Scale up of a Low Energy Process for the Production of Oil in Water Emulsions

Consistent with the technological advancements during the past 10- 15 years, numerous formulations and drug delivery concepts emerged for enhanced therapeutic applications. Because these formulations are relatively new, the industry needs to address several challenges, in this sense cold processed emulsions can be used. The aim of the present work is to study the risk associated to the scale transposition of a cold processed oil in water emulsion and access the production costs savings associated to this new process. The lab scale of the emulsion was developed by the preparation of the oil liquid phase (19%) at room temperature. The aqueous phase was prepared also at room temperature by dispersing the aqueous thickening agents in water, after the cetrimide (0.075 % w/w) and the pentanediol (10% w/w) were added to the aqueous solution and the resulting mixture was homogenized until a clear homogeneous gel was achieved. The emulsification phase was performed at room temperature by slowly adding the oil phase to the aqueous phase with high shear mixing at a rate about 12800 rpm/min (IKA® T25 Ultra Turrax). Two scales up were performed using the same methodology: ten-fold increase - pilot lab-scale (IKA® LR 2 ST) and a 100 fold increase - pilot industrial-scale (Dumek® Dumoturbo 25). The three scales were compared in terms of droplet size distribution measured by light scattering and the rheological profiles. The total production costs, for the cold process compared with a conventional hot process, were calculated taking into account the electrical and water costs. The results showed that the droplet size of the emulsion significantly decreased when the production scale was increased (23.23 ± 3.89 ?m; 18.42 ± 5.76 ?m and 6.37 ± 2.49 ?m, for lab, pilot-lab and pilot-industrial scale, respectively). Moreover, the industrial pilot-scale produced an emulsion with a monomodal population. The apparent viscosity values are in accordance with the latter results. The emulsion produced in the industrial pilot-scale seemed to be more structured. In conclusion the scale-up process led to more significant alterations on the rheological profile and on the droplet size distribution of the placebo produced by the industrialscale than the lab-scale production. This cold process allowed a total production savings of more than 17% when compared to the traditional hot process.