The 12th Annual Meeting of the Pharmaceutical Solid State Research Cluster, Date: 2018/09/12 - 2018/09/14, Location: Leuven, Belgium

Publication date: 2018-09-13

Author:

Batens, Maarten
Dewaele, Loís ; Teodorescu, Bianca ; Clasen, Christian ; Massant, Jan ; Van den Mooter, Guy

Abstract:

PURPOSE Electrospraying (ES), i.e. the formation of tiny droplets from a jet of conductive liquid under the influence of an electric field, could prove interesting as a particle engineering technique. Potential benefits of ES as an atomisation technique for protein formulations include the technique’s feasibility at ambient temperatures, minimising the risk of heat induced protein degradation, as well as the high encapsulation efficiency when using a coaxial setup. However, the physicochemical properties of aqueous solutions, the preferred medium for proteins when it comes to stability, make achieving a stable Taylor cone-jet mode challenging, something that is reflected by the fact that the majority of reported successful protein ES processes included either organic solvent emulsions or a mixture of an organic solvent and water1. Since using organic solvents in the feed solution would eliminate a major benefit of ES, we investigated the feasibility of ES of fully aqueous solutions containing bovine serum albumin (BSA) as a model protein as well as common protein stabilisers. METHODS The ES setup included a climate chamber, which allowed for the temperature and relative humidity control during the ES experiments (IME Technologies, NLD). Density, conductivity, viscosity and surface tension were determined for a selection of the liquid feed solutions. A Fastcam SA2 (Photron, JPN) was used to visualise spraying modes and SEM to assess powder characteristics. RESULTS An extensive excipient screening study was conducted to reduce the number of formulation factors and thus enable the subsequent mixture DoE’s, followed by three additional, confirmatory experiments. The addition of these confirmatory experiments to the model for the cone-jet stability response validated its predictive capabilities as well as the significance of the BSA concentration. Similar evaluation of the powder bed properties did not result in a statistically significant model. CONCLUSION The presented data confirms the feasibility of ES of fully aqueous protein solutions by use of a statistical approach combined with the characterisation of relevant physicochemical factors