Purpose: The purpose of this study is to develop a novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) for a water-insoluble oily drug, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) with improved stability and oral bioavailability.
Methods: Numerous S-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 and PXRD. Moreover, the solubility, dissolution, stability and pharmacokinetics of the selected S-SNEDDS were assessed compared with the drug and a commercial soft capsule.
Results: Sodium lauryl sulfate (SLS) and hydroxypropyl methylcellulose (HPMC) with the highest drug solubility were selected as surfactant and hydrophilic polymer, respectively. Among the antioxidants tested, only butylated hydroxyanisole (BHA) could completely protect the drug from oxidative degradation. The S-SNEDDS composed of PLAG/SLS/HPMC/BHA/calcium silicate at a weight ratio of 1: 0.25: 0.1: 0.0002: 0.5 provided an emulsion droplet size of less than 300 nm. In this S-SNEDDS, the drug and other ingredients might exist in the pores of carrier and attach onto its surface. It considerably improved the drug stability (about 100% vs. 70%, 60 °C for 5 days) and dissolution (about 80% vs. 20% in 60 min) compared to the commercial soft capsule. Moreover, the S-SNEDDS gave higher AUC, Cmax and Tmax values than the commercial soft capsule; in particular, the former improved the oral bioavailability of PLAG by about 3-fold. Our results suggested that this S-SNEDDS provided excellent stability and oral bioavailability of PLAG.
Conclusion: Thus, this S-SNEDDS would be recommended as a powerful oral drug delivery system for an oily drug, PLAG.
Eun Su Yang– College of Pharmacy, Hanyang University, South Korea
Dong Shik Kim– Hanyang University, Ansan
Sang Min Lee– Hanyang University, Ansan
Ji Eun Choi– Department of Pharmaceutical Engineering, Dankook University, South Korea
Min-Jong Choi– Department of Pharmaceutical Engineering, Dankook University, South Korea
Min Hyun Sung– Student, Yeungnam University, Gyeongsan
Chul Soon Yong– College of Pharmacy, Yeungnam University, South Korea
Jong Oh Kim– College of Pharmacy, Yeungnam University, South Korea
Sung Giu Jin– Department of Pharmaceutical Engineering, Dankook University, South Korea
Han-Gon Choi– College of Pharmacy, Hanyang University, South Korea