Mora-Castaño Gloria, Rodríguez-Pombo Lucía, Carou-Senra Paola, Januskaite Patricija, Rial Carlos, Bendicho-Lavilla Carlos, Couce Maria L, Millán-Jiménez Mónica, Caraballo Isidoro, Basit Abdul W, Alvarez-Lorenzo Carmen, Goyanes Alvaro
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidad de Sevilla, Seville 41012, Spain.
Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, I+D Farma (GI-1645), Facultad de Farmacia, Instituto de Materiales (iMATUS) and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, Santiago de Compostela 15782, Spain.
Int J Pharm. 2025 Jan 5;668:124964. doi: 10.1016/j.ijpharm.2024.124964. Epub 2024 Nov 16.
Biotinidase deficiency is a rare inherited disorder characterized by biotin metabolism issues, leading to neurological and cutaneous symptoms that can be alleviated through biotin administration. Three-dimensional (3D) printing (3DP) offers potential for personalized medicine production for rare diseases, due to its flexibility in designing dosage forms and controlling release profiles. For such point-of-care applications, rigorous quality control (QC) measures are essential to ensure precise dosing, optimal performance, and product safety, especially for low personalized doses in preclinical and clinical studies. In this work, we addressed QC challenges by integrating a precision balance into a direct powder extrusion pharmaceutical 3D printer (M3DIMAKER™) for real-time, in-line mass uniformity testing, a critical quality control step. Small and large capsule-shaped biotin printlets (3D printed tablets) for immediate- and extended-release were printed. The integrated balance monitored and registered each printlet's weight, identifying any deviations from acceptable limits. While all large printlet batches met mass uniformity criteria, some small printlet batches exhibited weight deviations. In vitro release studies showed large immediate-release printlets releasing 82% of biotin within 45 min, compared to 100% for small immediate-release printlets. For extended-release formulations, 35% of the drug was released from small printlets, whereas 24% was released from large printlets at the same time point. The integration of process analytical technology tools in 3DP shows promise in enhancing QC and scalability of personalized dosing at the point-of-care, demonstrating successful integration of a balance into a direct powder extrusion 3D printer for in-line mass uniformity testing across different sizes of capsule-shaped printlets.
生物素酶缺乏症是一种罕见的遗传性疾病，其特征为生物素代谢问题，可导致神经和皮肤症状，通过补充生物素可得到缓解。三维（3D）打印因其在剂型设计和控释曲线控制方面的灵活性，为罕见病的个性化药物生产提供了潜力。对于此类即时护理应用，严格的质量控制（QC）措施对于确保精确给药、最佳性能和产品安全性至关重要，尤其是在临床前和临床研究中针对低剂量个性化药物的情况。在这项工作中，我们通过将精密天平集成到直接粉末挤出式制药3D打印机（M3DIMAKER™）中，以进行实时在线质量均匀性测试这一关键的质量控制步骤，来应对质量控制挑战。我们打印了用于速释和缓释的小的和大的胶囊形状的生物素打印片（3D打印片剂）。集成天平监测并记录每个打印片的重量，识别出任何偏离可接受限度的情况。虽然所有大打印片批次均符合质量均匀性标准，但一些小打印片批次出现了重量偏差。体外释放研究表明，大的速释打印片在45分钟内释放了82%的生物素，而小的速释打印片为100%。对于缓释制剂，在同一时间点，小打印片中35%的药物被释放，而大打印片中24%的药物被释放。在3D打印中集成过程分析技术工具，有望提高即时护理中个性化给药的质量控制和可扩展性，证明了成功将天平集成到直接粉末挤出式3D打印机中，以对不同尺寸的胶囊形状打印片进行在线质量均匀性测试。
