The aim of this work was the development of extended release tablets of 500 mg of ciprofloxacin based on swellable drug polyelectrolyte matrices (SDPM). A set of complexes of carbomer, ciprofloxacin and sodium, (CB–Cip)50Nax, having a molar ratio Cip/CB acid groups of 0.5 and variable proportions of Na+ was used to prepare SDPM. Characterization of complexes by FT-IR, powder X-ray diffraction and thermal analysis revealed that Cip, in its protonated form, is ionically bonded to the functional groups of CB. Rates of fluid uptake of (CB–Cip)50Nax matrices as well as Cip release in simulated gastric fluid were modulated by changes in the proportion of Na+ incorporated in the complexes. A direct correlation between fluid uptake and delivery rate was observed along the series of matrices. Release rates were modulated from 1.4 mg/min to 25 mg/min in going from (CB–Cip)50Na10 to (CB–Cip)50Na14. The analysis of kinetic data suggest that rates of swelling, ionic pair dissociation and drug diffusion play a role in the kinetic control of delivery. Complexes were satisfactorily prepared and processed together with small amounts of antiadherent and lubricant excipients to obtain a series of extended release SDPM tablets through the current tableting technology processes. Cip release from matrices was widely modulated by the composition of the complexes yielding a flexible system that allows selecting a composition that releases in 120 min 90% of the dose in simulated gastric fluid.
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Financial support was received from CONICET, SECyT-UNC and FONCyT. J.M. Bermudez thanks SECyT-UNC for a research fellowship.
D. S. Roy, and B. D. Rohera. Comparative evaluation of rate of hydration and matrix erosion of HEC and HPC and study of drug release from their matrices. Eur. J. Pharm. Sci. 16:193–199 (2002).CrossRefGoogle Scholar
C. Ferrero, A. Muñoz-Ruiz, and M. R. Jimenez-Castellanos. Fronts movements as a useful tool for hydrophilic matrix release mechanism elucidation. Int. J. Pharm. 202:21–28 (2000).PubMedCrossRefGoogle Scholar
P. Colombo, R. Bettini, and N. A. Peppas. Observation of swelling and diffusion front position during swelling in hydroxypropylmethyl cellulose (HPMC)matrices containing a soluble drug. J. Controlled Release. 61:83–91 (1999).CrossRefGoogle Scholar
P. Colombo, R. Bettini, G. Massimo, et al. Drug diffusion front movement is important in drug release from swellable matrix tablets. J. Pharm. Sci. 84:991–997 (1995).PubMedCrossRefGoogle Scholar
A. F. Jimenez-Kairuz, J. M. Llabot, Allemandi, et al. Swellable drug–polyelectrolyte matrices (SDPM). Characterization and delivery properties. Int. J. Pharm. 288:87–99 (2005).PubMedCrossRefGoogle Scholar
M. V. Ramírez-Rigo, D. A. Allemandi, and R. H. Manzo. Swellable drug–polyelectrolyte matrices (SDPM) of alginic acid Characterization and delivery properties. Int. J. Pharm. 322:36–43 (2006).CrossRefGoogle Scholar
D. A. Quinteros, M. V. Ramirez Rigo, A. F. Jimenez-Kairuz, et al. Interaction between a cationic polymethacrylate (Eudragit E100) and anionic drugs. Eur. J. Pharm. Sci.331:72–79 (2008).PubMedGoogle Scholar
A. P. Vilches, A. F. Jimenez-Kairuz, F. Alovero, et al. Release kinetics and up-take studies of model fluoroquinolones from carbomer hydrogels. Int. J. Pharm. 246:17–24 (2002).PubMedCrossRefGoogle Scholar
H. Nogami, T. Nagai, E. Fukuoka, et al. Disintegration of the aspirin tablets containing potato starch and microcrystalline cellulose in various concentrations. Chem. Pharm. Bull. 17:1450–1455 (1969).PubMedGoogle Scholar
J. M. Llabot, R. H. Manzo, and D. A. Allemandi. Double-layered mucoadhesive tablets containing nystatin. AAPS PharmSciTech [serial online]3:Article 22 (2002).Google Scholar
P. Perez, J. M. Suñé-Negre, M. Miñarro, et al. A new expert systems (SeDeM Diagram) for control batch powder formulation and preformulation drugs products. Eur. J. Pharm. Biopharm. 64:351–359 (2006).PubMedCrossRefGoogle Scholar
M. Donbrow, and Y. Samuelov. Zero order drug delivery from double-layer porous films: release rate profiles from ethyl cellulose and polyethylene glycol mixtures. J Pharm Pharmacol. 32:463–470 (1980).PubMedGoogle Scholar
T. Higuchi. Rate of release of medicament from ointment bases containing drugs in suspension. J Pharm Sci. 50:874–875 (1961).PubMedCrossRefGoogle Scholar
T. Higuchi. Mechanism of sustained-action medication: theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 52:1145–1149 (1963).PubMedCrossRefGoogle Scholar
R. W. Korsmeyer, R. Gurny, E. M. Doelker, et al. Mechanism of solute release from porous hydrophilic polymers. Int. J. Phar. 15:25–35 (1983).CrossRefGoogle Scholar
N. A. Peppas. Analysis of Fickian and non Fickian drug release from Polymers. Pharm. Acta Helv. 60:110–111 (1985).PubMedGoogle Scholar
S. Žakelj, K. Šturm, and A. Kristl. Ciprofloxacin permeability and its active secretion through rat small intestine in vivo. Int. J. Pharm. 313:175–180 (2006).PubMedCrossRefGoogle Scholar
A. Kristl, and J. J. Tukker. Negative correlation of n-octanol/water partition coefficient and transport of some guanine derivatives through rat jejunum in vitro. Pharm. Res. 15:499–501 (1998).PubMedCrossRefGoogle Scholar
H. Sen, and R. S. Kshirsagar. Floating drug delivery systems: an approach to oral controlled drug delivery via gastric retention. J. Cont. Release. 63:235–259 (2002).Google Scholar
S. J. Hwang, H. Park, and K. Park. Gastric retentive drug-delivery systems. Crit. Rev. Ther. Drug Carrier Syst. 15:243–284 (1998).PubMedGoogle Scholar