ComparativeIn Vitroevaluation of cumulative release of the urinary antiseptics Nalidixic acid, Pipemidic acid, Cinoxacin, and norfloxacin from white beeswax Microspheres

The in vitro diffusion of nalidixic acid (1), pipemidic acid (2), cinoxacin (3), and norfloxacin (4) was studied. The transfer rate constants (kd) from simulated gastro-intestinal juices to simulated plasma, throughout artificial wall lipid membranes, were defined. The kd values suggested that the four drugs are absorbed both in gastric and intestinal environments in similar amounts. To obtain lack of gastric unwanted effects white beeswax microspheres containing 1, 2, 3, and 4 were investigated as a vehicle for the drug intestinal release; they were prepared by the meltable dispersion process using wetting agents. Discrete, 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 μm. The drug release was evaluated in vitro. Dissolution of entrapped active ingredients was greatly retarded allowing absorption only in the intestinal tract as result of microsphere formation.