Laser powder bed fusion of amitriptyline tablets via eutectic mixtures using sugar alcohols as binders

Abstract

Laser powder bed fusion is an additive manufacturing technique with a big potential for producing personalized pharmaceutical dosage forms on an industrial scale. To date, primarily thermoplastic polymers have been used as binding excipients in investigations. This work demonstrates that sugar alcohols erythritol, mannitol, and xylitol are excellent alternatives as binding excipients for laser powder bed fusion in terms of processability, content uniformity, and tablet strength. A robust dose calibration strategy demonstrates that tablets can be compounded with precise and accurate mass by powder bed fusion utilizing a laser as the only source of energy. Manufacturing without preheating reduces energy costs and reduces the risks of thermal degradation of API and excipients, which potentially improves the recyclability of residual powder. Amitriptyline hydrochloride was used as the model drug, as personalized medication of this compound is valuable for therapeutic dosing regimens in the treatment of depressive disorders. Phase diagrams showed that amitriptyline forms eutectic mixtures with sugar alcohols. We show that the formation of eutectic mixtures affords reduction of the laser energy density, thus further lowering the risk of thermal degradation. We demonstrate the great potential of sugar alcohols as binders in laser powder bed fusion with exploitable interactions with amitriptyline hydrochloride.