Elucidation of the mechanism of amorphization and dissolution of bad glass former as a function of drug-polymer interaction and preparation method

This fundamental interdisciplinary project is aimed at investigating the mechanism of amorphization and dissolution of bad glass former as a function of the drug-polymer interaction and preparation method. The model drug naproxen is a poorly soluble drug and a bad glass former (worst-case scenario). The effect of polymer and solvent properties (solubility parameters, interaction with drug, molecular weight, rheological properties, and glass transition temperature) on the solid-state stability of high drug-loaded ASD, thermodynamic and kinetic stabilization will be investigated. The effect of the manufacturing method (fluid bed coating and electrospinning), process parameters settings on the resulting solid-state of ASDs and their physical stability, as well as a comparison of the two methods, will be investigated. The effect of ASD composition (polymer type and drug load), manufacturing method, and dissolution rate of the polymer on the in-vitro drug dissolution profile in stomach- and intestine-mimicking conditions, release of drug and polymer, as well as critical parameters such as the limit of congruence, will be investigated. Algorithms for tailoring the main properties of fabricated ASD, including the dissolution profile, will be proposed. The project is interdisciplinary; it involves the following research areas: pharmaceuticals, material engineering, polymer chemistry, and physics. The project results are 3 publications, 3 conference theses, and a Latvian patent.