Skip to main content

Advertisement

SpringerLink
Log in

Development and Evaluation of Combined Effect Buccal Films for Treatment of Oral Candidiasis

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

Abstract

Buccal film formulations, including antifungal nystatin, anti-inflammatory agent hydrocortisone acetate, and local anesthetic lidocaine hydrochloride for pain relief, were developed. Bioadhesive films were fabricated with hydrophilic polymers, hydroxyethyl cellulose (HEC), and xanthan gum (XG) and dried in the incubator. Textural, swelling, and bioadhesive properties, physicochemical and in vitro release characteristics, and antifungal activities of bioadhesive films were evaluated.

Bioadhesive films significantly extended nystatin release by prolonging retention time of the target area formulation while rapidly releasing hydrocortisone acetate and lidocaine HCl, reducing drug administration. The polymer type affected bioadhesion strength and erosion ratio, and XG formulations had more polymer suitability. Consequently, XT-O2 formulation that was prepared with xanthan gum and tween 80, was best for its highest antifungal film activity (20.00 ± 0.07 mm), released nystatin (44.296% ± 1.695), and lowest erosion matrix (36.719% ± 0.249). The selected formulation can be used for compatibility, stability and in vivo studies targeted oral candidiasis infections.

Graphical Abstract

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. DeGregorio MW, Lee WM, Ries CA. Candida infections in patients with acute leukemia: ineffectiveness of nystatin prophylaxis and relationship between oropharyngeal and systemic candidiasis. Cancer. 1982;50(12):2780–4. https://doi.org/10.1002/1097-0142(19821215)50.

    Article  CAS  Google Scholar 

  2. Patel M, Coogan MM. Antifungal activity of the plant Dodonaea viscosa var. angustifolia on Candida albicans from HIV-infected patients. J Ethnopharmacol. 2008;118(1):173–6. https://doi.org/10.1016/j.jep.2008.03.009.

    Article  Google Scholar 

  3. Burgess DS, Hastings RW, Summers KK, Hardin TC, Rinaldi MG. Pharmacodynamics of fluconazole, itraconazole, and amphotericin B against Candida albicans. Diagn Microbiol Infect Dis. 2000;36(1):13–8. https://doi.org/10.1016/s0732-8893(99)00097-8.

    Article  CAS  Google Scholar 

  4. Watkins WJ, Renau TE. Chapter 14. Progress with antifungal agents and approaches to combat fungal resistance. Annual Reports in Medicinal Chemistry. Academic Press; 2000. p. 157–66.

  5. 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. https://doi.org/10.1016/j.jconrel.2006.04.012.

    Article  CAS  Google Scholar 

  6. Bennett JE. Antimicrobial agents: antifungal agents. In: A.G. Gilaman ASN, editor. The pharmacological basis of therapeutics. New York: McGraw-Hill; 1993. p. 1165–81.

  7. Brunton LL, Sandford. GL, Goodman. GA, L. PK. Goodman and Gilman's manual of pharmacology and therapeutics. New York: McGraw-Hill; 2008.

  8. Gu JM, Robinson JR, Leung SH. Binding of acrylic polymers to mucin/epithelial surfaces: structure-property relationships. Crit Rev Ther Drug Carrier Syst. 1988;5(1):21–67.

    CAS  Google Scholar 

  9. Adhikari SN, Nayak BS, Nayak AK, Mohanty B. Formulation and evaluation of buccal patches for delivery of atenolol. AAPS PharmSciTech. 2010;11(3):1038–44. https://doi.org/10.1208/s12249-010-9459-z.

    Article  CAS  Google Scholar 

  10. AlirezaMortazavi S, Smart JD. An in-vitro method for assessing the duration of mucoadhesion. J Control Release. 1994;31(2):207–12. https://doi.org/10.1016/0168-3659(94)00044-1.

    Article  Google Scholar 

  11. Merkle HP, Wolany G. Buccal delivery for peptide drugs. J Control Release. 1992;21(1):155–64. https://doi.org/10.1016/0168-3659(92)90017-L.

    Article  CAS  Google Scholar 

  12. Smart JD. An m vitro assessment of some mucosa-adhesive dosage forms. Int J Pharm. 1991;73(1):69–74. https://doi.org/10.1016/0378-5173(91)90101-S.

    Article  CAS  Google Scholar 

  13. Yildiz Pekoz A, Erdal S, Okyar A, Ocak M, Tekeli F, Kaptan E, et al. Preparation and in-vivo evaluation of dimenhydrinate buccal mucoadhesive films with enhanced bioavailability. Drug Dev Ind Pharm. 2016;42(6):916–25. https://doi.org/10.3109/03639045.2015.1091470.

    Article  CAS  Google Scholar 

  14. Pendela M, Kahsay G, Baekelandt I, Van Schepdael A, Adams E. Simultaneous determination of lidocaine hydrochloride, hydrocortisone and nystatin in a pharmaceutical preparation by RP-LC. J Pharm Biomed Anal. 2011;56(3):641–4. https://doi.org/10.1016/j.jpba.2011.06.028.

    Article  CAS  Google Scholar 

  15. Wong CF, Yuen KH, Peh KK. Formulation and evaluation of controlled release Eudragit buccal patches. Int J Pharm. 1999;178(1):11–22. https://doi.org/10.1016/s0378-5173(98)00342-1.

    Article  CAS  Google Scholar 

  16. Rasool BKA, Abu-Gharbieh E, Awni RA, Rasool AAA. In vitro release study of nystatin from chitosan buccal gel. Jordan Journal of Pharmaceutical Sciences. 2010;3:44–55.

    CAS  Google Scholar 

  17. de Aguiar MM, de Albuquerque RP, Marinho DS, Braga BR, Dornelas CB, Oliveira A, et al. Oral sustained release nystatin tablets for the treatment of oral candidiasis: formulation development and validation of UV spectrophotometric analytical methodology for content determination. Drug Dev Ind Pharm. 2010;36(5):594–600. https://doi.org/10.3109/03639040903384729.

    Article  CAS  Google Scholar 

  18. Ceschel GC, PMSLBCR. Design and evaluation of buccal adhesive hydrocortisone acetate (HCA) tablets. Drug Delivery. 2001;8(3):161–71. https://doi.org/10.1080/107175401316906937.

    Article  CAS  Google Scholar 

  19. Higuchi T. Rate of release of medicaments from ointment bases containing drugs in suspension. J Pharm Sci. 1961;50:874–5. https://doi.org/10.1002/jps.2600501018.

    Article  CAS  Google Scholar 

  20. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of potassium chloride release from compressed, hydrophilic, polymeric matrices: effect of entrapped air. J Pharm Sci. 1983;72(10):1189–91. https://doi.org/10.1002/jps.2600721021.

    Article  CAS  Google Scholar 

  21. Peppas NA. Analysis of Fickian and non-Fickian drug release from polymers. Pharm Acta Helv. 1985;60(4):110–1.

    CAS  Google Scholar 

  22. Patel VM, Prajapati BG, Patel MM. Design and characterization of chitosan-containing mucoadhesive buccal patches of propranolol hydrochloride. Acta Pharm. 2007;57(1):61–72. https://doi.org/10.2478/v10007-007-0005-9.

    Article  CAS  Google Scholar 

  23. Vishnu YV, Chandrasekhar K, Ramesh G, Rao YM. Development of mucoadhesive patches for buccal administration of carvedilol. Curr Drug Deliv. 2007;4(1):27–39. https://doi.org/10.2174/156720107779314785.

    Article  CAS  Google Scholar 

  24. Tirosh B, Baluom M, Nassar T, Friedman M, Rubinstein A. The effect of Eudragit RL-100 on the mechanical and mucoadhesion properties of polycarbophil dosage forms1The results reported here form part of the dissertation projects of M.B. and T.N., completed in partial fulfilment of the requirements of their respective PhD and MSc degrees at the Hebrew University of Jerusalem. The study has been presented in part at the 22nd International Symposium on Controlled Release of Bioactive Materials, Seattle, WA, 1995.1. J Controlled Release. 1997;45(1):57–64. https://doi.org/10.1016/S0168-3659(96)01545-3.

  25. Ritthidej GC, Phaechamud T, Koizumi T. Moist heat treatment on physicochemical change of chitosan salt films. Int J Pharm. 2002;232(1–2):11–22. https://doi.org/10.1016/s0378-5173(01)00894-8.

    Article  CAS  Google Scholar 

  26. Sezer AD, Hatipoğlu F, Cevher E, Oğurtan Z, Baş AL, Akbuğa J. Chitosan film containing fucoidan as a wound dressing for dermal burn healing: preparation and in vitro/in vivo evaluation. AAPS PharmSciTech. 2007;8(2):39. https://doi.org/10.1208/pt0802039.

    Article  Google Scholar 

  27. Avachat AM, Gujar KN, Wagh KV. Development and evaluation of tamarind seed xyloglucan-based mucoadhesive buccal films of rizatriptan benzoate. Carbohydr Polym. 2013;91(2):537–42. https://doi.org/10.1016/j.carbpol.2012.08.062.

    Article  CAS  Google Scholar 

  28. Rex J, Ghannoum M, Alexander B, David A, Brown S, Diekema D, et al. Method for antifungal disk diffusion susceptibility testing of yeasts; approved guideline-Second Edition. Pennsylvania, USA: Clinical and Laboratory Standards Institute M44-A2. 2009;29(17).

  29. Verma P, Ahuja M. Optimization, characterization and evaluation of chitosan-tailored cubic nanoparticles of clotrimazole. Int J Biol Macromol. 2015;73:138–45. https://doi.org/10.1016/j.ijbiomac.2014.10.065.

    Article  CAS  Google Scholar 

  30. Danglad-Flores JA, Eickelmann S, Riegler H. Deposition of polymer films by spin casting: a quantitative analysis. Chem Eng Sci. 2018;179:257–64.

    Article  CAS  Google Scholar 

  31. Nair AB, Kumria R, Harsha S, Attimarad M, Al-Dhubiab BE, Alhaider IA. In vitro techniques to evaluate buccal films. J Control Release. 2013;166(1):10–21. https://doi.org/10.1016/j.jconrel.2012.11.019.

    Article  CAS  Google Scholar 

  32. Nafee NA, Boraie MA, Ismail FA, Mortada LM. Design and characterization of mucoadhesive buccal patches containing cetylpyridinium chloride. Acta Pharm. 2003;53(3):199–212.

    CAS  Google Scholar 

  33. Perioli L, Ambrogi V, Rubini D, Giovagnoli S, Ricci M, Blasi P, et al. Novel mucoadhesive buccal formulation containing metronidazole for the treatment of periodontal disease. J Control Release. 2004;95(3):521–33. https://doi.org/10.1016/j.jconrel.2003.12.018.

    Article  CAS  Google Scholar 

  34. Singh S, Jain S, Muthu MS, Tiwari S, Tilak R. Preparation and evaluation of buccal bioadhesive films containing clotrimazole. AAPS PharmSciTech. 2008;9(2):660–7. https://doi.org/10.1208/s12249-008-9083-3.

    Article  CAS  Google Scholar 

  35. Preis M, Pein M, Breitkreutz J. Development of a taste-masked orodispersible film containing dimenhydrinate. Pharmaceutics. 2012;4(4):551–62. https://doi.org/10.3390/pharmaceutics4040551.

    Article  CAS  Google Scholar 

  36. Mady OY, Abulmeaty MMA, Donia AA, Al-Khureif AA, Al-Shoubki AA, Abudawood M, et al. Formulation and bioavailability of novel mucoadhesive buccal films for candesartan cilexetil in rats. Membranes (Basel). 2021;11(9). https://doi.org/10.3390/membranes11090659.

  37. Pastório NFG, Vecchi CF, Said Dos Santos R, Bruschi ML. Design of mucoadhesive strips for buccal fast release of tramadol. Pharmaceutics. 2021;13(8). https://doi.org/10.3390/pharmaceutics13081187.

  38. Tas C, Ozkan Y, Savaser A, Baykara T. In vitro release studies of chlorpheniramine maleate from gels prepared by different cellulose derivatives. Farmaco. 2003;58(8):605–11. https://doi.org/10.1016/s0014-827x(03)00080-6.

    Article  CAS  Google Scholar 

  39. Akash MSH, Khan IU, Shah SNH, Asghar S, Massud A, Qadir M, et al. Sustained release hydrophilic matrices based on xanthan gum and hydroxypropyl methylcellulose: development, optimization, in vitro and in vivo evaluation. Journal of applied pharmacy. 2010;2:89–103.

    Article  CAS  Google Scholar 

  40. Wu X, Desai KG, Mallery SR, Holpuch AS, Phelps MP, Schwendeman SP. Mucoadhesive fenretinide patches for site-specific chemoprevention of oral cancer: enhancement of oral mucosal permeation of fenretinide by coincorporation of propylene glycol and menthol. Mol Pharm. 2012;9(4):937–45. https://doi.org/10.1021/mp200655k.

    Article  CAS  Google Scholar 

  41. Chun M-K, Kwak B-T, Choi H-K. Preparation of buccal patch composed of carbopol, poloxamer and hydroxypropyl methylcellulose. Arch Pharmacal Res. 2003;26(11):973–8.

    Article  CAS  Google Scholar 

  42. Abou Hussein D, El-Nabarawi M, Shalaby S, El-Bary A. Cetylpyridinium chloride chitosan blended mucoadhesive buccal films for treatment of pediatric oral diseases. Journal of Drug Delivery Science and Technology. 2020;57: 101676. https://doi.org/10.1016/j.jddst.2020.101676.

    Article  CAS  Google Scholar 

  43. Samanthula K, Bairi A, Satla S, Cb M. Development, ın-vıtro and ex-vıvo evaluatıon of muco-adhesıve buccal tablets of hydralazıne hydrochlorıde. Brazilian Journal of Pharmaceutical Science. 2020;56:1–13. https://doi.org/10.1590/s2175-97902020000318635.

    Article  CAS  Google Scholar 

  44. Güngör S, Erdal M, Ozsoy Y. Plasticizers in Transdermal Delivery Systems. 2012. p. 91–112.

  45. Winarti L, Laksono BT, Sari LORK. Optimization of hydroxy propyl methyl cellulose and carbomer ın diltiazem hydrochloride mucoadhesive buccal film. Indonesıan J Pharm. 2021.

  46. Ghosal K, Ranjan A, Bhowmik BB. A novel vaginal drug delivery system: anti-HIV bioadhesive film containing abacavir. J Mater Sci Mater Med. 2014;25(7):1679–89. https://doi.org/10.1007/s10856-014-5204-6.

    Article  CAS  Google Scholar 

  47. Arora G, Malik K, Singh I. Formulation and evaluation of mucoadhesive matrix tablets of taro gum: optimization using response surface methodology. Polim Med. 2011;41(2):23–34.

    CAS  Google Scholar 

  48. Tzanova MM, Hagesaether E, Tho I. Solid lipid nanoparticle-loaded mucoadhesive buccal films - critical quality attributes and in vitro safety & efficacy. Int J Pharm. 2021;592: 120100. https://doi.org/10.1016/j.ijpharm.2020.120100.

    Article  CAS  Google Scholar 

  49. Peh KK, Wong CF. Polymeric films as vehicle for buccal delivery: swelling, mechanical, and bioadhesive properties. J Pharm Pharm Sci. 1999;2(2):53–61.

    CAS  Google Scholar 

  50. Ghosal K, Rajabalaya R, Maiti AK, Chowdhury B, Nanda A. Evaluation of physicochemical properties and in-vitro release profile of glipizide-matrix patch. Braz J Pharm Sci. 2010;46:213–8.

    Article  CAS  Google Scholar 

  51. Tejada G, Barrera MG, Piccirilli GN, Sortino M, Frattini A, Salomón CJ, et al. Development and evaluation of buccal films based on chitosan for the potential treatment of oral candidiasis. AAPS PharmSciTech. 2017;18(4):936–46. https://doi.org/10.1208/s12249-017-0720-6.

    Article  CAS  Google Scholar 

  52. Baus RA, Zahir-Jouzdani F, Dünnhaupt S, Atyabi F, Bernkop-Schnürch A. Mucoadhesive hydrogels for buccal drug delivery: ın vitro-in vivo correlation study. Eur J Pharm Biopharm. 2019;142:498–505. https://doi.org/10.1016/j.ejpb.2019.07.019.

    Article  CAS  Google Scholar 

  53. Nesseem DI, Eid SF, El-Houseny SS. Development of novel transdermal self-adhesive films for tenoxicam, an anti-inflammatory drug. Life Sci. 2011;89(13–14):430–8. https://doi.org/10.1016/j.lfs.2011.06.026.

    Article  CAS  Google Scholar 

  54. Ugoeze KC. Bioadhesive Polymers for Drug Delivery Applications. 2020.

  55. Rajesh N, Siddaramaiah. Feasibility of xanthan gum-sodium alginate as a transdermal drug delivery system for domperidone. J Mater Sci Mater Med. 2009;20(10):2085–9. https://doi.org/10.1007/s10856-009-3774-5.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the support of the Research Fund of Istanbul University (BAP-20892). This work has been granted a Turkish patent (Patent number is TR-2014/07775).

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, 34116, Istanbul, Türkiye

    Derya Arslan, Özlem Akbal Dağıstan, Erdal Cevher & Ayca Yildiz-Pekoz

  2. Department of Analytical Chemistry, Faculty of Pharmacy, Istanbul University, 34116, Istanbul, Türkiye

    Olcay Sagirli

  3. Department of Infectious Diseases and Clinical Microbiology, School of Medicine, Marmara University, Pendik Training and Research Hospital, 34899, Istanbul, Türkiye

    Lutfiye Mulazimoglu

Authors
  1. Derya Arslan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Özlem Akbal Dağıstan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olcay Sagirli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lutfiye Mulazimoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Erdal Cevher
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ayca Yildiz-Pekoz
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, A.Y.-P., D.A, O.A.-D.; data curation, D.A.; formal analysis, A.Y.-P., D.A, E.C.; funding acquisition, A.Y.-P., D.A.; investigation, D.A, O.A.-D.; methodology; A.Y.-P., L.M.; project administration, A.Y.-P., D.A, O.A.-D; resources, A.Y.-P.; supervision, A.Y.-P, O.A.-D.; validation, A.Y.-P., D.A., O.S., L.M.; writing—original draft, A.Y.-P., D.A, O.A.-D.; writing—review & editing, A.Y.-P., D.A, O.A.-D., L.M., E.C. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Ayca Yildiz-Pekoz.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Arslan, D., Akbal Dağıstan, Ö., Sagirli, O. et al. Development and Evaluation of Combined Effect Buccal Films for Treatment of Oral Candidiasis. AAPS PharmSciTech 24, 23 (2023). https://doi.org/10.1208/s12249-022-02477-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-022-02477-5

Keywords

Search

Navigation