Assessing Physical Stability of Colloidal Dispersions Using a Turbiscan Optical Analyzer.

The physical stability of aqueous colloidal dispersions containing highly concentrated droplets of poorly water-soluble drugs has recently been identified as one of the main considerations in developing amorphous solid dispersions (ASDs). The Turbiscan analyzer, an instrument based on multiple light scattering technology, was employed for the first time to assess colloidal dispersions with ritonavir as the model compound. The physical instability of ritonavir-rich droplets was monitored directly with and without the presence of candidate polymer additives at different drug concentrations and temperatures. The mechanism of the observed instability was confirmed to be coalescence of liquid droplets, based on the low glass transition temperature of water-saturated amorphous ritonavir determined using a newly developed experimental procedure. Temperature and solvent composition, within the range studied, have little influence on the kinetics of ritonavir coalescence. On the contrary, a higher concentration of drug, i.e., more droplets per unit volume, greatly accelerates the coalescence process. In addition, polymers with varying degrees of hydrophobicity resulted in different levels of effectiveness in stabilization, which is likely related to the strength of drug-polymer interactions and the corresponding differences in surface adsorption. This work demonstrates that the Turbiscan optical analyzer can be used as a rapid screening tool that provides a first-pass, high-throughput feasibility ranking of different excipients and additives to support the development of ASD formulations.