Ion-pairs of ibuprofen: increased membrane diffusion

Abstract

The purpose of the present study was to determine the influence of pH and ion-pairing on the permeation of ibuprofen across polydimethylsiloxane (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 1H NMR and 13C 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.

In Vitro Permeation Characterization of the Analgesic Ibuprofen and the Sunscreen Oxybenzone

“…Transmembrane permeation of ibuprofen observed from this study was significantly lower than that reported for both the single and the combined study designs (Al-Saidan, 2004;Hadgraft, Whitefield, & Rosher, 2003). Several previous studies also showed that ionization of ibuprofen helped increase its ability to penetrate through the stratum corneum and into the system, a method not utilized in this study (Al-saidan, 2004;Sarveiya, Templeton, & Benson, 2004). Nevertheless, oxybenzone in the single-component samples did yield permeation data comparable to those observed from other studies (Gustavsson Gonzales et al, 2002;Pont et al, 2004;Wang et al, 2006).…”

In Situ Artificial Membrane Permeation Assay under Hydrodynamic Control: Permeability-pH Profiles of Warfarin and Verapamil

“…Ion pairing is likely to be facilitated by the charged organic components within the membrane rather than the aqueous phase counter-ions of low lipophilicity. Ion-pairing mechanisms facilitating permeation/partition were reported in previous literature (43)(44)(45). This mechanism could explain the variation in both P u and P 0 .…”

Application of Cyclodextrins in Textile Dyeing

“…Here is one example: in cosmetic applications complexation has improved the photostability of sunscreens (Scalia et al, 1998;Scalia et al, 1999) but its influence on skin penetration behaviour is a compromise. There is an increasing effect due to better solubility (Vollmer et al, 1994;Legendre et al, 1995) but a decreasing effect resulting from using molecules with large relative molar masses (equivalent to more than 1000 Da) (Sarveiya et al, 2004;Simeoni et al, 2004;Williams et al, 1998). A recent trend is the use of modified cyclodextrin molecules.…”