ArticleMolecular pharmaceutics2025
Developing Multi-Component Solid Formulation Strategies for PROTAC Dissolution Enhancement.
Article in Molecular pharmaceutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- From prediction to performance:International journal of pharmaceutics: X · 2026Article
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8 authors.
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Abstract
PROTACs are an emerging class of beyond-rule-of-5 molecular drugs currently under clinical investigation for the treatment of malignant diseases and are capable of degrading previously "undruggable" protein targets. They are poorly crystallizable due to their structure, consisting of two ligands joined chemically by a flexible linker, yet the inherent insolubility of their amorphous phases hinders their development into sufficiently bioavailable medicines. Formulation approaches to improve the dissolution properties of PROTACs are required as a result, but research in this area is made even more challenging by the scarcity of available samples. In this work, amorphous solid dispersion (ASD) formulations of four cereblon-recruiting PROTACs 'AZ1-4' using hydroxypropyl methylcellulose acetate succinate (HPMCAS) as a polymer excipient are described. ASDs of AZ1 show up to a 2-fold increase in drug supersaturation compared to the pure amorphous API, observed up to a drug loading of 20% w/w. Preparing the ASDs by slurry conversion offers greater solubility enhancement over those prepared by solvent evaporation and maintains the dissolution advantage up to a higher drug load. Positive deviations from theoretical
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