Chapter 5 - Wet Granulation and Chemical Stability of Drug Products

Abstract

The wet granulation process was shown to have a negative impact on long-term stability of some drug products. The negative impact of wet granulation usually is associated with some loss of crystallinity or with increased contact between the drug substance and incompatible excipients. The effect of wet granulation on stability depends on the composition of the formulation and, in some cases, on the salt form of the drug substance. The increased contact of the drug substance and formulation components achieved in wet granulation can be leveraged to enhance the effectiveness of stabilizing excipients, such as pH modifiers. Stability of compounds undergoing hydrolytic degradation was shown to be dependent on the microenvironment pH and the manufacturing process. Selection of the proper pH modifier that provides the desired pH for optimum stability, together with the wet granulation process that maximizes its effect, was critical to dosage form stability. In the absence of the pH modifier, degradation rate was significantly higher because of some loss of crystallinity and increased moisture uptake of the formulation caused by wet granulation.