Swellable drug polyelectrolite matrices: preliminary rheological studies on carbomer-ciprofloxacin-sodium systems.

CHANAMPA, L.; RESSIA, J.; JIMENEZ KAIRUZ, AF.; VALLÉS, EM.

Córdoba

Congreso; 1ra. Reunión de Ciencias Farmacéuticas, RICiFa 2010; 2010

Facultad de Ciencias Químicas, Universidad Nacional de Córdoba.

Introducción Many controlled drug delivery systems have been introduced in pharmacotherapy along time exhibiting a number of advantages over conventional dosage forms. In the early works, novel swellable drug polyelectrolyte matrices (SDPM) obtained by compaction of powdered complexes of a polyelectrolyte (PE) fully or partially neutralized with a ionizable drug (D) have been developed using current tableting technology(1-2). Unlike traditional swellable hydrophilic matrices, SDPM?s contain a molecular dispersion of D in the mass of the matrix since D is ionically bonded to the functional groups of PE as a (PE-D) complex which is relevant to obtain: drug controlled release, drug chemical stability and aqueous compatibility increase, and/or multiparticulate delivery systems. Extended release SDPM, containing Ciprofloxacin (500mg) ? Carbomer complex, were prepared and evaluated by Bermudez et al. (3). They showed that water sorption and release properties were highly sensitive to material composition. It?s known that rheological studies can offer detailed structural information about dispersed polymeric system. In this way, a preliminary rheological study was conducted to associate the viscoeleastic characteristics (G?, G??, Tan α) of the hydrated matrices as a function of Na+ and water contents with the water sorption and Ciprofoxacin release behavior from SDPM. Materials and methods (CB-Cip)50 complexes were prepared (subindex 50 meaning the Cip molar percentage with respect to the CB ionizable carboxilic groups). Then, NaOH 1M was added in order to obtain a molar concentration of 5, 10 and 20% of sodium in the complexes. The resulting samples, labeled as (CB-Cip)50, (CB-Cip)50Na5, (CB-Cip)50Na10 y (CB-Cip)50Na20, were characterized by Differential Scanning Calorimetry (DSC) in a Perkin-Elmer Pyris I calorimeter. The sodium contaning complexes were hydrated using physiological solution (PS) at different concentrations, ranging from 19 to 29% w/w, depending on the ability of the powdered samples to absorb PS to acquire adequate consistency for being tested on the rheometer. Rheological characterization was performed in a TA Instruments AR-G2 rheometer, in small amplitude frequency sweep tests using 25 mm diameter parallel plates, at room temperature. In order to avoid dehydratation during the test the samples located between the plates were protected with thin layer of a low viscosity silicon oil. Results and conclusions DSC analysis showed that Cip the characteristic fusion peak of neat Cip (265-268°C) was not observed in any of the (CB-Cip)50Na complexes confirming the complete interaction between CB and Cip. The complexes showed a narrow window on their capacity to absorb PS in order to obtain the desired consistency for the rheological analysis. A further addition of PS caused the formation of a second phase. From the preparation of the samples for rheological tests, it was inferred that increasing the sodium concentration on the (CB-Cip)50Na complexes, increases the capacity of the complexes to absorb PS up to Na contents of about 10%. Higher contents of Na do not further augment the amount of PS absorbed by the complexes.