Stability Assessment of a Novel 3D-Printed Oral Dosage Form of Mexiletine Hydrochloride: A Six-Month Shelf-Life Study

This study presents the first evaluation of the shelf life of a novel three-dimensional (3D) printed formulation of Mexiletine Hydrochloride (HCl) over a six-month storage period. Mexiletine HCl was incorporated into a patient-personalized solid oral dosage form using a Semi-Solid Extrusion (SSE) 3D printing technique, and was then subjected to a preliminary stability assessment. We evaluated physical and chemical stability under ICH-recommended storage conditions, taking an important first step toward future full ICH-compliant studies. 3D-printed tablets were stored in a climatic cabinet, at 25 ± 2 °C and relative humidity 60 ± 5% (RH). The tablets were then evaluated for drug content analysis and impurities at 0 and 6 months of storage. Throughout the evaluation period, the printed tablets retained their physical characteristics, including shape and color, and exhibited no significant deviation in drug content and weight. Moreover, no detectable levels of degradation products or impurities were observed, as confirmed by validated analytical methods. These findings collectively indicate that the 3D-printed Mexiletine HCl formulation demonstrates excellent stability under room temperature storage conditions—information that is essential for advancing the formulation along regulatory and commercial pathways. Our data address the common trade-off between printability and stability, demonstrating that a formulation optimized for SSE printing can maintain stability under standard storage conditions.

本研究首次针对一款新型三维（3D）打印的盐酸美西律（Mexiletine Hydrochloride，HCl）制剂，开展了为期6个月的储存货架期评估。研究采用半固体挤出（Semi-Solid Extrusion，SSE）3D打印技术，将盐酸美西律制备为患者个性化口服固体制剂，并对其进行了初步稳定性考察。我们在国际人用药品注册技术协调会（ICH）推荐的储存条件下开展理化稳定性评价，为后续开展符合ICH规范的完整研究迈出了重要的第一步。将3D打印片剂置于恒温恒湿箱中，于25±2℃、相对湿度60±5%的条件下储存。分别于储存0个月和6个月时，对片剂进行药物含量分析与杂质检测。在整个评估周期内，打印所得片剂保留了包括形状、色泽在内的物理特性，药物含量与片重均无显著偏差。此外，经验证的分析方法证实，未检测到可观测水平的降解产物或杂质。上述研究结果共同表明，这款3D打印的盐酸美西律制剂在室温储存条件下表现出优异的稳定性——这一信息对于推动该制剂走向监管审批与商业化路径至关重要。本研究的数据解决了可打印性与稳定性之间常见的权衡难题，证实了针对半固体挤出打印优化的制剂，可在标准储存条件下维持稳定性。