Skip to main content
Log in

A New Bioerodible Polymer Insert for the Controlled Release of Metronidazole

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

This study evaluates a new class of bioerodible polymers as periodontal inserts for the controlled release of metronidazole. The system is based on association polymers formed from compatible blends of cellulose acetate phthalate (CAP) and a hydrophobic block copolymer of polyoxyethylene and polyoxypropylene, Pluronic L101. In addition to characterizing these polymers by thermal analysis, their erosion and metronidazole release characteristics were determined both in vitro, and in vivo using a rat model. The results show that increasing the concentration of Pluronic L101 in the blend to 50% and above leads to a sharp reduction in the rates of polymer erosion and metronidazole release. The characteristics of these slowly eroding films are potentially suitable for use as periodontal drug inserts with an effective duration of up to several days. Depending on the blend composition, the mechanism of metronidazole release was found to range from a surface erosion-controlled process to an erosion-modulated diffusion process. In all in vivo experiments, no signs of adverse tissue reactions were detected. Based on these results, prototype delivery inserts were designed and subsequently evaluated in volunteer patients. Preliminary results from this pilot study show that the metronidazole concentration in the gingival crevicular fluid was significant throughout the sampling period of up to 3 hr and remained well above the minimum inhibitory concentration for most periodontal pathogens. In addition, no discomfort or irritation was reported by the test subjects.

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

Similar content being viewed by others

REFERENCES

  1. J. Slots and T. Rams. Antibiotics in periodontal therapy: advantages and disadvantages. J. Clin. Periodontol. 17:479–493 (1990).

    Google Scholar 

  2. D. Steinberg, M. Friedman, A. Soskolne and M. Sela. A new degradable controlled release device for the treatment of periodontal disease. J. Periodontol. 61:393–398 (1990).

    Google Scholar 

  3. P. I. Lee. A coated absorbent substrate or shaped article, containing a water-soluble and/or volatile active agent. European Patent 0075540 B1, Oct. 22, (1986).

  4. P. I. Lee. Membrane-forming polymeric systems. U.S. Patent 4,729,190, Mar. 8, (1988).

  5. X. Xu and P. I. Lee. Programmable drug delivery from an erodible association polymer system. Pharm. Res. 10:1144–1152 (1993).

    Google Scholar 

  6. M. Alfano. The origin of gingival fluid. J. Theor. Biol. 47:127–136 (1974).

    Google Scholar 

  7. P. Birek, H. Grad, K. Gates, P. Baehni and P. I. Lee. A bioerodible drug delivery system containing metronidazole. J. Dent Res. 73:SI306 (1994).

    Google Scholar 

  8. C. M. Kaye, M. G. Sankey and L. A. Thomas. A rapid and specific semi-micro method involving high-pressure liquid chromatography for the assay of metronidazole in plasma, saliva, serum, urine and whole blood. Br. J. Clin. Pharmacol. 9:528–529 (1980).

    Google Scholar 

  9. G. Luce. Cellulose acetate phthalate: a versatile enteric coating. Pharm. Technol. 1:27–31 (1977).

    Google Scholar 

  10. I. Schmolka. A review of block copolymer surfactants. Journal of American Oil Chemists Society. 54:110–116 (1977).

    Google Scholar 

  11. R. Hunter and B. Bennett. The adjuvant activity of nonionic block polymer surfactants. II. Antibody formation and inflammation related to the structure of triblock and octablock copolymers. J. Immunol. 133:3167–3175 (1984).

    Google Scholar 

  12. T. G. Park, S. Cohen and R. Langer. Poly(L-lactic acid)/Pluronic blends: characterization of phase separation behavior, degradation, and morphology and use as protein-releasing matrices. Macromol. 25:116–122 (1992).

    Google Scholar 

  13. M. Bickel, J. Munoz and P. Giovannini. Acid-base properties of human gingival crevicular fluid. J. Dent. Res. 64:1218–1220 (1985).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gates, K.A., Grad, H., Birek, P. et al. A New Bioerodible Polymer Insert for the Controlled Release of Metronidazole. Pharm Res 11, 1605–1609 (1994). https://doi.org/10.1023/A:1018913921956

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1018913921956

Navigation