In vitro and ex vivo evaluation of an intestinal permeation enhancing self-microemulsifying drug delivery system (SMEDDS)

Abstract

The objective of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) that enhances drug absorption through intestinal membranes and to evaluate the mechanism of improvement. The developed formulation was optimized in order to reduce the droplet size and characterized in several environments. Furthermore, a pseudo-ternary phase diagram was mapped in order to identify the o/w microemulsion region. The formulation contains 30 % (m/m) Cremophor EL, 30 % (m/m) Capmul MCM, 10 % (m/m) propylene glycol and 30 % (m/m) Captex 355. Permeation studies were carried out in vitro on Caco-2 cell monolayers and ex vivo on rat intestine in Ussing-type chambers using model compounds rhodamine-123 (Rho-123) and fluorescein isothiocyanate-dextran 4 (FD4). The selected formulation improved in a concentration of 0.5 % (m/v) absorption of FD4 1.85-fold in vitro and 1.65-fold ex vivo via tight junction opening. Furthermore, the system had the ability to inhibit P-glycoprotein and improved the permeation of Rho-123 1.49 fold in vitro and 1.64 fold ex vivo. Stability studies were carried out to assure that the SMEDDS was stable during transport studies and in several media and buffers. According to these results, the developed formulation showed great promise in terms of improving the bioavailability of low-permeability drugs—often the rate-limiting step for oral drug delivery systems.