Oral bioavailability overview

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. 

This chapter presents an overview of amorphous spray-dried dispersions (SDDs), which have been successfully used as a platform technology to enhance the oral bioavailability of hundreds of compounds with low aqueous solubility. SDDs can be prepared with several nonionic polymers, such as polyvinylpyrrolidone (PVP) and cellulosic polymers, as well as with ionic polymers, such as hydroxypropyl... 

Fig. 21.9. A short overview, from in silico to in vivo in humans, of methods available to investigate and predict fraction dose absorbed and bioavailability following oral dosing.

This volume gives an overview of the current status and an outlook to future more reliable predictive approaches. It is subdivided in five sections dealing with studies of membrane permeability and oral absorption, drug dissolution and solubility, the role of transporters and metabolism in oral absorption, computational approaches to drug absorption and bioavailability, and finally with certain drug development issues. 

Despite their favourable properties, peptide-based drugs are under-represented in the pharmaceutical market. This discrimination is usually due to their poor bioavailability, which sometimes necessitates non-oral administration or even special medical devices such as inhalers. Another related major disadvantage of peptides is their low metabolic stability due to proteolytic degradation, hi addition, costs of goods for the drug substance are sometimes tremendous. Therefore, there is considerable interest to transform the active principle of biologically active peptides into small molecules with improved pharmacokinetic properties, hi this chapter, we present an overview of... 

Artursson, P. and Tavelin, S. (2003) Studies of membrane permeability and oral absorption 6 Caco-2 and emerging alternatives for prediction of intestinal drug transport a general overview, in Drug Bioavailability - Estimation of Solubility, Permeability and Absorption (eds H. van de Waterbeemd, H. Lennernas and P. Artursson), Wiley, pp. 72-89. 

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