Gastrointestinal lipophilic drug absorption solubility

In summary, nasal epithelial intercellular junctions are less restrictive compared to the gastrointestinal tract. Such polar pathways will mainly be responsible for the transport of water-soluble compounds, providing a relatively slow, but significant route which is dependent on the molecular weight of the diffusing species. Secondly, transcellular (lipoidal) pathways permit extremely rapid absorption of lipophilic drugs with a rate dependency based on cell membrane partitioning. 

Permeability and solubility/dissolution are two major determinants of gastrointestinal drug absorption. The prediction of solubility of molecules is more difficult than for lipophilicity. Solubility critically depends on the solid-state properties of compounds. The same compound can exist in amorphous or in several crystalline states and this can result in very different solubility of molecules. The prediction of crystalline properties, represented, for example, by the melting point, is one of the most difficult problems of physical chemistry. Like the octanol-water partition coefficient, water solubility critically depends on the pH and ionization state of molecules. 

The rate and extent of drug absorption from the gastrointestinal (GI) tract are very complex and affected by many factors. These include physico-chemical factors (solubility, lipophilicity, stabiUty, pK, polar surface area, presence of hydrogen... 

In absorption studies, the appUcation of colloidal systems, which show specific and unspecific interactions with mainly lipophilic substances is of main interest. An obvious application is the study of lipophilic and poorly absorbable drugs that are administered orally or transdermally. Such interactions with surface-active agents may either cause a diminution of the bioavailability by trapping the drug in the micelle or, on the other hand, lead to an improved solubility (prevention of the precipitation of the drug) and facilitated transfer of the solute across lipid membranes (e.g., the intestinal wall in the gastrointestinal tract) and therefore to an improved bioavailability. 

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