Quality by Design Methodology Applied to Process Optimization and Scale up of Curcumin Nanoemulsions Produced by Catastrophic Phase Inversion
catastrophic phase inversion, multiple linear regression, nanoemulsion, quality by design
In the presented study, we report development of a stable, scalable, and high-quality curcumin-loaded oil/water (o / w) nanoemulsion manufactured by concentration-mediated catastrophic phase inversion as a low energy nanoemulsification strategy. A design of experiments (DoE) was constructed to determine the effects of process parameters on the mechanical input required to facilitate the transition from the gel phase to the final o/w nanoemulsion and the long-term effects of the process parameters on product quality. A multiple linear regression (MLR) model was constructed to predict nanoemulsion diameter as a function of nanoemulsion processing parameters. The DoE and subsequent MLR model results showed that the manufacturing process with the lowest temperature (25 °C), highest titration rate (9 g/ minute), and lowest stir rate (100 rpm) produced the highest quality nanoemulsion. Both scales of CUR-loaded nanoemulsions (100 g and 500 g) were comparable to the drug-free optimal formulation with 148.7 nm and 155.1 nm diameter, 0.22 and 0.25 PDI, and 96.29 ± 0.76% and 95.60 ± 0.88% drug loading for the 100 g and 500 g scales, respectively. Photostability assessments indicated modest loss of drug ( < 10%) upon UV exposure of 24 h, which is appropriate for intended transdermal applications, with expected reapplication of every 6-8 h.
Adena, S. K., Herneisey, M., Pierce, E., Hartmeier, P. R., Adlakha, S., Hosfeld, M. A., Drennen, J. K., & Janjic, J. M. (2021). Quality by Design Methodology Applied to Process Optimization and Scale up of Curcumin Nanoemulsions Produced by Catastrophic Phase Inversion. Pharmaceutics, 13 (6). https://doi.org/10.3390/pharmaceutics13060880