A novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) for improved stability and oral bioavailability of an oily drug, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol

Drug Delivery

Kyeong Soo Kim¹  Eun Su Yang¹  Han Gon Choi¹  Dong Wuk Kim¹  Hye Hyun Yoo¹  Dong Shik Kim¹  Sung Giu Jin²  Jun-Pil Jee³  Kyung Taek Oh⁴  Chul Soon Yong⁵  Jong Oh Kim⁵  Yu Seok Youn⁶ 

[1] College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, Sangnok-gu, Ansan, South Korea;College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, Sangnok-gu, Ansan, South Korea;Department of Pharmaceutical Engineering, Dankook University, Cheonan, South Kore;College of Pharmacy, Chosun University, Gwangju, South Korea;College of Pharmacy, Chung-Ang University, Seoul, South Korea;College of Pharmacy, Yeungnam University, Gyongsan, South Korea;School of Pharmacy, Sungkyunkwan University, Jangan-gu, Suwon, South Korea;

关键词: Oily drug;    1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol;    S-SNEDDS;    hydroxypropyl methylcellulose;    calcium silicate;    solubility;    bioavailability;   

DOI  :  10.1080/10717544.2017.1344335

来源: Taylor & Francis

【 摘 要 】

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, 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. 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 d) 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. Thus, this S-SNEDDS would be recommended as a powerful oral drug delivery system for an oily drug, PLAG.

【 授权许可】

CC BY