sodium-dodecyl-sulfate and fexofenadine

The purpose of this study was to estimate passive permeability and efflux transport parameters of fexofenadine (FEX) from in vitro cell culture and in situ rat experiments and determine the dissolution profile of FEX in the absence and presence of sodium dodecyl sulfate (SDS). The dissolution rate of FEX was investigated at different pH values and in the presence of SDS. The permeability of FEX was determined in situ in small intestine of Wistar rats and in vitro in Caco-2 cell monolayer. Permeability of FEX was determined at different donor concentrations, and the effect of SDS at two concentration levels (10 and 50 μM) on FEX permeability was evaluated. The transepithelial electrical resistance values of the in vitro technique were measured to assess monolayer integrity before and after the permeability studies. The FEX permeability parameters in the absence and presence of SDS were estimated using Phoenix WinNonlin software program and compared with other laboratory results for both in vitro and in situ studies. The results showed that FEX has a low permeability in the paracellular permeability as well a potential inhibition of secretion mediated by P-glycoprotein (P(gp)), and its permeability increased with presence of SDS. The dissolution of FEX was pH-dependent and significantly enhanced, especially in the presence of 50 mg SDS.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biological Transport; Caco-2 Cells; Dose-Response Relationship, Drug; Electric Impedance; Histamine H1 Antagonists, Non-Sedating; Humans; Hydrogen-Ion Concentration; Intestinal Absorption; Male; Models, Biological; Permeability; Rats; Rats, Wistar; Sodium Dodecyl Sulfate; Solubility; Surface-Active Agents; Terfenadine

The purpose of this study was to estimate the effect of the anionic surfactant sodium dodecyl sulphate (SDS) on the permeability and dissolution of fexofenadine hydrochloride (FEX) and the transepithelial electrical resistance (TEER) with Caco-2 cells. The dissolution profile of FEX was evaluated at different pH values (1.2, 3.2, 4.2, 4.5, 5.2 and 6.8) at 37 +/- 0.5 degrees C and chracterized in presence of SDS. The dissolution of FEX was increased in the presence of SDS. For permeability studies, apical to basolateral and basolateral to apical permeability was assesed with various concentrations of FEX (50, 100, 500, 1000 and 5000 microM) and in the presence of SDS. The FEX transport changed with 10 and 50 microM of SDS and the TEER values, after 120 min, decreased. In conclusion, a low and concentration-dependent permeability was found for FEX across the Caco-2 cells. FEX transport increased and TEER decreased with increasing SDS concentrations. These results supports the use of SDS as anionic surfactant in these concentration; SDS can be used safely as permeation and dissolution enhancer for the oral delivery of FEX.

Topics: Algorithms; Caco-2 Cells; Chromatography, High Pressure Liquid; Electric Impedance; Epithelium; Histamine H1 Antagonists, Non-Sedating; Humans; Permeability; Sodium Dodecyl Sulfate; Solubility; Spectrometry, Fluorescence; Surface-Active Agents; Terfenadine