Discovery & Development US 2025 (Formerly: Formulation & Delivery - San Diego)

Beyond Solubility: Optimizing ASD Formulations for Complex Molecules

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Optimal formulation design identifies the simplest approach to meet the product profile. Basic API properties can be leveraged in a developability assessment to determine if an enabled formulation is required and to select an appropriate technology. When required, amorphous solid dispersions (ASD) are a common and precedented technology for solubility enhancement, but as molecular properties evolve, so must our strategy for evaluating and selecting an optimal ASD formulation.

As the molecular landscape becomes dominated by more complex molecules, such as PROTACs, with higher molecular weights, exceptionally low solubilities, and high glass transition temperatures, we shift our focus on ASD design beyond solubility. For these complex molecules, we assess the nuances of solubility and permeability limitations, while maintaining perspective on dosage form design, providing a more strategic approach to ASD formulation.

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Takeaways:

• Many molecules in today’s landscape require solubility enhancement, but are not rapid crystallizers

• ASD formulation design for these molecules goes beyond precipitation inhibition and should consider the formation of drug-polymer colloids

• Drug-polymer colloids do not enhance bioavailability for all molecules, but a simple PBBM model leveraging basic API properties can help to identify when these species are critical for maximizing performance

• A patient-centric approach to product design should always consider an integrated approach to development of the enabled intermediate and final drug product

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