In vitro-in situ permeability and dissolution of fexofenadine with kinetic modeling in the presence of sodium dodecyl sulfate


GUNDOGDU E., MANGAS-SANJUAN V., GONZALEZ-ALVAREZ I., BERMEJO M., KARASULU E.

EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS, cilt.37, ss.65-75, 2012 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 37 Konu: 1
  • Basım Tarihi: 2012
  • Doi Numarası: 10.1007/s13318-011-0059-4
  • Dergi Adı: EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS
  • Sayfa Sayıları: ss.65-75

Özet

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 mu M) 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.