ABSTRACT
The development of a meaningful dissolution procedure for drug
products at different development stages has been a consistent
challenge to the pharmaceutical industry.1,2 The objective of
dissolution testing, in general, varies during the development stages
of a dosage form.3 During preclinical development, dissolution plays
an important role of selecting appropriate drug substance and
dosage form for the toxicology formulation development to ensure
adequate bioavailability. The primary objective of dissolution testing
at phase 1 is to characterize the active pharmaceutical ingredient
(API), ensure that phase 1 formulation does not release faster
than the formulation used in the toxicology assessment, develop
first-in-human (FIH) formulations, and establish the preliminary
dissolution mechanism. During phases 2 and 3, the objective
shifts towards developing an understanding of the impact of key
formulation/process parameters on the dissolution profile and
an in vitro/in vivo correlation or relationship (IVIVC/IVIVR), if
possible. At product registration and beyond, the goal is to identify
a quality control (QC) dissolution test method for the product that
correlates to the clinical formulations. Dissolution testing is also
used by regulatory agencies for granting biowaivers and for post-
approval manufacturing changes. The FDA guidance for waivers of
in vivo bioavailability and bioequivalence studies (“Waiver of in vivo
Bioavailability and Bioequivalence Studies for Immediate-Release
Solid Oral Dosage Forms Based on a Biopharmaceutics Classification
System”) employs dissolution testing to demonstrate rapid dissolu-
tion of immediate-release solid oral dosage forms so that a biowaiver
can be granted.4 Continual evolution of these objectives during the
drug product life cycle may require different concentrations and,
therefore, require changes in the analytical finish.
