Drug Dissolution and Solubility

Tab. 21.1. Summary of physiological gastrointestinal characteristics in fasted and fed state of importance for drug dissolution and solubility.

This volume gives an overview of the current status and an outlook to future more reliable predictive approaches. It is subdivided in five sections dealing with studies of membrane permeability and oral absorption, drug dissolution and solubility, the role of transporters and metabolism in oral absorption, computational approaches to drug absorption and bioavailability, and finally with certain drug development issues. 

For highly permeable, poorly soluble drugs given in lower doses, the dissolution rate rather than the saturation solubility is the limiting factor. An increase in dissolution rate due to in vivo solubilization mediated by food intake could theoretically be obtained, but this situation is not always found in vivo. For example, food does not affect the rate and extent of bioavailability for candesartan cilexitil, a very poorly soluble compound [78], An in vitro dissolution and solubility study of this compound in simulated intestinal media provided a potential explanation it was revealed that the solubility was increased as a function of bile concentration as expected, whereas the dissolution rate was not increased by the higher bile concentrations being representative for the fed state (see Fig. 21.14). Thus, although... 

Granero GE, Ramachandran C, Amidon GL (2005) Dissolution and solubility behavior of fenofibrate in sodium lauryl sulfate solutions. Drug Dev. Ind. Pharm. 31 917-922. 

Kataoka, M. et al. (2006) Effect of food intake on the oral absorption of poorly water-soluble dtnug D assessment of drug dissolution and permeation assay syfetihnarm. Sci., 95 2051-2061. 

As reviewed in this chapter, certain means can be utilized to improve the bioavailability of lipophilic drugs, whether by formulative approach or molecular changes strategies. These means present a number of attractive propositions to the scientist, ranging from an enhancement of drug dissolution and solubilization by lipid-based formulation, increased solubility via the synthesis of a prodrug, specific delivery to the intestinal lymphatics, and reduction in enterocyte-hepatic presystemic metabolism and efflux systems. 

Formulation components may enhance the extent of oral drug bioavailability by altering the extent of absorption (by means of improvements in drug dissolution, GI solubility, GI stability, and intestinal permeability) or by reducing drug metabolism. Historically, the role of the liver in drug metabolism was considered para-... 

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