Oral Delivery Of Lipophilic Drugs Research Articles

Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs

Highly potent, but poorly water-soluble, drug candidates are common outcomes of contemporary drug discovery programmes and present a number of challenges to drug development - most notably, the issue of reduced systemic exposure after oral administration. However, it is increasingly apparent that formulations containing natural and/or synthetic lipids present a viable means for enhancing the oral bioavailability of some poorly water-soluble, highly lipophilic drugs. This Review details the mechanisms by which lipids and lipidic excipients affect the oral absorption of lipophilic drugs and provides a perspective on the possible future applications of lipid-based delivery systems. Particular emphasis has been placed on the capacity of lipids to enhance drug solubilization in the intestinal milieu, recruit intestinal lymphatic drug transport (and thereby reduce first-pass drug metabolism) and alter enterocyte-based drug transport and disposition.

Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs

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.