Preparation and Quality Control of 3D printed Spironolactone Gel-Tablets for Paediatric Patients
30 September 2026
T. Vincze 1, M. Tubic-Grozdanis 1, I. Krämer 1, J. Al-Gousous 2, P. Langguth 21. Department of Pharmacy, University Medical Center of Johannes Gutenberg-University, Langenbeckstr. 1, 55131 Mainz, Germany
2. Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudingerweg 5, 55128 Mainz, Germany
Background and importance
Spironolactone (SP) is widely used in pediatric patients with heart failure. 3D printing (3DP) offers the opportunity of preparing single-dose tablets in patient-individual weight-based doses according to a medical prescription in a pharmacy. Advantageous characteristics of 3DP gel tablets (GT) are easy administration, easy swallowing better palatability.
Aim and objectives
The aim of this study was to implement and validate pharmacy preparation and quality control of 4-20 mg SP GTs prepared by an innovative 3DP method. To analyse the SP content of the 3DP GTs, a stability-indicating HPLC assay was developed.
Materials and methods
4 mg (mass 200 mg), 10 mg (mass 500 mg), 20 mg (mass 1000 mg) SP GTs were prepared by mixing 2% (m/m) SP active substance with 2.6% (m/m) polysorbate 80, and 95.4% (m/m) Curablend® GT excipient base using a centrifuge (2600 rpm, 10 minutes). GTs were printed at 41°C in the 3D printer with integrated balance (Pharma Printer, CurifyLabs Oy). Three batches of 30 SP GTs of each strength were printed into blister packages and sealed.
The HPLC-UV assay was adapted from the USP monograph ‘SP tablets’ and based on C18 RP-HPLC column, methanol:water (60:40 v/v) eluent, and 240 nm detection wavelength. A 7-point calibration curve ranging from 25 to 75 ppm SP was generated by dissolving spironolactone CRS in acetonitrile:water 50:50 v/v. Inter- and intra-day precision were determined by assaying aliquots of 10 standard solutions containing 50 ppm SP and triplicate injections on three consecutive days. The SP content of 10 GT from each batch was determined by the validated HPLC assay. Samples were prepared by dissolving a SP GT in 50:50 (v/v) acetonitrile:water, sonicating 10 min. at 40°C, diluting, and filtering through 0.22 µm RC filter. Placebo tablets and forced degradation studies were also evaluated.
Results
Results of the forced degradation studies and placebo tablets confirmed the suitability of the HPLC assay. Linearity of calibration curve was proven by R²=0.9993. Intra-day precision amounted to RSD 0.084%, 0.116%, 0.151% on day 1-3, and inter-day precision to RSD 0.437%. The mean SP content of 4 mg, 10 mg, and 20 mg SP GTs amounted to 101.3%, 103.5%, and 104.8% of the nominal content, respectively. All batches met the specification of Ph. Eur. 2.9.6 for content, and the specifications of uniformity of content and mass (Ph. Eur. 2.9.40; Ph. Eur. 2.9.5.).
Discussion and conclusion
A robust and reliable HPLC assay was implemented and validated to determine the SP content of 4-20 mg 3DP GTs. The preparation process of SP GTs was shown to be reliable and reproducible. Further quality testing (water content, stability, disintegration, dissolution) of SP GTs is subject of ongoing investigations.