Barsaklardan Paraselüler Ilaç Absorpsiyonu Üzerine Permeabilite Artırıcı Ajanların Etkisinin Araştırılması

Abstract

The aim of this study was to investigate the effect of permeability enhancers on paracellular drug absorption. For this purpose, acyclovir classified as Class III drug (high solubility and low permeability) according to Biopharmaceutics Classification System and transported via paracellular pathway with passive diffusion was used as the model compound. Effect of excipients with polymer and surfactant properties (chitosan, dimethyl β-cyclodextrin, sodium caprate, sodium lauryl sulphate) on the absorption and permeability of acyclovir across different rat intestinal segments (jejunum, ileum and colon) was investigated using in situ intestinal perfusion studies. Initially, all segments were perfused simultaneously with acyclovir containing perfusion medium, and then perfused with acyclovir and permeability enhancer containing perfusion medium. Metoprolol and phenol red were added as the reference compounds to all perfusion mediums. Acyclovir, metoprolol and phenol red amounts in the samples were determined by means of a validated HPLC method. The results obtained from the perfusion studies indicated that sodium caprate has the highest permeability enhancing effect. Sodium caprate increased the permeability values of acyclovir 6.71-fold im jejunum, 6.83-fold in ileum and 4.14-fold in colon. Dimethlyl β-cyclodextrin has not demonstrated permeability enhancing effect on the selected model compound (acyclovir). On the other hand, although chitosan and sodium lauryl sulphate have permeability enhancing effect this effect was statiscally significant only in the jejunum (p=0.043). Even though, increase in permeation was observed in jejunum and colon, this increase was not significant (p>0.05). The results obtained from this study indicate that permeation enhancing agents can be effective in increasing bioavailability of compounds with low absorption and absorbed via paracellular route.