Production and stability of amorphous solid dispersions produced by a Freeze-drying method from DMSO

Abstract

Freeze drying is known to be able to produce an amorphous product, but this approach has been mostly used with water-based media. With APIs which are virtually water insoluble, a more appropriate freeze-drying medium would be an organic solvent. Little is known about this approach in terms of forming a stable freeze-dried amorphous product stabilized by small molecule excipient out of organic solvents. In the present study, freeze-drying of APIs from DMSO solutions was used to produce stable solid dispersions from binary mixtures of APIs containing at least one poorly water soluble or practically water-insoluble API. The developed freeze-drying method produced amorphous binary solid dispersions which remained amorphous for at least two days while the 13 best binary dispersions remained stable at room temperature for the entire study period of 127 days. Average residual DMSO levels in dried dispersions were 3.5% ± 1.6%. The developed method proved feasible in producing relatively stable amorphous solid dispersions from practically water insoluble drug compounds which could subsequently be used in further research purposes.

Keywords: Amorphous; DMSO; Freeze-drying; Solid dispersion.