Comparative Study of Content Uniformity Between Capsules and 3D-Printed Oral Forms Manufactured by Semi-Solid Extrusion
1 October 2025
L. Lemierrea,b, D. Stefanellia, S. Roulona, R. Mazet c, C. Curti d, I. Soulairola,b,ea MB Therapeutics, Montpellier, France
b ICGM, University of Montpellier, CNRS, ENSCM, Montpellier, France
c Pharmacy Department, CHU Grenoble Alpes, Grenoble, France
d Pharmacy Department, APHM, Marseille, France
e Pharmacy Department, CHU de Nîmes, Nîmes, France
Objective
This study aims to compare the manufacturing quality of 3D-printed oral forms (POFs), produced using an automated industrial semi-solid extrusion process, with that of manually prepared capsules made using semi-automatic capsule fillers in hospital pharmacies (PUI), focusing on content uniformity.
Methods
Three hospital pharmacies and one industrial partner (4 participants) each provided 60 oral dosage units containing a theoretical dose of 1.5 mg melatonin. Capsules were prepared in PUIs using comparable protocols (same capsule size, operating procedure, excipient composition, and mixing sequence). The POFs were manufactured using a semi-solid extrusion 3D printer (MED U PROD 1.0 ® – MB Therapeutics).
Content assays testing were centralized and performed using a validated HPLC method (ICH-compliant) in a PUI analytical laboratory. For each participant, 10 units were randomly selected from the 60-dose batch and individually analyzed. Compliance was assessed against the European Pharmacopoeia monographs 2.9.6 (uniformity of content of single-dose preparations) and 2.9.40 (uniformity of dosage units). Given the low API content (<2 mg), monograph 2.9.6 (test A for POFs, test B for capsules) is applicable. Monograph 2.9.40 is also relevant, as the active content is below 25 mg. A statistical analysis (Minitab®) was conducted, including Kruskal-Wallis, Tukey’s ANOVA, Levene’s test, and equivalence testing.
Results
All four participants met the requirements of monograph 2.9.6. However, PUIs 1 and 2 did not comply with the stricter limits of monograph 2.9.40. Statistical analysis revealed significant differences between the four datasets. Among all, PUI 3 and the industrial participant achieved full compliance with monograph 2.9.40 and also displayed the lowest variability around the mean.
Conclusion et discussion
All formulations complied with at least one applicable monograph on content uniformity. The 3D-printed oral forms demonstrated equivalent or superior content uniformity compared to the manually filled capsules from PUIs. This highlights the potential of 3D printing technology in the hospital compounding setting. Further studies involving multiple production batches are planned to assess the reproducibility of each process.