Ion-pairs of ibuprofen: increased membrane diffusion

The purpose of the present study was to determine the influence of pH and ion-pairing on the permeation of ibuprofen across polyclimethylsiloxane (PDMS) membrane. The solubility of ibuprofen sodium was determined at a range of pH values. Saturated solutions were then used to determine the influence of pH on diffusion across PDMS as a model membrane. The apparent partition coefficient of ibuprofen sodium between n-octanol and phosphate buffer at various pH values was also investigated. Organic salts of ibuprofen using ethylamine, diethylamine, triethylamine and ethylene diamine as counter-ions were synthesized and the influence of these counter-ions on the permeation of ibuprofen was studied. The presence of ion-pairing was confirmed using H-1 NMR and C-13 NMR. Diffusion studies at different pH values (4.0, 5.0, 6.0, 7.0 and 8.0) indicated that ibuprofen sodium flux increased significantly with increasing pH from 4.0 to 7.0. Above pH 7.0 a decrease in diffusion was observed. The permeability coefficient increased with an increase in the amount of unionized acid. The apparent partition coefficient was directly related to the steady-state flux. The steady-state flux of ibuprofen increased up to 16-fold using different counter-ions. The highest flux was measured from ibuprofen triethylamine. The flux of ibuprofen salts across a lipophilic membrane can be increased by formation of ion-pairs. The extent of enhancement is associated with the lipophilicity, extent of ion-pairing and reduction in charge over the drug molecule.