(T1030-06-35) Design and Development of Dose-Flexible Formulation of Pyrimethamine Using Binder Jet 3D Printing

Purpose: The development of pediatric dosage forms using 3D printing offers several advantages, particularly the ability to design highly porous structures that either dissolve quickly on the tongue or disperse easily in liquids for easier administration to children. This study aims to fabricate fast-dissolving pyrimethamine (PMT) printlets using binder jet 3D printing technology.

Methods: A number of trials were performed on the composition of the printlets to generate the preliminary data. The optimization of printlets was accomplished using Factorial design, manipulating process variables along with composition of excipients that consisted of 10-20% of HPMC, 10-15% of sucrose, 50-65% MCC, while the amount of drug was kept constant at 15%. The variables investigated were the number of sprays, percentage of HPMC and percentage of sugar. Various responses were assessed, including hardness, disintegration time, dissolution, and amorphization. In each batch 100 (10×10) printlets of different sizes 6 mm diameter × 3 mm height, 8 mm diameter × 3 mm height, 4 mm diameter × 3mm height were manufactured. The printlets were dried at a temperature of 50 °C and were characterized for weight, diameter, and thickness. The disintegration time (DT) of six printlets was determined in water at 37 °C using a USP disintegration apparatus (Vankel Varian VK-100, NC, USA). The characterization of the printlets was done by XRDP, FTIR, DSC, weight, Micro-X-ray-CT scan, hardness, and dissolution.

Results: Weight of the printlets from different printlet formulations varied from 41.5±0.4 to 92.4±0.5 mg. Hardness of printlets was observed to vary between 1.7±0.4 – 25.1±2.7 N. The hardness increased proportionally by increasing the percentage of HPMC and the number of sprays unlike DT, that showed inverse relation. Similarly, rate of dissolution decreased as the percentage of HPMC and number of sprays were increased. Assay of the printlets was found in the acceptable range of 98.8±2.0 to 102.5±1.5%. Disintegration time of the printlets varied from 3.0±0.0 to 85.3±5.8 seconds. The dissolution of all formulations completed in 10 minutes only and were in accordance with the USP monograph i.e. 80% in 45 mins. XRD did not show any physical transformation, since the drug stayed in its stable crystalline form. FTIR of the printelt formulation before and after the stability did not show any change in the shape or position of peaks. In use stability studies performed showed that the printlets were stable at 30 ^oC/75% RH, since no significant changes in assay and dissolution were observed.

Conclusion: PMT fast-dissolving printlets were effectively formulated using the Binder jet – 3D printing method. These printlets were porous, enhancing both disintegration and dissolution rates. Moreover, their dissolution profiles closely matched the USP monograph for pyrimethamine. The study suggests that these printlets are stable and may offer oral bioavailability comparable to existing market formulations.

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