Controlled Release of Diclofenac Sodium from Silica-Chitosan Composites


The release profiles of acidic form of diclofenac sodium adsorbed on mesoporous silicas (Silochrom and two samples of spherical silicas) were compared with the dissolution characteristics of the pure drug. Desorption of diclofenac sodium from impregnated silicas with various surface liophilicity and composites of silica with chitosan have been studied using rotating basket method in phosphate buffer, pH 6.8. Sedimentations of sodium diclofenac via adsorption and impregnation from alcohol solution on fumed silica and modified silicas with grafted aminopropyl and trimethylsilyl groups were carried out. Polymer-containing composites have been prepared by capsulation of silica particles with impregnated diclofenac sodium by protonated and deprotonated forms of chitosan. Effect of the silica surface nature on the active substance release rate was ascertained. Significant prolongation of diclofenac sodium release was detected in the case of application of hydrophobic silica as a carrier and protonated chitosan as a polymeric shell.

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R. Kozakevych, Y. Bolbukh and V. Tertykh, "Controlled Release of Diclofenac Sodium from Silica-Chitosan Composites," World Journal of Nano Science and Engineering, Vol. 3 No. 3, 2013, pp. 69-78. doi: 10.4236/wjnse.2013.33010.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] N. Gaddam and J. Aukunuru, “Systemic Delivery of Diclofenac Sodium after Topical Application of Gels Incorporated with Drug-Loaded Solid Lipid Nanoparticles (SLN),” Journal of Pharmaceutical Health Services Research, Vol. 2, No. 2, 2010, pp. 177-187.
[2] K. M. Manjanna, B. Shivakumar and T. M. P. Kumar, “Diclofenac Sodium Microbeads for Oral Sustained Drug Delivery,” International Journal of PharmTech Research, Vol. 1, No. 2, 2009, pp. 317-327.
[3] A. Chiarini, A. Tartarini and A. Fini, “pH-Solubility Relationship and Partition Coefficients for Some Anti-In-flammatory Arylaliphatic Acids,” Archiv der Pharmazie, Vol. 317, No. 3, 1984, pp. 268-273. doi:10.1002/ardp.19843170314
[4] A. S. Bravo, M. C. Lamas and C. J. Salomón, “In-Vitro Studies of Diclofenac Sodium Controlled-Release from Biopolymeric Hydrophilic Matrices,” Journal of Pharmaceutical Sciences, Vol. 5, No. 3, 2002, pp. 213-219.
[5] M. Bartolomei, P. Bertocchi, E. Antoniella and A. Rodomonte, “Physico-Chemical Characterisation and Intrinsic Dissolution Studies of a New Hydrate form of Diclofenac Sodium: Comparison with Anhydrous Form,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 40, No. 5, 2006, pp. 1105-1113. doi:10.1016/j.jpba.2005.09.009
[6] B. M. Al-Taani and B. M. Tashtoush, “Effect of Microenvironment pH of Swellable and Erodable Buffered Matrices on the Release Characteristics of Diclofenac Sodium,” AAPS PharmSciTech, Vol. 4, 2003, pp. 110-115. doi:10.1208/pt040343
[7] S. L. Collins, R. A. Moore, H. J. McQuay and P. J. Wiffen, “Oral Ibuprofen and Diclofenac in Post-Operative Pain: A Quantitative Systematic Review,” European Journal of Pain, Vol. 2, No. 4, 1998, pp. 285-291.
[8] J. Schwaiger, H. Ferling, U. Mallow, H. Wintermayr and R. D. Negele, “Toxic Effects of the Non-Steroidal Anti-Inflammatory Drug Diclofenac. Part I: Histopathological Alterations and Bioaccumulation in Rainbow Trout,” Aquatic Toxicology, Vol. 68, No. 2, 2004, pp. 141-150. doi:10.1016/j.aquatox.2004.03.014
[9] E. J. Hickey, R. R. Raje, V. E. Reid, S. M. Gross and S. D. Ray, “Diclofenac Induced in Vivo Nephrotoxicity May Involve Oxidative Stress-Mediated Massive Genomic DNA Fragmentation and Apoptotic Cell Death,” Free Radical Biology and Medicine, Vol. 31, No. 2, 2001, pp. 139-152. doi:10.1016/S0891-5849(01)00560-3
[10] C. C. Kao, S. C. Chen and M. T. Sheu, “Lag Time Method to Delay Drug Release to Various Sites in the Gastrointestinal Tract,” Journal of Controlled Release, Vol. 44, No. 2-3, 1997, pp. 263-270. doi:10.1016/S0168-3659(96)01529-5
[11] C. Barbé, J. Bartlett, L. Kong, K. Finnie, H. Q. Lin, M. Larkin, S. Calleja, A. Bush and G. Calleja, “Silica Particles: A Novel Drug-Delivery System,” Advanced Materials, Vol. 16, No. 21, 2004, pp. 1959-1966. doi:10.1002/adma.200400771
[12] Y. Zhou and X. Y. Wu, “Finite Element Analysis of Diffusional Drug Release from Complex Matrix Systems. I. Complex Geometries and Composite Structures,” Journal of Controlled Release, Vol. 49, No. 2-3, 1997, pp. 277 288. doi:10.1016/S0168-3659(97)00103-X
[13] S. W. Song, K. Hidajat and S. Kawi, “Functionalized SBA-15 Materials as Carriers for Controlled Drug Delivery: Influence of Surface Properties on Matrix-Drug Interactions,” Langmuir, Vol. 21, No. 21, 2005, pp. 9568-9575. doi:10.1021/la051167e
[14] W. J. Xu, Q. Gao, Y. Xu, D. Wu, Y. H. Sun, W. L. Shen and F. Deng, “Controlled Drug Release from Bifunctionalized Mesoporous Silica,” Journal of Solid State Chemistry, Vol. 181, No. 10, 2008, pp. 2837 2844. doi:10.1016/j.jssc.2008.07.011
[15] M. Manzano, V. Aina, C. O. Arean, F. Balas, V. Cauda, M. Colilla, M. R. Delgado and M. Vallet-Regi, “Studies on MCM-41 Mesoporous Silica for Drug Delivery: Effect of Particle Morphology and Amine Functionalization,” Chemical Engineering Journal, Vol. 137, No. 1, 2008, pp. 30-37. doi:10.1016/j.cej.2007.07.078
[16] M. Aw, S. Simovic, Y. Yu, J. Addai-Mensah and D. Losic, “Porous Silica Microshells from Diatoms as Biocarrier for Drug Delivery Applications,” Powder Technology, Vol. 223, 2012, pp. 52-58. doi:10.1016/j.powtec.2011.04.023
[17] M. D. Popova, á. Szegedi, I. N. Kolev, J. Mihály, B. S. Tzankov, G. T. Momekov, N. G. Lambov and K. P. Yoncheva, “Carboxylic Modified Spherical Mesoporous Silicas as Drug Delivery Carriers,” International Journal of Pharmaceutics, Vol. 436, No. 1-2, 2012, pp. 778-785. doi:10.1016/j.ijpharm.2012.07.061
[18] P. Kortesuo, M. Ahola, M. Kangas, I. Kangasniemi, A. Yli-Urpo and J. Kiesvaara, “In Vitro Evaluation of Sol-Gel Processed Spray Dried Silica Gel Microspheres as Carrier in Controlled Drug Delivery,” International Journal of Pharmaceutics, Vol. 200, No. 2, 2000, pp. 223-229. doi:10.1016/S0378-5173(00)00393-8
[19] K. Czarnobaj, “Preparation and Characterization of Silica Xerogels as Carriers for Drugs,” Drug Delivery, Vol. 15, No. 8, 2008, pp. 485-492. doi:10.1080/10717540802321495
[20] R. Jayakumar, D. Menon, K. Manzoor, S. V. Nair and H. Tamura, “Biomedical Applications of Chitin Nanomaterials: A Short Review,” Carbohydrate Polymers, Vol. 82, No. 2, 2010, pp. 227-232. doi:10.1016/j.carbpol.2010.04.074
[21] E. Hodgson and J. A. Goldstein, “Metabolism of Toxicants: Phase I Reactions and Pharmacogenetics,” In: E. Hodgson and R. C. Smart, Eds., Introduction to Biochemical Toxicology, 3rd Edition, Wiley-Interscience, New York, 2001, pp. 67-113.
[22] L. S. Fonseca, R. P. Silveira, A. M. Deboni, E. V. Benvenutti, T. M. Costa, S. S. Guterres and A. R. Pohlmann, “Nanocapsule@xerogel Microparticles Containing Sodium Diclofenac: A New Strategy to Control the Release of Drugs,” International Journal of Pharmaceutics, Vol. 358, No. 1-2, 2008, pp. 292-295. doi:10.1016/j.ijpharm.2008.02.005
[23] E. J. Lee, S. H. Jun, H. E. Kim, H. W. Kim, Y. H. Koh and J. H. Jang, “Silica Xerogel-Chitosan Nano-Hybrids for Use as Drug Eluting Bone Replacement,” Journal of Materials Science: Materials in Medicine, Vol. 21, No. 1, 2010, pp. 207-214. doi:10.1007/s10856-009-3835-9
[24] M. Prokopowicz, “Silica-Polyethylene Glycol Matrix Synthesis by Sol-Gel Method and Evaluation for Diclofenac Diethylammonium Release,” Drug Delivery, Vol. 14, 2007, pp. 129-138.
[25] J. H. Park, G. Saravanakumar, K. Kim and I. C. Kwon, “Targeted Delivery of Low Molecular Drugs Using Chitosan and Its Derivatives,” Advanced Drug Delivery Reviews, Vol. 62, No. 1, 2010, pp. 28-41. doi:10.1016/j.addr.2009.10.003
[26] M. Dash, F. Chiellini, R. M. Ottenbrite and E. Chiellinial, “Chitosan: A Versatile Semi-Synthetic Polymer in Biomedical Applications,” Progress in Polymer Science, Vol. 36, No. 8, 2011, pp. 981-1014. doi:10.1016/j.progpolymsci.2011.02.001
[27] I. Rashid, M. Al-Remawi, A. Eftaiha and A. Badwan, “Chitin-Silicon Dioxide Coprecipitate as a Novel Super Disintegrant,” Journal of Pharmaceutical Sciences, Vol. 97, No. 11, 2008, pp. 4955-4969. doi:10.1002/jps.21354
[28] Y. M. Bolbukh, P. O. Kuzema, V. A. Tertykh and B. Gawdzik, “Effect of Surface Hydride, Vinyl, and Methyl Groups on Thermal Stability of Modified Silica-Divinylbenzene-Di(methacryloyloxymethyl)naphthalene Composites,” International Journal of Polymeric Materials and Polymeric Biomaterials, Vol. 56, No. 3, 2007, pp. 803-823. doi:10.1080/00914030601163464
[29] R. B. Kozakevych, Y. M. Bolbukh and V. A. Tertykh, “Desorption of Diclofenac Sodium from Silica-Chitosan Composites,” Pharmaceutical Journal, Vol. 3, 2009, pp. 103-111.
[30] K. V. Katok, Y. Bolbukh and V. A. Tertykh, “Chemical Modification of Silica Surface by Immobilization of Amino Groups for Synthesis of Silver Nanoparticles, NATO Science Series II. Mathematics, Physics and Chemistry,” In: M. Vaclavikova, K. Vitale, G. Gallios and L. Ivanicova, Eds., Water Treatment Technologies for Removal of High-Toxicity Pollutants, Springer, New York, 2009, pp. 283-287. doi:10.1007/978-90-481-3497-7_29
[31] V. L. Gonçalves, M. C. M. Laranjeira, V. T. Fávere and R. C. Pedrosa, “Effect of Crosslinking Agent on Chitosan Microsheres in Controlled Release of Diclofenac Sodium,” Polímeros, Vol. 15, No. 1, 2005, pp. 6-12. doi:10.1590/S0104-14282005000100005
[32] F. Pati, B. Adhikari and S. Dhara, “Development of Chitosan-Tripolyphosphate Fibers through pH-Dependent Ionotropic Gelation,” Carbohydrate Research, Vol. 346, No. 16, 2011, pp. 2582-2588. doi:10.1016/j.carres.2011.08.028
[33] Ukrainian State Pharmacopoeia, “REREIG,” Kharkiv, Ukraine, 2001.
[34] J. C. McElnay and A. C. Nicol, “The Comparison of a Novel Continuous-Flow Dissolution Apparatus for Suppositories with the Rotating Basket Technique,” International Journal of Pharmaceutics, Vol. 19, No. 1, 1984, pp. 89-96. doi:10.1016/0378-5173(84)90135-2
[35] I. M. Kenawi, B. N. Barsoum and M. A. Youssef, “Cetirizine Dihydrochloride Interaction with Some Diclofenac Complexes,” European Journal of Pharmaceutical Sciences, Vol. 26, No. 3-4, 2005, pp. 341-348. doi:10.1016/j.ejps.2005.07.007
[36] M. L. Manca, M. Zaru, G. Ennas, D. Valenti, C. Sinico, G. Loy and A. M. Fadda, “Diclofenac-β-Cyclodextrin Binary Systems: Physicochemical Characterization and in Vitro Dissolution and Diffusion Studies,” AAPS PharmSciTech, Vol. 6, No. 3, 2005, pp. 464-472. doi:10.1208/pt060358
[37] J. Siepmann and F. Siepmann, “Mathematical Modeling of Drug Delivery,” International Journal of Pharmaceutics, Vol. 364, No. 2, 2008, pp. 328-343. doi:10.1016/j.ijpharm.2008.09.004
[38] S. Dash, P. N. Murthy, L. Nath and P. Chowdhur, “Kinetic Modeling on Drug Release from Controlled Drug Delivery Systems,” Acta Poloniae Pharmaceutic, Vol. 67, 2010, pp. 217-223.

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