CRBE Summit West

Beyond Solubility: Mechanistic Optimization of ASDs for Modern Small Molecules

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Key Takeaways:

• Amorphous solid dispersions (ASDs) are now mainstream for enhancing bioavailability of BCS II and IV compounds.

• Modern clinical molecules are increasingly complex—high molecular weight, high Tm/Tg, slow crystallizers—allowing them to sustain amorphous solubility during oral delivery.

• While solubility is limited by the amorphous state, ASDs can be optimized to improve exposure via solubilized species formation or dissolution kinetics.

• Understanding the rate-limiting step to absorption is critical; solubility-limited compounds can be classified as dissolution- or diffusion-limited to guide formulation beyond the amorphous form.

• An integrated approach to ASD development ensures robust, scalable, patient-centric products, leveraging new tools to characterize BCS II and BCS IV compounds and overcome absorption limitations.

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