Permeability of glibenclamide through a PAMPA membrane: the effect of co-amorphization

Abstract

Co-amorphous systems are an attractive alternative for amorphous solid polymer dispersions in the formulation of poorly soluble drugs. Several studies have revealed that co-amorphous formulations can enhance the dissolution properties of poorly-soluble drugs and stabilize them in the amorphous form. However, the interplay between the drug dissolution rate, drug supersaturation and different co-formers on membrane permeability of the drug for co-amorphous formulations remains unexplored.

By using side-by-side chambers, separated by a PAMPA (parallel artificial membrane permeability assay) membrane, we were able to simultaneously test dissolution and passive membrane permeability of the co-amorphous combinations (1:1 molar ratio) of a poorly soluble drug glibenclamide (GBC) in combination with two amino acids, either serine (SER) or arginine (ARG). In addition, a known passive permeability enhancer sodium lauryl sulfate (SLS) was included in the co-amorphous mixtures at two concentration levels. The mixtures were also characterized with respect to their solid-state properties and physical stability.

It was found that GBC mixtures with ARG and SLS had superior dissolution and physical stability properties which was attributable to the strong intermolecular interactions formed between GBC and ARG. These formulations also had optimal permeability properties due to their high concentration gradient promoting permeation and possible permeation enhancing effect of the co-formers ARG and SLS. Thus, simultaneous testing of dissolution and permeation through a PAMPA membrane may represent a simple and inexpensive tool for screening the most promising amorphous formulations in further studies.