Impact of cartridge storage on the stability of 3D-printed oral dosage forms manufactured by semi-solid extrusion

Objective
Three-dimensional (3D) printing of personalized medicines requires semi-solid formulations that remain suitable after storage for manufacturing of printed oral forms (POFs). This study evaluated the impact of cartridge storage on the chemical and microbiological stability of POFs produced by semi-solid extrusion. The quality of POFs manufactured from freshly prepared cartridges was compared with that of POFs produced from cartridges stored for six months under long-term conditions before printing.

Methods
Five batches of a semi-solid formulation containing an active pharmaceutical ingredient (API) were prepared and filled into cartridges. POFs were manufactured using semi-solid extrusion 3D printing. Stability studies were conducted according to ICH Q1A(R2) under long-term conditions (25°C/60% RH, up to 12 months) and accelerated conditions (40°C/75% RH, up to 6 months).
API content and content uniformity were assessed according to Ph. Eur. 2.9.40. Acceptance Value (AV) was calculated from the mean API content and standard deviation of 10 randomly selected POFs and considered compliant when AV ≤ 15. Microbiological quality was evaluated according to Ph. Eur. 5.1.4.

Results
POFs manufactured from freshly prepared cartridges remained compliant with Ph. Eur. specifications throughout the entire stability study, with results available up to 12 months under long-term conditions and up to 6 months under accelerated conditions. AV values ranged from 10.0 to 14.1 and remained below the acceptance limit at all time points. Mean API content stayed close (between 97.67 % and 99,77 %) to the label claim with limited variability.
POFs manufactured from cartridges stored for six months under long-term conditions also met content uniformity requirements throughout the ongoing stability study. To date, results are available up to 1 month under long-term conditions and 6 months under accelerated conditions. AV values ranged from 6.6 to 8.8, remaining well below the acceptance threshold. Mean API content remained close to the label claim (between 97.56 and 101.77 %) with no evidence of degradation or increased variability after cartridge storage.
Microbiological quality remained compliant throughout the study. TAMC and TYMC were below specification limits, and Escherichia coli was not detected in any sample.

Discussion and conclusion
All POFs complied with Ph. Eur. requirements for content uniformity and microbiological quality throughout the investigated storage periods. Cartridges stored for six months under long-term conditions produced POFs with comparable API content, content uniformity, and microbiological quality to those manufactured from freshly prepared cartridges. These results support the suitability of cartridge storage as a strategy for the production of personalized medicines by semi-solid extrusion 3D printing.

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