Spherical agglomerates of alpha lipoic acid: The preparation process, formation mechanism and properties optimization

Abstract

As one of the most commonly used natural compounds, Alpha lipoic acid (ALA) faces challenges in pharmaceutical process due to its poor bulk density and flowability. In this work, ALA was prepared into spherical agglomerates by quasi-emulsion solvent diffusion method and showed improved micromeritic properties. Through in-situ monitoring and molecular dynamic simulation, the formation of ALA spherical agglomerates was proved to be driven by the outward diffusion of the internal organic phase, which belongs to the “solid sphere” model. It was found that the particle size of the spherical agglomerates could be reduced by the addition of polyvinylpyrrolidone K30 (PVP K30) to stabilize the emulsion, while the increasing concentration (from 0.25 % to 10.00 %) increased the particle size (from 164 to 350 nm) by reducing interfacial tension. The spherical agglomeration of ALA met the requirements for direct compression, and the study of the formation mechanism and process control will be beneficial for the design of other spherical agglomerates.