Liquid product formulation often offers advantages over traditionally more common solid formulation unit operations, such as granulation, powder blending and tableting. Common delivery methods for liquid formulations include capsules, syrups, injectables, topical creams and metered dose inhalers (MDI). Whether developing and manufacturing product in the form of solid suspensions or liquid emulsions, particle/droplet size distribution and stability are critical to ensure optimal manufacturability, bioavailability and shelf-life. However, inconsistencies in the particle/droplet size distribution often occur during development and scale-up due to changing raw materials, surfactants, or process dynamics such as homogenization, agglomeration/coalescence, and temperature gradients.
This paper, which will be presented at American Association of Pharmaceuticals Scientists (AAPS) Annual Meeting 2010, focuses on a series of industrial case studies where in situ particle and droplet size characterization tools (FBRM® and PVM®) are used to understand, characterize and control complex particle and droplet formation and formulation processes. In situ monitoring eliminates the need to sample and allows dynamic particle and droplet changes to be visualized in real time. Special attention will be paid to studying the impact of agitation, temperature and formulation components on the stability of final products as well the optimization of particle and droplet size dimension to improve product quality. Finally, a scale-up study will be presented that shows how in situ droplet size characterization of an emulsion can ensure efficient and cost effective scale-up from 5L to 150L.