(198a) Quality By Design in Nanomedicine: Application to a Microemulsion Delivery System
AIChE Annual Meeting
Monday, October 29, 2018 - 3:30pm to 5:00pm
Microemulsions, a type of nanomedicine characterized by droplet diameter of 15-50 nm, are thermodynamically stable colloidal dispersions which are used to increase drug solubility and half-life. Microemulsions are safe, given that they can be developed with biodegradable, generally regarded as safe (GRAS) oils and surfactants. For these reasons, we chose microemulsions as our model nanoformulation. First, the quality target product profile (QTPP) of the microemulsion product was defined. After defining the associated critical quality attributes (CQAs), critical material attributes (CMAs), and critical process parameters (CPPs), we compiled a library of modes of failure during product manufacturing and ranked them using failure modes, effects, and criticality analysis (FMECA). We used the results of risk assessment to create a design of experiments (DOE) to which we fit multiple linear regression and logistic regression models to predict microemulsion properties and probability of meeting CQA specifications. We performed comprehensive quality control analyses to evaluate CQAs and overall were able to identify stable microemulsion formulations in a timely manner using a small number of experimental runs. Finally, we demonstrate the loading capability with multiple BCS class II drugs to demonstrate the versatility of this formulation and investigate the scale-up of the optimized microemulsion. Adapting this QbD methodology to other nanomedicine products is of value for time and resource minimization as well as smoothing the path to regulatory approval.