Design of experiments approach to assess the impact of API particle size on freeze-dried bulking agents

Abstract

The current work aimed at the thorough characterization of freeze-dried bulking agent structures loaded with different particle sizes of active pharmaceutical ingredient (API). Using Design of Experiments, a D-Optimal screening design was conceived in order to evaluate the influence of the formulation factors on the features of the obtained structures. The selected formulation factors were API particle size (X1), the type of the bulking agent (X2) and the ratio of the bulking agent (X3). The disintegration time, the dissolution profile and the texture characteristics were studied. The particle size of the API (ibuprofen) influenced the dissolution and the highest dissolution ratios were obtained for trehalose. The texture characteristics of the structures were influenced by the type and the ratios of bulking agents, by increasing the ratio of the bulking agent, the measured parameters were improved. Maltodextrin conducted to robust structures for which, according to the XRPD results, the particles are to a certain degree in an amorphous state. The obtained results represent a contribution to the actual knowledge in this area that can be further used in development of lyophilized pharmaceutical forms.