The limiting role of mucus in drug absorption: Drug permeation through mucus solution

Abstract

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 solutions, either bovine serum albumin (BSA) or purified porcine gastric mucus, on the permeability behavior of five drugs was studied. The drugs chosen were isoniazid, pentamidine, rifampicin, p-aminosalicylic acid, and pyrazinamide, all of which can be potentially delivered as pulmonary aerosols. BSA was included in the permeability studies for comparison 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 permeability coefficients were calculated for each barrier in the series barrier system, with a protein solution being one of the barriers. The protein solutions significantly reduced the permeability of the drugs studied compared with their permeability through blank buffer solution. 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 permeability coefficients need to be considered for all compounds that must traverse any mucosal surface prior to absorption or action.