Pansare Swaroop J, Kayalar Canberk, Shaikh Rizwan, Dongala Bhanu P, Thota Sunil K, Kuttolamadom Mathew A, Rahman Ziyaur, Khan Mansoor A
Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Texas A&M University, College Station, TX 77843, USA; The Department of Engineering Technology and Industrial Distribution, Texas A&M University, College Station, TX 77843, USA.
Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Texas A&M University, College Station, TX 77843, USA; The Department of Engineering Technology and Industrial Distribution, Texas A&M University, College Station, TX 77843, USA.
Int J Pharm. 2025 Sep 15;682:125942. doi: 10.1016/j.ijpharm.2025.125942. Epub 2025 Jul 13.
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.
由于各种因素，坚持儿科HIV治疗仍然是实现儿童理想治疗效果的一项挑战，其中最主要的因素是缺乏剂量灵活的儿科复方制剂。因此，该研究旨在通过研究在选择性激光烧结（SLS）3D打印技术中配方和工艺变量如何相互作用，来创建一种对儿科患者友好的拉米夫定（3TC）和替诺福韦酯富马酸盐（TDF）打印片剂组合。采用Plackett-Burman筛选设计来确定影响产品质量的关键因素。评估了包括配方和工艺参数在内的八个因素，以确定其主要影响。这些因素包括1:1比例的复方药物百分比（30-40%）、科丽素®IR（0-57%）、羟丙基甲基纤维素（0-67%）、蔗糖（0-67%）和甘露醇（0-57%）、表面温度（80-100°C）和腔室温度（60-80°C）以及激光扫描速度（250-300毫米/秒）。考察了这些因素对七个响应指标的影响：休止角、硬度、崩解时间、3TC含量测定、TDF含量测定以及3TC和TDF在10分钟时的溶出度。结果表明，药物比例为1:1且载药量为40%时所制备的打印片剂符合美国药典的含量测定和溶出标准。表面温度、科丽素IR用量和激光扫描速度对打印片剂性能有显著影响（p<0.05）。包括差示扫描量热法、X射线衍射和近红外高光谱成像在内的表征技术证实，两种药物均有效掺入打印片剂中，同时保持了稳定性和均匀性。因此，通过研究变量之间的相互作用及其结果以及表征研究，本研究支持将SLS 3D打印作为一种有前景的方法，用于开发对儿科患者友好的复方抗病毒疗法，以提高给药灵活性并改善依从性。
