Commonly used dissolution methods may not be appropriate for new dosage forms or poorly soluble drugs. For those cases, specialized testing methods may need to be developed.
For instance, dosage forms that supersaturate require accurate characterization of the dissolved, free drug concentration because that is the form that can be absorbed in vivo. However, the drug in supersaturated solutions may nucleate and precipitate. Small drug particles may also be introduced into the dissolution medium from solid dispersion or nanoparticle dosage forms. Commonly used testing methods, such as sampling by syringe then filtering with a 0.2 micron filter, can allow nuclei and small particles to pass before assay, resulting in significant overestimation of the dissolved absorbable drug concentration. Similar problems are anticipated with fiber optics methods due to the probe gaps being large compared to nanoscale particles.
Microscopically heterogeneous dissolution media present special challenges. When dissolving poorly soluble drugs in commonly used compendial media, such as those that include surfactants well above the critical micelle concentration, drug partitioning into micelles can increase the apparent dissolution but mask the free dissolved concentration in the aqueous medium. Again, since this corresponds to the absorbable form of the drug, these tests may be poorly suited for correlating in vitro dissolutions with in vitro performance.
Physical Pharmaceutica has developed methods for the following: