Skip to main content
SpringerLink
Log in

Microemulsion-Based Mucoadhesive Buccal Wafers: Wafer Formation, In Vitro Release, and Ex Vivo Evaluation

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

Abstract

Microemulsion has the potentials to enhance dissolution as well as facilitate absorption and permeation of poorly water-soluble drugs through biological membranes. However, its application to govern a controlled release buccal delivery for local treatment has not been discovered. The aim of this study is to develop microemulsion-based mucoadhesive wafers for buccal delivery based on an incorporation of the microemulsion with mucoadhesive agents and mannitol. Ratio of oil to surfactant to water in the microemulsion significantly impacted quality of the wafers. Furthermore, the combination of carbopol and mannitol played a key role in forming the desired buccal wafers. The addition of an extra 50% of water to the formulation was suitable for wafer formation by freeze-drying, which affected the appearance and distribution of carbopol in the wafers. The amount of carbopol was critical for the enhancement of mucoadhesive properties and the sustained drug release patterns. Release study presented a significant improvement of the drug release profile following sustained release for 6 h. Ex vivo mucoadhesive studies provided decisive evidence to the increased retention time of wafers along with the increased carbopol content. The success of this study indicates an encouraging strategy to formulate a controlled drug delivery system by incorporating microemulsions into mucoadhesive wafers.

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. Talegaonkar S, Azeem A, Ahmad FJ, Khar RK, Pathan SA, Khan ZI. Microemulsions: a novel approach to enhanced drug delivery. Recent Pat Drug Deliv Formul. 2008;2(3):238–57.

    Article  CAS  PubMed  Google Scholar 

  2. Tran TT-D, Tran KA, Tran PH. Modulation of particle size and molecular interactions by sonoprecipitation method for enhancing dissolution rate of poorly water-soluble drug. Ultrason Sonochem. 2015;24:256–63. doi:10.1016/j.ultsonch.2014.11.020.

    Article  CAS  PubMed  Google Scholar 

  3. Tran TT-D, Tran PH-L, Nguyen MNU, Tran KTM, Pham MN, Tran PC, et al. Amorphous isradipine nanosuspension by the sonoprecipitation method. Int J Pharm. 2014;474(1–2):146–50. doi:10.1016/j.ijpharm.2014.08.017.

    Article  CAS  PubMed  Google Scholar 

  4. Van Ngo H, Nguyen PK, Van Vo T, Duan W, Tran V-T, Tran PH-L, et al. Hydrophilic-hydrophobic polymer blend for modulation of crystalline changes and molecular interactions in solid dispersion. Int J Pharm. 2016;513(1–2):148–52. doi:10.1016/j.ijpharm.2016.09.017.

    Article  CAS  PubMed  Google Scholar 

  5. Nguyen TN-G, Tran PH-L, Van Vo T, Duan W, Tran TT-D. Development of a sustained release solid dispersion using swellable polymer by melting method. Pharm Res. 2016;33(1):102–9.

    Article  CAS  PubMed  Google Scholar 

  6. Williams AC, Timmins P, Lu M, Forbes RT. Disorder and dissolution enhancement: deposition of ibuprofen on to insoluble polymers. Eur J Pharm Sci. 2005;26(3–4):288–94. doi:10.1016/j.ejps.2005.06.006.

    Article  CAS  PubMed  Google Scholar 

  7. Nguyen TN-G, Tran PH-L, Tran TV, Vo TV, Tran TT-D. Development of a modified—solid dispersion in an uncommon approach of melting method facilitating properties of a swellable polymer to enhance drug dissolution. Int J Pharm. 2015;484:228–34. doi:10.1016/j.ijpharm.2015.02.064.

    Article  CAS  PubMed  Google Scholar 

  8. Saito M, Ugajin T, Nozawa Y, Sadzuka Y, Miyagishima A, Sonobe T. Preparation and dissolution characteristics of griseofulvin solid dispersions with saccharides. Int J Pharm. 2002;249(1–2):71–9. doi:10.1016/S0378-5173(02)00455-6.

    Article  CAS  PubMed  Google Scholar 

  9. Tran TT-D, Tran PH-L, Khanh TN, Van TV, Lee B-J. Solubilization of poorly water-soluble drugs using solid dispersions. Recent Pat Drug Deliv Formul. 2013;7(2):122–33.

    Article  CAS  PubMed  Google Scholar 

  10. Wong JW, Yuen KH. Improved oral bioavailability of artemisinin through inclusion complexation with β- and γ-cyclodextrins. Int J Pharm. 2001;227(1–2):177–85. doi:10.1016/S0378-5173(01)00796-7.

    Article  CAS  PubMed  Google Scholar 

  11. Tran TT-D, Tran PH-L, Lee B-J. Dissolution-modulating mechanism of alkalizers and polymers in a nanoemulsifying solid dispersion containing ionizable and poorly water-soluble drug. Eur J Pharm Biopharm. 2009;72(1):83–90. doi:10.1016/j.ejpb.2008.12.009.

    Article  CAS  PubMed  Google Scholar 

  12. Tran TT-D, Tran PH-L, Choi H-G, Han H-K, Lee B-J. The roles of acidifiers in solid dispersions and physical mixtures. Int J Pharm. 2010;384(1-2):60–6. doi:10.1016/j.ijpharm.2009.09.039.

    Article  CAS  PubMed  Google Scholar 

  13. Tran TT-D, PHL T, Lim J, Park JB, Choi SK, Lee BJ. Physicochemical principles of controlled release solid dispersion containing a poorly water-soluble drug. Ther Deliv. 2010;1(1):51–62. doi:10.4155/tde.10.3.

    Article  CAS  PubMed  Google Scholar 

  14. Tran PHL, Tran HTT, Lee B-J. Modulation of microenvironmental pH and crystallinity of ionizable telmisartan using alkalizers in solid dispersions for controlled release. J Control Release. 2008;129(1):59–65. doi:10.1016/j.jconrel.2008.04.001.

    Article  CAS  PubMed  Google Scholar 

  15. Tran PHL, Tran TTD, Lee SA, Nho VH, Chi SC, Lee BJ. Roles of MgO release from polyethylene glycol 6000-based solid dispersions on microenvironmental pH, enhanced dissolution and reduced gastrointestinal damage of telmisartan. Arch Pharm Res. 2011;34(5):747–55. doi:10.1007/s12272-011-0508-2.

    Article  CAS  PubMed  Google Scholar 

  16. Tran PHL, Tran TTD, Park JB, Min DH, Choi HG, Han HK, et al. Investigation of physicochemical factors affecting the stability of a pH-modulated solid dispersion and a tablet during storage. Int J Pharm. 2011;414(1-2):48–55. doi:10.1016/j.ijpharm.2011.04.065.

    Article  CAS  PubMed  Google Scholar 

  17. Tran TTD, Tran PHL, Park J-B, Lee B-J. Effects of solvents and crystallization conditions on the polymorphic behaviors and dissolution rates of valsartan. Arch Pharm Res. 2012;35(7):1223–30. doi:10.1007/s12272-012-0713-7.

    Article  CAS  PubMed  Google Scholar 

  18. Tran PH-L, Tran TT-D, Lee B-J. Enhanced solubility and modified release of poorly water-soluble drugs via self-assembled gelatin–oleic acid nanoparticles. Int J Pharm. 2013;455(1–2):235–40. doi:10.1016/j.ijpharm.2013.07.025.

    Article  CAS  PubMed  Google Scholar 

  19. Tran PH-L, Tran TT-D, Piao ZZ, Van Vo T, Park JB, Lim J, et al. Physical properties and in vivo bioavailability in human volunteers of isradipine using controlled release matrix tablet containing self-emulsifying solid dispersion. Int J Pharm. 2013;450(1–2):79–86. doi:10.1016/j.ijpharm.2013.04.022.

    Article  CAS  PubMed  Google Scholar 

  20. Feeney OM, Crum MF, McEvoy CL, Trevaskis NL, Williams HD, Pouton CW, et al. 50 years of oral lipid-based formulations: Provenance, progress and future perspectives. Adv Drug Deliv Rev. 2016;101:167–94. doi:10.1016/j.addr.2016.04.007.

    Article  CAS  PubMed  Google Scholar 

  21. Borkar N, Holm R, Yang M, Müllertz A, Mu H. In vivo evaluation of lipid-based formulations for oral delivery of apomorphine and its diester prodrugs. Int J Pharm. 2016;513(1–2):211–7. doi:10.1016/j.ijpharm.2016.09.024.

    Article  CAS  PubMed  Google Scholar 

  22. Carrière F. Impact of gastrointestinal lipolysis on oral lipid-based formulations and bioavailability of lipophilic drugs. Biochimie. 2016;125:297–305. doi:10.1016/j.biochi.2015.11.016.

    Article  PubMed  Google Scholar 

  23. Patel A, Patel J. Mucoadhesive microemulsion based prolonged release vaginal gel for anti-fungal drug. Am J PharmTech Res. 2012;2(4):649–61.

    Google Scholar 

  24. Patel R, Patel Z, Patel K, Patel M. Micro emulsion based gel: recent expansions for topical drug delivery system. J Med Pharm Allied Sci. 2014;1:1–15.

    Google Scholar 

  25. Jha SK. Microemulsions-potential carrier for improved drug delivery. Asian J Biomed Pharm Sci. 2012;1(1):5–9.

  26. Gundogdu E, Baspinar Y, Koksal C, Ince I, Karasulu E. A microemulsion for the oral drug delivery of pitavastatin. Pharmaceutica Analytica Acta. 2013;4(1):1–5.

    Article  Google Scholar 

  27. Kumria R, Nair AB, Goomber G, Gupta S. Buccal films of prednisolone with enhanced bioavailability. Drug Deliv. 2016;23(2):471–8.

    Article  CAS  PubMed  Google Scholar 

  28. Zakeri-Milani P, Nezhadi SH, Barzegar-Jalali M, Mohammadi L, Nokhodchi A, Valizadeh H. Studies on dissolution enhancement of prednisolone, a poorly water-soluble drug by solid dispersion technique. Adv Pharm Bull. 2011;1(1):48.

    PubMed  PubMed Central  Google Scholar 

  29. Kumria R, Nair AB, Goomber G, Gupta S. Buccal films of prednisolone with enhanced bioavailability. Drug Deliv. 2014;23(1):1-8.

  30. Chauhan CS, Naruka PS, Rathore RS, Badadwal V. Formulation and evaluation of prednisolone tablet for colon targeted drug delivery system. J Chem Pharm Res. 2010;2(4):993–8.

    CAS  Google Scholar 

  31. Ghabanchi J, Bahri Najafi R, Haghnegahdar S. Treatment of oral inflammatory diseases with a new mucoadhesive prednisolone tablet versus triamcinolone acetonide paste. IRCMJ. 2009;11(2):155–9.

    Google Scholar 

  32. Iram Shahzadi, Muhammad Irfan Masood, Farzana Chowdhary, Aftab Ahmad Anjum, Muhammad Awais Nawaz, Iram Maqsoo, Muhammad Quaid Zaman. Microemulsion formulation for topical delivery of miconazole nitrate. Int J Pharm Sci Rev Res. 2014:24(2):31.

  33. Rasal A, Mahajan H, Shaikh H, Surana S. Development and characterization of nasal mucoadhesive microemulsion of sumatriptan succinate. Indian J Novel Drug Deliv. 2010;2:103–8.

    Google Scholar 

  34. Ho HO, Hsiao CC, Sheu MT. Preparation of microemulsions using polyglycerol fatty acid esters as surfactant for the delivery of protein drugs. J Pharm Sci. 1996;85(2):138–43.

    Article  CAS  PubMed  Google Scholar 

  35. Nirmala m, Mukherjee A, Chandrasekaran N. Enhanced solubilization of aqueous insoluble anti-hypertensive drug. Int J Pharm Pharm Sci. 2012;4(5):366–8.

    CAS  Google Scholar 

  36. Sabale V, Vora S. Formulation and evaluation of microemulsion-based hydrogel for topical delivery. Int J Pharm Investig. 2012;2(3):140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Shafiq S, Shakeel F, Talegaonkar S, Ahmad FJ, Khar RK, Ali M. Development and bioavailability assessment of ramipril nanoemulsion formulation. Eur J Pharm Biopharm. 2007;66(2):227–43.

    Article  CAS  PubMed  Google Scholar 

  38. Yadav S, Khatri J, Bhalerao S. Development and evaluation of an ocular anti-inflammatory microemulsion. Int J Pharm Technol. 2012;4(2):4218–30.

    CAS  Google Scholar 

  39. Nguyen MN-U, Vo TV, Tran PH-L, Tran T-D, editors. Development of a zein-based system for colon specific delivery. Sixth International Conference on the Development of Biomedical Engineering in Vietnam; 2016; Vietnam.

  40. Patel VM, Prajapati BG, Patel HV, Patel KM. Mucoadhesive bilayer tablets of propranolol hydrochloride. AAPS PharmSciTech. 2007;8(3):E203–E8.

    Article  PubMed Central  Google Scholar 

  41. SYED HK, PEH K. Identification of phases of various oil, surfactant/co-surfactants and water system by ternary phase diagram. Acta Pol Pharm. 2014;71(2):301.

    PubMed  Google Scholar 

  42. Agrawal OP, Agrawal S. An overview of new drug delivery system: microemulsion. Asian J Pharm Sci Tech. 2012; 2: 1: 5. 2012; 12:5-12.

  43. Wang Z, Mu H-J, Zhang X-M, Ma P-K, Lian S-N, Zhang F-P, et al. Lower irritation microemulsion-based rotigotine gel: formulation optimization and in vitro and in vivo studies. Int J Nanomedicine. 2015;10:633.

    PubMed  PubMed Central  Google Scholar 

  44. Harris RA, Shumbula PM, van der Walt H. Analysis of the interaction of surfactants oleic acid and oleylamine with iron oxide nanoparticles through molecular mechanics modeling. Langmuir. 2015;31(13):3934–43.

    Article  CAS  PubMed  Google Scholar 

  45. Verma S, Kaul M, Rawat A, Saini S. An overview on buccal drug delivery system. Int J Pharm Sci Res. 2011;2(6):1303–132.

    CAS  Google Scholar 

  46. Bobade NN, Atram SC, Wankhade VP, Pande DS, Tapar DK, Bobade MNN. A review on buccal drug delivery system. Int J Pharm Sci Res. 2013;3:35–40.

    Google Scholar 

Download references

Acknowledgements

This research is funded by the Vietnam National Foundation for Science and Technology Development (NAFOSTED) under grant number 106-YS.05-2015.02.

Author information

Authors and Affiliations

  1. Pharmaceutical Engineering Laboratory, Biomedical Engineering Department, International University, Vietnam National University, Ho Chi Minh City, Vietnam

    Minh Nguyet Pham, Toi Van Vo & Thao Truong-Dinh Tran

  2. Faculty of Pharmacy, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam

    Van-Thanh Tran

  3. School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia

    Phuong Ha-Lien Tran

Authors
  1. Minh Nguyet Pham
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Toi Van Vo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Van-Thanh Tran
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Phuong Ha-Lien Tran
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thao Truong-Dinh Tran
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Phuong Ha-Lien Tran or Thao Truong-Dinh Tran.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

Electronic supplementary material

ESM 1

(DOCX 617 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pham, M.N., Van Vo, T., Tran, VT. et al. Microemulsion-Based Mucoadhesive Buccal Wafers: Wafer Formation, In Vitro Release, and Ex Vivo Evaluation. AAPS PharmSciTech 18, 2727–2736 (2017). https://doi.org/10.1208/s12249-017-0754-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-017-0754-9

KEY WORDS

Search

Navigation