Abstract
Printing of phase 1 and 2a clinical trial formulations represents an interesting industrial application of powder bed printing. Formulations for clinical trials are challenging because they should enable flexible changes in the strength of the dosage form by varying the active pharmaceutical ingredient (API) percentage and tablet mass. The aim of this study was to investigate how powder bed 3D printing can be used for development of flexible platforms for clinical trials, suitable for both hydrophilic and hydrophobic APIs, using only conventional tableting excipients. A series of pre-formulation and formulation studies were performed to develop two platform formulations for clinical trials using acetaminophen and diclofenac sodium as model compounds and lactose and starch as excipients. The results showed that the type of starch used as the formulation binder must be optimized based on the type of API. Moreover, powder blend flow and liquid penetration ability proved to be critical material attributes (CMAs) that need to be controlled, particularly at high drug loading. Optimization of these CMAs was performed by selecting the appropriate particle size of the API or by addition of silica. A critical process parameter that had to be controlled for production of tablets of good quality was the quantity of the printing ink. After optimization of both the formulation and process parameters, two platform formulations, that is, one for each API, were successfully developed. Within each platform, drug loading from 5 up to 50% w/w and tablet mass from 50 to 500 mg were achieved. All 3D-printed tablets could be produced at tensile strength above 0.2 MPa, and most tablets could enable immediate release (i.e., >80% w/w within 30 min).