Absorption, drug improving poor oral

Kondo, N., Iwao, T., Masuda, H., Yamanouchi, K., Ishihara, Y., Yamada, N., Haga, T., Ogawa, Y., and Yokoyama, K. (1993) Improved oral absorption of a poorly water-soluble drug, HO-221, by wet-bead milling producing particles in submicron regioOhem. Pharm. Bull., 41 737-740. 

Not withstanding the use of nanoparticles for intravenous and topical applications, improvement in oral bioavailability is one of the most important contributions attained through nanotechnology. Molecules that are poorly water soluble may be poorly absorbed because of a lack of sufficient concentrations of solubilized drug. Formulations that are amorphous can overcome this by supersaturation of the dissolution medium allowing for greater absorption of the delivered dose. However, stability problems are significant for... 

If a drug fails to meet present day standards because of low in vitro potency, metabolic, or chemical instability, poor oral absorption or high degree of serum and tissue binding, experience teaches that the prospects for improvement via structural modification are good—if systematic structural modification with retention of biological activity is feasible. The clinically established semisynthetic cephalosporins, rifamycin SV and rifampicin represent precisely this kind of improvement, while laboratory data indicate that it has also been achieved in the coumermycin series as well (96, 97). 

Since the first series of compounds were poorly soluble in water, the next crucial phase of the project set out to increase the water solubility of the drug candidates in order to increase absorption from the gastrointestinal tract. Further refinements led to a candidate that was not only well absorbed when administered orally to animals, but also had outstanding antimalarial profiles both in vitro and in vivo. In comparison to available semi-synthetic artemisinins, the drug candidate OZ 277 (Scheme 27) exhibits structural simplicity, an economically feasible and scalable synthesis, superior antimalarial activity and an improved pharmaceutical profile. The toxicological profiles are also acceptable and this drug candidate entered first into man studies during 2004. 

Kondo N, Iwao T, Hira KI, et al. Improved oral absorption of enteric coprecipitates of a poorly soluble drug. J Pharm Sci 1994 83(4) 586-570. 

Kai T, Akiyama Y, Nomura S, Sato M. Oral absorption improvement of poorly soluble drug using solid dispersion technique. Chem Pharm Bull 1996 44(3) 568-571. 

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