Pg. Bhat et al., THE LIMITING ROLE OF MUCUS IN DRUG ABSORPTION - DRUG PERMEATION THROUGH MUCUS SOLUTION, International journal of pharmaceutics, 126(1-2), 1995, pp. 179-187
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.