Application of experimental design for the development of soft-capsules through a prilling, inverse gelation process

The aim of this research was to develop a robust process capable of producing soft-capsules with hydrophilic core for topical administration by means of an inverse gelation. While this method is extensively studied to prepare particles with oily content, its knowledge space in the case of the proposed application is limited. Therefore, a half-fractional factorial design with 5 factors at two levels with resolution V was employed, to meet the scientific requirements in accordance with the Quality by Design approach. Kojic acid, an unstable skin whitening agent, was selected as the active ingredient for its easy detectability. Soft-capsules where produced through a vibrating nozzle device, dripping a thickened calcium chloride solution into an alginate bath. The experimental design applied revealed the effect of several Critical Process Parameters such as the solution's composition, frequency and flow-rate onto Critical Quality Attributes of the produced soft-capsules as for example drug content, encapsulation efficiency, size, shape and mechanical strength. The overall knowledge gained through the DoE exercise showed that the inverse gelation process was capable of producing soft-capsules with the desired attributes, resistant enough to allow handling during storage, but also easily ruptured when applied onto the skin, without leaving residues.