Abstract

The present study details the development of a small-scale spray-drying approach
for the routine screening of amorphous solid dispersions (ASDs). This strategy
aims to overcome the limitations of standard screening methodologies like
solvent casting and quench cooling to predict drug-polymer miscibility of spraydried
solid dispersions (SDSDs) and therefore to guarantee appropriate carrier
and drug-loading (DL) selection. A DoE approach was conducted to optimize
process conditions of ProCept 4M8-TriX spray-drying to maximize the yield
from a 100 mg batch of Itraconazole/HPMCAS-LF and Itraconazole/Soluplus
40:60 (w/w). Optimized process parameters include: inlet temperature, pump
speed, drying and atomizing airflows. Identified process conditions derived from
the DoE analysis were further i) tested with Itraconazole, Naproxen and seven
polymers, ii) adapted for small cyclone use, iii) downscaled to 20 mg batch
production. Drug-polymer miscibility was systematically characterized using
modulated differential scanning calorimetry (mDSC). Spray-drying was
identified as a well-suited screening approach: mean yield of 10.1 to 40.6% and
51.1 to 81.0% were obtained for 20 and 100 mg ASD productions, respectively.
Additionally, this work demonstrates the interest to move beyond conventional
screening approaches and integrate spray-drying during screening phases so that
a greater prediction accuracy in terms of SDSDs miscibility and performance can
be obtained.
Keywords: amorphous solid dispersions; spray-dryer; design of experiments;
screening; miscibility; solvent casting; quench cooling; polymers