Preliminary rheological studies on carbomer-ciprofloxacin-sodium as modified release systems

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

Rósario

Congreso; 2ra. Reunión Internacional de Ciencias Farmacéuticoas RICiFa 2012.; 2012

Universidad Nacional de Rosario

Introduction Pharmaceutical technology has been developing modified release drug delivery systems (MRS) which offer numerous pharmacotherapeutic advantages over conventional dosage forms. Thus, many MRS have been introduced over time, exhibiting a series of advantages over conventional dosage forms. To this effect, swellable drug polyelectrolyte matrices (SDPM) have been developed. These are obtained by compaction of powdered complexes of a polyelectrolyte (PE) fully or partially neutralized with a ionizable drug (F), using the regular compaction technique (1-2). PE-F complexes contain a molecular dispersion of F in the matrix where F is ionically bonded to the ionizable groups of PE, which acts as a reservoir, releasing it slowly. This is relevant to obtain: modified release, drug chemical stability and aqueous compatibility increase. PE-F systems containing Ciprofloxacin (500mg), Carbomer and different molar percentages of Na+, (CB-Cip)50Nax, which are the object of this study, were originally prepared and evaluated by Bermúdez(3). They showed that water sorption and release were highly sensitive to Na+ concentration in materials. It is known that rheological studies can offer detailed structural information about dispersed polymeric systems. For this reason, a preliminary rheological study was conducted to determine if it is possible to associate the viscoeleastic properties of the hydrated matrices as a function of Na+, water content and drug release mechanism from PE-F matrices. Materials and methods (CB-Cip)50 complexes were prepared, where 50% of carboxylic groups of CB were neutralized with Cip, and then mixed in a mortar until a semi-solid paste was obtained. Additionally, appropriate amounts of Na (OH) 1M were added in order to obtain molar concentrations of 5, 10, 12, 14 and 20% of sodium in the complexes. The resulting samples were labeled as: (CB-Cip)50 Nax, subindex x meaning Na concentration. Complexes that contained sodium were hydrated using distilled water (DW) to a concentration of 21 w/w. Rheological characterization was performed in a TA Instruments AR-G2 rheometer, in small amplitude frequency sweep tests using 25 mm diameter parallel plates, at 32°C. Results and conclusions Variation of elastic module G’ as a function of frequency () was graphed as from frequency sweep tests at 32°C. Results evidenced that Na+ concentrations between 10 and 12% showed a significant decrease in the value of G’. On the other hand, and according to Bermúdez (3), a significant increase in the release rate of SDPM carbomer-ciprofloxacin (CB-Cip) was observed at the same concentrations of Na+. This discloses the existence of coincidences between the minimum values of G’ that were obtained and concentrations of Na where a notable change in the release rate of Cip and fluid sorption is registered.