Development of self-microemulsifying bilayer tablets for pH-independent fast release of candesartan cilexetil

Abstract

The aim of this study was to design self-microemulsifying tablets for pH-independent fast release of poorly soluble candesartan cilexetil (CDC). To improve the solubility of CDC, a self-microemulsifying drug delivery system (SMEDDS) was prepared composed of Capryol 90, Tween 80 and tetraglycol at a ratio of 5:35:60. Drug containing SMEDDS was adsorbed onto Fujicalin and Neusilin UFL2, respectively, used as solidification carriers and subsequently compressed into tablets (self-microemulsifying tablet, SMET). SMET using Fujicalin (R) exhibited immediate CDC release in pH 1.2 medium while Neusilin (R) UFL2-based SMET showed fast release, especially at pH 6.5. Thus, optimized SMET could be produced with one layer of Fujicalin and the other layer with Neusilin UFL2, demonstrating CDC release of 75% of the initial dose within 15 min in all pH conditions (1.2, 4.5, and 6.5). The average diameter of emulsion droplets formed from SMET was less than 200nm. It was thus expected that Fujicalin (R) and Neusilin (R) UFL2-based bi-layer SMET would overcome low oral bioavailability of CDC due to its limited solubility at physiological pH conditions in the gastrointestinal tract.