Possibilities and Limiting Factors for the Use of Dissolution as a Quality Control Tool to Detect Presence of Crystallinity for Amorphous Solid Dispersions: An Experimental and Modeling Investigation.

In this article, experiments on tablets containing a model compound, grazoprevir, were conducted to explore how media selection for a quality control dissolution method can influence the sensitivity for the dissolution method toward drug crystallinity detection in an amorphous solid dispersion formulation. The experiment shows that under ideal nonsink conditions with respect to crystalline solubility, dissolution can indeed be predictive of crystallinity in the formulation. However, the limit of detection for crystallinity with quality control dissolution can change based on inherent variabilities in the drug product. In addition, it is demonstrated that the method's sensitivity and accuracy might be reduced if the crystalline particles are sufficiently small with respect to the solid dispersion particles. To further demonstrate the limits of the dissolution method, a dissolution model was also explored to simulate and predict the sensitivity of the dissolution response toward crystallinity based on solubility in the media and particle size of the crystals.