COMPARATIVE IN-VITRO EVALUATION OF CUMULATIVE RELEASE OF THE URINARY ANTISEPTICS NALIDIXIC-ACID, PIPEMIDIC ACID, CINOXACIN, AND NORFLOXACINFROM WHITE BEESWAX MICROSPHERES

The in vitro diffusion of nalidixic acid (1), pipemidic acid (2), cino xacin (3), and norfloxacin (4) was studied. The transfer rate constant s (k(d)) from simulated gastro-intestinal juices to simulated plasma, throughout artificial wall lipid membranes, were defined. The k(d) val ues suggested that the four drugs are absorbed both in gastric and int estinal environments in similar amounts. To obtain lack of gastric unw anted effects white beeswax microspheres containing 1, 2, 3, and 4 wer e investigated as a vehicle for the drug intestinal release; they were prepared by the meltable dispersion process using wetting agents. Dis crete, reproducible free flowing microspheres were obtained. The drug content increased when the particle size growed; it ranged from 4% to 18%. More than 95% of the isolated microspheres were of particle size range 100-500 mu m. The drug release was evaluated in vitro. Dissoluti on of entrapped active ingredients was greatly retarded allowing absor ption only in the intestinal tract as result of microsphere formation.