Skip to main content

Advertisement

SpringerLink
Log in

Studies on Transdermal Delivery Enhancement of Zidovudine

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

Abstract

The purpose of this study was to investigate physicochemical characteristics and in vitro release of zidovudine from monolithic film of Eudragit RL 100 and ethyl cellulose. Films included 2.5% or 5% (w/w) zidovudine of the dry polymer weight were prepared in various ratios of polymers by solvent evaporation method from methanol/acetone solvent mixture. The release studies were carried out by vertical Franz cells (2.2 cm2 area, 20 ml receptor fluid). Ex vivo studies were done on Wistar rat skin within the films F6 (Eudragit RL100) and F7 (Eudragit RL100/Ethylcellulose, 1:1) consisting 5% (w/w) zidovudine in comparison with the same amount of free drug. Either iontophoresis (0.1 and 0.5 mA/cm2 direct currents, Ag/AgCl electrodes) or dimethyl sulfoxide (pretreatment of 1% and 5%, w/w, solutions) were used as enhancers. Films consisting of ethyl cellulose under the ratio of 50% (w/w) gave similar release profiles, and the highest in vitro cumulative released amount was achieved with F6 film which gave the closest results with the free drug. This result could be due to the high swelling capacity and re-crystallization inhibition effect of RL 100 polymer which also influenced the film homogenization. All the films were fitted to Higuchi release kinetics. It was also observed that both 0.5-mA/cm2 current and 5% (w/w) dimethyl sulfoxide applications significantly increased the cumulative permeated amount of zidovudine after 8 h; however, the flux enhancement ratio was higher for 0.5-mA/cm2 current application, especially within F6 film. Thus, it was concluded that Eudragit RL100 film (F6) could be further evaluated for the transdermal application of zidovudine.

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. T. Pongjangyakul, S. Prakongpan, and A. Priprem. Acrylic matrix type nicotine transdermal patches: In vitro evaluations and batch-to-batch uniformity. Drug Dev. Ind. Pharm. 29:843–853 (2003).

    Article  Google Scholar 

  2. Y. N. Kalia, and R.H. Guy. Interaction between penetration enhancers and iontophoresis: Effect on human skin impedance in vivo. J. Control. Release 44:33–42 (1997).

    Article  CAS  Google Scholar 

  3. A. K. Banga. Electrically assisted transdermal delivery of drugs. In D. L. Wise (ed.), Handbook of Pharmaceutical Controlled Release Technology, Marcel Dekker, New York, 2000, pp. 567–581.

    Google Scholar 

  4. A. R. Denet, B. Ucakar, and V. P. Preat. Transdermal delivery of timolol and atenolol using electroporation and iontophoresis in combination: A mechanistic approach. Pharm. Res. 2012:1946–1951 (2003).

    Article  PubMed  CAS  Google Scholar 

  5. A. C. Hirsch, R. S. Upasani, and A. K. Banga. Factorial design approach to evaluate interactions between electrically assisted enhancement and skin stripping for delivery of tacrine. J. Control. Release 1031:113–121 (2005).

    Article  PubMed  CAS  Google Scholar 

  6. A. Kuksal, A. K. Tiwary, N. K. Jain, and S. Jain. Formulation and in vitro, in vivo evaluation of extended-release matrix tablet of zidovudine: influence of combination of hydrophilic and hydrophobic matrix formers. AAPS Pharm. Sci. Tech. 7(1):Article 1, E1–E9. doi:10.128/pt070101 (2006).

  7. S. Y. Oh, S. Y. Jeong, T. G. Park, and J. H. Lee. Enhanced transdermal delivery of AZT (Zidovudine) using iontophoresis and penetration enhancer. J.Controlled Rel. 51:161–168 (1998).

    Article  CAS  Google Scholar 

  8. D. D. Kim, and Y. W. Chien. Transdermal delivery of dideoxynucleoside-type anti-HIV drugs. 1. Stability studies for hairless rat skin permeation. J. Pharm. Sci. 849:1061–1066 (1995).

    Article  PubMed  CAS  Google Scholar 

  9. S. Narishetty, and R. Panchagnula. Effect of l-menthol and 1-8-cineole on phase behaviour and molecular organisation of SC lipids and skin permeation of zidovudine. J. Control. Release 102:59–70 (2005).

    Article  PubMed  CAS  Google Scholar 

  10. N. S. Thomas, and R. Panchagnula. Combination strategies to enhance transdermal permeation of zidovudine (AZT). Pharmazie. 58:895–898 (2003).

    PubMed  CAS  Google Scholar 

  11. D. D. Kim, and Y. W. Chien. Transdermal delivery of dideoxynucleoside-type anti-HIV drugs. 2. The effect of vehicle and enhancer on skin permeation. J. Pharm. Sci. 852:214–219 (1996).

    Article  PubMed  CAS  Google Scholar 

  12. T. T. Kararli, C. F. Kirchhoff, and S. C. Penzotti Jr. Enhancement of transdermal transport of azidothymidine (AZT) with novel terpene and terpene like enhancers: In vivo–in vitro correlations. J. Control. Release 34:43–51 (1995).

    Article  CAS  Google Scholar 

  13. F. Acartürk, and A. Şencan. Investigation of the effect of different adjuvants on felodipine release kinetics from sustained release monolithic films. Int. J. Pharm. 131:183–189 (1996).

    Article  Google Scholar 

  14. V. Kusum Devi, S. Saisivam, G. R. Maria, and P. U. Deepti. Design and evaluation of matrix controlled transdermal patches of verapamil hydrochloride. Drug Dev. Ind. Pharm. 295:495–503 (2003).

    Article  PubMed  CAS  Google Scholar 

  15. S. P. Gupta, and S. K. Jain. Development of matrix-membrane transdermal drug delivery system for atenolol. Drug Delivery 11:281–286 (2004).

    Article  PubMed  CAS  Google Scholar 

  16. S. Mutalik, N. Udupa, S. Kumar, S. Agarwal, G. Subramanian, and A. K. Ranjith. Glipizide matrix transdermal systems for diabetes mellitus: Preparation, in vitro and preclinical studies. Life Sci. 79:1568–1577 (2006).

    Article  PubMed  CAS  Google Scholar 

  17. U. Ubaidulla, M. Reddy, K. Ruckmani, F. J. Ahmad, and R. K. Khar. Transdermal therapeutic system of carvedilol: Effect of hydrophilic and hydrophobic matrix on in vitro and in vivo characteristics. AAPS Pharm. Sci. Tech. 8(1):Article 2. doi:10.1208/pt0801002 (2007).

  18. R. Bodmeier, and O. Paeratakul. Propranolol HCl release from acrylic films prepared from aqueous latexes. Int. J. Pharm. 59:197–204 (1990).

    Article  CAS  Google Scholar 

  19. S. Y. Lin, Y. Y. Lin, and C. L. Cheng. Studies on the compatibility, efficiency and permanence of plasticizers on drug-free or drug-loaded Eudragit-E-films. Pharmazie. 50:801–809 (1995).

    CAS  Google Scholar 

  20. Ö. İnal, M. Kılıçarslan, N. Arı, and T. Baykara. In vitro and in vivo transdermal studies of atenolol using iontophoresis. Acta Pol. Pharm. Drug Res. 651:29–36 (2008).

    Google Scholar 

  21. Röhm Pharma Catalogue. 2000. Röhm Pharma Data Sheet, HTML\files\pharma4_ formulation\4.6.1.pdf.

  22. ICH Guideline. 2005. Validation of Analytical Procedures: Text and Methodology Q2 (R1), http:/www.ich.gov/LOB/media/MEDIA417.pdf.

  23. A. Akhgari, F. Farahmand, H. Afrasiabi Garekani, F. Sadeghi, and T.F. Vandamme. Permeability and swelling studies on free films containing inulin in combination with different polymethacrylates aimed for colonic drug delivery. Eur. J. Pharm. Sci. 28:307–314 (2006).

    Article  PubMed  CAS  Google Scholar 

  24. C. Padula, S. Nicoli, P. Colombo, and P. Santi. Single-layer transdermal film containing lidocaine: Modulation of drug release. Eur. J. Pharm. Biopharm. 663:422–428 (2007).

    Article  PubMed  CAS  Google Scholar 

  25. S. Santoyo, A. Arellano, P. Ygartua, and C. Martin. Penetration enhancer effects on the in vitro percutaneous absorption of piroxicam trough rat skin. Int. J. Pharm. 1051:219–224 (1995).

    Article  Google Scholar 

  26. O. Pillai, and R. Panchangula. Transdermal delivery of insulin from poloxamer gel: Ex vivo and in vivo permeation studies in rat using iontophoresis and chemical enhancers. J. Control. Release 89:127–140 (2003).

    Article  PubMed  CAS  Google Scholar 

  27. S. T. Narishetty, and R. Panchagnula. Transdermal delivery system for zidovudine: In vitro, ex vivo, in vivo evaluation. Biopharm. Drug Disp. 251:9–20 (2004).

    Article  CAS  Google Scholar 

  28. A. Femenia-Font, C. Balaguer-Fernandez, V. Merino, V. Rodilla, and A. Lopez-Castellano. Effect of chemical enhancers on the in vitro percutaneous absorption of sumatriptan succinate. Eur. J. Pharm. Biopharm. 61:50–55 (2005).

    Article  PubMed  CAS  Google Scholar 

  29. B. Uslu, and S. A. Özkan. Determination of lamivudine and zidovudine in binary mixtures using first derivative spectrophotometric, first derivative of the ratio-spectra and high-performance liquid chromatography–UV methods. Anal. Chim. Acta. 466:175–185 (2002).

    Article  CAS  Google Scholar 

  30. M. Aqil, and A. Ali. Monolithic matrix type transdermal drug delivery systems of pinacidil monohydrate: In vitro characterization. Eur. J. Pharm. Biopharm. 54:161–164 (2002).

    Article  PubMed  CAS  Google Scholar 

  31. P. N. Kotiyan, and P. R. Vavia. Eudragits: Role as crystallization inhibitors in drug-in-adhesive transdermal systems of estradiol. Eur. J. Pharm. Biopharm. 52:173–180 (2001).

    Article  PubMed  CAS  Google Scholar 

  32. J. Siepmann, F. Lecomte, and R. Bodmeier. Diffusion-controlled drug delivery systems: Calculation of the required composition to achieve desired release profiles. J. Control. Release 60:379–389 (1999).

    Article  PubMed  CAS  Google Scholar 

  33. N. Yuksel, A.E. Kanık, and T. Baykara. Comparison of in vitro dissolution profiles by ANOVA-based, model-dependent and-independent methods. Int. J. Pharm. 209:57–67 (2000).

    Article  PubMed  CAS  Google Scholar 

  34. P. Costa, and J. M. Sausa Lobo. Evaluation of mathematical models describing drug release from estradiol transdermal systems. Drug Dev. Ind. Pharm. 291:89–97 (2003).

    Article  PubMed  CAS  Google Scholar 

  35. A. C. Williams, and B. W. Barry. Penetration enhancers. Adv. Drug Del. Rev. 56:603–618 (2004).

    Article  CAS  Google Scholar 

  36. A. N. C. Anigbogu, A. C. Williams, B. W. Barry, and H. G. M. Edwards. Fourier transform Raman spectroscopy of interactions between the penetration enhancer dimethyl sulfoxide and human stratum corneum. Int. J. Pharm. 1252:265–282 (1995).

    Article  CAS  Google Scholar 

  37. A. A. S. Araujo, S. Storpirtis, L. P. Mercuri, F. M. S. Carvalho, M. S. Filho, and J. R. Matos. Thermal analysis of the antiretroviral zidovudine (AZT) and evaluation of the compatibility with excipients used in solid dosage forms. Int. J. Pharm. 2602:303–314 (2003).

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The authors wish to thank Drogsan Pharmaceuticals, Ankara, Turkey/Cipla Inc., India for their support in providing zidovudine.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Technology, Faculty of Pharmacy, Ankara University, Tandoğan, Ankara, 06100, Turkey

    Evrim Atilay Takmaz, Özge Inal & Tamer Baykara

Authors
  1. Evrim Atilay Takmaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Özge Inal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tamer Baykara
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tamer Baykara.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Takmaz, E.A., Inal, Ö. & Baykara, T. Studies on Transdermal Delivery Enhancement of Zidovudine. AAPS PharmSciTech 10, 88–97 (2009). https://doi.org/10.1208/s12249-008-9179-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-008-9179-9

Key words

Search

Navigation