Improved Dissolution and Oral Bioavailability of Valsartan Using a Solidified Supersaturable Self-Microemulsifying Drug Delivery System Containing Gelucire (R) 44/14

Abstract

To improve the dissolution and oral bioavailability of valsartan (VST), we previously formulated a supersaturable self-microemulsifying drug delivery system (SuSMED) composed of Capmul (R) MCM (oil), Tween (R) 80 (surfactant), Transcutol (R) P (cosurfactant), and Poloxamer 407 (precipitation inhibitor) but encountered a stability problem (Transcutol (R) P-induced weight loss in storage) after solidification. In the present study, replacing Transcutol (R) P with Gelucire (R) 44/14 resulted in a novel SuSMED formulation, wherein the total amount of surfactant/cosurfactant was less than that of the previous formulation. Solidified SuSMED (S-SuSMED) granules were prepared by blending VST-containing SuSMED with selective solid carriers, L-HPC and Florite (R) PS-10, wherein VST existed in an amorphous state. S-SuSMED tablets fabricated by direct compression with additional excipients were sufficiently stable in terms of drug content and impurity changes after 6 months of storage at accelerated conditions (40 +/- 2 degrees C and 75 +/- 5% relative humidity). Consequently, enhanced dissolution was obtained (pH 1.2, 2 h): 6-fold for S-SuSMED granules against raw VST; 2.3-fold for S-SuSMED tablets against Diovan (R) (reference tablet). S-SuSMED tablets increased oral bioavailability in rats (10 mg/kg VST dose): approximately 177-198% versus raw VST and Diovan (R). Therefore, VST-loaded S-SuSMED formulations might be good candidates for practical development in the pharmaceutical industry.