Gursoy R Neslihan, Benita Simon
Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 06100 Ankara, Turkey.
Biomed Pharmacother. 2004 Apr;58(3):173-82. doi: 10.1016/j.biopha.2004.02.001.
The oral delivery of hydrophobic drugs presents a major challenge because of the low aqueous solubility of such compounds. Self-emulsifying drug delivery systems (SEDDS), which are isotropic mixtures of oils, surfactants, solvents and co-solvents/surfactants, can be used for the design of formulations in order to improve the oral absorption of highly lipophilic drug compounds. SEDDS can be orally administered in soft or hard gelatin capsules and form fine relatively stable oil-in-water (o/w) emulsions upon aqueous dilution owing to the gentle agitation of the gastrointestinal fluids. The efficiency of oral absorption of the drug compound from the SEDDS depends on many formulation-related parameters, such as surfactant concentration, oil/surfactant ratio, polarity of the emulsion, droplet size and charge, all of which in essence determine the self-emulsification ability. Thus, only very specific pharmaceutical excipient combinations will lead to efficient self-emulsifying systems. Although many studies have been carried out, there are few drug products on the pharmaceutical market formulated as SEDDS confirming the difficulty of formulating hydrophobic drug compounds into such formulations. At present, there are four drug products, Sandimmune and Sandimmun Neoral (cyclosporin A), Norvir (ritonavir), and Fortovase (saquinavir) on the pharmaceutical market, the active compounds of which have been formulated into specific SEDDS. Significant improvement in the oral bioavailability of these drug compounds has been demonstrated for each case. The fact that almost 40% of the new drug compounds are hydrophobic in nature implies that studies with SEDDS will continue, and more drug compounds formulated as SEDDS will reach the pharmaceutical market in the future.
由于疏水性药物在水中的溶解度较低，其口服给药面临着重大挑战。自乳化药物递送系统（SEDDS）是油、表面活性剂、溶剂和助溶剂/表面活性剂的各向同性混合物，可用于设计制剂，以提高高度亲脂性药物化合物的口服吸收。SEDDS可以通过软胶囊或硬胶囊口服给药，并在胃肠道液体的温和搅动下，在水稀释后形成相对稳定的水包油（o/w）细乳液。药物化合物从SEDDS中的口服吸收效率取决于许多与制剂相关的参数，如表面活性剂浓度、油/表面活性剂比例、乳液的极性、液滴大小和电荷，所有这些本质上都决定了自乳化能力。因此，只有非常特定的药用辅料组合才能产生高效的自乳化系统。尽管已经进行了许多研究，但制药市场上以SEDDS形式配制的药品很少，这证实了将疏水性药物化合物配制成此类制剂的难度。目前，制药市场上有四种药品，即山地明和新山地明（环孢素A）、诺利华（利托那韦）和福妥维塞（沙奎那韦），其活性成分已被配制成特定的SEDDS。在每种情况下，这些药物化合物的口服生物利用度都有显著提高。几乎40%的新药化合物本质上是疏水性的，这一事实意味着对SEDDS的研究将继续，未来会有更多以SEDDS形式配制的药物化合物进入制药市场。
