External factors, such as temperature and viscosity of the dissolution medium can influence the dissolution rate of a drug substance or a drug product. This is in part due to their effect on the diffusivity of a drug molecule. According to the Stokes-Einstein equation, the diffusion coefficient of a spherical molecule in solution is given by kT
onqr where T is the temperature, r is the radius of a molecule in solution, n is the viscosity of the solution, and k is the Boltzmann constant. This equation indicates that diffusion is enhanced with increasing temperature but is reduced with increasing viscosity.
Solution hydrodynamics also play an important role in determining the dissolution rate. One possible mechanism by which solution hydrodynamics influences the dissolution rate is through their effect on the stationary diffusion layer around the drug molecule, as shown in (3.7). Since the thickness of this layer at the surface of the drug is determined by the shear force exerted by the fluid, an increase in the agitation (or stirring) rate may cause h to decrease, resulting in the improvement of drug dissolution. This hydrodynamic effect is demonstrated in the dissolution study of aspirin tablets, which shows that the dissolution half life of an aspirin tablet decreases with increasing agitation intensity (Levy et al., 1965). In addition, Armenante and Muzzio studied the velocity and shear stress/strain distribution in the USP Apparatus II (paddle). Their result shows that the flow rate and shear rate vary significantly at different locations near the vessel bottom of the Apparatus II, thus resulting in different dissolution rates (Armenante and Muzzio, 2005).
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