In vitro release evaluation of two model NSAIDs from interpolyelectrolyte-drug complexes in solid state

GARCÍA, MC; TIMOFIEJUK, E; MANZO, RH; JIMENEZ-KAIRUZ, AF

Córdoba

Congreso; 3 rd International Meeting on Pharmaceutical Sciences; 2014

Facultad de Ciencias Químicas, Universidad Nacional de Córdoba y Coorganizada por la Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario

Interpolyelectrolyte complexes with ionizable drugs of opposite charge (IPEC) are an attractive strategy, which has been exploited in order to obtain new carrier and modified drug release systems (1,2). The IPEC can be obtained by spontaneous electrostatic association or acid-base reaction, in aqueous dispersion or hydroalcoholic mixtures. The objectives of this work were to obtain IPEC in solid state, based on two polymethacrylates of opposite charge (Eudragit-EPO and Eudragit-L100) neutralized with Naproxen and Ketoprofen and to evaluated the release behavior according to the composition of the system, contained of NaCl and pH of medium. The IPEC were obtained by two methods: 1) complex coacervation in aqueous medium (Scheme-1) and subsequent obtention of the solid state complex by lyophilization, 2) Wet blending of the solids materials and evaporation of solvent, using hydroalcoholic mixture as reaction medium (not contain NaCl). The solids were sieved (30/40-mesh). Dissolution of IPEC, contained in hard gelatin capsules (200-mg) were carried out in 900-ml of buffer solutions of pH 1.2 and 6.8 (Apparatus-1, 100-r.p.m., 37°C, by triplicate). Drug released determination was performed by UV-spectrophotometry. The IPEC obtained by lyophilization showed: at pH 1.2, controlled release of ketoprofen and release rate changes with the composition of IPEC (Q4h between 80 and 20%) were observed. While naproxen was released more slowly, showing a minor dependence with IPEC composition (Q4h between 45 and 25%). At pH 6.8 a significant changes and opposite release profiles were observed. The release profiles from IPEC without NaCl showed decreased in release rate and changes in kinetic control, which can be attributed to the greater influence of ion exchange and wettability of the solids on release performance. These complexes behave as a reservoir that slowly released of NSAIDs, thus the IPEC systems exhibited interesting properties to design multiparticulate drug delivery systems for oral route.