Skip to main content
SpringerLink
Log in

Pulsatile Drug Release from an Insoluble Capsule Body Controlled by an Erodible Plug

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose. The objective of this study was to develop and evaluate a pulsatile drug delivery system based on an impermeable capsule body filled with drug and an erodible plug placed in the opening of the capsule body.

Methods. The erodible plugs were either prepared by direct compression followed by placing the tablets in the capsule opening or by congealing a meltable plug material directly within the capsule opening. The disintegration/erosion properties of these plugs were determined and optimized for the final delivery system. In order to assure rapid drug release of the capsule content after erosion of the plug, various excipients (fillers, effervescent agents) and drugs with different solubilities were evaluated. The lag time prior to drug release and the subsequent drug release were investigated as function of capsule content, plug composition, plug preparation technique, plug hardness, weight, and thickness.

Results. The erosion time of the compressed plugs increased with increasing molecular weight of the hydrophilic polymer (e.g. hydroxypropyl methylcellulose, polyethylene oxide), decreasing filler (lactose) content and decreased with congealable lipidic plugs with increasing HLB-value and inclusion of surfactants. For complete and rapid release of the drug from the capsule body, effervescent agents had to be included in the capsule content. The drug delivery system showed typical pulsatile release profiles with a lag time followed by a rapid release phase. The lag time prior to the pulsatile drug release correlated well with the erosion properties of the plugs and, besides the composition of the plug, could be controlled by the thickness (weight) of the plug.

Conclusions. A single-unit, capsular-shaped pulsatile drug delivery system was developed wherein the pulsatile release was controlled by the erosion properties of a compressed or congealed plug placed within the opening of the capsule opening.

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

Similar content being viewed by others

REFERENCES

  1. R. Gurny, H. E. Junginger, and N. A. Peppas. Pulsatile Drug Delivery; Current Applications and Future Trends, Wissenschaftliche Verlagsgesellschaft, Stuttgart, 1993.

    Google Scholar 

  2. G. Van den Mooter, C. Samyn, and R. Kinget. The relation between swelling properties and enzymatic degradation of azo polymers designed for colon-specific drug delivery. Pharm. Res. 11:1737–1741 (1994).

    Article  PubMed  Google Scholar 

  3. A. Rubinstein, B. Tirosh, M. Baluom, T. Nassar, A. David, R. Radai, I. Gliko-Kabir, and M. Friedman. The rationale for peptide drug delivery to the colon and the potential of polymeric carriers as effective tools. J. Control. Release 46:59–73 (1997).

    Article  Google Scholar 

  4. Y. Hirakawa, H. Yoshino, E. Fukui, and T. Hanamori, EP 0,671,168, Pharmaceutical preparation controlled to release medicinal active ingredient at targeted site in intestinal tract, Sep. 13, 1995.

  5. W. Phuapradit, A. Railkar, and N. H. Shah. EP 0,673,645, Pharmaceutical composition, Sep. 27, 1995.

  6. S. Poli, C. Busetti, and L. Moro. EP 0,572,942, Oral pharmaceutical compositions for specific colon delivery, Dec. 8, 1993.

  7. T. Siriä, M. Mäkimartti, S. Liukko-Sipi, and M. Marvola. Development and biopharmaceutical evaluations of a new press-coated prolonged-release salbutamol sulphate tablet in man. Eur. J. Pharm. Sciences 1:195–201 (1994).

    Google Scholar 

  8. I. Krögel and R. Bodmeier. Evaluation of the floating properties of coated drug delivery systems containing effervescent excipients. Eur. J. Pharm. Biopharm. 42(Suppl.):21 (1996).

    Google Scholar 

  9. I. Krögel and R. Bodmeier. Development of floating or pulsatile DDS based on effervescent cores. Proceed. Intern. Symp. Control. Rel. Bioact. Mater. 24:237–238 (1997).

    Google Scholar 

  10. S. Ueda, T. Hata, S. Asakura, H. Yamaguchi, M. Kotani, and Y. Ueda. Development of a novel drug release system, time-controlled explosion system (TES). I. Concept and design. J. Drug Targeting 2:35–44 (1994).

    Google Scholar 

  11. S. Ueda, H. Yamaguchi, M. Kotani, S. Kimura, Y. Tokunaga, A. Kagayama, and T. Hata. Development of a novel drug release system, time-controlled explosion system (TES). II. Design of multiparticulate TES and in vitro drug release properties. Chem. Pharm. Bull. 42:359–363 (1994).

    Google Scholar 

  12. S. Ueda, R. Ibuki, S. Kimura, S. Murata, T. Takahashi, Y. Tokunaga, and T. Hata. Development of a novel drug release system, time-controlled explosion system (TES). III. Relation between lag time and membrane thickness. Chem. Pharm. Bull. 42:364–367 (1994).

    Google Scholar 

  13. U. Conte, A. La Manna, and P. Colombo. US Patent 4,865,849, Tablet for pharmaceutical use able to release active substances at successive times, Sep. 12, 1989.

  14. M. E. McNeil, A. Rashid, and H. N. E. Stevens. WO 90/09168, Dispensing device, Aug. 23, 1990.

  15. I. R. Wilding, S. S. Davis, M. Bakhshaee, H. N. E. Stevens, R. A. Sparrow, and J. Brennan. Gastrointestinal transit and systemic absorption of captopril from a pulsed-release formulation. Pharm. Res. 9:654–657 (1992).

    PubMed  Google Scholar 

  16. P. J. Gilchrist, J. M. Hebden, C. G. Wilson, R. C. Spiller, A. C. Perkins, and J. S. Binns. Regional differences in colonic absorption? — A study using the Pulsincap™ delivery system. Proceed. Intern. Symp. Control. Rel. Bioact. Mater. 22:206–207 (1995).

    Google Scholar 

  17. J. Binns, H. N. E Stevens, J. McEwen, G. Pritchard, F. M. Brewer, A. Clarke, E. S. Johnson, and I. McMillan. The tolerability of multiple oral doses of Pulsincap™ capsules in healthy volunteers. J. Control. Release 38:151–158 (1996).

    Google Scholar 

  18. J. R. Crison, P. R. Siersma, M. D. Taylor, and G. L. Amidon. Programmable oral release technology, Port Systems®: A novel dosage form for time and site specific oral drug delivery. Proceed. Intern. Symp. Control. Rel. Bioact. Mater. 22:278–279 (1995).

    Google Scholar 

  19. P. S.-L. Wong, F. Theeuwes, S. D. Larsen, and L. C. Dong. Osmotic device for delayed delivery of agent, Jul. 2, 1996.

  20. R. Bodmeier and I. Krögel. Release device with progammable drug release, German patent application #196 19 050, May (1996).

  21. H. N. E. Stevens, A. Rashid, and M. Bakhshaee. PCT WO 91/12795, Dispensing Device, Sep. 5, 1991.

  22. R. Bodmeier and O. Paeratakul. Mechanical properties of dry and wet cellulosic and acrylic polymer films prepared from aqueous colloidal polymer dispersions. Pharm. Res. 11:882–888 (1994).

    PubMed  Google Scholar 

  23. R. Bodmeier and O. Paeratakul. Dry and wet strength of polymeric films prepared from an aqueous colloidal polymer dispersion, Eudragit® RS30D. Int. J. Pharm. 96:129–138 (1993).

    Google Scholar 

  24. F. Kuppler, M. Wesseling, and R. Bodmeier. Development of a method for measuring the tackiness of acrylic and cellulosic polymer coatings. Eur. J. Pharm. Biopharm. 42(Suppl.):14 (1996).

    Google Scholar 

  25. I. Krögel and R. Bodmeier. Evaluation of a pulsatile drug delivery system based on an erodible plug within an insoluble capsule body. Pharm. Res. 13(Suppl.):304 (1996).

    Google Scholar 

  26. D. A. Alderman. A review of cellulose ethers in hydrophilic matrices for oral controlled-release dosage forms. Pharm. Tech. & Prod. Mfr. 5:1–9 (1984).

    Google Scholar 

  27. J. L. Ford, M. H. Rubinstein, and J. E. Hogan. Formulation of sustained release promethazine hydrochloride tablets using hydroxypropyl methylcellulose matrices. Int. J. Pharm. 24:327–338 (1985).

    Google Scholar 

  28. L. W. S. Cheong, P. W. S. Heng, and L. F. Wong. Relationship between polymer viscosity and drug release from a matrix system. Pharm. Res 9:1510–1514 (1992).

    PubMed  Google Scholar 

  29. J. Gustafsson, H. Ljusber-Wahren, M. Almgren, and K. Larsson. Cubic lipid-water phase dispersed into submicron particles. Langmuir 12:4611–4613 (1996).

    Google Scholar 

  30. H. Ljusberg-Wahren, L. Nyberg, and K. Larsson. Dispersion of the cubic liquid crystalline phase—structure, preparation and functionality aspects. Chemistry Today 6 (1996).

  31. C.-M. Chang and R. Bodmeier. Effect of dissolution media and additives on the drug release from cubic phase delivery systems. J. Contr. Release 46:215–222 (1997).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, 12169, Berlin, Germany

    Ina Krögel & Roland Bodmeier

Authors
  1. Ina Krögel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roland Bodmeier
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Krögel, I., Bodmeier, R. Pulsatile Drug Release from an Insoluble Capsule Body Controlled by an Erodible Plug. Pharm Res 15, 474–481 (1998). https://doi.org/10.1023/A:1011940718534

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1011940718534

Search

Navigation