Enhanced oral bioavailability of valsartan using a polymer-based supersaturable self-microemulsifying drug delivery system

Dong Woo Yeom,1,* Bo Ram Chae,2,* Ho Yong Son,1 Jin Han Kim,1 Jun Soo Chae,1 Seh Hyon Song,2 Dongho Oh,2 Young Wook Choi1 1College of Pharmacy, Chung-Ang University, Seoul, 2Daewon Pharm. Co., Ltd, Seoul, Republic of Korea *These authors contributed equally to this work Abstract: A novel, supersaturable self-microemulsifying drug delivery system (S-SMEDDS) was successfully formulated to enhance the dissolution and oral absorption of valsartan (VST), a poorly water-soluble drug, while reducing the total quantity for administration. Poloxamer 407 is a selectable, supersaturating agent for VST-containing SMEDDS composed of 10% Capmul® MCM, 45% Tween® 20, and 45% Transcutol® P. The amounts of SMEDDS and Poloxamer 407 were chosen as formulation variables for a 3-level factorial design. Further optimization was established by weighting different levels of importance on response variables for dissolution and total quantity, resulting in an optimal S-SMEDDS in large quantity (S-SMEDDS_LQ; 352 mg in total) and S-SMEDDS in reduced quantity (S-SMEDDS_RQ; 144.6 mg in total). Good agreement was observed between predicted and experimental values for response variables. Consequently, compared with VST powder or suspension and SMEDDS, both S-SMEDDS_LQ and S-SMEDDS_RQ showed excellent in vitro dissolution and in vivo oral bioavailability in rats. The magnitude of dissolution and absorption-enhancing capacities using quantity-based comparisons was in the order S-SMEDDS_RQ > S-SMEDDS_LQ > SMEDDS > VST powder or suspension. Thus, we concluded that, in terms of developing an effective SMEDDS preparation with minimal total quantity, S-SMEDDS_RQ is a promising candidate. Keywords: valsartan, SMEDDS, supersaturation, factorial design, optimization, bio­availability&nbsp