Xu Lei, Yang Qingliang, Qiang Wei, Li Huijie, Zhong Weizhen, Pan Siying, Yang Gensheng
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.
Research Institute of Pharmaceutical Particle Technology, Zhejiang University of Technology, Hangzhou 310014, China.
Pharmaceutics. 2021 Oct 17;13(10):1717. doi: 10.3390/pharmaceutics13101717.
Three-dimensional (3D) printing technology, specifically stereolithography (SLA) technology, has recently created exciting possibilities for the design and fabrication of sophisticated dosages for oral administration, paving a practical way to precisely manufacture customized pharmaceutical dosages with both personalized properties and sustained drug release behavior. However, the sustained drug release achieved in prior studies largely relies on the presence of hydrophilic excipients in the printing formulation, which unfortunately impedes the printability and formability of the corresponding printing formulations. The current study developed and prepared mini-sized oral pellets using the SLA technique and successfully accomplished a hydrophilic excipient-independent drug release behavior. With ibuprofen as the model drug, the customized photopolymerizable printing formulation included polyethylene glycol diacrylate (PEGDA) as a monomer and diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (TPO) as a photoinitiator. The produced mini-sized pellets were thoroughly investigated for various factors, including their printability, physical properties, microscopic features, drug content, and drug-release profiles. The drug release profiles from the printed pellets that were larger size (3 mm and 6 mm) followed the Ritger-Peppas model, demonstrating that the release was influenced by both the diffusion of the dissolved drug and by the erosion of the hydrophilic excipients (PEG400). The profiles from the smaller printed pellets (1 mm and 2 mm) followed first release kinetics, not only illustrating that the release was impacted only by drug diffusion, but also indicating that there is a size boundary between the dependent and independent hydrophilic excipients. These results could create practical benefits to the pharmaceutical industry in terms of the design and development personalized dosages using the SLA printing technique with controllable drug release by manipulating size alone.
三维（3D）打印技术，特别是立体光刻（SLA）技术，最近为口服复杂剂型的设计和制造创造了令人兴奋的可能性，为精确制造具有个性化特性和持续药物释放行为的定制药物剂型铺平了一条切实可行的道路。然而，先前研究中实现的持续药物释放很大程度上依赖于打印配方中亲水性辅料的存在，不幸的是，这阻碍了相应打印配方的可打印性和可成型性。当前的研究使用SLA技术开发并制备了微型口服微丸，并成功实现了不依赖亲水性辅料的药物释放行为。以布洛芬为模型药物，定制的可光聚合打印配方包括聚乙二醇二丙烯酸酯（PEGDA）作为单体和二苯基（2,4,6-三甲基苯甲酰基）氧化膦（TPO）作为光引发剂。对所生产的微型微丸进行了全面研究，考察了各种因素，包括它们的可打印性、物理性质、微观特征、药物含量和药物释放曲线。较大尺寸（3毫米和6毫米）打印微丸的药物释放曲线遵循Ritger-Peppas模型，表明释放受溶解药物的扩散和亲水性辅料（PEG400）的侵蚀影响。较小尺寸（1毫米和2毫米）打印微丸的曲线遵循一级释放动力学，这不仅说明释放仅受药物扩散影响，还表明在依赖和亲水辅料独立之间存在尺寸界限。这些结果对于制药行业在使用SLA打印技术设计和开发具有可控药物释放的个性化剂型方面，仅通过控制尺寸就能带来实际益处。
