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

Abstract

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.

Novel Therapeutic Hybrid Systems Using Hydrogels and Nanotechnology: A Focus on Nanoemulgels for the Treatment of Skin Diseases

“…More work should be done to assess these formulations' true safety and long-term applicability, in the context of the current regulatory framework, in order to determine the ability of these nanoformulations for bioaccumulation and interference with the body's immune system (phagocytosis by immune cells), although this might be a bigger concern for transdermal drug delivery than for topical drug delivery [269,270]. Additionally, scale-up potential should also be determined, in order to assess the limitations facing any transition from a laboratory bench scale to an industrial manufacturing scale, so that these promising preparations can one day reach the pharmaceutical market [108,[271][272][273].…”

Design Expert-Implemented Nimodipine-Loaded Lyophilized Nanoemulsifying Drug Delivery System for Improved Oral Bioavailability and Physical Stability

“…The S mix was prepared by mixing surfactant and co-surfactant at a 3:2 ratio as selected from the pseudo ternary phase diagram with the maximum area covered for the region of nanoemulsion followed by the addition of distilled water dropwise and again vortexed for 10 min. 16,23 The mixture of S mix and water was added to the oil phase and vortexed for another 10 min to get transparent o/w nanoemulsion.…”

“…In the current research, the concept of QbD has been implemented to predict the potential impacts of Critical Material Attributes (CMAs) and Critical Process Parameters (CPPs) as independent variables on Critical Quality Attributes (CQAs) as dependent variables of NIMO nanoemulsion to obtain desired Quality Target Product Profile (QTPP). 16,17 Shambhavi Dhananjay Acharya et al, 2020 fabricated a QbD-driven curcumin-loaded nanoemulsion and reported a thermodynamically stable nanoemulsion with more cytotoxic potential as compared to pure drug using HT29 cell lines.…”

Current Advances in Lipid Nanosystems Intended for Topical and Transdermal Drug Delivery Applications

“…During the formulation development of nanoemulsions, a prudent selection of the most promising emulsifier systems based on their solubility and emulsification ability has to be made using a pseudoternary phase diagram that is constructed from different formulation components [ 69 ]. In addition to phase diagrams, a quality by design approach is also recommended to systematically refine the desirable physicochemical properties of nanoemulsion formulations in order to meet specific drug delivery requirements, either for topical (promote drug deposition in epidermis and dermis layers of the skin) or for transdermal applications (effective flux of drug through skin into blood circulation) [ 70 , 71 ].…”