Skip to main content
SpringerLink
Log in

A Refined Thin-Film Model for Drug Dissolution Considering Radial Diffusion – Simulating Powder Dissolution

  • Original Research Article
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose

We aim to present a refined thin-film model describing the drug particle dissolution considering radial diffusion in spherical boundary layer, and to demonstrate the ability of the model to describe the dissolution behavior of bulk drug powders.

Methods

The dissolution model introduced in this study was refined from a radial diffusion-based model previously published by our laboratory (So et al. in Pharm Res. 39:907–17, 2022). The refined model was created to simulate the dissolution of bulk powders, and to account for the evolution of particle size and diffusion layer thickness during dissolution. In vitro dissolution testing, using fractionated hydrochlorothiazide powders, was employed to assess the performance of the model.

Results

Overall, there was a good agreement between the experimental dissolution data and the predicted dissolution profiles using the proposed model across all size fractions of hydrochlorothiazide. The model over-predicted the dissolution rate when the particles became smaller. Notably, the classic Nernst-Brunner formalism led to an under-estimation of the dissolution rate. Additionally, calculation based on the equivalent particle size derived from the specific surface area substantially over-predicted the dissolution rate.

Conclusion

The study demonstrated the potential of the radial diffusion-based model to describe dissolution of drug powders. In contrast, the classic Nernst-Brunner equation could under-estimate drug dissolution rate, largely due to the underlying assumption of translational diffusion. Moreover, the study indicated that not all surfaces on a drug particle contribute to dissolution. Therefore, relying on the experimentally-determined specific surface area for predicting drug dissolution is not advisable.

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

Access this article

Log in via an institution

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
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Dokoumetzidis A, Macheras P. A century of dissolution research: from Noyes and Whitney to the biopharmaceutics classification system. Int J Pharm. 2006;321(1–2):1–11.

    Article  CAS  PubMed  Google Scholar 

  2. Siepmann J, Siepmann F. Mathematical modeling of drug dissolution. Int J Pharm. 2013;453(1):12–24.

    Article  CAS  PubMed  Google Scholar 

  3. Nernst W. Theorie der Reaktionsgeschwindigkeit in heterogenen Systemen. Z Phys Chem. 1904;47(1):52–5.

    Article  CAS  Google Scholar 

  4. Noyes AA, Whitney WR. The rate of solution of solid substances in their own solutions. J Am Chem Soc. 1897;19(12):930–4.

    Article  Google Scholar 

  5. Sugano K. Aqueous boundary layers related to oral absorption of a drug: from dissolution of a drug to carrier mediated transport and intestinal wall metabolism. Mol Pharm. 2010;7(5):1362–73.

    Article  CAS  PubMed  Google Scholar 

  6. Armenante PM, Kirwan DJ. Mass transfer to microparticles in agitated systems. Chem Eng Sci. 1989;44(12):2781–96.

    Article  CAS  Google Scholar 

  7. Assunção M, Vynnycky M, Moroney KM. On the dissolution of a solid spherical particle. Phys Fluids. 2023;35(5):053605.

  8. Wang J, Flanagan DR. General solution for diffusion-controlled dissolution of spherical particles. 1. Theory. J Pharm Sci. 1999;88(7):731–8.

    Article  CAS  PubMed  Google Scholar 

  9. So C, Chiang P-C, Mao C. Modeling drug dissolution in 3-dimensional space. Pharm Res. 2022;39(5):907–17.

    Article  CAS  PubMed  Google Scholar 

  10. Wang J, Flanagan DR. General solution for diffusion-controlled dissolution of spherical particles. 2. Evaluation of experimental data. J Pharm Sci. 2002;91(2):534–42.

    Article  CAS  PubMed  Google Scholar 

  11. Crank J. The mathematics of diffusion. Bristol: Oxford University Press; 1975.

    Google Scholar 

  12. Anderberg E, Bisrat M, Nyström C. Physicochemical aspects of drug release. VII. The effect of surfactant concentration and drug particle size on solubility and dissolution rate of felodipine, a sparingly soluble drug. Int J Pharm. 1988;47(1–3):67–77.

    Article  CAS  Google Scholar 

  13. Anderberg E, Nyström C. Physicochemical aspects of drug release: X. Investigation of the applicability of the cube root law for characterization of the dissolution rate of fine particulate materials. Int J Pharm. 1990;62(2–3):143–51.

    Article  CAS  Google Scholar 

  14. Bisrat M, Nyström C. Physicochemical aspects of drug release. VIII. The relation between particle size and surface specific dissolution rate in agitated suspensions. Int J Pharm. 1988;47(1–3):223–31.

    Article  CAS  Google Scholar 

  15. De Almeida LP, Simões S, Brito P, Portugal A, Figueiredo M. Modeling dissolution of sparingly soluble multisized powders. J Pharm Sci. 1997;86(6):726–32.

    Article  PubMed  Google Scholar 

  16. Hintz RJ, Johnson KC. The effect of particle size distribution on dissolution rate and oral absorption. Int J Pharm. 1989;51(1):9–17.

    Article  CAS  Google Scholar 

  17. Chu KR, Lee E, Jeong SH, Park E-S. Effect of particle size on the dissolution behaviors of poorly water-soluble drugs. Arch Pharmacal Res. 2012;35:1187–95.

    Article  CAS  Google Scholar 

  18. Avdeef A. Leakiness and size exclusion of paracellular channels in cultured epithelial cell monolayers-interlaboratory comparison. Pharm Res. 2010;27(3):480–9.

    Article  CAS  PubMed  Google Scholar 

  19. Grymonpré W, Verstraete G, Vanhoorne V, Remon JP, De Beer T, Vervaet C. Downstream processing from melt granulation towards tablets: In-depth analysis of a continuous twin-screw melt granulation process using polymeric binders. Eur J Pharm Biopharm. 2018;124:43–54.

    Article  PubMed  Google Scholar 

  20. Gray V, Kelly G, Xia M, Butler C, Thomas S, Mayock S. The science of USP 1 and 2 dissolution: present challenges and future relevance. Pharm Res. 2009;26:1289–302.

    Article  CAS  PubMed  Google Scholar 

  21. Higuchi WI. Diffusional models useful in biopharmaceutics: drug release rate processes. J Pharm Sci. 1967;56(3):315–24.

    Article  CAS  Google Scholar 

  22. Sugano K. Introduction to computational oral absorption simulation. Expert Opin Drug Metab Toxicol. 2009;5(3):259–93.

    Article  CAS  PubMed  Google Scholar 

  23. Jia W, Yawman PD, Pandya KM, Sluga K, Ng T, Kou D, Nagapudi K, Luner PE, Zhu A, Zhang S, Hou HH. Assessing the interrelationship of microstructure, properties, drug release performance, and preparation process for amorphous solid dispersions via noninvasive imaging analytics and material characterization. Pharm Res. 2022;39(12):3137–54.

    Article  CAS  PubMed  Google Scholar 

  24. Levich VG. Physicochemical hydrodynamics:(by) veniamin G. Levich. Transl. by Scripta Technica, Inc. Englewood Cliffs: Prentice-Hall; 1962.

  25. Shekunov B, Montgomery ER. Theoretical analysis of drug dissolution: I. Solubility and intrinsic dissolution rate. J Pharm Sci. 2016;105(9):2685–97.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Synthetic Molecule Pharmaceutical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA

    Karthik Salish, Chi So, Hao Helen Hou & Chen Mao

  2. BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Gyeonggi, 10326, Republic of Korea

    Seong Hoon Jeong

Authors
  1. Karthik Salish
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chi So
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seong Hoon Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hao Helen Hou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chen Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chen Mao.

Ethics declarations

Competing Interests

The authors declare that they have no conflicts of interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Salish, K., So, C., Jeong, S.H. et al. A Refined Thin-Film Model for Drug Dissolution Considering Radial Diffusion – Simulating Powder Dissolution. Pharm Res (2024). https://doi.org/10.1007/s11095-024-03696-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11095-024-03696-0

Keywords

Search

Navigation