Skip to main content

Advertisement

SpringerLink
Log in

Bioadhesive Films Containing Benzocaine: Correlation Between In Vitro Permeation and In Vivo Local Anesthetic Effect

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

ABSTRACT

Purpose

The aim of this work was to develop anesthetic bioadhesive films containing benzocaine and study their in vitro skin permeation and in vivo performance, in comparison with commercial formulations.

Methods

Films containing 3% and 5% w/w of benzocaine were prepared and characterized by weight, drug content, thickness and morphology. In vitro permeation assays were performed in vertical diffusion cells using full-thickness pig ear skin as barrier. Intensity and duration of analgesia were evaluated in rats by tail-flick test, and skin histological analysis was carried out.

Results

Tail-flick test showed that the duration of benzocaine-induced analgesia was significantly prolonged with the films compared to commercial creams, in agreement with the higher in vitro permeation. Histological analysis of the rat tail skin did not reveal morphological tissue changes nor cell infiltration signs after application of the commercial creams or films.

Conclusions

Results from our study indicate that the films developed in this work can be considered as innovative dermal/transdermal therapeutic systems for benzocaine local delivery.

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
Fig. 5
Fig. 6

Similar content being viewed by others

REFERENCES

  1. Harmatz A. Local anesthetics: uses and toxicities. Surg Clin North Am. 2009;89:587–98.

    Article  PubMed  Google Scholar 

  2. Butterworth JF, Strichartz GR. Molecular mechanisms of local anesthesia: a review. Anesthesiology. 1990;72:711–34.

    Article  PubMed  CAS  Google Scholar 

  3. Yanagidate F, Strichartz GR. Local anesthetics. Handb Exp Pharmacol. 2007;177:95–127.

    Article  PubMed  CAS  Google Scholar 

  4. Al-Melh MA, Anderson L. Comparison of topical anesthetics (EMLA/Oraqix vs. benzocaine) on pain experienced during palatal needle injection. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103:16–20.

    Article  Google Scholar 

  5. Roos TC, Merk HF. Allergic contact dermatitis from benzocaine ointment during tretment of herpes zoster. Contact Dermatitis. 2001;44:97–130.

    Article  Google Scholar 

  6. de Padua CA, Schnuch A, Nink K, Pfahlberg A, Uter W. Allergic contact dermatitis to topical drugs-epidemiological risk assessment. Pharmacoepidemiol Drug Saf. 2008;17:813–21.

    Article  PubMed  Google Scholar 

  7. Young KD. What’s new in topical anesthesia. Clin Pediatr Emerg Med. 2007;8:232–9.

    Article  Google Scholar 

  8. Shin SC, Lee KW, Yang CH. Preparation and evaluation of bioadhesive benzocaine gels for enhancement local anesthetic effects. Int J Pharm. 2003;260:77–81.

    Article  PubMed  CAS  Google Scholar 

  9. Mura P, Maestrelli F, Gonzalez-Rodriguez ML, Michelacci I, Ghelardini C, Rabasco AM. Development, characterization of benzocaine-loaded liposomes. Eur J Pharm Biopharm. 2007;67:86–95.

    Article  PubMed  CAS  Google Scholar 

  10. Maestrelli F, Capasso G, Gonzalez-Rodriguez ML, Rabasco AM, Mura P. Effect of preparation technique on the properties and in vivo efficacy of benzocaine-loaded ethosomes. J Liposome Res. 2009;4:1–8.

    Article  Google Scholar 

  11. Padula C, Colombo G, Nicoli S, Catellani PL, Massimo G, Santi P. Bioadhesive film for the transdermal delivery of lidocaine: in vitro and in vivo behavior. J Control Release. 2003;88:277–85.

    Article  PubMed  CAS  Google Scholar 

  12. Padula C, Nicoli S, Aversa V, Colombo P, Falson F, Pirot F, et al. Bioadhesive film for dermal and transdermal drug delivery. Eur J Dermatol. 2007;17:309–12.

    PubMed  CAS  Google Scholar 

  13. Nussinovitch A, Gal A, Padula C, Santi P. Physical characterization of a new skin bioadhesive film. AAPS PharmSciTech. 2008;9:458–63.

    Article  PubMed  CAS  Google Scholar 

  14. Padula C, Nicoli S, Colombo P, Santi P. Single-layer transdermal film containing lidocaine: modulation of drug release. Eur J Pharm Biopharm. 2007;66:422–8.

    Article  PubMed  CAS  Google Scholar 

  15. Nicoli S, Colombo P, Santi P. Release and permeation kinetics of caffeine from bioadhesive transdermal films. AAPS J. 2005;7:E218–23.

    Article  PubMed  CAS  Google Scholar 

  16. Nicoli S, Penna E, Padula C, Colombo P, Santi P. New transdermal bioadhesive film containing oxybutynin: in vitro permeation across rabbit ear skin. Int J Pharm. 2006;325:2–7.

    Article  PubMed  CAS  Google Scholar 

  17. Femenia-Font A, Padula C, Marra F, Balaguer-Fernandez C, Merino V, Lopez-Castellano A, et al. Bioadhesive monolayer film for the in vitro transdermal delivery of sumatriptan. J Pharm Sci. 2006;95:1561–9.

    Article  PubMed  CAS  Google Scholar 

  18. Nicoli S, Cella S, Aversa V, Santi P. Transdermal film containing nicotine and bupropion for combined smoking cessation therapy. Pharm Technol Eur. 2008;20:613–21.

    Google Scholar 

  19. Padula C, Nicoli S, Santi P. Innovative formulations for the delivery of levothyroxine to the skin. Int J Pharm. 2009;372:12–6.

    Article  PubMed  CAS  Google Scholar 

  20. Narang PK, Bird G, Crouthamel WG. High-performance liquid chromatographic assay for the benzocaine an p-aminobenzoic acid including preliminary stability data. J Pharm Sci. 1980;69:1384–7.

    Article  PubMed  CAS  Google Scholar 

  21. Nagorsen DW, Peterson RL. Mammal collectors’ manual: a guide for collecting, documenting and preparing mammal specimens for scientific research, Royal Ontario Museum; 1980.

  22. Zar JH. Biostatistical analysis. New Jersey: Prentice Hall; 1996.

    Google Scholar 

  23. Nathan D, Sakr A, Lichtin JL, Bronaugh RL. In vitro skin absorption and metabolism of benzoic acid, p-aminobenzoic acid, and benzocaine in the hairless guinea pig. Pharm Res. 1990;7:1147–51.

    Article  PubMed  CAS  Google Scholar 

  24. Godwin D, Kim N. Influence of Transcutol® CG on the skin accumulation and transdermal permeation of ultraviolet absorbers. Eur J Pharm Biopharm. 2002;53:23–7.

    Article  PubMed  CAS  Google Scholar 

  25. Mura P, Faucci M, Bramanti G, Corti P. Evaluation of transcutol as a clonazepam transdermal permeation enhancer from hydrophilic gel formulations. Eur J Pharm Sci. 2000;9:365–72.

    Article  PubMed  CAS  Google Scholar 

  26. Narishetty ST, Panchagnula R. Transdermal delivery system for zidovuline: in vitro, ex vivo and in vivo evaluation. Biopharm Drug Dispos. 2004;25:9–20.

    Article  PubMed  CAS  Google Scholar 

  27. Catz P, Friend D. Transdermal delivery of levonorgestrel VIII. Effects of enhancers on rat skin, hairless mouse skin, hairless guinea pig skin, and human skin. Int J Pharm. 1990;58:93–102.

    Article  CAS  Google Scholar 

  28. Schmook FP, Maingassner JG, Billich A. Comparison of human skin or epidermis models with human and animal skin in in-vitro percutaneous absorption. Int J Pharm. 2001;215:51–6.

    Article  PubMed  CAS  Google Scholar 

  29. Surber C, Smith E, Schwarb F, Maibach H. Drug concentration in the skin. In: Bronaugh R, Maibach H, editors. Percutaneous absorption. Drugs and the pharmaceutical sciences. New York: Marcel Dekker; 1999. p. 347–74.

    Google Scholar 

  30. Rougier A, Dupuis D, Lotte C, Maibach H. Stripping method for measuring percutaneous absorption in vivo. In: Bronaugh R, Maibach H, editors. Percutaneous absorption. Drugs and the pharmaceutical sciences. New York: Marcel Dekker; 1999. p. 375–94.

    Google Scholar 

Download references

ACKNOWLEDGEMENTS

The authors are grateful to Comissão de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES, Brazil, protocol 0115-070) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Brazil, protocol 06/00121-9).

Author information

Authors and Affiliations

  1. Human and Natural Sciences Center, Federal University of ABC—UFABC, Santo André, SP, Brazil

    Daniele Ribeiro de Araujo

  2. Department of Biochemistry, State University of Campinas—UNICAMP, Campinas, SP, Brazil

    Daniele Ribeiro de Araujo, Cíntia Maria Saia Cereda & Eneida de Paula

  3. Clinical Pharmacology and Gastroenterology Unit-UNIFAG, São Francisco University, Bragança Paulista, SP, Brazil

    Giovana Radomille Tófoli

  4. Faculty of Dentistry, São Leopoldo Mandic, Campinas, SP, Brazil

    Rui Barbosa Brito Jr.

  5. Department of Pharmacy, University of Parma—UNIPR, Viale G.P. Usberti 27/a, 43124, Parma, Italy

    Cristina Padula, Sara Nicoli & Patrizia Santi

Authors
  1. Daniele Ribeiro de Araujo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cristina Padula
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cíntia Maria Saia Cereda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Giovana Radomille Tófoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rui Barbosa Brito Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eneida de Paula
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sara Nicoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Patrizia Santi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patrizia Santi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

de Araujo, D.R., Padula, C., Cereda, C.M.S. et al. Bioadhesive Films Containing Benzocaine: Correlation Between In Vitro Permeation and In Vivo Local Anesthetic Effect. Pharm Res 27, 1677–1686 (2010). https://doi.org/10.1007/s11095-010-0151-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-010-0151-5

KEY WORDS

Search

Navigation