Design of SLS 3D-printed pediatric combination printlets of lamivudine and tenofovir disoproxil fumarate by understanding the impact of formulation and process variables on flow, spectral, thermal and performance characteristics.

Adherence to pediatric HIV therapy continues to be a challenge for achieving the desired therapeutic outcomes in children due to various factors, the primary one being the lack of availability of a dose-flexible pediatric combination formulation. The study thus aimed to create a pediatric-friendly combination of lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) printlets by examining how formulation and process variables interact within selective laser sintering (SLS) 3D printing technology. A Plackett-Burman screening design was used to pinpoint critical factors impacting product quality. Eight factors, encompassing both formulation and process parameters, were assessed to identify the main effects. These include the percentage of combination drug (30-40 %) in a 1:1 ratio, Kollicoat® IR (0-57 %), hydroxypropyl methyl cellulose (0-67 %), sucrose (0-67 %), and mannitol (0-57 %), surface (80-100 °C) and chamber temperature (60-80 °C), and laser scanning speed (250-300 mm/sec). The influence of these factors was examined in relation to seven responses: angle of repose, hardness, disintegration time, assay of 3TC, assay of TDF, and dissolution of 3TC and TDF at 10 min. The results showed that a 1:1 drug ratio with 40 % loading produced printlets meeting USP assay and dissolution standards. Surface temperature, KCIR amount, and laser scanning speed significantly influenced printlet performance (p < 0.05). Characterization techniques, including differential scanning calorimetry, X-ray diffraction, and near-infrared hyperspectral imaging, confirmed that both drugs were effectively incorporated in the printlets while maintaining stability and uniformity. Thus, by studying the interplay of variables and their outcomes alongside characterization studies, this research supports the use of SLS 3D printing as a promising method for developing pediatric-friendly combination antiviral therapies that enhance dosing flexibility and improve adherence potential.