THE EFFECT OF INTESTINAL BACTERIA ADHERENCE ON DRUG DIFFUSION THROUGHSOLID FILMS UNDER STATIONARY CONDITIONS

Purpose. To study the in vitro and in vivo the role of surface bacteri al adhesion on the diffusion of model drugs at stationary conditions. Methods. Salicylic acid (SA) diffusion through ethyl cellulose (EC) fi lms was measured in vitro in side-by-side diffusion cells with and wit hout E. coli of intestinal origin. Insulin (I) release from paper stri ps coated or uncoated with pectin films, with or without antibiotic tr eatment, was measured in vivo in conscious rats after cecal implantati on by comparing blood glucose levels at T-max of the pharmacodynamic e ffect. Results. During five hours of diffusion studies which were perf ormed immediately following incubation of EC films with bacteria, the diffusion rate of SA throughout the films was 2.72-fold lower in the p resence of bacteria compared with the diffusion rate in the control st udies conducted without bacteria. The mean blood glucose levels droppe d in the rat to 40.6 +/- 21.6% of glucose basal levels within 2.4 +/- 1.4 h when uncoated I solid carriers were used. Glucose levels did nor change for pectin-coated dosage forms. After antibiotic treatment whi ch prevented the formation of bacterial biofilm on the surface of the I solid dosage forms, blood glucose levels dropped to 22.0 +/- 4.7% an d 50.9 +/- 20.5% of glucose basal levels within 7.4 +/- 2.6 h and 1.8 +/- 0.9 h for pectin uncoated or coated dosage forms, respectively. Ma ximum bacterial adherence occurred at stationary conditions (RPM = 0), while at maximum agitation (200 RPM), almost no adherence occurred. C onclusions. (a) Bacterial adherence slows down the diffusion rate of S A through EC films; (b) Under stationary conditions bacterial adherenc e may also interfere with drug release from biodegradable (pectin) fil ms; (c) Successful functioning of biodegradable colon-specific deliver y systems depends on agitation and surface friction in the lumen of th e colon.