716 B. K. Nanjwade et al.: An early stimulus for the use of lipid vehicles for drug formulation was the observation of improved bioavailability when poorly water-soluble drugs were co-administered with food. A well-known example is the suspension of phenytoin in corn oil [31] which considerably improved oral bioavailability as compared to the aqueous suspension. Abrams et al. studied the oral dose proportionality of a lipophilic steroid derivative, (5α,17β)-2-chloro-3-[(4-nitrophenoxy)imino]androstan-17-yl acetate (an o-aryl oxime of 2α-chlorodihydrotestosterone; nisterime acetate) when administered to rats as either solution in sesame oil or aqueous suspension [32]. The threefold higher bioavailability from sesame oil solution was attributed to improved solubilisation and dissolution in oil, which represent prerequisites for enhanced absorption. Unfortunately, many poorly water-soluble drugs also exhibit limited solubility in pharmaceutically relevant lipids. A promising approach to improve lipid solubility of drugs with insufficient lipid solubility is the design of low melting, lipophilic prodrugs. For example, Yamoka et al. took account for the low equilibrium lipid solubility of phenytoin by synthesising a range of low melting prodrugs with enhanced lipid solubility [33]. The enhancement in oral bioavailability of a hydrophobic amine antimalarial, prepared as an oleic acid solution in a soft gelatin capsule, is typical for the situation where formulation of a poorly water soluble drug in lipid can provide effective oral delivery [34]. Oral administration as a solution in oleic acid was also effective in enhancing the absorption of cinnarizine. [35]. Digestibility of the Lipid Vehicles Lipids are typically classified according to their chemical structure, polarity, characteristics, and degree of interaction with water. Nevertheless, when assessing lipids as vehicles, their digestibility has to be considered. Non-digestible lipids such as mineral oil, e.g. liquid paraffin and sucrose polyesters, essentially remain unabsorbed in the intestinal lumen and can actually limit or even reduce drug absorption by retaining a considerable amount of co- administered drug. Digestive lipids comprise dietary lipids such as glycosides, fatty acids, phospholipids, cholesterol esters as well as various synthetic derivatives. The rate and extent of digestion, the colloidal phases formed and pharmacological effects of the digestion products represent potential factors influencing release of the API from the vehicle and its absorption. Table 5 lists selected studies where the effects of different lipids on drug absorption have been investigated. Patton and Gilford demonstrated improved oral bioavailability of triamterene in rats when administered in 1ml lipid solution as compared to aqueous suspensions [36]. Myers and Stella [37] investigated the effects of non-digestible and digestible lipid vehicles on the oral bioavailability of penclomedine, a highly lipophilic, poorly water-soluble cytotoxic agent. The absolute bioavailability of penclomedine in the rat after administration in various lipids is higher than that of the aqueous suspension. Sci Pharm. 2011; 79: 705–727