Impact of drug loading on the compaction properties of itraconazole-PVPVA amorphous solid dispersions

Abstract

The impact of drug loading on the compaction properties of itraconazole (ITZ)- poly(vinylpyrrolidone-co-vinyl-acetate) (PVPVA) amorphous solid dispersions (ASDs) was studied. Neat amorphous ITZ, amorphous PVPVA, and their ASDs from 20% to 80% ITZ loadings were prepared by spray drying. Physical characterization showed that all powders have comparable particle size and morphology. All samples were equilibrated under 33% RH prior to compaction studies using a compaction simulator. Tabletability and compactability profiles of the ASD powders differed significantly, while their compressibility was similar. At compaction pressures from 50 to 150 MPa, tensile strength of ASD compacts increased with the increase of ITZ loading, reaching to the maximum at 40–60% ITZ loadings and then decreased as ITZ loading further increased. However, at the compaction pressure of 200 MPa, a monotonic decrease of tensile strength with the increase of ITZ loading was observed. In addition, except for the ASD with 20% ITZ loading, the detrimental effect of compaction pressure on tensile strength was observed at pressures at or above 150 MPa. Overall, this work highlights the importance of evaluating the compaction properties of ASD intermediates prior to downstream tablet development, especially if a high drug loading ASD is desired.