Quality by Design Methodology Applied to Process Optimization and Scale up of Curcumin Nanoemulsions Produced by Catastrophic Phase Inversion

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.

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Article information: Adena, S.K.R.; Herneisey, M.; Pierce, E.; Hartmeier, P.R.; Adlakha, S.; Hosfeld, M.A.I.; Drennen, J.K.; Janjic, J.M. Quality by Design Methodology Applied to Process Optimization and Scale up of Curcumin Nanoemulsions Produced by Catastrophic Phase Inversion. Pharmaceutics 2021, 13, 880. https://doi.org/10.3390/pharmaceutics13060880