Bioavailability drug dissolution

Mechanisms of dissolution kinetics of crystals have been intensively studied in the pharmaceutical domain, because the rate of dissolution affects the bioavailability of drug crystals. Many efforts have been made to describe the crystal dissolution behavior. A variety of empirical or semi-empirical models have been used to describe drug dissolution or release from formulations [1-6]. Noyes and Whitney published the first quantitative study of the dissolution process in 1897 [7]. They found that the dissolution process is diffusion controlled and involves no chemical reaction. The Noyes-Whitney equation simply states that the dissolution rate is directly proportional to the difference between the solubility and the solution concentration ... 

The absorption of class III drugs is limited by their permeability over the intestinal wall. Thus, as this process is not at all modeled by the classical in vitro dissolution test, no IVIVC should be expected. When drug dissolution becomes slower than gastric emptying, a reduction in the extent of bioavailability will be found in slower dissolution rates as the time when the drug is available for permeation over the gut wall in the small intestine will then be reduced. Thus, the same type of relationship can be expected between bioavailability and in vitro dissolution, as shown in Fig. 21.12 for a class I drug. 

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. 

Before 1990 Acceptable oral bioavailability, based on in vitro drug dissolution studies—... 

The rate and extent of absorption of drug Y will be a function of its solubility, intestinal permeability, and stability in the gastrointestinal fluids and dissolution rate. Differences in the absorption of two phannaceutically equivalent products should then primarily be a function of their in vivo dissolution rate differences, assuming the excipients used do not alter bioavailability [38]. Therefore, the key question here is Does an in vitro dissolution test emulate in vivo drug dissolution ... 

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-... 

The goal of correlating in vitro drug dissolution and in vivo bioavailability data engendered the BCS. ... 

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