RÉSUMÉ
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.
RÉSUMÉ
Aluminum salts are the most popular adjuvants applied in human vaccines currently. However,they can′t achieve satisfying results in the development of novel vaccines because of the cellular immune responses induced by them are weak and their adjuvant activities for some novel vaccines are poor, especially in vaccination against peptide antigens with small molecular weight. cGAMP (cyclic guanosine monophosphate-adenosine monophosphate) has recently been known as a mammalian second messenger, which plays an important role in the innate immune signaling pathway and is capable of boosting the immuno-genicity of vaccines,activating antigen-presenting cells and enhancing specific T cell responses. cGAMP is expected to become a new generation of vaccine adjuvants against infectious diseases and cancer. In this re-view,we summarize the application and current situation of vaccine adjuvants, describe the discovery of cGAMP and its mechanism as a vaccine adjuvant,and focus on the advances in using cGAMP in the fields of vaccination against infectious diseases, intradermal immunization and tumor immunotherapy. Finally, it is also pointed out that cGAMP,as a novel vaccine adjuvant,will have a broad prospect of application in areas such as anti-tumor,anti-virus,anti-inflammatory and vaccines.