Drug bioavailability improvement, methods

Application of ultra-high-throughput in silico estimation of biopharmaceutical properties to the generation of rule-based computational alerts has the potential to improve compound selection to those drug candidates that are likely to prove less troublesome in their development. The extension of purely in silico methods to the realm of mechanistic simulation further enhances our ability to predict the impact of physiological and biochemical process on drug absorption and bioavailability. 

Because most proteins are susceptible to protease degradation and denaturation in biologic fluids, most biopharmaceuticals must be administered by intravenous, intramuscular, or subcutaneous injection (see Table 5.5). High concentrations of proteases are found in the gastrointestinal tract, nasal mucosa, bronchioles, and alveoli, which severely limit the bioavailability of protein pharmaceuticals after oral, intranasal, and inhalation administration. Diffusional barriers to the passage of relatively large macromolecules preclude transdermal and mucosal administration of protein pharmaceuticals. Research is under way to develop methods that will protect protein drugs from proteolysis and improve transmembrane diffusion. 

Another method of improving bioavailability for these poorly soluble drugs is to prepare an amorphous formulation, since an amorphous form allows fasterdissolution of the drug in comparison to its corresponding crystalline form. An amorphous formulation is prepared by incorporating the... 

Chaumeil, J. C. (1998) Micronization A method of improving the bioavailability of poorly soluble drugs, Methods Find. Exp. Clin. Pharmacol., 20 211-215. 

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