THE LIMITING ROLE OF MUCUS IN DRUG ABSORPTION - DRUG PERMEATION THROUGH MUCUS SOLUTION

A purified model in vitro mucus system containing primarily the large, 400 kDa glycoprotein fraction of mucus has been developed for use in drug permeability and drug binding studies. The effect of protein solu tions, either bovine serum albumin (BSA) or purified porcine gastric m ucus, on the permeability behavior of five drugs was studied. The drug s chosen were isoniazid, pentamidine, rifampicin, p-aminosalicylic aci d, and pyrazinamide, all of which can be potentially delivered as pulm onary aerosols. BSA was included in the permeability studies for compa rison with previously obtained data regarding their binding behaviors to mucin relative to BSA. A custom membrane holder with a 3 mm chamber for mucin or other solutions was used in a Side-Bi-Side(R) diffusion apparatus to measure drug permeation through the solutions. Apparent p ermeability coefficients were calculated for each barrier in the serie s barrier system, with a protein solution being one of the barriers. T he protein solutions significantly reduced the permeability of the dru gs studied compared with their permeability through blank buffer solut ion. Both the lag time and the steady-state flux of the compounds were altered in the presence of protein indicating that there is more than protein binding affecting permeability. Such reductions in permeabili ty coefficients need to be considered for all compounds that must trav erse any mucosal surface prior to absorption or action.