个性化剂量熔融沉积成型3D打印茶碱片剂的制备和体外评价

Preparation and in vitro evaluation of FDM 3D printed theophylline tablets with personalized dosage

目的:探究以熔融沉积成型(fused deposition modeling,FDM)3D打印技术制备用于个性化治疗的不同剂量片剂的可行性,并对所制备的FDM 3D打印片剂进行相关的体外质量评价。方法:采用聚乙烯醇(polyvinyl alcohol,PVA)丝材,通过FDM 3D打印技术制备中空的、三种大小的片剂外壳;以茶碱为模型药物,将20、50和100 mg三种剂量的茶碱分别填充于片剂的空腔内。以扫描电镜(scanning electron microscopy,SEM)观察制剂的外观形态,以称重法考察片剂的质量差异,以片剂硬度测定仪测定片剂的硬度,采用紫外-可见分光光度法(ultraviolet and visible spectrophotometry,UV-Vis)测定片剂中的药物含量,并用溶出仪对片剂的体外释药行为进行表征。结果:制备出的FDM 3D打印片剂形态良好,无打印缺陷,片剂的直径与厚度均与设计相符,扫描电镜观察可以看出层与层之间紧密连接,能清晰观察到制剂的细微结构;三种大小的片剂平均质量分别为(150.5±2.3)mg、(293.6±2.6)mg和(456.2±5.6)mg,其质量差异均低于5%;片剂的硬度均超过了200 N;测得三种片剂中茶碱含量分别为加入量(20、50和100 mg)的98.2%、97.2%和97.9%,相对标准偏差分别为1.06%、1.15%和0.63%;三种剂量片剂释药80%的时间均在30 min以内。结论:采用FDM 3D打印技术成功制备了20、50和100 mg三种不同剂量的茶碱片剂,且打印的茶碱片剂质量良好。

Objective:To explore the feasibility of preparing different doses of tablets for personalized treatment by fused deposition modeling(FDM)3D printing technology,and to evaluate the in vitro quality of the FDM 3D printed tablets.Methods:Three different sizes of hollow tablets were prepared by fused deposition modeling 3D printing technology with polyvinyl alcohol(PVA)filaments.Theophylline was chosen as the model drug.In the study,20 mg,50 mg and 100 mg of theophylline was filled into the cavity of the tablets,respectively.The microscopic morphology of the tablets was observed by scanning electron microscopy(SEM).The weight variation of the tablets was investigated by weighing method.The hardness of the tablets was measured by tablet hardness tester.The contents of the drugs in the tablets were determined by ultraviolet and visible spectrophotometry(UV-Vis),and the dissolution apparatus was used to assay the in vitro drug release of the tablets.Results:The prepared FDM 3D printed tablets were all in good shape without printing defects.And there was no leakage phenomenon.The diameter and thickness of the tablets were consistent with the design.The layers were tightly connected,and the fine structure of the formulation could be clearly observed without printing defects by scanning electron microscopy.The average weight of the three sizes of tablets was(150.5±2.3)mg,(293.6±2.6)mg and(456.2±5.6)mg,respectively.The weight variation of the three sizes of tablets were boss less than 5%,which met the requirements;The hardness of the tablets all exceeded 200 N;The contents of theophylline in the three tablets were 98.0%,97.2%and 97.9%of the dosage(20 mg,50 mg and 100 mg),and the relative standard deviation(RSD)was 1.06%,1.15%and 0.63%respectively;The time for 80%drug released from the three dosage of tablets was within 30 min.Conclusion:Three different dosages of theophylline tablets were successfully prepared by FDM 3D printing technology in this study.The exploration may bring beneficial for the preparation of personalized dose preparations.We expect that with the development of 3D printing technology,FDM 3D printed personalized tablets can be used in the clinic as soon as possible to provide personalized treatment for patients.