The Effect of Inorganic Salt on Disintegration of Tablets with High Loading of Amorphous Solid Dispersion Containing Copovidone.

Abstract

While including amorphous solid dispersion (ASD) in tablet formulations is increasingly common, tablets containing high ASD loading are associated with slow disintegration, which presents a challenge to control pill burden for less potent compounds. We use a model ASD, composed of a hydrophobic drug with copovidone and a non-ionic surfactant, to explore formulation options that can prevent slow disintegration. In addition to the ASD loading, the pH of the disintegration medium and the inclusion of inorganic salts in the tablet also have an impact on the tablet disintegration time. Certain kosmotropic salts, when added in the formulation, can significantly accelerate tablet disintegration, though the rank order in their effectiveness does not exactly follow the Hofmeister series at pH1.8. The particle size and dissolution rate of the salt can contribute to its overall effectiveness. We provided a mechanistic explanation of the disintegration process: fast-dissolving kosmotropic salt results in a concentrated salt solution inside the restrained tablet matrix, thus inhibiting the dissolution of copovidone and preventing polymer gelling which is the main cause leading the slow disintegration. The outcome of this study has enabled the design of a higher ASD loading platform formulation for copovidone based ASD. Graphical Abstract MicroCT aids the mechanistic understanding of the role of inorganic salt in the tablet disintegration of amorphous solid dispersion based formulation.