Personalized medicine: a quality by design approach to printable tablet production†

Abstract

The versatility afforded by emerging additive manufacturing technologies (e.g., 3D printing and precision drop-on-demand deposition) has enabled the rapid and agile production of personalized medicine. The on-demand customization capabilities of these technologies provide novel avenues for point-of-care or distributed pharmaceutical manufacturing and compounding applications. Quality by design principles were used to investigate the production of solid tablet dosage forms for narrow therapeutic index (warfarin), selective serotonin reuptake inhibitor (citalopram), and medical countermeasure (doxycycline) drugs. We examined critical material attributes, critical process parameters, and critical quality attributes for the semisolid extrusion of pharmaceutical tablet excipients and drop-on-demand active pharmaceutical ingredient (API) ink dosing. Detailed investigations optimized the API ink formulation – specifically fluid properties relative to the tablet semisolid excipient, excipient temperature and physical state (i.e., solid vs. liquid), and solidification time – allowing for API and excipient mixing and redistribution. Personalized drug dosages, adjusted doses, and tapered regimens were manufactured, demonstrating accurate API quantity and required production content uniformity, as specified by the U.S. Pharmacopeia. Atline API ink verification and inline drop counting control strategies were employed and confirmed by post-production quantification measurements to properly maintain tablet-to-tablet quality assurance.