Water-soluble drugs oral absorption

Orally administered dosage forms are absorbed into the systemic circulation following dissolution in the GI tract. Because substances must be in solution for the absorption from the GI lumen, the absorption rate of poorly water-soluble drugs is limited by their rate of dissolution. The dissolution rate is affected by the unique physicochemical properties of the drug and by physiological factors the pH, composition, and hydrodynamics of the GI medium. 

He X, Sugawara M, Kobayashi M, Takekuma Y, Miyazaki K (2003) An in vitro system for prediction of oral absorption of relatively water-soluble drugs and ester prodrugs. Int J Pharm 263 35 14... 

Kataoka M, Masaoka Y, Yamazaki Y, Sakane T, Sezaki H, Yamashita S (2003) In vitro system to evaluate oral absorption of poorly water-soluble drugs Simultaneous analysis on dissolution and permeation of drugs. Pharm Res 20 1674-1680... 

Takano, R. et al., Oral absorption of poorly water-soluble drugs computer simulation of fraction absorbed in humans from a miniscale dissolution fgb rm. Res., 23, 1144, 2006. 

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. 

To date, the challenges associated with development of an oral MR dosage form for water-insoluble drugs have not been systematically studied and discussed. In many cases, the physicochemical properties of the drug and its sensitivity to the conditions of the Gl track make it more difL cult to attain the desired absorption and PK proLle. This is a clear point of concern in developing a MR product for poorly water-soluble drugs. 

Amphiphilic poly(ethylene glycol)-alkyl dextran ethers are emerging as vehicles in the oral delivery of poorly water soluble drugs [251,268,269]. They form polymer micelles of low critical association concentrations (CAC) and small micelle sizes in aqueous solution. Particulate delivery systems lead to an enhancement of the absorption efficiency and bioavailability of highly hpophihc drugs orally applied, and provide the drug with some level of pro-... 

Ascites affects the volume of distribution of water-soluble drugs and may impair oral absorption of drugs, as the bowel may be oedematous. 

Lipid-based formulations of poorly water soluble drugs offer large versatility for oral administration as they can be formulated as solutions, gels, suspensions, emulsions, self-emulsifying systems, multiple emulsions, microemulsions, liposomes, and solid dispersions. " Administration of a drug in a lipidic vehicle/formu-lation can enhance the absorption and oral bioavailability via a combination of various mechanisms " " that are briefly summarized as follows ... 

Enteric delivery has also been demonstrated to improve the absorbance of some poorly water-soluble drugs. Since there is vastly more surface area for drug absorption in the small intestine than in the stomach targeting the delivery of the maximum dissolved drug concentrations to the small intestine can substantially improve oral absorption. This mode of delivery has been demonstrated to be beneficial for poorly water-soluble drugs such as albendazole and itraconazole (30-32). 

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