In vitro drug release study of methacrylate polymer blend system: effect of polymer blend composition, drug loading and solubilizing surfactants on drug release

Abstract

The application of polymers as the drug delivery systems for treating oral infections is a relatively new area of research. The present study was to test the release of the antibacterial drug chlorhexidine diacetate (CHDA), the antifungal drug Nystatin (NYS) and the antiviral drug acyclovir (ACY) from polymer blends of poly(ethyl methacrylate) and poly(n-hexyl methacrylate) of different compositions. The effects of polymer blend composition, drug loading and solubilizing surfactants on the release of the drugs have been studied. Measurements of the in vitro rate of drug release showed a sustained release of drug over extended periods of time. Drug release rates decreased with increasing PEMA content in polymer blends. CHDA release rates increased steadily with increasing drug load. The drug release rates increased with the addition of surfactants. This study demonstrates that the three therapeutic agents show a sustained rate of drug release from polymer blends of PEMA and PHMA over extended periods of time. By varying polymer blend compositions as well as the drug concentration (loading), it is possible to control the drug release rates to a desired value. The drug release rate is enhanced by addition of surfactants that solubilize drugs in the polymer blends.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. 1.

    Ahrends J, Ruben J. Fluoride release from a composite resin. Quintessence Int. 1988;9:513–4.

    Google Scholar 

  2. 2.

    Behrend B, Geurtsen W. Long-term effects of four extraction media on the fluoride release from our polyacid-modified composite resins (compomer) and one resin-modified glass-ionomer cement. J Biomed Mater Res. 2001;58:631–7.

    Article  CAS  PubMed  Google Scholar 

  3. 3.

    Rothwell M, Anstice HM, Pearson GJ. The uptake and release of fluoride by ion-leaching cements after exposure to toothpaste. J Dent. 1998;26:591–7.

    Article  CAS  PubMed  Google Scholar 

  4. 4.

    Patel MP, Pearson GJ, Braden M, Mirza MA. Fluoride ion release from two methacrylate polymer systems. Biomater. 1998;19:1911–7.

    Article  CAS  Google Scholar 

  5. 5.

    Addy M, Handley R. The effects of the incorporation of chlorhexidine acetate on some physical properties of polymerized and plasticized acrylics. J Oral Rehabil. 1981;8:155–63.

    Article  CAS  PubMed  Google Scholar 

  6. 6.

    Wilson SJ, Wilson HJ. The release of chlorhexidine from modified dental acrylic resin. J Oral Rehabil. 1993;20:311–9.

    Article  CAS  PubMed  Google Scholar 

  7. 7.

    Lee DY, Spangberg LSW, Bok YB, Lee CY, Lee KY. The sustaining effect of three polymers on the release of chlorhexidine from a controlled release drug device for root canal disinfection. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100:105–11.

    Article  PubMed  Google Scholar 

  8. 8.

    Yue IC, Poff J, Cortes ME. A novel polymeric chlorhexidine delivery device for the treatment of periodontal disease. Biomater. 2004;25:3743–50.

    Article  CAS  Google Scholar 

  9. 9.

    Patel MP, Braden M, Downer S. Heterocyclic methacrylate based drug release polymer system. J Mater Sci: Mater Med. 1994;5:793–7.

    Article  Google Scholar 

  10. 10.

    Parker S, Patel MP, Tibald J, Braden M. Two methacrylate based materials for intra-oral drug delivery. Plast Rubber Compos Process Appl. 1997;26:298–302.

    CAS  Google Scholar 

  11. 11.

    Patel MP, Cruchley AT, Coleman DC, Swai H, Braden M, Williams DM. A polymeric system for the intra-oral delivery of an anti-fungal agent. Biomater. 2001;22:2319–24.

    Article  CAS  Google Scholar 

  12. 12.

    Sipos TT, Lebanon NJ. Intra-oral device containing 2-hydroxyethyl methacrylate-methyl methacrylate copolymer for slow medicament release. European Patent No. 569797, 861993.

  13. 13.

    Nerurkar MJ, Zenter GM, Rytting JH. Effect of chloride on the release of chlorhexidine salts from methyl methacrylate-2-hydroxyethyl methacrylate copolymer reservoir devices. J Control Rel. 1995;33:357–63.

    Article  CAS  Google Scholar 

  14. 14.

    Leung D, Spratt DA, Pratten J, Gulabivala K, Mordan NJ, Young AM. Chlorhexidine-releasing methacrylate dental composite materials. Biomater. 2005;26:7145–53.

    Article  CAS  Google Scholar 

  15. 15.

    Veleva AN, Khan SA, Cooper SL. Oxidative and hydrolytic stability of a novel terpolymer for biomedical applications. J Biomed Mater Res. 2005;74A:117–23.

    Article  CAS  Google Scholar 

  16. 16.

    Fussell GW, Cooper SL. Synthesis and characterization of acrylic terpolymers with RGD peptides for biomedical applications. Biomater. 2004;25:2971–8.

    Article  CAS  Google Scholar 

  17. 17.

    Udipi K, Cheng P, Chen M, Lyu SP. Biocompatible controlled released coatings for medical devices and related methods. US Patent No. 2005084515, 2005.

  18. 18.

    Mir GN, Lawrence WH, Autian J. Toxicology and pharmacological actions of methacrylate monomers. I. Effects on isolated, perfused rabbit heart. J Pharm Sci. 1973;62:778–82.

    Article  CAS  PubMed  Google Scholar 

  19. 19.

    Reynolds J. Martindale the extra pharmacopoeia. 28th ed. London: The Pharmaceutical Press; 1982. p. 729.

    Google Scholar 

  20. 20.

    Rangel-Yagui CO, Pessoa A Jr, Tavares LC. Micellar solubilization of drugs. J Pharm Pharm Sci. 2005;8:147–63.

    CAS  PubMed  Google Scholar 

  21. 21.

    Lawrence MJ. Surfactant systems: their use in drug delivery. Chem Soc Rev. 1994;23:417–24.

    Article  CAS  Google Scholar 

  22. 22.

    Attwood D, Florence AT. Surfactant systems: their chemistry, pharmacy and biology. London: Chapman and Hall; 1983.

    Google Scholar 

  23. 23.

    Florence AT. Drug solubilization in surfactant systems. In: Yalkowsky SH, editor. Techniques of solubilization of drugs. New York: Marcel Dekker Inc.; 1981.

    Google Scholar 

  24. 24.

    Andersen T, Gram-Hansen M, Pedersen M, Rassing MR. Chewing gum as a drug delivery system for nystatin influence of solubilising agents upon the release of water insoluble drugs. Drug Dev Ind Pharm. 1990;16:1985–94.

    Article  CAS  Google Scholar 

  25. 25.

    Padmavathy T, Randall MK, Khin LT, Preisser JS, Kalachandra S. Effects of solubilizing surfactants and loading of antiviral antimicrobial, and antifungal drugs on their release rates from ethylene vinyl acetate copolymer. Dent Mater. 2007;23:977–82.

    Article  Google Scholar 

  26. 26.

    Hanaee J, Javadzadeh Y, Taftachi S, Farid D, Nokhodchi A. The role of various surfactants on the release of salbutamol from suppositories. IL Farmaco. 2004;59:903–6.

    Article  CAS  PubMed  Google Scholar 

  27. 27.

    Buckton G, Efentakis M, Al-Hmoud H, Rajan Z. The influence of surfactants on drug release from acrylic matrices. Int J Pharm. 1991;74:169–74.

    Article  CAS  Google Scholar 

  28. 28.

    Efentakis M, Al-Hmoud H, Buckton G, Rajan Z. The influence of surfactants on drug release from a hydrophobic matrix. Int J Pharm. 1991;70:153–8.

    Article  CAS  Google Scholar 

  29. 29.

    Schott H, Chong KL, Feldman S. The role of surfactants in the release of very slightly soluble drugs from tablets. J Pharm Sci. 1982;71:1038–45.

    Article  CAS  PubMed  Google Scholar 

  30. 30.

    Pitt C, Cha Y, Shah S, Zhu K. Blends of PVA and PGLA: control of the permeability and degradability of hydrogels by blending. J Control Rel. 1992;19:189–99.

    Article  CAS  Google Scholar 

  31. 31.

    Park T, Cohen S, Langer R. Poly(l-lactic acid)/pluronic blends: characterization of phase separation behavior degradation, and morphology and use as protein-releasing matrixes. Macromolecules. 1992;25:116–22.

    Article  CAS  ADS  Google Scholar 

  32. 32.

    Edlund U, Albertsson A-C. Microspheres from poly(d, l-lactide)/poly(1, 5-dioxepan-2-one) miscible blends for controlled drug delivery. J Bioactive Compatible Polym. 2000;15:214–29.

    Article  CAS  Google Scholar 

  33. 33.

    Lecomte F, Siepmann J, Walther M, Macrae R, Bodmeier R. Blends of enteric and GIT-insoluble polymers used for film coating: physicochemical characterization and drug release patterns. J Control Rel. 2003;89:457–71.

    Article  CAS  Google Scholar 

  34. 34.

    Mi F, Shyu S, Lin Y, Wu Y, Peng C, Tsai Y. Chitin/PLGA blend microspheres as a biodegradable drug delivery system: a new delivery system for protein. Biomater. 2003;24:5023–36.

    Article  CAS  Google Scholar 

  35. 35.

    Kenawy E, Bowlin G, Mansfiel K, Layman J, Simpson D, Sanders E, et al. Release of tetracycline hydrochloride from electrospun poly(ethylene-co-vinylacetate), poly(lactic acid) and a blend. J Control Rel. 2002;81:57–64.

    Article  CAS  Google Scholar 

  36. 36.

    Shen Y, Sun W, Zhu K, Shen Z. Regulation of biodegradability and drug release behavior of aliphatic polyesters by blending. J Biomed Mater Res. 2000;50:528–35.

    Article  CAS  PubMed  Google Scholar 

  37. 37.

    Thomas P, Padmaja T, Kulkarni M. Polyanhydride blend microspheres: novel carriers for the controlled release of macromolecular drugs. J Control Rel. 1997;43:273–81.

    Article  Google Scholar 

  38. 38.

    Lin DM, Kalachandra S, Valiyaparambil J, Offenbacher S. A polymeric device for delivery of anti-microbial and anti-fungal drugs in the oral environment: effect of temperature and medium on the rate of drug release. Dent Mater. 2003;19:589–96.

    Article  CAS  PubMed  Google Scholar 

  39. 39.

    Padmavathy T, Alimohammadi N, Kalachandra S. Poly(ethylene-co-vinyl acetate) copolymer matrix for delivery of chlorhexidine and acyclovir drugs for use in the oral environment: effect of drug combination copolymer composition and coating on the drug release rate. Dent Mater. 2007;23:404–9.

    Article  Google Scholar 

  40. 40.

    Bicerano J. Prediction of polymer properties. New York: Marcel Dekker, Inc; 1993.

    Google Scholar 

  41. 41.

    Brandrup J, Immergut EH. Polymer handbook. 3rd ed. New York: Wiley; 1989.

    Google Scholar 

  42. 42.

    Donbrow M, Friedman M. Enhancement of permeability of ethyl cellulose films for drug penetration. J Pharm Pharmacol. 1975;27:633–46.

    CAS  PubMed  Google Scholar 

  43. 43.

    Hsu TTP, Langer R. Polymers for the controlled release of macromolecules: effect of molecular weight of ethylene-vinyl acetate copolymer. J Biomed Mater Res. 1985;19:445–60.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by NIH-NIDCR Grant R01 DE 15267. The authors wish to thank Dr. Anton Schindler, Principal Scientist, Research Triangle Institute, Research Triangle Park, North Carolina, USA, for his valuable suggestions. We also thank Dr. John S. Preisser, Associate Professor, Department of Biostatistics, University of North Carolina, Chapel Hill for his help with the statistical analysis.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Jun Li.

Additional information

Dr. Siddugari (‘Sid’) Kalachandra, Research Professor in the University of North Carolina’s School of Dentistry, died on March 14, 2008.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Li, J., Barrow, D., Howell, H. et al. In vitro drug release study of methacrylate polymer blend system: effect of polymer blend composition, drug loading and solubilizing surfactants on drug release. J Mater Sci: Mater Med 21, 583–588 (2010). https://doi.org/10.1007/s10856-009-3899-6

Download citation

Keywords

  • Surfactant
  • Release Rate
  • Drug Release
  • HEMA
  • Polymer Blend