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

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 180 μm, 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.

Attenuation of the Atmospheric Migration Ability of Polychlorinated Naphthalenes (PCN-2) Based on Three-dimensional QSAR Models with Full Factor Experimental Design.

Based on the experimental subcooled liquid vapor pressures (P L) of 17 polychlorinated naphthalene (PCN) congeners, one type of three-dimensional quantitative structure-activity relationship (3D-QSAR) models, comparative molecular similarity indices analysis (CoMSIA), was constructed with Sybyl software. Full factor experimental design was used to obtain the final regulation scheme for PCN, and then carry out modification of PCN-2 to significantly lower its P L. The contour maps of CoMSIA model showed that the migration ability of PCN decreases when the Cl atoms at the 2-, 3-, 4-, 5-, 6-, 7- and 8-positions of PCNs are replaced by electropositive groups. After modification of PCN-2, 12 types of new modified PCN-2 compounds were obtained with lnP L values two orders of magnitude lower than that of PCN-2. In addition, there are significant differences between the calculated total energies and energy gaps of the new modified compounds and those of PCN-2.

Modification of PBDEs (BDE-15, BDE-47, BDE-85 and BDE-126) biological toxicity, bio-concentration, persistence and atmospheric long-range transport potential based on the pharmacophore modeling assistant with the full factor experimental design.

In this study, the properties of AhR binding affinity, bio-concentration factor, half-life and vapor pressure were selected as the typical indicators of biological toxicity, bio-concentration, persistence and atmospheric long-range transport potential for polybrominated diphenyl ethers (PBDEs), respectively. A three-dimensional pharmacophore modeling assistant with a full factor experimental design for each property was used to reveal the significant pharmacophore features and the substituent effects to obtain reasonable modified schemes for the selected target PBDEs. Finally, the performances of the persistent organic pollutant (POP) properties, the synthesis feasibility and the fire resistance of the modified compounds were evaluated. The most influential pharmacophore feature for all POP properties was the hydrophobic group, especially the vinyl and propyl groups. Modified compounds with two additional hydrophobic groups exhibited a better regulatory performance. The average reduction in the proportions of the four POP properties for the modified compounds (except for 3-phenyl-BDE-15) was 70.60%, 52.44%, 47.04% and 70.88%. In addition, the energy and the C-Br bond dissociation enthalpy of the four typical PBDEs were higher than those of the modified compounds (except for 3-phenyl-BDE-15), indicating the synthesis feasibility and the lower energy barrier of the modified compounds to release Br free radicals to provide fire resistance.