Lipid-based formulations approach enhancement

The knowledge and rationale accumulated thus far regarding the lipid-based formulation approach for enhancing oral absorption of lipophilic compounds have been presented in this section. Additional comprehensive review articles are also recommended [44—46],... 

Use of these semisolid and solid approaches can potentially alleviate the chemical stability problems sometimes observed for liquid-Llled formulations, and may eventually offer the possibility of development of a tablet dosage form using conventional equipment. Liquid lipid-based formulations, however, generally afford the greatest enhancement of bioavailability for water-insoluble drugs, as well as affording more rapid development for First-in-Human studies. Any decisions on the best formulation route would have to be evaluated on a case-by-case basis. 

In conclusion, the recent increase in the number of water-insoluble drug candidates will doubtless enhance the importance of oral lipid-based formulations in the coming years. If a candidate has adequate solubility in the vehicles described in this chapter, lipid-based systems will usually provide an attractive approach for efLcient in-house development of clinical and commercial formulations. 

As reviewed in this chapter, certain means can be utilized to improve the bioavailability of lipophilic drugs, whether by formulative approach or molecular changes strategies. These means present a number of attractive propositions to the scientist, ranging from an enhancement of drug dissolution and solubilization by lipid-based formulation, increased solubility via the synthesis of a prodrug, specific delivery to the intestinal lymphatics, and reduction in enterocyte-hepatic presystemic metabolism and efflux systems. 

The results presented in this chapter demonstrate that enhanced immunogenic efficacy can be achieved by using liposphere-based formulations, indicating the potential usefulness of lipospheres in the formulation of human and veterinary vaccines. The liposphere approach employs the fat-lipid environment to achieve several goals to serve as a carrier to protect the antigen, to serve as a depot, and to provide a surface interphase necessary for adjuvant activity. The ability to provide different surface... 

In this chapter we will provide a brief overview of the early approaches to bioavailability enhancement by use of simple lipid-based delivery systems (lipid solutions, emulsions etc), and then describe recent progress in the application of self-emulsifying- and microemulsion-based formulations. The effects of lipids on the oral bioavailability of co-administered poorly water-soluble drugs may also be classified from a mechanistic (and to a degree, historical) perspective as physicochemically mediated effects (solubility, dissolution, surface area) and biochemically mediated effects (metabolism, transport related events), and these will be approached separately. It is readily apparent, however, that in many cases physicochemically and biochemically mediated mechanisms will operate side by side. In some instances, bioavailability may also be enhanced by the stimulation of intestinal lymphatic transport, and these studies will be addressed in a separate section. 

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