Skip to main content
SpringerLink
Log in

Polymer Percolation Threshold in HPMC Extended Release Formulation of Carbamazepine and Verapamil HCl

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

The principles of the percolation theory were applied to further understand and design hydroxypropyl methylcellulose (HPMC) extended release matrix tablets containing carbamazepine and verapamil HCl. This statistical theory studies disordered or chaotic systems where the components are randomly distributed in a lattice. The application of this theory to study the hydration and drug release of hydrophilic matrices allows describing the changes in hydration and drug release kinetics of swellable matrices. The aim of this work was to study and develop extended release matrix formulations for carbamazepine and verapamil HCl, containing hypromellose (HPMC, METHOCEL™ Premium K100M CR) as rate controlling polymer using the concepts of percolation theory. The knowledge of the percolation threshold of the components of the matrix formulations contributes to improve their design. First, reducing the time to market and second, avoiding to formulate in the nearby of the percolation threshold, which will result in a lower variability. Therefore these formulations will be more robust when they are prepared at industrial scale. The HPMC percolation threshold for drugs with very different water solubilities was determined and it was shown that there was no significant influence of drug solubility on the HPMC critical concentration threshold (excipient percolation threshold). This may be related to the versatility and broad functionality of the swelling hydrophilic matrices.

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

Similar content being viewed by others

References

  1. Colombo P, Bettini R, Santi P, Peppas NA. Swellable matrices for controlled drug delivery: gel layer behavior, mechanism and optimal performance. Pharm Sci Tech Today. 2000;3:198–204.

    Article  CAS  Google Scholar 

  2. Varma M, Kaushal A, Garg A, Garg S. Factors affecting mechanism and kinetics of drug release from matrix-based oral controlled drug delivery systems. Am J Drug Del. 2004;2(1):43–57.

    Article  CAS  Google Scholar 

  3. Levina M, Rajabi-Siahboomi AR. The influence of excipients on drug release from hydroxypropyl methylcellulose matrices. J Pharm Sci. 2004;93(11):2746–54.

    Article  CAS  PubMed  Google Scholar 

  4. Patel DM, Patel NM, Pandya NN, Jogani PD. Gastroretentive drug delivery system of carbamazepine: formulation optimization using simplex lattice design: a technical note. AAPSPharmSciTech. 2007;8(1):Article 11. doi: 10.1208/pt0801011

  5. Passirini N, Perissutti B, Albertini B, Voinovich D, Moneghini M, Rodriguz L. Controlled release of verapamil hydrochloride from waxy microparticles prepared by spray congealing. J Control Release. 2003;88(2):263–75.

    Article  Google Scholar 

  6. Caraballo I, Millán M, Rabasco AM. Relationship between drug percolation threshold and particle size in matrix tablets. Pharm Res. 1996;13:387–90.

    Article  CAS  PubMed  Google Scholar 

  7. Fuertes I, Miranda A, Millán M, Caraballo I. Estimation of the percolation thresholds in acyclovir hydrophilic matrix tablets. Eur J Pharm Biopharm. 2006;64:336–42.

    Article  CAS  PubMed  Google Scholar 

  8. Miranda A, Millán M, Caraballo I. Study of the critical points in the release and hydration kinetics of swellable matrix type controlled delivery systems. Int J Pharm. 2006;311:75–81.

    Article  CAS  PubMed  Google Scholar 

  9. Miranda A, Millán M, Caraballo I. Study of the critical points in lobenzarit disodium hydrophilic matrices for controlled drug delivery. Chem Pharm Bull. 2006;54(5):598–602.

    Article  CAS  PubMed  Google Scholar 

  10. Miranda A, Millán M, Caraballo I. Investigation of the influence of particle size on the excipient percolation thresholds of HPMC hydrophilic matrix tablets. J Pharm Sci. 2007;96:2745–56.

    Article  Google Scholar 

  11. Gonçalves-Araújo T, Rajabi-Siahboomi AR, Caraballo I. Application of percolation theory in the study of an extended release verapamil hydrochloride formulation. Int J Pharm. 2008;361:112–7.

    Article  PubMed  Google Scholar 

  12. Leuenberger H, Leu R, Bonny JD. Application of percolation theory and fractal geometry to tablet compaction. Drug Dev Ind Pharm. 1992;18:6723–766.

    Article  Google Scholar 

  13. Ford JL, Mitchell K, Rowe P, Armstrong DJ, Elliot PNC, Rostron C et al. Mathematical modelling of drug release from hydroxypropylmethylcelluose matrices: effect of temperature. Int J Pharm. 1991;71:95–104.

    Article  CAS  Google Scholar 

  14. Stauffer D, Aharony A (1992) Introduction to percolation theory, 2nd ed., Francis, London, Washington, DC.

  15. Leuenberger H, Rohera BH, Haas C. Percolation theory—a novel approach to solid dosage form design. Int J Pharm. 1987;38:109–15.

    Article  CAS  Google Scholar 

  16. Millán M, Caraballo I, Rabasco A. The role of the drug/excipient particle size ratio in the percolation model for tablets. Pharm Res. 1998;15(2):220–4.

    Article  Google Scholar 

Download references

Acknowledgments

The authors wish to express their gratitude to Colorcon for funding this study and for the supply of METHOCEL™ and Recordatti for the supply of the carbamazepine and verapamil HCl.

Author information

Authors and Affiliations

  1. Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Seville, Seville, Spain

    Tamara Gonçalves-Araújo & Isidoro Caraballo

  2. Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Federal University of Ceará, Fortaleza, Brazil

    Tamara Gonçalves-Araújo

  3. Colorcon Ltd., 415 Moyer Boulevard, P.O. Box 24, West Point, Pennsylvania, 19486-0024, USA

    Ali R. Rajabi-Siahboomi

Authors
  1. Tamara Gonçalves-Araújo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ali R. Rajabi-Siahboomi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Isidoro Caraballo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tamara Gonçalves-Araújo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gonçalves-Araújo, T., Rajabi-Siahboomi, A.R. & Caraballo, I. Polymer Percolation Threshold in HPMC Extended Release Formulation of Carbamazepine and Verapamil HCl. AAPS PharmSciTech 11, 558–562 (2010). https://doi.org/10.1208/s12249-010-9408-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-010-9408-x

Key words

Search

Navigation