The Effect of Intestinal Bacteria Adherence on Drug Diffusion Through Solid Films Under Stationary Conditions
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Purpose. To study the in vitro and in vivo the role of surface bacterial adhesion on the diffusion of model drugs at stationary conditions.
Methods. Salicylic acid (SA) diffusion through ethyl cellulose (EC) films was measured in vitro in side-by-side diffusion cells with and without E. coli of intestinal origin. Insulin (I) release from paper strips coated or uncoated with pectin films, with or without antibiotic treatment, was measured in vivo in conscious rats after cecal implantation by comparing blood glucose levels at Tmax of the pharmacodynamic effect.
Results. During five hours of diffusion studies which were performed immediately following incubation of EC films with bacteria, the diffusion rate of S A throughout the films was 2.72-fold lower in the presence of bacteria compared with the diffusion rate in the control studies conducted without bacteria. The mean blood glucose levels dropped 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 not change for pectin-coated dosage forms. After antibiotic treatment which prevented the formation of bacterial biofilm on the surface of the I solid dosage forms, blood glucose levels dropped to 22.0 ± 4.7% and 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. Maximum bacterial adherence occurred at stationary conditions (RPM = 0), while at maximum agitation (200 RPM), almost no adherence occurred.
Conclusions. (a) Bacterial adherence slows down the diffusion rate of SA through EC films; (b) Under stationary conditions bacterial adherence may also interfere with drug release from biodegradable (pectin) films; (c) Successful functioning of biodegradable colon-specific delivery systems depends on agitation and surface friction in the lumen of the colon.
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