(693f) Drug Form Considerations in Continuous Solution Processing of Oral Solid Dosage Products

The pharmaceutical industry is moving toward continuous manufacturing for small molecule API products and new technologies must be developed to process APIs and excipients into solid oral dosages such as tablets. Solution processing, where the drug and excipients are processed together as a liquid or suspension, has distinct advantages in improving mixing and reducing powder handling. Various techniques have been adopted from the plastics industry for solution processing of pharmaceuticals such as hot melt extrusion, electrospinning, film casting and 3D printing. In all of these, it is a challenge to control whether the drug is crystalline or amorphous and which polymorph results. We specifically focus on two manufacturing techniques, electrospinning and 3D printing, and show that we can prepare tablets containing crystalline or amorphous APIs as desired with acceptable dissolution properties in simulated gastric fluid. By starting with a high loading of API in a polymer solution with a non-solvent for the API, we can 3D print tablets containing crystalline API. Due to the high loading of large particles, the rheology of the suspensions is a crucial parameter for the printability and we have shown that this can be controlled through the particle loading and polymer molecular weight. We can also electrospin fibers containing crystalline API through a mixture of a non-solvent, polymer and API crystals, but by dissolving the API in a good solvent mixed with the polymer, we can prepare fibers containing amorphous API with similar processing conditions. These studies aim to improve control over drug form in solution processing, while expanding the utility of 3D printing and electrospinning for pharmaceuticals.