Department of Pharmaceutics, King Saud University, Riyadh, Kingdom of Saudi Arabia.
J Pharm Pharmacol. 2010 Feb;62(2):173-80. doi: 10.1211/jpp.62.02.0004.
The objective of this study was to prepare a self-emulsifying drug delivery system (SEDDS) for oral bioavailability enhancement of a poorly water-soluble drug, etodolac. The SEDDS formulations were optimized by evaluating their ability to self-emulsify when introduced to an aqueous medium under gentle agitation, and by determination of the particle size of the resulting emulsion.
An optimized formulation of SEDDS (composed of 20% etodolac, 30% oil Labrafac WL1349, 10% Lauroglycol 90 and 40% Labrasol) was selected for bioavailability assessment in rabbits. The anti-inflammatory effect was also determined in rats, and compared with powder drug and etodolac suspension in water (50 mg/kg).
The peak plasma concentration of 16.4 +/- 1.1 microg/ml appeared after 1.3 +/- 0.2 h, whereas with powder drug and etodolac suspension the values were 7.5 +/- 0.5 and 10.6 +/- 0.7 microg/ml at 4.2 +/- 0.4 and 2.4 +/- 0.2 h, respectively. The AUC(0-8) of the etodolac SEDDS formulation was 2.3 times that of the pure drug and 1.4 times that of the suspension form. SEDDS formulation exhibits a 21% increase in paw thickness compared with a 39% increase on oral administration of etodolac suspension after 4 h at the same dose of the drug (20 mg/kg).
The result indicates the utility of SEDDS for the oral delivery of etodolac and potentially other lipophilic drugs.
本研究旨在制备一种自乳化药物传递系统（SEDDS），以提高一种水溶性差的药物依托度酸的口服生物利用度。通过评估SEDDS 制剂在温和搅拌下引入水介质时自乳化的能力，并测定所得乳剂的粒径，对 SEDDS 制剂进行优化。
选择一种优化的 SEDDS 制剂（由 20%依托度酸、30%油 Labrafac WL1349、10%Lauroglycol 90 和 40%Labrasol 组成）用于兔体内生物利用度评估。还在大鼠中测定了抗炎作用，并与粉末药物和水（50mg/kg）中的依托度酸混悬液进行比较。
16.4±1.1μg/ml 的峰值血浆浓度出现在 1.3±0.2h 后，而粉末药物和依托度酸混悬液的相应浓度分别为 4.2±0.4 和 2.4±0.2h 时的 7.5±0.5 和 10.6±0.7μg/ml。SEDDS 制剂的 AUC（0-8）是纯药物的 2.3 倍，是混悬液形式的 1.4 倍。SEDDS 制剂与相同剂量（20mg/kg）的依托度酸混悬液口服给药相比，在 4 小时时的爪厚度增加了 21%，而依托度酸混悬液的爪厚度增加了 39%。
结果表明 SEDDS 可用于依托度酸及其他亲脂性药物的口服递送。
