Design and Evaluation of the Release Characteristics of Caffeine-Loaded Microcapsules in a Medicated Chewing Gum Formulation

  • Nima Mohammadi
  • Mohammad Reza Ehsani
  • Hossein Bakhoda


The aim of this study was to microencapsulate caffeine by the emulsion technique, trying to control its release from a medicated chewing gum. Three formulations were prepared using alginate, alginate-starch, and alginate-starch with chitosan coating as the wall materials. These microcapsules were characterized with regard to the morphology studied by using an optical microscope and scanning electron microscopy (SEM), particle size, and encapsulation efficiency. The microcapsules were then incorporated into the chewing gums. The chewing gums were characterized by thermal behavior (by differential scanning calorimetry [DSC]), texture profile analysis [TPA], and sensory evaluation. Furthermore, the release of caffeine from the chewing gum was studied in vitro using the masticatory simulator and in vivo by a chew-out study. The microcapsules revealed a spherical form and high encapsulation efficiency, representing the success of the technique. The outcomes indicated that it is possible to encapsulate caffeine with the techniques employed and the microcapsules prolonged the release of caffeine throughout mastication. The chewing gum containing alginate-starch with chitosan-coated microcapsules showed the great potential of the microcapsule in controlling the release of the caffeine from the chewing gum, thereby delaying its bitterness.


Texture profile analysis Differential scanning calorimetry Masticatory simulator Optical microscope Chewing simulator 


Compliance with Ethical Standards

Conflict of Interests

The authors declare that they have no conflict of interest.


  1. 1.
    J. Jacobsen, L.L. Christrup, N.-H. Jensen, J. Am, Drug Deliv. 2(2), 75–88 (2004)CrossRefGoogle Scholar
  2. 2.
    Y. Patel, A. Shukla, V. Saini, N. Shrimal, P. Sharma, Int. J. Pharm. Sci. Res. 2, 748 (2011)Google Scholar
  3. 3.
    T. Garg, A.K. Goyal, Drug Deliv. Lett. 4(1), 72–78 (2014)CrossRefGoogle Scholar
  4. 4.
    T. Baier, G. Dupeux, S. Herbert, S. Hardt, D. Quere, Control. Eng. 53, 12 (2012)Google Scholar
  5. 5.
    K.R. Shah, T.A. Mehta, Int. J. PharmTech Res. 6, 35 (2014)Google Scholar
  6. 6.
    S.A. Chaudhary, A.F. Shahiwala, Expert Opin. Drug Deliv. 7(7), 871–885 (2010)CrossRefGoogle Scholar
  7. 7.
    O. Akbal, E. Cevher, A.O. Araman, Istanbul J. Pharm. 47(2), 45–51 (2017)CrossRefGoogle Scholar
  8. 8.
    T. McMahon, M. Avtn, D.G. Newman, Aviat. Sp. Environ. Med. 82(4), 490–491 (2011)CrossRefGoogle Scholar
  9. 9.
    A. Aslani, A. Ghannadi, F. Rostami, Adv. Biomed. Res. 5, 130 (2016)CrossRefGoogle Scholar
  10. 10.
    G.H. Kamimori, C.S. Karyekar, R. Otterstetter, D.S. Cox, T.J. Balkin, G.L. Belenky, N.D. Eddington, Int. J. Pharm. 234(1-2), 159–167 (2002)CrossRefGoogle Scholar
  11. 11.
    C.D. Paton, T. Lowe, A. Irvine, Eur. J. Appl. Physiol. 110(6), 1243–1250 (2010)CrossRefGoogle Scholar
  12. 12.
    A. Belscak-Cvitanovic, D. Komes, S. Karlović, S. Djaković, I. Špoljarić, G. Mršić, D. Ježek, Food Chem. 167, 378–386 (2015)CrossRefGoogle Scholar
  13. 13.
    E.C. Ilha, T. da Silva, J.G. Lorenz, G. de Oliveira Rocha, E.S. Sant’Anna, Eur. Food Res. Technol. 240(5), 977–984 (2015)CrossRefGoogle Scholar
  14. 14.
    L. Bagheri, A. Madadlou, M. Yarmand, M.E. Mousavi, Food Res. Int. 62, 1113–1119 (2014)CrossRefGoogle Scholar
  15. 15.
    V. Nedovic, A. Kalusevic, V. Manojlovic, S. Levic, B. Bugarski, Procedia Food Sci. 1, 1806–1815 (2011)CrossRefGoogle Scholar
  16. 16.
    H.J. Gwak, J.H. Lee, T.W. Kim, H.J. Choi, J.Y. Jang, S. Lee II, H.W. Park, Food Sci. Biotechnol. 24(6), 2155–2160 (2015)CrossRefGoogle Scholar
  17. 17.
    S. Ray, U. Raychaudhuri, R. Chakraborty, Food Biosci. 13, 76–83 (2016)CrossRefGoogle Scholar
  18. 18.
    X. Yang, G. Wang, X. Zhang, J. Pharm. Sci. 93(2), 293–299 (2004)CrossRefGoogle Scholar
  19. 19.
    M.R. Amiryousefi, M. Mohebbi, S. Golmohammadzadeh, A. Koocheki, Flavour Fragr. J. 31(2), 163–172 (2016)CrossRefGoogle Scholar
  20. 20.
    M.A.K. Zanjani, M.R. Ehsani, B. Ghiassi Tarzi, A. Sharifan, J. Food Process. Preserv. 42(1), e13318 (2018)CrossRefGoogle Scholar
  21. 21.
    A. Belšćak-Cvitanović, R. Stojanović, V. Manojlović, D. Komes, I.J. Cindrić, V. Nedović, B. Bugarski, Food Res. Int. 44(4), 1094–1101 (2011)CrossRefGoogle Scholar
  22. 22.
    M.G. Santos, D.A. Carpinteiro, M. Thomazini, G.A. Rocha-Selmi, A.G. da Cruz, C.E.C. Rodrigues, C.S. Favaro-Trindade, Food Res. Int. 66, 454–462 (2014)CrossRefGoogle Scholar
  23. 23.
    G.A. Rocha-Selmi, F.T. Bozza, M. Thomazini, H.M.A. Bolini, C.S. Fávaro-Trindade, Food Chem. 139(1-4), 72–78 (2013)CrossRefGoogle Scholar
  24. 24.
    M.A. Khosravi Zanjani, B.G. Tarzi, A. Sharifan, N. Mohammadi, Iran. J. Pharm. Res. 13, 843 (2014)Google Scholar
  25. 25.
    M. Fahimdanesh, N. Mohammadi, H. Ahari, M.A. Khosravi Zanjani, F. Zamani Hargalani, K. Behrouznasab, African J. Microbiol. Res. 6, 6853 (2013)CrossRefGoogle Scholar
  26. 26.
    Y. Luo, Q. Wang, Int. J. Biol. Macromol. 64, 353–367 (2014)CrossRefGoogle Scholar
  27. 27.
    M. Paradkar, B. Gajra, B. Patel, Saudi Pharm. J. 24(2), 153–164 (2016)CrossRefGoogle Scholar
  28. 28.
    R. Kumar, P. Solanki, and A. Chandra, (2014)Google Scholar
  29. 29.
    D. Poncelet, in Surf. Chem. Biomed. Environ. Sci., 23–34 (2006)Google Scholar
  30. 30.
    C. Chranioti, A. Nikoloudaki, C. Tzia, Carbohydr. Polym. 127, 252–263 (2015)CrossRefGoogle Scholar
  31. 31.
    W. Krasaekoopt, B. Bhandari, H.C. Deeth, LWT - Food Sci. Technol. 39(2), 177–183 (2006)CrossRefGoogle Scholar
  32. 32.
    M.A. Khosravi Zanjani, N. Mohammadi, H. Ahari, B. Ghiassi Tarzi, H. Bakhoda, J. Iran, Nutr. Sci. Food Technol. 8, 125 (2014)Google Scholar
  33. 33.
    N. Mohammadi, H. Ahari, M. Fahimdanesh, M.A. Khosravi Zanjani, A.A. Anvar, E. Shokri, Iran. J. Vet. Med 6, 259 (2012)Google Scholar
  34. 34.
    M.A. Khosravi Zanjani, B. Ghiassi Tarzi, A. Sharifan, N. Mohammadi, H. Bakhoda, M.M. Madanipour, African J. Microbiol. Res. 6, 5511 (2012)Google Scholar
  35. 35.
    C. Kvist, S.B. Andersson, S. Fors, B. Wennergren, J. Berglund, Int. J. Pharm. 189(1), 57–65 (1999)CrossRefGoogle Scholar
  36. 36.
    D. NA, J. FARAJ, Y. CAPAN, K. LEUNG, P. DELUCA, J. Control. Release 107(1), 122–130 (2005)CrossRefGoogle Scholar
  37. 37.
    J. Welti-Chanes, F. Vergara-Balderas, E. Pérez, D. Bermúdez, A. Valdez-Fragoso, and H. Mújica-Paz, in Food Eng. Integr. Approaches, edited by G. F. Gutiérrez-López, G. V Barbosa-Cánovas, J. Welti-Chanes, and E. Parada-Arias (Springer New York, New York, NY, 2008), pp. 139–153Google Scholar
  38. 38.
    A. Homayouni, A. Azizi, M.R. Ehsani, M.S. Yarmand, S.H. Razavi, Food Chem. 111(1), 50–55 (2008)CrossRefGoogle Scholar
  39. 39.
    W. Krasaekoopt, S. Watcharapoka, LWT - Food Sci. Technol. 57(2), 761–766 (2014)CrossRefGoogle Scholar
  40. 40.
    S. Gunasekaran, S. Ko, L. Xiao, J. Food Eng. 83(1), 31–40 (2007)CrossRefGoogle Scholar
  41. 41.
    D. Pasrija, P.N. Ezhilarasi, D. Indrani, C. Anandharamakrishnan, LWT - Food Sci. Technol. 64(1), 289–296 (2015)CrossRefGoogle Scholar
  42. 42.
    F. Mehta, P. Trivedi, Sch. Res. Libr. Arch. Appl. Sci. Res. 4, 781 (2012)Google Scholar
  43. 43.
    F. Mehta, P. Trivedi, Int J PharmTech Res 4, 889 (2012)Google Scholar
  44. 44.
    Y. Morjaria, W.J. Irwin, P.X. Barnett, R.S. Chan, B.R. Conway, Dissolution Technol. 11(2), 12–15 (2004)CrossRefGoogle Scholar
  45. 45.
    S. Chaudhary, A. Shahiwala, Int. J. Pharm. Investig. 2(3), 123–133 (2012)CrossRefGoogle Scholar
  46. 46.
    F.F. Mehta, R. Rajagopalan, P. Trivedi, Trop. J. Pharm. Res. 16(7), 1489 (2017)CrossRefGoogle Scholar
  47. 47.
    J. Welti-Chanes, F. Vergara-Balderas, E. Perez, D. Bermudex, A. Valdex-Fragose, and H. Mujica-Paz, in Food Eng. Integr. Approaches, edited by G. F. Gutiérrez-López, G. V Barbosa-Cánovas, J. Welti-Chanes, and E. Parada-Arias (Springer New York, New York, NY, 2008), pp. 139–153Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Food Science and Technology, Science and Research BranchIslamic Azad UniversityTehranIran
  2. 2.Department of Agricultural Mechanization, Science and Research BranchIslamic Azad UniversityTehranIran

Personalised recommendations