Noyes-Whitney model

With very few exceptions, dissolution of the drug substance in the GI tract milieu is a prerequisite for drug absorption following oral administration. For Class II compounds, the rate-limiting factor in their intestinal absorption is dissolution /solubility [23-25]. Hence, in-depth understanding of this process is essential in the oral delivery of low-solubility compounds. Factors governing the dissolution process can be directly identified from the following equation, based on the Nernst-Brunner and Levich modifications of the Noyes-Whitney model [26-28] ... 

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 ... 

Although the Noyes-Whitney equation has been used widely, it has been shown to be inadequate in modeling either S-shape experimental data or data with a steeper initial slope. Therefore, a more general function, based on the Weibull distribution [8], was proposed [9] and applied empirically and successfully to all types of dissolution curves [10] ... 

Intellipharm PK (Intellipharm, LCC, Niantic, CT, USA) is a commercially available computer program that is based on a mixing tank model ([28] www.intellipharm.com). Intellipharm PK utilizes Noyes-Whitney dissolution... 

FIGURE 2 Noyes-Whitney dissolution model where Ci is the drug solubility at the same conditions as the particle surface, Cb is the concentration in the bulk dissolution medium and A is the thickness of the boundary or diffusion layer. 

As the drug particle dissolves, a saturated solution (stagnant layer) is formed at the immediate surface around the particle. The dissolved dmg in the saturated solution gradually diffuses to the surrounding regions. The overall rate of drug dissolution may be described by the Noyes-Whitney equation which models drug dissolution in terms... 

Using a mathematical simulation model based on the Noyes-Whitney equation, Nicolaides and coworkers tested the predictability of two 2-step biorelevant dissolution models (fasted and fed state), compared to a compendial model using water and SIF media (USP). Solid formulations of four BCS Class II drug compounds [troglitazone (log P 2.7 pKa 6.1 and 12.0), atovaquone (log P 5.1 non-ionizable), sanfetrinem cilexetil (Log P 3.0 and 3.1 (two diastereoisomers non-ionizable) and GV150013X (log P 5.4 non-ionizable)] were used. In vitro dissolution data were compared to clinical studies, using the respective formulation. 

The diffusion layer theory is the most useful and best known model for transport-controlled dissolution and satisfactorily accounts for the dissolution rates of most pharmaceutical solids. In this model, the dissolution rate is controlled by the rate of diffusion of solute molecules across a thin diffusion layer. With increasing distance from the surface of the solid, the solute concentration decreases in a nonlinear manner across the diffusion layer. The dissolution process at steady state is described by the Noyes-Whitney equation ... 

In order to extend the range of Equation 17.10 from sparingly soluble to more soluble substances, Brunner and Tolloczko (1900) modiLed Noyes and Whitney s model to account for the changing surface area with time ... 

In the majority of dissolution phenomena, the solvation step is almost instantaneous. The diffusion process is much slower and, therefore constitutes the rate limiting step. Noyes and Whitney (1897) developed an equation based on Pick s second law of diffusion to describe dissolution within the scope of their model, and report the relation ... 

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