Model-Informed Personalized Solid Dosage Formulation via Novel Additive Manufacturing Approach

Personalized medicine represents the next pharmaceutical therapy standard, requiring a manufacturing shift towards custom-made drug products. Warfarin sodium, the poster child of model-informed dose tailoring, combines different doses of standardized tablets or their splitting. Both approaches represent challenges. To unlock the full potential of personalized medicine, innovative formulation technologies are needed. This study reports a proof-of-concept for a liquid-based additive manufacturing approach to produce a solid dosage form, crystalline solid dispersions (CSD) that enables personalized dosages. The formulation process involves dispensing a solution (drug substance, solvent, polymer) into a carrier (capsule), followed by an antisolvent crystallization. Critical process parameters temperature, concentration, and antisolvent composition as well as key performance metrics were evaluated to ensure robust crystalline solid dispersion manufacturing. CSD formulations were characterized using a wide array of characterization techniques (e.g., PXRD, Raman, DSC, and TGA). In addition, the obtained CSDs were compared with commercial warfarin sodium tablets following US Pharmacopeia (USP) methods for drug content, content uniformity, and dissolution studies. The developed workflow and insights presented provides a customizable, scalable solution for other drug substance – polymer – solvent systems while advancing the understanding of the crystallization process needed for the intensification of the formulation process.