黏结剂喷射型3D打印复方双层片中的缓释打印工艺研究

Binder jet 3D printing composite bilayer tablet of extended-release printing technology in the study

基于创伤救治中镇痛抗炎的双重需求,本研究以对乙酰氨基酚、盐酸莫西沙星为模型药,采用黏结剂喷射型3D打印技术开发具有双相释药系统的复方双层片。因3D打印工艺复杂,各个参数之间存在相互影响,通过对工艺的优化可以较为直观地确定关键工艺参数之间的关系。本研究通过对缓释层片剂工艺的优化以保持片剂机械性能的同时实现释放的调控,利用三个中心点23的全因子实验设计,分析显著影响缓释层片剂质量属性的因子及因子之间的交互作用,并通过响应优化器获得了最优的缓释工艺参数:喷墨量为10(约为13.8 pL),厚度为180μm,运行速度为360 mm·s^(-1)。对3D打印复方双层片进行体外释放研究表明,3D打印片剂和市售片剂的体外释放均符合Ritger-Peppas释药模型;孔隙率结果表明该制剂的速释层孔隙多、孔径较大,可实现速释层在15 min内的溶出度大于85%的要求,缓释层内部孔径较大,但仍能持续长达8 h的缓慢释放,其机制可能与HPMC胶凝化延缓释放有关。本研究在验证3D打印复方双层片设计目标合理性的基础上,也为3D打印复杂制剂的制备提供了理论依据。

Based on the dual needs of analgesia and anti-inflammation in trauma treatment,this study uses acetaminophen and moxifloxacin hydrochloride as active pharmaceutical ingredients and develops a composite bilayer tablet with a dual-phase drug release system by using binder jet 3D printing technology.Due to the complexity of the 3D printing process,there is an interaction between the various parameters.Through the optimization of the process,the relationship between the key process parameters can be determined more intuitively.In this study,the process of extended-release tablets was optimized to maintain the mechanical properties of the tablets while realizing the regulation of release.The full-factor experimental design of three central points 23 was used to analyze the factors that significantly affect the quality attributes of extended-release tablets and the interaction between factors.The optimal extended-release process parameters were obtained by the response optimizer:the inkjet quantity of the printing ink was 10(about 13.8 pL),the powder thickness was 180μm,and the running speed was 360 mm·s^(-1).The in vitro of release of 3D printed composite bilayer tablets showed that the in vitro of release of 3D printed tablets and commercially available tablets conformed to the Ritger-Peppas release model.The results of porosity showed that the immediate-release layer of the preparation has many pores and large pore size,and the dissolution of the immediate release layer within 15 min was greater than 85%.The internal pore size of the extended release layer is large,but it can still release slowly for up to 8 h,the mechanism may be related to the extended release of HPMC gelation.On the basis of verifying the rationality of the design goal of 3D printed composite bilayer tablets,this study also provides a theoretical basis for the preparation of 3D printing complex preparations.