Erodible poly(ortho ester) drug delivery systems: In vitro erosion in canine and USP-simulated gastric juice

Abstract

In vitro erosion of poly(ortho ester) devices labelled with [ 14C] 1, 6-hexanediol was examined in canine gastric juice, USP-simulated gastric juice and pH 7 phosphate buffer. Two percent phthalic anhydride effectively minimized major differences in erosion ratesand lag times observed at pH 7 and pH 1.5 without anhydride catalyst. USP-simulated gastric juice afforded erosion profiles identical to those obtained with canine gastric juice. Data were obtained which indicated that inclusion of pepsin (0.32%) in the dissolution medium prolonged the lag time approximately 2 hours when compared to pepsin-free medium. Erosion rates were unchanged. The effect of pepsin was not dependent on pH in the range of pH 1.5–7.0. Bovine serum albumin afforded a similar response even though the net charge on bovine serum albumin is positive at pH 1.5 (pepsin's net charge is negative at pH 1.5). The use of 125I-labelled bovine serum albumin indicated protein adsorption on the surface of the polymer devices. The effect of bovine serum albumin on release lag time was rapid and readily reversible by transferring the device to protein-free medium. Dual release experiments monitoring 14C-diol release and Amaranth red marker release indicated both release lag times were similarly affected by the presence of pepsin in the dissolution medium. The release rate of Amaranth red appeared to be slightly reduced by erosion in protein-containing medium. The data demonstrate that protein in the erosion medium can significantly effect erosion lag time and identifies a potential additional determinant of drug release when poly(ortho ester) devices are employed in in vivo applications.