3D printed tacrolimus suppositories for the treatment of ulcerative colitis

Ulcerative colitis is a global health problem,affecting millions of individuals worldwide.As an inflammatory condition localised in the large intestine,rectal delivery of immunosuppressive therapies such as tacrolimus is a promising strategy to maximise drug concentration at the site of action whilst minimising systemic side effects.Here,for the first time,self-supporting 3D-printed tacrolimus suppositories were prepared without the aid of moulds using a pharmaceutical semi-solid extrusion(SSE)3D printer.The suppositories were printed vertically in three different sizes using combinations of two lipid pharmaceutical excipients(Gelucire 44/14 or Gelucire 48/16)and coconut oil.Although both suppository formulations had the appropriate viscosity characteristics for printing,the Gel 44 formulation required less energy and force for extrusion compared to the Gel 48 system.The Gel 44 disintegrated more rapidly but released tacrolimus more slowly than the Gel 48 suppositories.Although the tacrolimus release profiles were significantly different,both suppository systems released more than 80% drug within 120 min.DSC and XRD analysis was inconclusive in determining the solid-state properties of the drug in the suppositories.In summary,this article reports on the fabrication of 3D printed selfsupporting suppositories to deliver personalised doses of a narrow therapeutic index drug,with potential benefits for patients with ulcerative colitis.

Control strategy and methods for continuous direct compression processes

We presented a control strategy for tablet manufacturing processes based on continuous direct compression.The work was conducted by the experts of pharmaceutical companies,machine suppliers,academia,and regulatory authority in Japan.Among different items in the process,the component ratio and blended powder content were selected as the items requiring the control method specific to continuous manufacturing different from the conventional batch manufacturing.The control and management of the Loss in Weight(LIW)feeder were deemed the most important,and the Residence Time Distribution(RTD)model were regarded effective for setting the control range and for controlling of the LIW feeder.Based on these ideas,the concept of process control using RTD was summarized.

Study on the interaction of anticancer drug mitoxantrone with DNA by fluorescence and Raman spectroscopies

Mitoxantrone, a clinically useful antitumour antibiotic for leukaemia and breast cancer, has received more attentions. In this paper, the interaction between mitoxantrone and calf thymus DNA is investigated by Raman and fluorescence spectroscopies, and the binding site of mitoxantrone to calf thymus DNA is explored. The results showed that mitoxantrone interacts with calf thymus DNA bases by the intercalation of anthracycline into the base pair plane of adenine （A） and thymine （T）, and it results in the disruption of the hydrogen bonds between calf thymus DNA bases, and thus the calf thymus DNA double-strand can be disrupted into the B-form DNA double-strand scgments.

Dual ligands relay-promoted transformation of unstrained ketones to polyfluoroarenes and nitriles

C-C bond activation has emerged as a powerful tool for the construction of complex molecules.Herein,we report a dual ligands relay-promoted transformation of unstrained aryl,alkenyl and alkynyl ketones to the corresponding polyfluoroarenes and nitriles via C-C(=O)bond cleavage and subsequent decarboxylative arylation process.Various polyfluoroarene and nitrile products are obtained in one pot under cyanide-free conditions.The protocol features high atom economy,broad functional group tolerance and excellent heterocyclic compatibility.The late-stage functionalization of the drug and natural product demonstrated the synthetic utility of our protocol.Furthermore,the decisive role of the dual ligands was clarified and the mechanistic rationale including theβ-C elimination as the rate-limiting step was supported by detailed density functional theory(DFT)studies.

Spectral feature matching based on partial least squares

We investigate the spectral approaches to the problem of point pattern matching, and present a spectral feature descriptors based on partial least square （PLS）. Given keypoints of two images, we define the position similarity matrices respectively, and extract the spectral features from the matrices by PLS, which indicate geometric distribution and inner relationships of the keypoints. Then the keypoints matching is done by bipartite graph matching. The experiments on both synthetic and real-world data corroborate the robustness and invariance of the algorithm.