Skip to main content
SpringerLink
Log in

Lyophilized Sustained Release Mucoadhesive Chitosan Sponges for Buccal Buspirone Hydrochloride Delivery: Formulation and In Vitro Evaluation

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

Abstract

This work aims to prepare sustained release buccal mucoadhesive lyophilized chitosan sponges of buspirone hydrochloride (BH) to improve its systemic bioavailability. Chitosan sponges were prepared using simple casting/freeze-drying technique according to 32 factorial design where chitosan grade was set at three levels (low, medium, and high molecular weight), and concentration of chitosan solution at three levels (0.5, 1, and 2%). Mucoadhesion force, ex vivo mucoadhesion time, percent BH released after 8 h (Q8h), and time for release of 50% BH (T50%) were chosen as dependent variables. Additional BH cup and core buccal chitosan sponge were prepared to achieve uni-directional BH release toward the buccal mucosa. Sponges were evaluated in terms of drug content, surface pH, scanning electron microscopy, swelling index, mucoadhesion strength, ex vivo mucoadhesion time, and in vitro drug release. Cup and core sponge (HCH 0.5E) were able to adhere to the buccal mucosa for 8 h. It showed Q8h of 68.89% and exhibited a uni-directional drug release profile following Higuchi diffusion model.

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
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Pedro AS, Albuquerque EC, Ferreira D, Sarmento B. Chitosan: an option for development of essential oil delivery systems for oral cavity care? Carbohydr Polym. 2009;76:501–8.

    Article  CAS  Google Scholar 

  2. Dasha M, Chiellini F, Ottenbriteb RM, Chiellini E. Chitosan—a versatile semi-synthetic polymer in biomedical applications. Prog Polym Sci. 2011;36:981–1014.

    Article  Google Scholar 

  3. Bernkop-Schnurch A, Dunnhaupt S. Chitosan-based drug delivery systems. Eur J Pharm Biopharm. 2012;81(3):463–9.

    Article  PubMed  Google Scholar 

  4. Patel VF, Liu F, Brown MB. Advances in oral transmucosal drug delivery. J Control Release. 2011;153(2):106–16.

    Article  CAS  PubMed  Google Scholar 

  5. Oungbho K, Müller BW. Chitosan sponges as sustained release drug carriers. Int J Pharm. 1997;156:229–37.

    Article  CAS  Google Scholar 

  6. Lai HL, Abu'Khalil A, Craig DQ. The preparation and characterisation of drug-loaded alginate and chitosan sponges. Int J Pharm. 2003;251(1–2):175–81.

    Article  CAS  PubMed  Google Scholar 

  7. Ayensu I, Mitchell JC, Boateng JS. Development and physico-mechanical characterisation of lyophilised chitosan wafers as potential protein drug delivery systems via the buccal mucosa. Colloids Surf B: Biointerfaces. 2012;91:258–65.

    Article  CAS  PubMed  Google Scholar 

  8. Boateng JS, Auffret AD, Matthews KH, Humphrey MJ, Stevens HN, Eccleston GM. Characterisation of freeze-dried wafers and solvent evaporated films as potential drug delivery systems to mucosal surfaces. Int J Pharm. 2010;389(1–2):24–31.

    Article  CAS  PubMed  Google Scholar 

  9. Shen EC, Wang C, Fu E, Chiang CY, Chen TT, Nieh S. Tetracycline release from tripolyphosphate-chitosan cross-linked sponge: a preliminary in vitro study. J Periodontal Res. 2008;43(6):642–8.

    Article  CAS  PubMed  Google Scholar 

  10. Madhav NV, Shakya AK, Shakya P, Singh K. Orotransmucosal drug delivery systems: a review. J Control Release. 2009;140(1):2–11.

    Article  CAS  PubMed  Google Scholar 

  11. Sudhakar Y, Kuotsu K, Bandyopadhyay AK. Buccal bioadhesive drug delivery—a promising option for orally less efficient drugs. J Control Release. 2006;114(1):15–40.

    Article  CAS  PubMed  Google Scholar 

  12. Shumilov M, Touitou E. Buspirone transdermal administration for menopausal syndromes, in vitro and in animal model studies. Int J Pharm. 2010;387(1–2):26–33.

    Article  CAS  PubMed  Google Scholar 

  13. Nash JR, Nutt DJ. Pharmacotherapy of anxiety. In: Holsboer F, Ströhle A, editors. Anxiety and anxiolytic drugs. Germany: Springer; 2005. p. 469–501.

    Chapter  Google Scholar 

  14. Gannu R, Yamsani SK, Palem CR, Yamsani VV, Kotagiri H, Yamsani MR. Development of high performance liquid chromatography method for buspirone in rabbit serum: application to pharmacokinetic study. Anal Chim Acta. 2009;647(2):226–30.

    Article  CAS  PubMed  Google Scholar 

  15. Moffat AC, Osselton MD, Widdop B. Monographs: buspirone. In: Watts J, editor. Clarke’s analysis of drugs and poisons. 4th ed. London: Pharmaceutical Press; 2011. p. 1014–5.

    Google Scholar 

  16. Sakr A, Andheria M. Pharmacokinetics of buspirone extended-release tablets: a single-dose study. J Clin Pharmacol. 2001;41(7):783–9.

    Article  CAS  PubMed  Google Scholar 

  17. Kassem MA, Elmeshad AN, Fares AR. Enhanced bioavailability of buspirone hydrochloride via cup and core buccal tablets: formulation and in vitro/in vivo evaluation. Int J Pharm. 2014;463(1):68–80.

    Article  CAS  PubMed  Google Scholar 

  18. Foda NH, El-laithy HM, Tadros MI. Implantable biodegradable sponges: effect of interpolymer complex formation of chitosan with gelatin on the release behavior of tramadol hydrochloride. Drug Dev Ind Pharm. 2007;33(1):7–17.

    Article  CAS  PubMed  Google Scholar 

  19. Darwish MK, Elmeshad AN. Buccal mucoadhesive tablets of flurbiprofen: characterization and optimization. Drug Discov Ther. 2009;3(4):181–9.

    CAS  PubMed  Google Scholar 

  20. Patel VM, Prajapati BG, Patel MM. Formulation, evaluation, and comparison of bilayered and multilayered mucoadhesive buccal devices of propranolol hydrochloride. AAPS PharmSciTech. 2007;8(1):E147–54.

    Article  PubMed Central  Google Scholar 

  21. Morsi NM, Abdelbary GA, Ahmed MA. Silver sulfadiazine based cubosome hydrogels for topical treatment of burns: development and in vitro/in vivo characterization. Eur J Pharm Biopharm. 2013.

  22. Perioli L, Ambrogi V, Giovagnoli S, Ricci M, Blasi P, Rossi C. Mucoadhesive bilayered tablets for buccal sustained release of flurbiprofen. AAPS PharmSciTech. 2007;8(3):E54.

    Article  PubMed  Google Scholar 

  23. Perioli L, Ambrogi V, Pagano C, Scuota S, Rossi C. FG90 chitosan as a new polymer for metronidazole mucoadhesive tablets for vaginal administration. Int J Pharm. 2009;377(1–2):120–7.

    Article  CAS  PubMed  Google Scholar 

  24. Al-Zoubi N, Alkhatib HS, Bustanji Y, Aiedeh K, Malamataris S. Sustained-release of buspirone HCl by co spray-drying with aqueous polymeric dispersions. Eur J Pharm Biopharm. 2008;69(2):735–42.

    Article  CAS  PubMed  Google Scholar 

  25. Joshi GV, Kevadiya BD, Bajaj HC. Design and evaluation of controlled drug delivery system of buspirone using inorganic layered clay mineral. Microporous Mesoporous Mater. 2010;132:526–30.

    Article  CAS  Google Scholar 

  26. Foda NH, El-laithy HM, Tadros MI. Optimization of biodegradable sponges as controlled release drug matrices. I. Effect of moisture level on chitosan sponge mechanical properties. Drug Dev Ind Pharm. 2004;30(4):369–79.

    Article  CAS  PubMed  Google Scholar 

  27. Higuchi T. Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963;52:1145–9.

    Article  CAS  PubMed  Google Scholar 

  28. Peppas NA, Sahlin JJ. A simple equation for the description of solute release. III. Coupling of diffusion and relaxation. Int J Pharm. 1989;57:169–72.

    Article  CAS  Google Scholar 

  29. Korsmeyer R, Gumy R, Doelker E, Buri P, Peppas N. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15:25–35.

    Article  CAS  Google Scholar 

  30. Harland RS, Gazzaniga A, Sangalli ME, Colombo P, Peppas NA. Drug/polymer matrix swelling and dissolution. Pharm Res. 1988;5(8):488–94.

    Article  CAS  PubMed  Google Scholar 

  31. Ritger PL, Peppas NA. A simple equation for description of solute release II. fickian and anomalous release from swellable devices. J Control Release. 1987;5:37–42.

    Article  CAS  Google Scholar 

  32. Lehr CM, Bouwstra JA, Schacht EH, Junginger HE. In vitro evaluation of mucoadhesive properties of chitosan and some other natural polymers. Int J Pharm. 1992;78:43–8.

    Article  CAS  Google Scholar 

  33. Park H, Amiji M, Park K. Mucoadhesive hydrogels effective at neutral pH. Proc Int Symp Control Rel Bioact Mater. 1989;16:217–8.

    Google Scholar 

  34. Abruzzo A, Bigucci F, Cerchiara T, Cruciani F, Vitali B, Luppi B. Mucoadhesive chitosan/gelatin films for buccal delivery of propranolol hydrochloride. Carbohydr Polym. 2011;87:581–8.

    Article  Google Scholar 

  35. Agnihotri SA, Aminabhavi TM. Controlled release of clozapine through chitosan microparticles prepared by a novel method. J Control Release. 2004;96(2):245–59.

    Article  CAS  PubMed  Google Scholar 

  36. Polk A, Amsden B, De Yao K, Peng T, Goosen MF. Controlled release of albumin from chitosan-alginate microcapsules. J Pharm Sci. 1994;83(2):178–85.

    Article  CAS  PubMed  Google Scholar 

  37. Ko JA, Park HJ, Hwang SJ, Park JB, Lee JS. Preparation and characterization of chitosan microparticles intended for controlled drug delivery. Int J Pharm. 2002;249(1–2):165–74.

    Article  CAS  PubMed  Google Scholar 

  38. Genta I, Perugini P, Pavanetto F. Different molecular weight chitosan microspheres: influence on drug loading and drug release. Drug Dev Ind Pharm. 1998;24(8):779–84.

    Article  CAS  PubMed  Google Scholar 

  39. Varshosaz J, Karimzadeh S. Development of crosslinked chitosan films for oral mucosal delivery of lidocaine. Res Pharm Sci. 2007;2:43–52.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El Aini Street, Cairo, 11562, Egypt

    Mohamed A. A. Kassem, Aliaa N. ElMeshad & Ahmed R. Fares

Authors
  1. Mohamed A. A. Kassem
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aliaa N. ElMeshad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ahmed R. Fares
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ahmed R. Fares.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kassem, M.A.A., ElMeshad, A.N. & Fares, A.R. Lyophilized Sustained Release Mucoadhesive Chitosan Sponges for Buccal Buspirone Hydrochloride Delivery: Formulation and In Vitro Evaluation. AAPS PharmSciTech 16, 537–547 (2015). https://doi.org/10.1208/s12249-014-0243-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-014-0243-3

KEY WORDS

Search

Navigation