Mohsin Kazi, Alamri Rayan, Ahmad Ajaz, Raish Mohammad, Alanazi Fars K, Hussain Muhammad Delwar
Kayyali Chair for Pharmaceutical Industry, Department of Pharmaceutics, King Saud University, Riyadh, Saudi Arabia.
Department of Clinical Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Int J Nanomedicine. 2016 Jun 14;11:2829-38. doi: 10.2147/IJN.S104187. eCollection 2016.
Self-nanoemulsifying drug delivery systems (SNEDDS) have become a popular formulation option as nanocarriers for poorly water-soluble drugs. The objective of this study was to investigate the factor that can influence the design of successful lipid formulation classification system (LFCS) Type III SNEDDS formulation and improve the oral bioavailability (BA) of fenofibrate.
LFCS Type III SNEDDS were designed using various oils, water-soluble surfactants, and/or cosolvents (in considering the polarity of the lipids) for the model anticholesterol drug, fenofibrate. The developed SNEDDS were assessed visually and by measurement of the droplet size. Equilibrium solubility of fenofibrate in the SNEDDS was conducted to find out the maximum drug loading. Dynamic dispersion studies were carried out (1/100 dilution) in water to investigate how much drug stays in solution after aqueous dispersion of the formulation. The BA of SNEDDS formulation was evaluated in the rat.
The results from the characterization and solubility studies showed that formulations containing mixed glycerides were highly efficient SNEDDS as they had higher solubility of the drug and produced nanosized droplets. The dispersion studies confirmed that SNEDDS (containing polar mixed glycerides) can retain >98% drug in solution for >24 hours in aqueous media. The in vivo pharmacokinetics parameters of SNEDDS formulation in comparison with pure drug showed significant increase in C max and AUC0- t , ~78% and 67%, respectively. The oral BA of fenofibrate from SNEDDS in rats was ~1.7-fold enhanced as compared with the BA from pure drug.
Fenofibrate-loaded LFCS Type III SNEDDS formulations could be a potential oral pharmaceutical product for administering the poorly water-soluble drug, fenofibrate, with an enhanced oral BA.
自纳米乳化药物递送系统（SNEDDS）已成为一种流行的制剂选择，作为难溶性药物的纳米载体。本研究的目的是探讨能够影响成功的脂质制剂分类系统（LFCS）III型SNEDDS制剂设计的因素，并提高非诺贝特的口服生物利用度（BA）。
针对模型抗胆固醇药物非诺贝特，使用各种油、水溶性表面活性剂和/或助溶剂（考虑脂质的极性）设计LFCS III型SNEDDS。通过目视评估和测量液滴大小对所开发的SNEDDS进行评估。进行非诺贝特在SNEDDS中的平衡溶解度研究以确定最大载药量。在水中进行动态分散研究（1/100稀释），以研究制剂在水性分散后有多少药物保留在溶液中。在大鼠中评估SNEDDS制剂的BA。
表征和溶解度研究的结果表明，含有混合甘油酯的制剂是高效的SNEDDS，因为它们具有更高的药物溶解度并产生纳米级液滴。分散研究证实，SNEDDS（含有极性混合甘油酯）在水性介质中可使>98%的药物在溶液中保留>24小时。与纯药物相比，SNEDDS制剂的体内药代动力学参数显示Cmax和AUC0 - t分别显著增加约78%和67%。与纯药物的BA相比，大鼠中SNEDDS中非诺贝特的口服BA提高了约1.7倍。
载有非诺贝特的LFCS III型SNEDDS制剂可能是一种潜在的口服药物产品，用于给药难溶性药物非诺贝特，并提高口服BA。
