Skip to main content

Advertisement

SpringerLink
Log in

Enhanced Topical Delivery of Terbinafine Hydrochloride with Chitosan Hydrogels

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

Abstract

Chitosan-based carriers have important potential applications for the administration of drugs. In the present study, topical gel formulations of terbinafine hydrochloride (T-HCl) were prepared using different types of chitosan at different molecular weight, and the antifungal inhibitory activity was evaluated to suggest an effective formulation for the treatment of fungal infections. The characteristics of gel formulations were determined with viscosity measurements and texture profile analysis. Stability studies were performed at different temperatures during 3 months. The ex vivo permeation properties were studied through rat skin by using Franz diffusion cells. The antifungal inhibitory activity of formulations on Candida species and filamentous fungi was also examined with agar-cup method. The microbiological assay was found suitable for determination of in vitro antifungal activity of T-HCl. A marketed product was used to compare the results. The antifungal activity of T-HCl significantly increased when it was introduced into the chitosan gels. A higher drug release and the highest zone of inhibition were obtained from gels prepared with the lowest molecular weight chitosan (Protasan UP CL 213) compared to that of other chitosan gels and marketed product. These results indicated the advantages of the suggested formulations for topical antifungal therapy against Candida species and filamentous fungi.

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

Similar content being viewed by others

References

  1. Alberti I, Kalia YN, Naik A, Bonny JD, Guy RH. Effect of ethanol and isopropyl myristate on the availability of topical terbinafine in human stratum corneum, in vivo. Int J Pharm. 2001;219:11–19.

    Article  PubMed  CAS  Google Scholar 

  2. Shishu G, Aggarwal N. Preparation of hydrogels of griseofulvin for dermal application. Int J Pharm. 2006;326:20–24.

    Article  PubMed  CAS  Google Scholar 

  3. Csoka I, Csanyi E, Zapantis G, Nagy E, Feher-Kiss A, Horvath G, et al. In vitro and in vivo percutaneous absorption of topical dosage forms: case studies. Int J Pharm. 2005;291:11–19.

    Article  PubMed  CAS  Google Scholar 

  4. Valenta C, Auner BG. The use of polymers for dermal and transdermal delivery. Eur J Pharm Biopharm. 2004;58:279–289.

    Article  PubMed  CAS  Google Scholar 

  5. Tas C, Ozkan Y, Savaser A, Baykara T. In vitro release studies of chlorpheniramine maleate from gels prepared by different cellulose derivatives. Il Farmaco. 2003;58:605–611.

    Article  PubMed  CAS  Google Scholar 

  6. Wang YY, Hong CT, Chiu WT, Fang JY. In vitro and in vivo evaluations of topically applied capsaicin and nonivamide from hydrogels. Int J Pharm. 2001;224:89–104.

    Article  PubMed  CAS  Google Scholar 

  7. Fakhry A, Schneider GB, Zaharias R, Senel S. Chitosan supports the initial attachment and spreading of osteoblast preferentially over fibroblasts. Biomaterials. 2004;25:2075–2079.

    Article  PubMed  CAS  Google Scholar 

  8. Ikinci G, Senel S, Akıncıbay H, Kas S, Ercis S, Wilson CG, et al. Effect of chitosan on a peridontal pathogen Prophyromonas gingivalis. Int J Pharm. 2002;235:121–127.

    Article  PubMed  CAS  Google Scholar 

  9. Jumaa M, Furkert FH, Müler BW. A new lipid emulsion formulation with high antimicrobial efficacy using chitosan. Eur J Pharm Biopharm. 2002;53:115–123.

    Article  PubMed  CAS  Google Scholar 

  10. No HK, Park NY, Lee SH, Meyers SP. Antibacterial activity of chitosans and chitosan oligomers with different molecular weights. Int J Food Microbiol. 2002;74:65–72.

    Article  PubMed  CAS  Google Scholar 

  11. Alberti I, Kalia YN, Naik A, Bonny JD, Guy RH. In vivo assessment of enhanced topical delivery of terbinafine to human stratum corneum. J Control Release. 2001;71:319–327.

    Article  PubMed  CAS  Google Scholar 

  12. Balfour JA, Faulds D. Terbinafine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in superficial mycoses. Drugs. 1992;43:259–284.

    Article  PubMed  CAS  Google Scholar 

  13. Kazakov PV, Golosov SN. A simple method for obtaining terbiınafine hydrochloride. Pharm Chem J. 2004;38:34–36.

    Article  Google Scholar 

  14. Gené J, Azón-Masoliver A, Guarro J, De Febrer G, Martínez A, Grau C, et al. Cutaneous infection caused by Aspergillus ustus, an emerging opportunistic fungus in immunosuppressed patients. J Clin Microbiology. 2001;39:1134–1136.

    Article  Google Scholar 

  15. Sen M, Uzun C, Güven O. Controlled release of terbinafine hydrochloride from pH sensitive poly(acrylamide/maleic acid) hydrogels. Int J Pharm. 2000;203:149–157.

    Article  PubMed  CAS  Google Scholar 

  16. Karavana (Hızarcıoglu) S, Guneri P, Ertan G. Benzydamine hydrochloride buccal bioadhesive gels designed for oral ulcers: preparation, rheological, textural, mucoadhesive and release properties. Pharm Dev Tech. 2009; in press doi:10.1080/10837450902882351.

  17. Sen M, Yakar A. Controlled release of antifungal drug terbinafine hydrochloride from poly(N-vinyl 2-pyrrolidone/itaconic acid) hydrogels. Int J Pharm. 2001;228:33–41.

    Article  PubMed  CAS  Google Scholar 

  18. NCCLS, National Committee for Clinical Laboratory Standards. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard. NCCLS document M38-A (ISBN 1-56238-470-8). Wayne: NCCLS; 2002.

  19. NCCLS, National Committee for Clinical Laboratory Standards. Method for antifungal disk diffusion susceptibility testing of yeasts; proposed guideline. NCCLS document M44-P (ISBN 1-56238-488-0). Wayne: NCCLS; 2003.

  20. Nesseem DI. Formulation and evaluation of itraconazole via liquid crystal for topical delivery system. J Pharm Biomed Analysis. 2001;26:387–399.

    Article  CAS  Google Scholar 

  21. Dawson B, Trapp RG. Basic and clinical biostatistics. USA: McGraw Hill; 2001. p. 161–182.

    Google Scholar 

  22. Daniel WW. Biostatistics; a foundation for analysis in the health sciences. New York: Wiley; 1983. p. 459–483.

    Google Scholar 

  23. Anchisi C, Maccioni AM, Meloni MC. Physical properties of chitosan dispersions in glycolic acid. Il Farmaco. 2004;59:557–561.

    Article  PubMed  CAS  Google Scholar 

  24. Jones D, Lawlor MS, Woolfson AD. Examination of the flow rheological and textural properties of polymer gels composed of poly(methylvinylether-comaleic anhydride) and poly(vinylpyrrolidone): rheological and mathematical interpretation of textural parameters. J Pharm Sci. 2002;91:2091–2101.

    Article  Google Scholar 

  25. Ruel-Gariepy E, Chenite A, Chaput C, Guirguis S, Leroux JC. Characterization of thermosensitive chitosan gels for the sustained delivery of drugs. Int J Pharm. 2000;203:89–98.

    Article  PubMed  CAS  Google Scholar 

  26. Aksungur P, Sungur A, Ünal S, Iskit AB, Squier CA, Senel S. Chitosan delivery systems for the treatment of oral mucositis: in vitro and in vivo studies. J Control Release. 2004;98:269–279.

    Article  PubMed  CAS  Google Scholar 

  27. Senel S, Ikinci G, Kas S, Yousefi-Rad A, Sargon MF, Hıncal AA. Chitosan films and hydrogels of chlorhexidine gluconate for oral mucosal delivery. Int J Pharm. 2000;193:197–203.

    Article  PubMed  CAS  Google Scholar 

  28. Qin C, Li H, Xiao Q, Liu Y, Zhu J, Du Y. Water-solubility of chitosan and its antimicrobial activity. Carbonhydrate Polym. 2006;63:367–374.

    Article  CAS  Google Scholar 

  29. Kumar MNVR, Muzzarelli RAA, Muzzarelli C, Sashiwa H, Domb AJ. Chitosan chemistry and pharmaceutical perspectives. Chem Rev. 2004;104:6017–6084.

    Article  PubMed  Google Scholar 

  30. Cardoso SG, Schapoval EES. Microbiological assay for terbinafine hydrochloride in tablets and creams. Int J Pharm. 2000;203:109–113.

    Article  PubMed  CAS  Google Scholar 

  31. Gil-Lamaignere C, Müler FMC. Differential effects of the combination of caspofungin and terbinafine against Candida albicans, Candida dubliniensis and Candida kefyr. Int J Antimicrob Agents. 2004;23:520–523.

    Article  PubMed  CAS  Google Scholar 

  32. Karaarslan A, Arikan S, Ozcan M, Ozcan KM. In vitro activity of terbinafine and itraconazole against Aspergillus species isolated from otomycosis. Mycoses. 2003;47:284–287.

    Article  Google Scholar 

  33. Lim SH, Hudson SM. Review of chitosan and its derivatives as microbial agents and their uses as textile chemicals. J Macromol Sci: Part C-Polym Rev. 2003;43:223–229.

    Google Scholar 

  34. Gupta KC, Ravi Kumar MNV. pH dependent hydrolysis and drug release behavior of chitosan/poly(ethylene glycol) polymer network microspheres. J Materials Sci: Materials in Medicine. 2001;12:753–759.

    Article  CAS  Google Scholar 

  35. Kang IJ. A study on the effective application chitosan to drug delivery system. The 7th Asia-Pacific Chitin and Chitosan Symposium, Korea; 23/26 April. 2006, p. 273.

  36. Bae K, Jun EJ, Lee SM, Paik DI, Kim JB. Effect of water-soluble reduced chitosan on Streptococcus mutans, plaque regrowth and biofilm vitality. Clin Oral Invest. 2006;10:102–107.

    Article  CAS  Google Scholar 

  37. Garg S, Naidu J, Singh SM, Nawange SR, Jhara N, Saxena M. In itro activity of terbinafine against Indian clinical isolates of Candida albicans and non-albicans using a macrodilution method. J Mycol Med. 2006;16:119–125.

    Google Scholar 

  38. Petrayni G, Meingassner JG, Mieth H. Antifungal activity of the allylamine derivative terbinafine in vitro. Antimicrob Agents Chemother. 1987;31:1365–1368.

    Google Scholar 

Download references

Acknowledgments

We would like to express our grateful acknowledgments to Prof. Dr. Sevda Şenel for her guidance and help throughout this work.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ege, 35100, Bornova, Izmir, Turkey

    İpek Özcan, Buket Aksu, Tamer Güneri & Özgen Özer

  2. Department of Biology, Basic & Industrial Microbiology, Faculty of Science, University of Ege, Bornova, Izmir, Turkey

    Özlem Abacı & Alev Haliki Uztan

  3. Department of Statistic, Faculty of Science, University of Ege, Bornova, Izmir, Turkey

    Hayal Boyacıoğlu

Authors
  1. İpek Özcan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Özlem Abacı
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alev Haliki Uztan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Buket Aksu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hayal Boyacıoğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tamer Güneri
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Özgen Özer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to İpek Özcan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Özcan, İ., Abacı, Ö., Uztan, A.H. et al. Enhanced Topical Delivery of Terbinafine Hydrochloride with Chitosan Hydrogels. AAPS PharmSciTech 10, 1024–1031 (2009). https://doi.org/10.1208/s12249-009-9299-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-009-9299-x

Key words

Search

Navigation