(411b) An Optimization-Based Approach to Identify Thermodynamically Stable Blends for Spray Drying Dispersions
AIChE Annual Meeting
Tuesday, November 15, 2022 - 3:51pm to 4:12pm
In this work, we present a systematic approach for identifying optimal (i) API-polymer and (ii) API-polymer-solvent formulations that meet desired physicochemical properties and can lead to drug products with improved bioavailability . In particular, we employ property-prediction models to estimate solubility, miscibility and the glass transition temperature of a wide range of binary and ternary blends. In addition, we use optimisation models  to identify improved formulations that yield high solubility and stability of formulations with high drug loading. Multi-objective optimization is also utilized to model and identify optimal solutions of competing objectives. The design methodology is demonstrated with the help of a model drug, naproxen, where optimal polymers and solvents are selected to maximize drug loading while ensuring phase stability and a sufficiently high glass transition temperature of the final blend. A ranked list of optimal blends with different chemicals and compositions is obtained by introducing integer cut inequalities into the model, and proper phase diagrams of the best binary and ternary mixtures are constructed. Finally, the proposed model is used to generate a library of optimal formulations for various SDD systems that is used to identify better-performing designs and guide experimental work.
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