SLA型3D打印技术制备盐酸文拉法辛-盐酸氟西汀多层片  

Preparation of venlafaxine hydrochloride and fluoxetine hydrochloride multilayer tablets by stereolithography 3D printing technology

作　　者：徐雷 潘偲莹 陈红梅[1] 杨庆良 杨根生[2] XU Lei;PAN Siying;CHEN Hongmei;YANG Qingliang;YANG Gensheng(Dept.of Clinical Pharmacy,Hangzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University,Hangzhou 310007,China;College of Pharmaceutical Science,Zhejiang University of Technology,Hangzhou 310014,China)

机构地区：[1]浙江中医药大学附属杭州市中医院临床药学室,杭州310007 [2]浙江工业大学药学院,杭州310014

出　　处：《中国药房》2024年第13期1600-1604,共5页China Pharmacy

基　　金：浙江省自然科学基金项目(No.LY20B060007)。

摘　　要：目的 采用立体光刻成型(SLA)3D打印技术制备盐酸文拉法辛-盐酸氟西汀多层片,并进行质量评价和体外释放考察。方法 以盐酸文拉法辛/盐酸氟西汀、光聚合单体PEGDA 400、致孔剂PEG 300、光引发剂TPO和光吸收剂柠檬黄等组成处方,采用SLA型3D打印技术制备外径10 mm、内径5 mm、厚度6 mm的盐酸文拉法辛-盐酸氟西汀多层片,然后对其外观、三维尺寸、重量均匀度、药物含量、内部结构特征以及体外释放特性进行考察。结果 该多层片的打印成型性良好,边缘平滑圆整,大小、厚度均匀,外径、内径、厚度分别为(10.06±0.26)、(4.94±0.06)、(5.80±0.12) mm(RSD分别为2.58%、1.21%、2.07%,n=20);重量差异符合药典要求;两药含量分别为(7.96±0.09)、(11.26±0.46) mg/片。X射线衍射表征和扫描电镜表征结果显示,该多层片中两种药物分子以无定形结构存在,盐酸文拉法辛层溶出后产生明显的孔道结构,而盐酸氟西汀层未出现孔道结构。盐酸文拉法辛层和盐酸氟西汀层在24 h时的累积释放率分别为(91.88±0.94)%、(106.25±1.28)%,符合Rigter-Peppas释放模型。结论 本研究采用SLA型3D打印技术成功制备了盐酸文拉法辛-盐酸氟西汀多层片,该多层片成型性良好,且符合Rigter-Peppas释放模型。OBJECTIVE To prepare venlafaxine hydrochloride and fluoxetine hydrochloride multiplayer tablets by stereolithography(SLA)3D printing technology,and to conduct its quality evaluation and in vitro release investigation.METHODS Using venlafaxine hydrochloride/fluoxetine hydrochloride,photopolymerization monomer PEGDA 400,porogen PEG 300,photoinitiator TPO and light absorber citrine as formulation,SLA 3D printer technology was employed to prepare venlafaxine hydrochloride and fluoxetine hydrochloride multiplayer tablets,with outer diameter of 10 mm,inner diameter of 5 mm,and thickness of 6 mm.Moreover,the tablets’appearance,three-dimensional dimensions,weight uniformity,drug content,internal structural characteristics and in vitro release characteristics were all investigated.RESULTS The multilayer tablets had good printing formability,smooth and round edges,and uniform size and thickness;the outer diameter,inner diameter and thickness were(10.06±0.26),(4.94±0.06),(5.80±0.12)mm(RSD=2.58%,1.21%,2.07%,n=20),and the weight difference all met the requirements.The contents of venlafaxine hydrochloride and fluoxetine hydrochloride were(7.96±0.09)and(11.26±0.46)mg/tablet,respectively.The results of X-ray diffraction and scanning electron microscopy characterization showed that the two drug molecules in the multilayer film existed in an amorphous structure;after the dissolution of the venlafaxine hydrochloride layer,a clear pore structure was formed,while the fluoxetine hydrochloride layer did not show any pore structure.According to the release curve,24 h accumulative release rates of venlafaxine hydrochloride layer and fluoxetine hydrochloride layer were(91.88±0.94)%and(106.25±1.28)%,which were in line with Rigter-Peppas release model.CONCLUSIONS This study successfully prepared venlafaxine hydrochloride and fluoxetine hydrochloride multilayer tablets using SLA 3D printing technology;the multilayer tablets have the advantages of excellent printing formability,which are in line with Rigter-Peppas release model.

关 键 词：立体光刻成型 3D打印技术 多层片 盐酸文拉法辛 盐酸氟西汀 个性化制剂 

分 类 号：R943[医药卫生—药剂学]