(252g) Downstream Processing of a Ternary Amorphous Solid Dispersion: The Impacts of Spray Drying and Hot Melt Extrusion on Powder Flow, Compression and Dissolution

Abstract

Downstream
processing aspects of a stable form of amorphous itraconazole exhibiting
enhanced dissolution properties were studied. Preparation of this ternary
amorphous solid dispersion by either spray drying or hot melt extrusion led to
significantly different powder processing properties. Particle size and
morphology was analysed using scanning electron microscopy. Flow, compression,
blending and dissolution were studied using rheometry, compaction simulation
and a dissolution kit. The spray dried material exhibited poorer flow and
reduced sensitivity to aeration relative to the milled extrudate. Good
agreement was observed between differing forms of flow measurement, such as
Flow Function, Relative flow function, Flow rate index, Aeration rate, the
Hausner ratio and the Carr index. The stability index indicated that both
powders were stable with respect to agglomeration, de-agglomeration and
attrition. Tabletability and compressibility studies showed that spray dried
material could be compressed into stronger compacts than extruded material.
Blending of the powders with low moisture, freely-flowing excipients was shown
to influence both flow and compression. Porosity studies revealed that blending
could influence the mechanism of densification in extrudate and blended
extrudate formulations. Following blending, the powders were compressed into
four 500 mg tablets, each containing a 100 mg dose of amorphous itraconazole.
Dissolution studies revealed that the spray dried material released drug faster
and more completely and that blending excipients could further influence the
dissolution rate.