alexa Influence of physicochemical properties on dissolution of drugs in the gastrointestinal tract.
Materials Science

Materials Science

Journal of Nanomedicine & Nanotechnology

Author(s): Hrter D, Dressman JB

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Abstract The rate-limiting step to absorption of drugs from the gastrointestinal (GI) tract is often dissolution from the dosage form. Consideration of the Noyes-Whitney dissolution model shows that drug diffusivity, solubility in the gastrointestinal contents, the surface area of the solid wetted by the lumenal fluids and the GI hydrodynamics all play a role in determining the in vivo dissolution rate. Solubility in the GI contents is determined by aqueous solubility, crystalline form, drug lipophilicity, solubilization by native surfactants and co-ingested foodstuffs, and pK(a) in relation to the GI pH profile. Compounds with aqueous solubilities lower than 100 microg/ml often present dissolution limitations to absorption. The dose:solubility ratio of the drug provides an estimate of the volume of fluids required to dissolve an individual dose, and when this volume exceeds 1 l, dissolution is often problematic. The surface area of a drug available for dissolution depends on the particle size of the solid and its ability to be wetted by lumenal fluids. Other physiological factors that can play a role in dissolution include the viscosity of the lumenal contents, through its effect on the diffusivity, and mixing and flow patterns within the gut. In order to better predict in vivo dissolution of drugs, dissolution tests which more adequately simulate the physiological conditions are needed.
This article was published in Adv Drug Deliv Rev and referenced in Journal of Nanomedicine & Nanotechnology

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