A critical review of traditional and advanced characterisation tools to drive formulators towards the rational development of 3D printed oral dosage forms.

The high degree of precision and control of 3D printing has given formulators the autonomy to engineer sophisticated and personalised medicines, starting a revolution in pharmaceutics. In addition, dosage forms with tailored drug release profile can be produced by changing some parameters of the 3D printing processes. Therefore, 3D printed medicines must be characterised in an orthogonal approach, to establish their physicochemical and biopharmaceutical features, and consequently to understand how these characteristics can be customised by changing the formulation and process parameters to ensure medicines' safety and efficacy. Given the recent regulation and commercialisation of 3D printed medicines, several methods and techniques have been transposed from official compendia; however, formulators must still make a critical assessment of their practical implications. A comprehensive review of the findings obtained by the characterisation of 3D printed oral dosage forms using traditional and advanced techniques is therefore presented here, to drive formulators towards a rational pharmaceutical development pathway. The characterisation methods have been classified in terms of their physicochemical or biopharmaceutical character. Interestingly, beyond the rise of modern characterisation techniques, the reassessment of data obtained by traditional methods has provided knowledge and a solid foundation to support the evolution of 3D printing techniques in pharmaceutics.

Integrating pressure sensor control into semi-solid extrusion 3D printing to optimize medicine manufacturing.

Semi-solid extrusion (SSE) is a three-dimensional printing (3DP) process that involves the extrusion of a gel or paste-like material via a syringe-based printhead to create the desired object. In pharmaceuticals, SSE 3DP has already been used to manufacture formulations for human clinical studies. To further support its clinical adoption, the use of a pressure sensor may provide information on the printability of the feedstock material in situ and under the exact printing conditions for quality control purposes. This study aimed to integrate a pressure sensor in an SSE pharmaceutical 3D printer for both material characterization and as a process analytical technology (PAT) to monitor the printing process. In this study, three materials of different consistency were tested (soft vaseline, gel-like mass and paste-like mass) under 12 different conditions, by changing flow rate, temperature, or nozzle diameter. The use of a pressure sensor allowed, for the first time, the characterization of rheological properties of the inks, which exhibited temperature-dependent, plastic and viscoelastic behaviours. Controlling critical material attributes and 3D printing process parameters may allow a quality by design (QbD) approach to facilitate a high-fidelity 3D printing process critical for the future of personalized medicine.