In this chapter, we delve into the process of determining the intrinsic dissolution rate, a crucial factor in the characterization of bulk drug substances and excipients. The intrinsic dissolution rate refers to how quickly pure substances dissolve under conditions of constant surface area. External factors like hydrodynamics (test apparatus, disk rotation speed, or fluid flow) and test conditions (temperature, fluid viscosity, pH, and buffer strength for ionizable compounds) also play a role in influencing the dissolution rate.
To measure the intrinsic dissolution rate, the material’s surface area is exposed to an appropriate dissolution medium while maintaining consistent temperature, stirring rate, and pH. Typically, the intrinsic dissolution rate is expressed as milligrams per minute per square centimeter (mg/min/cm²).
The experimental setup involves a punch and die made of hardened steel. The die contains a cavity, where a measured amount of the material is placed for testing. Compressing the material with a benchtop tablet press forms a compacted pellet with a defined surface area exposed at the bottom of the die.
The die cavity’s design allows at least 50% to 75% of the compacted pellet to dissolve without falling out. The die is attached to a holder, which is connected to a laboratory stirring device. The die assembly, along with the compacted pellet, is submerged in the dissolution medium and rotated by the stirring device.
To prepare for the test, the material is accurately weighed and placed in the die cavity. Controlled compression results in a stable, non-disintegrating compacted pellet. Any loose powder on the die’s surface is removed using compressed air or nitrogen.
In the testing procedure, the die-holder assembly is positioned in the dissolution test chuck, ensuring that the exposed surface of the compacted pellet is at a specific distance from the bottom of the vessel. Care is taken to minimize any wobbling and to prevent the formation of air bubbles on the compacted pellet or die surface, as these could interfere with fluid flow.
The analysis is performed following the guidelines outlined in the individual monograph, with an emphasis on maintaining sink conditions throughout the test. Data regarding the cumulative amount of the test specimen dissolved at each time point is corrected for any sampling losses. To calculate the intrinsic dissolution rate, a plot of the cumulative amount of the test specimen dissolved per unit area of the compacted pellet is created against time until 10% dissolution is reached. Linear regression is then applied to the data points up to and including the time point at which 10% dissolution occurs. The intrinsic dissolution rate of the test specimen, represented as mg per minute per cm², is determined from the slope of the regression line.
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