Amorphous solid dispersions of BCS class II drugs: A rational approach to solvent and polymer selection

• Published in: Chemical engineering research & design 2016-06, Vol.110, p.192-199
• Main Authors: Davis, Mark T., Egan, David P., Kuhs, Manuel, Albadarin, Ahmad B., Griffin, Ciara S., Collins, John A., Walker, Gavin M.
• Format: Article
• Language: English
• Subjects: Amorphous solid dispersions; Formulation; Poorly water soluble drugs; Solvent casting; Stability
• ISSN: 0263-8762
• DOI: 10.1016/j.cherd.2016.04.008

•Miniaturised solvent casting (MSC) is a useful pre-formulation technique.•Four drugs, seven polymers and five solvent systems were tested.•The stability of the formulations against crystallisation was measured over time.•A rational ASD selection should take physiochemical properties of drug, polymer and solvent into account.•The properties of the solvent will affect the stability of the amorphous film even after solvent has been removed. Miniaturised solvent casting (MSC) has been developed as a method for screening the stability of amorphous solid dispersions (ASD) of BCS class II drugs. The aim of the work was to further develop a rapid screening technique for drug–polymer amorphous dispersions made by solvent removal techniques. A second aim was to assess the impact of varying dissolution solvent on the resultant ASD stability. The technique was rapid, repeatable and practically straightforward. Storage stability of resultant ASD films was monitored over 4 weeks. The method is suited to pre-formulation as a risk-reduction tool during the formulation of drug product. Four drugs, seven polymers and five solvents have been examined. The resultant ASD films were monitored for stability and homogeneity over a four week period using polarised light microscopy (PLM), X-ray powder diffraction (XRD) and photography. A qualitative scoring system indicating the approximate proportion of amorphous and crystalline content of the films was developed. Results were rationalised against the physiochemical properties of the drugs, the functionality of the polymeric excipients and the physical properties of the solvents.