Acta Pharm. 54 (2004) 339-345

Preparation and ex vivo evaluation of TEC as an absorption enhancer for poorly absorbable compounds in colon specific drug delivery

PARISA YOUNESSI,¹ MOHAMMAD REZA AVADI,^2,3  KOOROUSH SHAMIMI,⁴  ASSAL MIR MOHAMMAD SADEGHI,³  LEILA MOEZI,⁴  ELAHEH NAHID,¹  KHOSROW BAYATI,^1,3 AHMAD REZA DEHPOUR⁴ and MORTEZA RAFIEE-TEHRANI^1,*

rafitehr@ams.ac.ir

¹Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
²Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
³Hakim Pharmaceutical Company , Tehran, Iran
⁴Faculty of Medicine, Tehran University of Medical Sciences,Tehran, Iran

In previous studies, it was established that chitosan and its quaternized derivatives are potent enhancers of hydrophilic compounds absorption across intestinal epithelia. The aim of this study was to evaluate the application of a new quaternized chitosan, triethyl chitosan (TEC), in pharmaceutical approaches. TEC was synthesized by a one step process via a 2² factorial design to optimize the preparation conditions. In ex vivo experiments, everted rat colon sac was used to determine the effect of TEC on the penetration of hydrophilic compounds of different molecular masses (e.g., sodium fluorescein and brilliant blue) through colonic epithelia in comparison with chitosan at pH 7.4. These studies indicated a significant increase in absorption of sodium fluorescein and brilliant blue in the presence of TEC compared to chitosan. TEC bearing positive charge is able to interact with the tight junctions of colon epithelia and hence increase the permeation of sodium fluorescein and brilliant blue through the tight junctions. This investigation has shown that triethyl chitosan could be used as a penetration enhancer for poorly absorbable compounds in the colon drug delivery system.

Keywords: triethyl chitosan, absorption enhancer, colon