Development and full characterization of chitosan-carbopol matrix for the delivery of antifungal agents

REAL, D.; MARTINEZ, M.V.; FRATTINI, A.; SOAZO, M.; SALOMON, C.J.; OLIVIERI, A.C.; LEONARDI, D.

Rosario

Congreso; II Reunión Internacional de Ciencias Farmacéuticas RICIFA 2012; 2012

Introduction Chitosan (CH) is a cationic biocompatible polymer usually employed as drugs carrier. CH can be the matrix for microparticles, nanoparticles, or films, among others (1-3). Mechanical properties of CH matrixes may be improved when CH forms polyelectrolyte complexes with other oppositely charged polymers (4). Carbopol 971NF (CB) is an anionic polymer frequently employed in drug delivery gel systems for buccal, trans dermic, ocular, rectal, and nasal applications (5). The interaction between the polymers may produce a polymeric matrix which could be able to transport and release different drugs. Thus, the aims of this work was the development of polymeric matrixes loaded with econazole nitrate (ECN) as model drug, and the full characterize these systems. Materiales and Methods CH (1% w/w) was solubilized in aqueous lactic acid solution (2% v/v) and stirred overnight. CB solutions (1% w/v) were prepared by dissolution in water. CH solutions were dripped to the CB solutions, then sorbitol (S), as plasticizer, and ECN were added and the mixture was stirred at 200 rpm during 2 h. The solutions were cast on Petri-dishes and dried in an oven at 25°C, RH (58%). After drying, matrixes were neutralized in casting (6). Composition of the analyzed matrixes were 100%CH and 0%CB; 90%CH and 10%CB and finally 80%CH and 20%CB; all three formulations were loaded with 1% ECN and plasticized with 1% S. Mechanical strengths of the systems were evaluated. Interactions between polymers were analyzed by Fourier-transform infrared spectroscopy (FTIR), thermal gravimetry analysis and differential thermal analysis (DTA-TGA). Morphology of the matrixes was investigated by scanning electron microscopy (SEM) and by atomic force microscopy (AFM). Studies of water uptake and dissolution profiles of ECN were carried out in neutral and acidic medium. Results The mechanical properties of all matrixes were in adequate range, however, these properties were poorer when the drug was loaded, probably because crystals of ENC produce network outages and therefore reduce the polymeric interactions between the polymers. Matrixes prepared with CB showed an evident wrinkle pattern, probably due to the strong interactions between the polymers, which were observed by FTIR and DTA-TGA. All matrixes showed a loss of weight during the water uptake assay. This fact could be attributed to the partial solubilization of CB in the medium pH 7.2 or CH dissolution at pH 4.2 generating both the erosion of the matrix. The ECN was release in both neutral and acid medium, probably by a combination between the processes of drug diffusion and matrix erosion. Conclusion The application of matrices based on polyelectrolyte complexes generated by CH/CB interactions to load and release ECN was demonstrated. These matrices are potential candidates for the development of alternative pharmaceutical forms for the treatment of mycosis. Acknowledgments The National University of Rosario (UNR), the National Council Research (CONICET, Argentina), and ANPCyT (Agencia Nacional de Promoción Científica y Tecnológica), are gratefully acknowledged for financial support.  References 1) Shah PP, Mashru RC. Influence of chitosan crosslinking on bitterness of mefloquine hydrochloride microparticles using central composite design. J Pharm Sci. 2009;98:690?703. 2) Illum L. Nanoparticulate systems for nasal delivery of drugs: A real improvement over simple systems? J Pharm Sci. 2007;96:473-483. 3) Vargas M, Albors A, Chiralt A, Gonzalez-Martinez C. Characterization of chitosan-oleic acid composite films. Food Hydrocol. 2009;23:536-547. 4) Nitayaphat, W Jiratumnukul N, Charuchinda S, Kittinaovarat S. Mechanical properties of chitosan/bamboo charcoal composite films made with normal and surface oxidized charcoal. Carbohy Polym. 2009;78:444-448. 5) Barreiro-Iglesias R, Alvarez-Lorenzo C, Concheiro A. Incorporation of small quantities of surfactants as a way to improve the rheological and diffusional behavior of carbopol gels. J Controll Rel. 2001;77:59-75. 6) Cardenas G, Miranda P. FTIR and TGA studies of Chitosan composite films. J Chil Chem Soc. 2004;49(4):291-295.