Development of PLAG-loaded solid SNEDDS formulation

Abstract

To develop a novel HPMC/calcium silicate-based solid self-nanoemulsifying drug delivery system (SNEDDS) of water insoluble oily drug, 1-palmitoyl-2-linoleoyl-3-acetyl-rac–glycerol (PLAG) with improved stability and oral bioavailability, numerous solid SNEDDS were prepared with surfactant, hydrophilic polymer, antioxidant and calcium silicate (porous carrier) using the spray drying method. Their physicochemical properties were evaluated using emulsion droplet size analysis, SEM, PXRD and DSC. Moreover, the solubility, dissolution, stability and pharmacokinetics of selected solid SNEDDS were assessed compared with drug and commercial soft capsule. Sodium laurylsulfate (SLS) and hydroxypropyl methylcellulose (HPMC) with highest drug solubility were selected a surfactant and hydrophilic polymer, respectively. Among antioxidants tested, butylated hydroxyanisole (BHA) gave highest drug stability; thus BHA was selected as an antioxidant. The solid SNEDDS composed of PLAG/SLS/HPMC/BHA/calcium silicate at the weight ratio of 1:0.25:0.1:0.0002:0.5 provided the emulsion droplet size of less than 300 nm. In this solid SNEDDS, drug and other ingredients might be existed into pore of calcium silicate and attached onto its surface. It improved the drug stability (99.7 ± 0.3 vs. 67.9 ± 4.3 % at 5 days), solubility (about 2.5 vs. 0 mg/ml) and dissolution (about 80 vs. 20 % in pH 6.8 buffer solution containing 2.5% SLS for 60 min) compared to commercial soft capsule. Moreover, solid SNEDDS gave higher AUC, Cmax and Tmax values than did the commercial soft capsule; specially, the former improved about 3-fold oral bioavailability of PLAG. Our results suggested that this solid SNEDDS provided excellent drug solubility, stability and oral bioavailability of PLAG. Thus, this solid SNEDDS system would be recommended as a powerful oral drug delivery system for an oily drug, PLAG.