IVIVC Benefits and Categories
IVIVC can benefit drug development programs in many ways and for a variety of regulatory submissions. IVIVC analyses can be used for:
Reducing regulatory burden.
Developing dissolution methods.
Designing drug formulations.
Establishing dissolution specifications.
There are three primary IVIVC categories—Level A, Level B, and Level C. Level A is the most common type of IVIVC as it provides the most informative and useful correlation data. A Level A IVIVC is the only the category that can be used for a regulatory submission. Level C can be useful in the early stages of drug development and is the second most common. Level B and multiple Level C correlations are comparatively rare.
Level A IVIVC
Level A correlation is generally linear and represents a point-to-point relationship between the in vitro dissolution rate and the in vivo input rate of the drug from the dosage form. Level A IVIVC is commonly estimated by a two-stage procedure that includes deconvolution followed by comparison of the amount of drug absorbed to the amount of drug dissolved. In such a correlation, the mathematical descriptions for the in vitro dissolution curve and the in vivo input rate curve are the same. You should use Level A IVIVC correlation if you are demonstrating an IVIVC relationship for two or more formulations that have different release rates.
Level B IVIVC
Level B correlation represents a relationship between the mean in vitro dissolution time and the mean residence time or the mean in vivo dissolution time using all the in vitro and in vivo data. Because Level B correlation does not reflect the actual in vivo plasma level curves, it is not considered to be a point-to-point correlation.
Level C IVIVC
Level C correlation involves determining the relationship between one in vivo pharmacokinetic (PK) parameter such as Cmax, AUC, or Tmax, which is the time to reach maximum plasma concentration, and one in vitro dissolution time point (t50%, t90%, and so on). Level C correlation does not reflect the complete shape of the plasma concentration time curve, which is a critical factor for determining the performance of extended release products.