(T1230-06-39) Understanding the Interplay between Formulation and Process Variables to Fabricate Combination Printlets of Lamivudine and Tenofovir Disoproxil Fumarate for Pediatric Populations

Purpose: To develop dose-flexible, pediatric-friendly printlets containing a 1:1 combination of lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) using selective laser sintering (SLS) 3D printing technology, and to systematically evaluate the influence of formulation and process variables on printlet quality attributes.

Methods: A Plackett-Burman screening design was employed to evaluate the effects of eight critical factors, including amount of combination drug (30-40%) [X1] in a 1:1 ratio, the amount of KCIR (0-57%) [X2], the amount of HPMC E3 (0-67%) [X3], the amount of sucrose (0-67%) [X4], the amount of mannitol (0-57%) [X5], surface temperature (80-100 °C) [X6], chamber temperature (60-80 °C) [X7], and laser scanning speed (250-300 mm/sec) [X8]. Twelve printlet formulations were manufactured with a 30–40% combination drug load using an SLS printer. Printlets were characterized for flowability by angle of repose [Y1], mechanical strength by hardness [Y2], disintegration time (DT) [Y3], drug content by assay of 3TC [Y4] and of TDF [Y5],  , and dissolution at 10 minutes (3TC T₁₀) [Y6], and (TDF T₁₀) [Y7]. Physicochemical and solid-state characterization was performed using DSC, XRPD, and near-infrared hyperspectral imaging to assess drug distribution and crystallinity.

Results: Drug loading up to 40% resulted in acceptable powder flow and printability. Surface temperature, KCIR content, and scanning speed significantly influenced critical attributes (p < 0.05). Elevated surface temperatures and slower scan speeds led to partial thermal degradation of TDF, reducing its assay (61.2–97.0%) but not that of 3TC (91.7–108.5%). HPMC increased disintegration time and reduced dissolution due to hydrogel formation, whereas sucrose accelerated disintegration and enhanced dissolution. DSC and XRPD confirmed partial amorphization of TDF post-printing, while PCA analysis of NIR images revealed uniform drug distribution within the matrix.

Conclusion: This study demonstrates that pediatric combination printlets of 3TC and TDF can be fabricated using SLS 3D printing with up to 40% drug loading. The selection of excipients and optimization of process parameters are crucial for ensuring drug stability, mechanical strength, rapid disintegration, and pharmacopeial dissolution. The findings highlight the potential of SLS in enabling customizable, multi-drug pediatric therapies.

References: 1. Awad, A., Fina, F., Goyanes, A., Gaisford, S., Basit, A.W., 2021. Advances in powder bed fusion 3D printing in drug delivery and healthcare. Advanced Drug Delivery Reviews 174, 406-424
2. Barakh Ali, S.F., Mohamed, E.M., Ozkan, T., Kuttolamadom, M.A., Khan, M.A., Asadi, A., Rahman, Z., 2019. Understanding the effects of formulation and process variables on the printlets quality manufactured by selective laser sintering 3D printing. International Journal of Pharmaceutics 570, 118651
3. Kayalar, C., Pansare, S.J., Sibhat, G., Kuttolamadom, M., Rahman, Z., Khan, M.A., 2025. Development and Characterization of Printlets of Lamivudine for Pediatric Patients Using Selective Laser Sintering. Pharmaceuticals 18, 356

Acknowledgements: This work was supported by NIH grants 1R01HD110552-01A1 and 1R01HD112077-01. The authors declare no conflicts of interest


Overview of Understanding the interplay between formulation and process variables to fabricate combination printlets of Lamivudine and Tenofovir disoproxil fumarate for pediatric populations