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Native and polymeric β-cyclodextrins in performance improvement of chitosan films aimed for buccal delivery of poorly soluble drugs

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Journal of Inclusion Phenomena and Macrocyclic Chemistry Aims and scope Submit manuscript

Abstract

β-Cyclodextrin (βCD) and its soluble polymeric derivative (EPIβCD) were used to improve the effectiveness of chitosan-based bucco-adhesive film formulations containing bupivacaine hydrochloride and triclosan as poorly-soluble model drugs. The film formulations were characterized in terms of swelling, mucoadhesion and in vitro drug release, while possible interactions between the components were investigated by DSC and FTIR analyses. For both drugs EPIβCD showed a higher solubilizing efficiency than βCD; however cyclodextrin effectiveness in improving the release rate from film formulations was influenced by their different interactions with chitosan. Free βCD acted as a channelling agent, favouring the film swelling, while EPIβCD due to interaction with chitosan caused an opposite effect. βCD was the optimal partner for bupivacaine-loaded films in terms of film swelling, mucoadhesion and drug release. Contrariwise, EPIβCD was the best partner for triclosan-loaded films, allowing the highest drug release rate increase, due to its higher solubilizing ability with respect to βCD. Addition of the suitable cyclodextrin enabled formulation of buccal films with suitable drug release properties.

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References

  1. Bruschi, M.L., de Freitas, O.: Oral bioadhesive drug delivery systems. Drug Dev. Ind. Pharm. 31, 293–310 (2005)

    CAS  Google Scholar 

  2. Salamat-Miller, N., Chittchang, M., Johnston, T.P.: The use of mucoadhesive polymers in buccal drug delivery. Adv. Drug Del. Rev. 57, 1666–1691 (2005)

    Article  CAS  Google Scholar 

  3. Illum, L.: Chitosan and its use as a pharmaceutical excipients. Pharm. Res. 15, 1326–1331 (1998)

    Article  CAS  Google Scholar 

  4. Paul, W., Sharma, C.P.: Chitosan, a drug carrier for the 21st century. STP Pharma. Sci. 10, 5–22 (2000)

    CAS  Google Scholar 

  5. Hejazi, R., Amiji, M.: Chitosan based gastrointestinal delivery systems. J. Control. Release 89, 151–165 (2003)

    Article  CAS  Google Scholar 

  6. Kean, T., Thanou, M.: Biodegradation, biodistribution and toxicity of chitosan. Adv. Drug Del. Rev. 62, 3–11 (2010)

    Article  CAS  Google Scholar 

  7. Rodrigues, L.B., Leite, H.F., Yoshida, M.I., Saliba, J.B., Cunha, J.A.S., Faraco, A.A.G.: In vitro release and characterization of chitosan films as dexamethasone carrier. Int. J. Pharm. 368, 1–6 (2009)

    Article  CAS  Google Scholar 

  8. Zheng, L.Y., Zhu, J.F.: Study on antimicrobial activity of chitosan with different molecular weights. Carbohydr. Polym. 54, 527–530 (2003)

    Article  CAS  Google Scholar 

  9. Andrews, G.P., Laverty, T.P., Jones, D.S.: Mucoadhesive polymeric platforms for controlled drug delivery. Eur. J. Pharm. Biopharm. 71, 505–518 (2009)

    Article  CAS  Google Scholar 

  10. Ueno, H., Mori, T., Fujinaga, T.: Topical formulations and wound healing application of chitosan. Adv. Drug Del. Rev. 52, 105–115 (2001)

    Article  CAS  Google Scholar 

  11. Meechan, J.G.: Inra-oral topical anaesthetics: a review. J. Dent. 28, 3–14 (2000)

    Article  CAS  Google Scholar 

  12. Hirayama, F., Uekama, K.: Cyclodextrin-based drug release system. Adv. Drug Del. Rev. 36, 125–141 (1999)

    Article  CAS  Google Scholar 

  13. Bibby, D.C., Davies, N.M., Tucker, I.G.: Mechanisms by which cyclodextrins modify drug release from polymeric drug delivery systems. Int. J. Pharm. 197, 1–11 (2000)

    Article  CAS  Google Scholar 

  14. Panagakos, F.S., Volpe, A.R., Petrone, M.E., DeVizio, W., Davies, R.M., Proskin, H.M.: Advancerd oral antibacterial/anti-inflammatory technology: a compressive review of the clinical benefits of a triclosan/copolymer/fluoride dentifrice. J. Clin. Dent. 16, S1–S19 (2005)

    Google Scholar 

  15. Senel, S., Hincal, A.A.: Drug permeation enhancement via buccal route: possibilities and limitations. J. Control. Release 72, 133–144 (2001)

    Article  CAS  Google Scholar 

  16. Jug, M., Mennini, N., Melani, F., Maestrelli, F., Mura, P.: Phase solubility, 1H-NMR and molecular modelling studies of bupivacaine hydrochloride complexation with different cyclodextrin derivates. Chem. Phys. Lett. 500, 347–354 (2010)

    Article  CAS  Google Scholar 

  17. Jug, M., Kosalec, I., Maestrelli, F., Mura, P.: Analysis of triclosan inclusion complexes with β-cyclodextrin and its water-soluble polymeric derivative. J. Pharm. Biomed. Anal. 54, 1030–1039 (2011)

    Article  CAS  Google Scholar 

  18. Jug, M., Bengez, S., Bećirević-Laćan, M.: Novel cyclodextrin-based film formulation intended for buccal delivery of atenolol. Drug Dev. Ind. Pharm. 35, 796–807 (2009)

    Article  CAS  Google Scholar 

  19. Jug, M., Maestrelli, F., Bragagni, M., Mura, P.: Preparation and solid state characterization of bupivacaine hydrochloride cyclodextrin complexes aimed for buccal delivery. J. Pharm. Biomed. Anal. 52, 9–18 (2010)

    Article  CAS  Google Scholar 

  20. Bretram, U., Bodmeier, R.: In situ gelling, bioadhesive nasal inserts for extended drug delivery: In vitro characterization of a new nasal dosage form. Eur. J. Pharm. Sci. 27, 62–71 (2006)

    Article  Google Scholar 

  21. Mizrahi, B., Domb, A.-J.: Mucoadhesive tablet releasing iodine for treating oral infections. J. Pharm. Sci. 96, 3144–3150 (2007)

    Article  CAS  Google Scholar 

  22. Mura, P., Corti, G., Cirri, M., Maestrelli, F., Mennini, N., Bragagni, M.: Development of mucoadhesive films for buccal administration of flufenamic acid: effect of cyclodextrin complexation. J. Pharm. Sci. 99, 3019–3029 (2010)

    CAS  Google Scholar 

  23. Dong, Y., Ruan, Y., Wang, H., Zhao, Y., Bi, D.: Studies on glass transition temperature of chitosan with four techniques. J. Appl. Poly. Sci. 93, 1553–1558 (2004)

    Article  CAS  Google Scholar 

  24. Jug, M., Bećirević-Laćan, M.: Development of a cyclodextrin-based nasal delivery system for lorazepam. Drug Dev. Ind. Pharm. 34, 817–826 (2008)

    Article  CAS  Google Scholar 

  25. Raghavan, S.L., Trividic, A., Davis, A.F., Hadgraft, J.: Crystallization of hydrocortizone acetate: influence of polymers. Int. J. Pharm. 212, 213–221 (2001)

    Article  CAS  Google Scholar 

  26. Niederwanger, V., Gozzo, F., Griesser, U.J.: Characterization of four crystal polymorphs and a monohydrate of s-bupivacaine hydrochloride (levobupivacaine hydrochloride). J. Pharm. Sci. 98, 1064–1074 (2009)

    Article  CAS  Google Scholar 

  27. Wang, Q.Z., Chen, X.G., Shi Xi Wang, N.L., Liu, C.S., Meng, X.H., Liu, C.G.: Protonation constants of chitosan with different molecular weight and degree of deacetylation. Carbohydr. Polym. 65, 194–201 (2006)

    Article  CAS  Google Scholar 

  28. Bergström, C.A.S., Luthman, K., Artursson, P.: Accuracy of calculated pH-dependent aqueous solubility. Eur. J. Pharm. Sci. 22, 387–398 (2004)

    Article  Google Scholar 

  29. Duan, M.S., Zhao, N., Össurardóttir, Í., Thorsteinsson, T., Loftsson, T.: Cyclodextrin solubilisation of the antibacterial agents triclosan and triclocarban. Formation of aggregates and higher-order complexes. Int. J. Pharm. 297, 213–222 (2005)

    Article  CAS  Google Scholar 

  30. Eouani, C., Piccerelli, P., Prinderre, P., Bourret, E., Joachim, J.: In vitro comparative study of buccal mucoadhesive performance of different polymeric films. Eur. J. Pharm. Sci. 52, 45–55 (2001)

    CAS  Google Scholar 

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Acknowledgments

Financial support from MIUR and a personal Post doctoral grant to M. Jug from the National Foundation for Science, Higher Education and Technological Development of the Republic of Croatia are greatly acknowledged.

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Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, 10000, Zagreb, Croatia

    Mario Jug

  2. Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Florence, Via Schiff 6-Sesto Fiorentino, 50019, Florence, Italy

    Francesca Maestrelli & Paola Mura

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  1. Mario Jug
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  2. Francesca Maestrelli
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Correspondence to Mario Jug.

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Jug, M., Maestrelli, F. & Mura, P. Native and polymeric β-cyclodextrins in performance improvement of chitosan films aimed for buccal delivery of poorly soluble drugs. J Incl Phenom Macrocycl Chem 74, 87–97 (2012). https://doi.org/10.1007/s10847-011-0086-4

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  • DOI: https://doi.org/10.1007/s10847-011-0086-4

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