Dissolution rate, continuous-flow method

The wide variety of methods for determining the dissolution rates of solids may be categorized either as batch methods (Fig. 13A) or as continuous-flow methods (Fig. 13B). The common batch-type dissolution methods are derived from the beaker-stirrer method of Levy and Hayes [89] and include a number of thoroughly standardized procedures, especially those defined by the U.S. Pharmacopoeia [90]. 

Continuous flow methods have the advantages that sink conditions can be easily achieved, and that a change in dissolution rate is reflected in a change in [9]. At the same time, they require a significant flow rate that may require relatively large volumes of dissolution medium. Should the solid be characterized by a low solubility and a slow dissolution rate, will be small, and a very sensitive analytical method would be required. 

Continuous-flow (i.e., column dissolution) methods, depicted schematically in Fig. 13B, have limited, but growing, application [92-94]. The volume flow rate, dVIdt, of the dissolution medium must remain constant to achieve the steady state shown in Fig. 14B, so that... 

A variant on the dissolution methods discussed uses neither basket nor paddle. Convection is achieved by solvent flow through a chamber such as that drawn in Fig. 12.4. Dissolution data obtained from such a system where continuous monitoring of dmg concentration is achieved must be interpreted with care as the concentration-time profile will be dependent on the volume of solvent, its flow rate and the distance of the detection device from the flow cell, or rather the void volume of solvent. 

For sparingly soluble substances, the volume in standard vessel methods may not be sufficient to dissolve the dose. In this case, the USP IV flow-through method is beneficial, since it provides a continuous renewal of the dissolution fluid. However, the maximum flow rate will limit the apparent solubility in this procedure. Sufficient solubility will not be obtained for a rapidly releasing formulation of a drug with very low solubility in relation to the dose. 

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