These experiments demonstrate the proof of concept that a dispersion experiment can be performed within a T-junction microfluidics
chip system. When individual droplets of SGF were mixed with formulations at the T-junction, the model compounds either stayed
in solution or precipitated out. When the compounds did precipitate out, information about the physical form of the precipitated
chemical entity was obtained as the microfluidic chip is visualized under polarized light microscopy.
As there are significant benefits, scaling down redispersibility experiments also was explored by other groups. Dai and Mansky
(12, 13) describe a method using a 96-well plate that uses a small amount of compound to screen the solubilizing effect of
several excipients once dispersed into simulated intestinal fluid [SIF]. The method is further validated by comparing the
results of the miniaturized experiments to traditional formulation dissolution testing and actual in vivo studies (14). In
addition, Gopinathan et al. (15) developed a 96-well plate based high-throughput formulation screening strategy. The company
TransForm (16, 17) has developed similar high-throughput formulations screens, even extending to a 384-well plate. For these
examples, the reagents are mixed by vortexing or sonicating the plate, or in some cases, heating to solubilize the initial
compound. These examples illustrate the direction the pharmaceutical industry is headed with respect to formulation screening
in the discovery space: using small amounts of compound to evaluate many different formulations. The experiments detailed
in this article are complementary as they use microfluidic technology, specifically T-junction droplet generation. Although
not as developed as the aforementioned examples, this method offers the potential benefit of in situ mixing that droplet microfluidics
offers (18, 19). This feature would be beneficial when highly viscous formulations are evaluated and may be a better representation
of how formulations are dynamically mixed in the gastrointestinal tract. Further, microfluidic technology has the potential
to consume even less compound than what would be used in a 384-well plate experiment.
Future experiments under consideration by the authors include a two-step SGF and fasted state SIF redispersibility study that
would more closely mimic the transport of a compound from the acidic environment of the stomach to the more neutral pH (i.e.,
pH 6.5) of the small intestine. In addition, the system can be temperature-controlled, and the effect of temperature on these
types of experiments may be explored.
In summary, scaling down redispersibility experiments to the microfluidic scale has the potential to have significant impact
on how formulations are screened in the pharmacuetical industry. Performing redispersibility experiments on a much smaller
scale allows more formulations to be screened in vitro using less material. When combined with more powerful detection techniques, the experiment also can provide more understanding
of the behavior of the physical phase in the gastrointestinal environment. This information can help formulation development
scientists identify and understand the most effective formulations for future in vivo experiments more efficiently.