Answers are grounded in this paper and cite their sources.
Evaluates lipophilic salts' effect on solid-state properties and organic solubility, suggesting enhanced manufacturability.
Amorphous solid dispersion (ASD) manufacturability is constrained by active pharmaceutical ingredient physicochemical properties; high melting point (Tm) and high glass transition temperature (Tg) limit hot-melt extrusion (HME), and low organic solubility limits spray-drying (SD) throughput. We evaluated lipophilic counterion choice as a solid-state design lever to enable ASD manufacturability by SD or HME. Nine lipophilic salts of atazanavir (ATZ) and mebendazole (MBZ) were prepared with sulfate and sulfonate counterions spanning a range of chain lengths and steric bulk, and characterized by 1H nuclear magnetic resonance spectroscopy, powder X-ray diffraction, differential scanning calorimetry, and polarized light microscopy. Lipophilic salts showed Tm and Tg reductions relative to their free base, with Tg reductions of up to approximately 30 °C. Organic solubility in ethanol, acetone, and tetrahydrofuran improved 2–15× or greater across most salt-solvent combinations. Vacuum compression molding confirmed that a representative lipophilic salt (ATZ-pTSA) enables thermal amorphization at HME-relevant processing temperatures, where the ATZ free base does not fully melt or dissolve into the model polymer. Counterion choice functions as a solid-state design lever for ASD manufacturability through a proposed lattice-packing disruption mechanism that simultaneously reduces Tm and Tg and improves organic solubility.
No takes yet. Share an insight, caveat, or question.
Petrova et al. (2026) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: