthalmol. 110:90–101 (2003).Google Scholar
  5. 5.
    5. J. H. Wood, J. E. Syarto, and H. Letterman. Improved holder for intrinsic dissolution rate studies. J. Pharm. Sci. 54:1068 (1965).Google Scholar
  6. 6.
    6. N. Khoury, J. W. Mauger, and S. Howard. Dissolution rate studies from a stationary disk/rotating fluid system. Pharm. Res. 5:495–500 (1988).Google Scholar
  7. 7.
    7. A. C. Shah and K. G. Nelson. Evaluation of a convective diffusion drug dissolution rate model. J. Pharm. Sci. 64:1518–1520 (1975).Google Scholar
  8. 8.
    8. K. G. Nelson and A. C. Shah. Convective diffusion model for a transport-controlled dissolution rate process. J. Pharm. Sci. 64:610–614 (1975).Google Scholar
  9. 9.
    9. V. Levich. Physicochemical Hydrodynamics, Prentice-Hall, Englewood Cliffs, NJ, 1962, p. 48.Google Scholar
  10. 10.
    10. K. G. Nelson and A. C. Shah. Mass transport in dissolution kinetics I: Convective diffusion to assess the role of fluid viscosity under force flow conditions. J. Pharm. Sci. 76:799–802 (1987).Google Scholar
  11. 11.
    11. A. C. Shah and K. G. Nelson. Mass transport in dissolution kinetics II: Convective diffusion to assess role of viscosity under conditions of gravitational flow. J. Pharm. Sci. 76:910–913 (1987).Google Scholar
  12. 12.
    12. P. J. Missel, L. E. Stevens and J. W. Mauger. Dissolution of anecortave acetate in a cylindrical flow cell: re-evaluation of convective diffusion/drug dissolution for sparingly soluable drugs. Pharm. Dev. Tech. 9:453–459 (2004).Google Scholar
  13. 13.
    13. R. B. Bird, W. E. Stewart, and E. N. Lightfoot. Transport Phenomena, Wiley, New York, 1960, pp. 551–552.Google Scholar

Copyright information

© Springer Science+Business Media, Inc. 2004

Authors and Affiliations

  • Paul J. Missel
    • 1
  • Larry E. Stevens
    • 1
  • John W. Mauger
    • 2
  1. 1.Drug Delivery, Alcon Research Ltd.Fort WorthUSA
  2. 2.University of UtahSalt Lake CityUSA

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