Critical process parameters of gelatin microparticle fabrication with a water-in-oil emulsion method

Gelatin-based microparticles have received growing attention as versatile biomaterials over the years. In this study, we investigated the fabrication process of gelatin microparticles with an emulsifier-free water-in-oil technique using design of experiments (DoE). We executed three DoEs for two different gelatin types (type A and type B). We demonstrated that stirring speed is the most significant factor affecting shape parameters of sphericity of particles derived from both gelatin types. An effect of process temperature was only significant for gelatin type A particles. Water-to-oil phase volume ratio was only investigated for type B gelatin and found to impact particle sphericity of microparticles. We also showed a correlation between particle size distribution and shape factors, where an inferior particle shape quality was associated with finer particles. Through 21 verification batches at constant factor settings, we demonstrated high process performance for microparticles (gelatin type B). Overall, we demonstrated effective control in particle size distribution and particle shape factors for both gelatin types. The fabricated gelatin microparticles will subsequently be chemically crosslinked and the achieved control of particle sphericity will be beneficial for the quality of the crosslinked particles.