Abstract
In this work, chitosan films were prepared by a casting/solvent evaporation methodology using pectin or hydroxypropylmethyl cellulose to form polymeric matrices. Miconazole nitrate, as a model drug, was loaded into such formulations. These polymeric films were characterized in terms of mechanical properties, adhesiveness, and swelling as well as drug release. Besides, the morphology of raw materials and films was investigated by scanning electron microscopy; interactions between polymers were analyzed by infrared spectroscopy and drug crystallinity studied by differential scanning calorimetry and X-ray diffraction. In addition, antifungal activity against cultures of the five most important fungal opportunistic pathogens belonging to Candida genus was investigated. Chitosan:hydroxypropylmethyl cellulose films were found to be the most appropriate formulations in terms of folding endurance, mechanical properties, and adhesiveness. Also, an improvement in the dissolution rate of miconazole nitrate from the films up to 90% compared to the non-loaded drug was observed. The in vitro antifungal activity showed a significant activity of the model drug when it is loaded into chitosan films. These findings suggest that chitosan-based films are a promising approach to deliver miconazole nitrate for the treatment of candidiasis.
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References
Krajewska B. Application of chitin- and chitosan-based materials for enzyme immobilizations: a review. Enzym Microb Technol. 2004;35(2–3):126–39.
Ravi Kumar MNV. A review of chitin and chitosan applications. React Funct Polym. 2000;46(1):1–27.
Luo Y, Wang Q. Recent development of chitosan-based polyelectrolyte complexes with natural polysaccharides for drug delivery. Int J Biol Macromol. 2014;64:353–67.
Sakloetsakun D, Preechagoon D, Bernkop-Schnurch A, Pongjanyakul T. Chitosan-gum arabic polyelectrolyte complex films: physicochemical, mechanical and mucoadhesive properties. Pharm Dev Technol. 2016;21(5):590–9.
Kaur A, Kaur G. Mucoadhesive buccal patches based on interpolymer complexes of chitosan–pectin for delivery of carvedilol. Saudi Pharm J. 2012;20(1):21–7.
Bigucci F, Luppi B, Cerchiara T, Sorrenti M, Bettinetti G, Rodriguez L, et al. Chitosan/pectin polyelectrolyte complexes: Selection of suitable preparative conditions for colon-specific delivery of vancomycin. Eur J Pharm Sci. 2008;35(5):435–41.
Pandey S, Mishra A, Raval P, Patel H, Gupta A, Shah D. Chitosan–pectin polyelectrolyte complex as a carrier for colon targeted drug delivery. J Young Pharm. 2013;5(4):160–6.
Siddaramaiah, Kumar P, Divya KH, Mhemavathi BT, Manjula DS. Chitosan/HPMC polymer blends for developing transdermal drug delivery systems. J Macromol Sci A. 2006;43(3):601–7.
Tonglairoum P, Ngawhirunpat T, Rojanarata T, Kaomongkolgit R, Opanasopit P. Fabrication of a novel scaffold of clotrimazole-microemulsion-containing nanofibers using an electrospinning process for oral candidiasis applications. Colloids Surf B. 2015;126:18–25.
Tonglairoum P, Ngawhirunpat T, Rojanarata T, Panomsuk S, Kaomongkolgit R, Opanasopit P. Fabrication of mucoadhesive chitosan coated polyvinylpyrrolidone/cyclodextrin/clotrimazole sandwich patches for oral candidiasis. Carbohydr Polym. 2015;132:173–9.
Spampinato C, Leonardi D. Candida infections, causes, targets, and resistance mechanisms: traditional and alternative antifungal agents. Biomed Res Int. 2013;2013:13.
Peh K, Khan T, Ch’ng H. Mechanical, bioadhesive strength and biological evaluations of chitosan films for wound dressing. J Pharm Pharm Sci. 2000;3(3):303–11.
Domján A, Bajdik J, Pintye-Hódi K. Understanding of the plasticizing effects of glycerol and PEG 400 on chitosan films using solid-state NMR spectroscopy. Macromolecules. 2009;42(13):4667–73.
Abruzzo A, Bigucci F, Cerchiara T, Cruciani F, Vitali B, Luppi B. Mucoadhesive chitosan/gelatin films for buccal delivery of propranolol hydrochloride. Carbohydr Polym. 2012;87(1):581–8.
Real DA, Martinez MV, Frattini A, Soazo M, Luque AG, Biasoli MS, et al. Design, characterization, and in vitro evaluation of antifungal polymeric films. AAPS PharmSciTech. 2013;14(1):64–73.
Sezer AD, Hatipoglu F, Cevher E, Oğurtan Z, Bas 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):E94–E101.
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.
Eouani C, Piccerelle P, Prinderre P, Bourret E, Joachim J. In-vitro comparative study of buccal mucoadhesive performance of different polymeric films. Eur J Pharm Biopharm. 2001;52(1):45–55.
Giovino C, Ayensu I, Tetteh J, Boateng JS. An integrated buccal delivery system combining chitosan films impregnated with peptide loaded PEG-b-PLA nanoparticles. Colloids Surf, B. 2013;112:9–15.
Rai VK, Dwivedi H, Yadav NP, Chanotiya CS, Saraf SA. Solubility enhancement of miconazole nitrate: binary and ternary mixture approach. Drug Dev Ind Pharm. 2014;40(8):1021–9.
Clinical and Laboratory Standards Institute W, PA. Method for antifungal disk diffusion susceptibility testing of yeasts. Approved guideline. Second edition 2008:Document M44-A2.
Wang Y, Li P, Kong L. Chitosan-modified PLGA nanoparticles with versatile surface for improved drug delivery. AAPS PharmSciTech. 2013;14(2):585–92.
Zhong L, Zhu X, Luo X, Su W. Dissolution properties and physical characterization of telmisartan–chitosan solid dispersions prepared by mechanochemical activation. AAPS PharmSciTech. 2013;14(2):541–50.
Calce E, Bugatti V, Vittoria V, De Luca S. Solvent-free synthesis of modified pectin compounds promoted by microwave irradiation. Molecules. 2012;17(10):12234–42.
Karavas E, Georgarakis E, Bikiaris D. Application of PVP/HPMC miscible blends with enhanced mucoadhesive properties for adjusting drug release in predictable pulsatile chronotherapeutics. Eur J Pharm Biopharm. 2006;64(1):115–26.
Sahoo S, Chakraborti CK, Behera PK, Mishra S. Spectroscopic investigations of a controlled release mucoadhesive suspension. Asian J Pharm Clin Res. 2011;4(2):63–70.
Espinosa-Andrews H, Sandoval-Castilla O, Vázquez-Torres H, Vernon-Carter EJ, Lobato-Calleros C. Determination of the gum Arabic–chitosan interactions by Fourier Transform Infrared Spectroscopy and characterization of the microstructure and rheological features of their coacervates. Carbohydr Polym. 2010;79(3):541–6.
Pal K, Banthia AK, Majumdar DK. Preparation and characterization of polyvinyl alcohol-gelatin hydrogel membranes for biomedical applications. AAPS PharmSciTech. 2007;8(1):21–5.
Gupta A, Kar HK. Solid state compatibility studies of miconazole using thermal and spectroscopic methods. Adv Anal Chem. 2015;5(3):51–5.
Ribeiro A, Figueiras A, Santos D, Veiga F. Preparation and solid-state characterization of inclusion complexes formed between miconazole and methyl-β-cyclodextrin. AAPS PharmSciTech. 2008;9(4):1102–9.
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.
Vuddanda PR, Montenegro-Nicolini M, Morales JO, Velaga S. Effect of plasticizers on the physico-mechanical properties of pullulan based pharmaceutical oral films. Eur J Pharm Sci. 2017;96:290–8.
Morales JO, Su R, McConville JT. The influence of recrystallized caffeine on water-swellable polymethacrylate mucoadhesive buccal films. AAPS PharmSciTech. 2013;14(2):475–84.
Nagahama H, Maeda H, Kashiki T, Jayakumar R, Furuike T, Tamura H. Preparation and characterization of novel chitosan/gelatin membranes using chitosan hydrogel. Carbohydr Polym. 2009;76(2):255–60.
Vieira MGA, da Silva MA, dos Santos LO, Beppu MM. Natural-based plasticizers and biopolymer films: a review. Eur Polym J. 2011;47(3):254–63.
Silva CL, Pereira JC, Ramalho A, Pais AACC, Sousa JJS. Films based on chitosan polyelectrolyte complexes for skin drug delivery: development and characterization. J Membr Sci. 2008;320(1–2):268–79.
Sanyang M, Sapuan S, Jawaid M, Ishak M, Sahari J. Effect of plasticizer type and concentration on tensile, thermal and barrier properties of biodegradable films based on sugar palm (Arenga pinnata) starch. Polymers. 2015;7(6):1106.
Gratieri T, Gelfuso GM, Rocha EM, Sarmento VH, de Freitas O, Lopez RFV. A poloxamer/chitosan in situ forming gel with prolonged retention time for ocular delivery. Eur J Pharm Biopharm. 2010;75(2):186–93.
Tasdighi E, Jafari Azar Z, Mortazavi SA. Development and in-vitro evaluation of a contraceptive vagino-adhesive propranolol hydrochloride gel. Iran J Pharm Res. 2012;11(1):13–26.
Morales JO, McConville JT. Manufacture and characterization of mucoadhesive buccal films. Eur J Pharm Biopharm. 2011;77(2):187–99.
Yusif RM, Hashim IIA, Mohamed EA, Badria FA-E. Gastroretentive matrix tablets of boswellia oleogum resin: preparation, optimization, in vitro evaluation, and cytoprotective effect on indomethacin-induced gastric ulcer in rabbits. AAPS PharmSciTech. 2016;17(2):328–38.
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.
Grabovac V, Guggi D, Bernkop-Schnürch A. Comparison of the mucoadhesive properties of various polymers. Adv Drug Deliv Rev. 2005;57(11):1713–23.
Park H, Park K, Kim D. Preparation and swelling behavior of chitosan-based superporous hydrogels for gastric retention application. J Biomed Mater Res A. 2006;76(1):144–50.
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. 2010;99(7):3019–29.
Shen J-N, Yu C-C, Zeng G-N, van der Bruggen B. Preparation of a facilitated transport membrane composed of carboxymethyl chitosan and polyethylenimine for CO2/N2 separation. Int J Mol Sci. 2013;14(2):3621.
Dobaria NB, Badhan AC, Mashru RC. A novel itraconazole bioadhesive film for vaginal delivery: design, optimization, and physicodynamic characterization. AAPS PharmSciTech. 2009;10(3):951–9.
Freiberg S, Zhu X. Polymer microspheres for controlled drug release. Int J Pharm. 2004;282(1):1–18.
Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm. 2000;50(1):47–60.
Craig DQM. The mechanisms of drug release from solid dispersions in water-soluble polymers. Int J Pharm. 2002;231(2):131–44.
Acknowledgements
The authors gratefully acknowledge the Universidad Nacional de Rosario, Argentina and CONICET Argentina for the financial support. We would like to thank the staff from the English Department (Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario) for their assistance in the language correction of the manuscript.
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Guest Editors: Claudio Salomon, Francisco Goycoolea, and Bruno Moerschbacher
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Tejada, G., Barrera, M.G., Piccirilli, G.N. et al. Development and Evaluation of Buccal Films Based on Chitosan for the Potential Treatment of Oral Candidiasis. AAPS PharmSciTech 18, 936–946 (2017). https://doi.org/10.1208/s12249-017-0720-6
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DOI: https://doi.org/10.1208/s12249-017-0720-6