(T1330-05-26) Development and Characterization of Dose Flexible Printlets of Lamivudine Using Binder Jet – 3D Printing

Purpose: The use of lamivudine in children is well-established, and it is included in the recommended antiretroviral therapy (ART) regimens for pediatric patients with HIV. Pediatric patients need dose flexible delivery systems due to variability in the physiology of children where fixed dose therapy or combinations won’t work and may lead to over or under dose in the pediatric patients. An ideal pediatric dosage form should be able to titrate doses, so that all age groups up to 17 years of children can be covered by a single product. Creating pediatric dosage forms through 3D printing presents numerous benefits. These forms can be tailored to have high porosity, enabling them to either dissolve rapidly on the tongue or disperse easily in a liquid before giving them to children. The aim of this study is to produce fast-dissolving printlets of Lamivudine (LMV) using the binder jet 3D printing.

Methods: A number of trials were performed on the composition of the printlets. The optimization of printlets was accomplished using factorial design, manipulating process variables along with composition of excipients that consisted of 10-30% of HPMC, 20-40% of lactose, while the amount of drug was kept constant at 50%. The variables investigated were the number of sprays, layer thickness, print delay time between the layers, drying temperature of printlets and the percentage of HPMC. Various responses were assessed, including hardness, disintegration time, dissolution, amorphization, physiochemical properties. 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 different temperatures 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. Stability studies of the printlets was performed at in use condition, 30 ^oC/75% RH.

Results: Weight of the printlets from different printlet formulations varied from 40±0.3 to 91±0.4 mg. Hardness of printlets was observed to vary between 2.5±0.5 – 20.1±2.8 N. Assay of the printlets was found in the acceptable range of 96.8±2.0 to 101.9±1.5%. Disintegration time of the printlets varied from 3.0±0.0 to 121.3±5.8 seconds. The dissolution of all the formulations was in the range of 85 to 100 % in 20 minutes as per the specifications mentioned for the Lamivudine tablets in the USP mongraph. XRD and DSC 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. 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: LMV fast-dissolving printlets were successfully created using the Binder jet – 3D printing method. These printlets were porous, enhancing both disintegration and dissolution rates. Moreover, their dissolution profiles match with the USP monograph for Lamivudine tablets. The study suggests that these printlets are stable and may offer oral bioavailability comparable to existing market formulations.

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Acknowledgements: The authors do no show any conflict of interest.