708 B. K. Nanjwade et al.: state. Although the specific mechanisms of absorption of the lipid digestion products have not been elucidated yet, the common role of the intestinal mixed micellar phase to solubilise these poorly water-soluble compounds and to provide a concentration gradient for absorption of lipids and presumably of drugs solubilised in this phase is generally accepted. Micelles are not absorbed intact, and lipids are suggested to be absorbed from a monomolecular intermicellar phase [9–11]. The dissociation of monomolecular lipids from the mixed micellar phase prior to absorption may be stimulated by a microclimate of lower pH at the intestinal absorptive site [12, 13]. Lipids and GI-transit profiles The products of lipid digestion delay gastric emptying, and much pharmaceutical interest has focused on the relationship between gastric emptying, food ingestion, and the transit behavior of non-disintegrating controlled release dosage forms. Although there is little information as to how small pharmaceutically relevant volumes of lipid impact on transit profiles, it is likely that any effect would not significantly impact the bioavailability of the co- administered drug [4]. Lipids and intestinal permeability Constituents of the mixed micellar phase can modify the intestinal permeability of poorly water-soluble compounds via three mechanisms. Firstly, the presence of lipid digestion products and bile salts may alter the intrinsic permeability of the intestinal membrane, leading to increased absorption via paracellular or transcellular routes. Secondly, solubilisation of lipophilic drugs within bile salt mixed micelles may facilitate diffusion through the aqueous diffusion layer, improving absorption. Thirdly, and conversely, drug solubilisation may decrease the intermicellar ‘free’ fraction of drug, which could potentially lead to a decrease in absorption. These divergent effects are likely to provoke sometimes contradictory reports about drug absorption after administration as solubilised surfactant- based systems [8]. Factors Affecting Bioavailability of Lipid-Based Formulations Lipid Digestion If the drug possesses high affinity to the lipid vehicle, it can be assumed that the API moves apparently together with vehicle in the GI-tract, revealing that digestibility of lipid would be as important as gastric emptying rate of the same. Thus, careful selection of the lipid vehicle can control the absorption rate of drug. GI lipid digestion consists of three sequential steps: (i) the dispersion of fat globules to yield a fine emulsion, (ii) the enzymatic hydrolysis of fatty acid esters at the emulsion-water interface, and (iii) the desorption and dispersion of insoluble lipid products for subsequent absorption [14, see Fig. 2]. Sci Pharm. 2011; 79: 705–727