Ion pair approach of ampicillin using in vitro methods.

The hydrophilic drug ampicillin (AP) was comprehensively studied in vitro with focus on an ion pair approach of AP. The influence of the counter ions in comparison with AP derivatives was studied on the water solubility, lipid partition, and transport across artificial lipid membranes as well as using an in vitro absorption model system. It was found that the water solubility of AP is pH dependent. The water solubility is markedly increased by derivatives such as bacampicillin (BAP). In contrast, the lipid partition and the transport across lipid membranes of AP were markedly enhanced by counter ions, particularly by dodecylsulfate (DS). However, ion pair formation is only in acidic solution (pH 2.5) possible. Taking this into account the same increase of the bioavailability of AP was obtained in the presence of DS as after application of BAP using the in vitro absorption model system.