Improved transport apparatus for examining diffusion of drugs across isolated tissues and synthetic membranes.
A three-compartment diffusion apparatus that can accommodate synthetic as well as small isolated biological membranes such as rat intestine was developed and tested. The diffusion of drug from two outer donor cells into a central recipient cell allows for more membrane surface exposure and greater sensitivity in assaying as compared with previously published techniques. Reproducibility values for the synthetic membrane were equivalent to those obtained in more elaborate designs, while the reproducibility for biological membranes compared favorably with everted gut preparations and a similar diffusion apparatus. The clearance, per square centimeter of membrane, of salicylamide at pH 7.4 and 37 degrees was 0.288 ml/hr/cm2, which agreed with previous literature reports of different techniques. Although the diffusion through  a synthetic membrane was more rapid, introduction of a nonionic surfactant enhanced the biological perfusion rate while having no significant effect on the synthetic barrier. The enhancement of the diffusion rate effected by 0.1 and 0.01% (w/v) surfactant was about twofold, rapid in onset, and not progressive, giving clearance values per square centimeter of 0.606 and 0.537 ml/hr/cm2, respectively.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002482:Cellulose; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation; D004058:Diffusion; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations; D051381:Rats; D012457:Salicylamides / Q000378:metabolism; D013501:Surface-Active Agents / Q000494:pharmacology; D013997:Time Factors
D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations; D012457:Salicylamides; D013501:Surface-Active Agents; D002482:Cellulose