Lipophilic drug absorption enhancing

To enhance absorption, it is important to identify the rate-limiting step in this process and to counter the relevant barrier in each case. The possible solutions for the absorption barriers facing lipophilic drug absorption are presented according to their physiological order, i.e., issues concerning the GI lumen (preenterocyte), followed by issues associated with the enterocyte and onward. However, it should be noted that a few concepts affect more than one step of the absorption process. 

The complexity and dynamism of the postdigestive intestinal contents (in terms of the interconversion and equilibrium-driven transfer of lipids across the various dispersed species) is a likely contributor to the uncertainty in defining the effects of lipids on drug absorption. Conversely, a more complete understanding of this preabsorptive phase and its interaction with lipophilic drugs will enhance appreciation of the effects of lipids on drug absorption and improve the ability to select appropriate lipid excipients. 

Some drug absorption enhancers are capable of loosening tight junctions (zonula occludens) and thereby facilitate paracellular absorption of drug molecules and improve the bioavailability of active pharmaceutical ingredients with low membrane permeability. The penetration enhancers include chelating agents [e.g., ethylenediaminetetraacetic acid), toxins [e.g., zonula occludens toxin), plant-derived materials [e.g., aloe vera gel), and cationic polymers. Polycationic lipophilic-core dendrons, which form lipophilic ion-pairs with heparin, were studied as a system for oral delivery of heparin. ... 

Doxycycline tends to be more active against some bacteria than other tetracyclines. This is probably due to its slower excretion rather than to enhanced oral absorption. Doxycycline is used in cases where cost is unimportant. It is a very lipophilic drug that shows a high bioavailability, being almost completely absorbed after oral administration to different animal species except chickens (250, 251). 

The ability of lipid vehicles (either in the pharmaceutical formulation or in food) to enhance the absorption of lipophilic drugs has been well known for many years. Recently, successful bioavailability enhancement utilizing lipid-based formulations has been accomplished with the immunosuppressive agent cyclosporine A (Neoral, Novartis Pharmaceuticals Corporation, East Hanover, NJ), and for the two HIV protease inhibitors ritonavir (Norvir, Abbott Laboratories, IL) and saquinavir (Fortovase, Roche Pharmaceuticals, Nutley, NJ). Consequently, considerable interest in lipid-based formulations has been aroused. 

The mechanisms by which lipid-based formulations enhance the absorption of lipophilic drugs are ... 

Many reports have indicated the findings that the effects of CyDs on the rectal delivery of drugs depend markedly on vehicle type (hydrophilic or oleaginous), physicochemical properties of the complexes, and an existence of tertiary excipients such as viscous polymers. The enhancing effects of CyDs on the rectal absorption of lipophilic drugs are generally based on the improvement of the release from vehicles and the dissolution rates in rectal fluids, whereas those of CyDs on the rectal delivery of poorly absorbable drugs such as antibiotics, peptides,... 

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