Physico-mechanical characterization and interactions with excipients of D-003, a mixture of fatty acids isolated from sugar cane wax

El D-003 es un nuevo producto que consiste en una mezcla de ácidos grasos de elevado peso molecular (desde C24:0 hasta C36:0), donde cada uno de ellos está en una proporción reproducible. Este producto presenta efectos antiplaquetarios y como reductor del colesterol. Como parte de los estudios de formulación del D-003 fueron llevadas a cabo la caracterización físico-mecánica y su interacción con excipientes para tabletas. El presente estudio utilizó la calorimetría diferencial de barrido (CDB) y la termogravimetría (TG) con el objetivo de evaluar la estabilidad térmica y las transiciones características del D-003 en presencia de diversos excipientes. Fueron medidas otras propiedades, tales como el ángulo de contacto, solubilidad, humectabilidad, distribución del tamaño de partículas, propiedades de fluido, densidades por asentamiento, por vertido y de alta presión, así como la reducción de volumen bajo compresión. Estos estudios, según nuestro conocimiento, no han sido previamente reportados para estos ácidos. Los estudios por CDB demostraron que no hubo interacción química o física entre el D-003 y los excipientes investigados. También, los análisis termogravimétricos probaron la elevada estabilidad térmica del D-003, el cual es estable y funde sin descomposición hasta temperaturas tan elevadas como 220 °C. Los lotes industriales estudiados mostraron adecuada pureza y distribución uniforme del tamaño de partícula, buenas propiedades de fluido, compresibilidad y cohesión, lo cual sustenta que sea un polvo apropiado para la elaboración de tabletas revestidas como forma terminada. Sin embargo, la muy baja solubilidad del D-003 en la mayoría de los disolventes, especialmente en agua, es el aspecto más crítico para el desarrollo la forma terminada, lo cual es importante para decidir la formulación del revestimiento.D-003 is a new product consisting of a mixture of fatty acids of very high molecular weight (from C24:0 to C36:0) in a reproducible proportion each, with cholesterol-lowering, and antiplatelet effects. As part of the formulation studies of D-003 a physico-mechanical characterization and its interaction with tablet excipients were carried out. The present study used differential scanning calorimetry (DSC) and thermogravimetry (TG) in order to evaluate the characteristic transitions and thermal stability of D- 003 in presence of several excipients. Other properties, such as the angle of contact, solubility, wettability, particle size distribution, flow properties, tapped, bulk and at high pressure densities, as well as volume reduction under compression were measured. These studies, to our knowledge, have not been previously reported to these fatty acids. DSC studies demonstrated that there was no chemical or physical interaction between D-003 and the investigated excipients. Also, thermogravimetric analysis proved the high thermal stability of D-003, which melts without decomposition and is stable at temperatures as high as 220 °C. Industrial batches of D-003 showed adequate purity and uniform particle size distribution, good flow properties, compressibility and compactability, which support a suitable powder for manufacturing film-coated tablets as finished forms. Nevertheless, the very low solubility of D-003 in most solvents, especially in water, is the most critical aspect for developing the finished form, being relevant to decide the coating formulation.Colegio de Farmacéuticos de la Provincia de Buenos Aire

A global metagenomic map of urban microbiomes and antimicrobial resistance

We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities.Funding: the Tri-I Program in Computational Biology and Medicine (CBM) funded by NIH grant 1T32GM083937; GitHub; Philip Blood and the Extreme Science and Engineering Discovery Environment (XSEDE), supported by NSF grant number ACI-1548562 and NSF award number ACI-1445606; NASA (NNX14AH50G, NNX17AB26G), the NIH (R01AI151059, R25EB020393, R21AI129851, R35GM138152, U01DA053941); STARR Foundation (I13- 0052); LLS (MCL7001-18, LLS 9238-16, LLS-MCL7001-18); the NSF (1840275); the Bill and Melinda Gates Foundation (OPP1151054); the Alfred P. Sloan Foundation (G-2015-13964); Swiss National Science Foundation grant number 407540_167331; NIH award number UL1TR000457; the US Department of Energy Joint Genome Institute under contract number DE-AC02-05CH11231; the National Energy Research Scientific Computing Center, supported by the Office of Science of the US Department of Energy; Stockholm Health Authority grant SLL 20160933; the Institut Pasteur Korea; an NRF Korea grant (NRF-2014K1A4A7A01074645, 2017M3A9G6068246); the CONICYT Fondecyt Iniciación grants 11140666 and 11160905; Keio University Funds for Individual Research; funds from the Yamagata prefectural government and the city of Tsuruoka; JSPS KAKENHI grant number 20K10436; the bilateral AT-UA collaboration fund (WTZ:UA 02/2019; Ministry of Education and Science of Ukraine, UA:M/84-2019, M/126-2020); Kyiv Academic Univeristy; Ministry of Education and Science of Ukraine project numbers 0118U100290 and 0120U101734; Centro de Excelencia Severo Ochoa 2013–2017; the CERCA Programme / Generalitat de Catalunya; the CRG-Novartis-Africa mobility program 2016; research funds from National Cheng Kung University and the Ministry of Science and Technology; Taiwan (MOST grant number 106-2321-B-006-016); we thank all the volunteers who made sampling NYC possible, Minciencias (project no. 639677758300), CNPq (EDN - 309973/2015-5), the Open Research Fund of Key Laboratory of Advanced Theory and Application in Statistics and Data Science – MOE, ECNU, the Research Grants Council of Hong Kong through project 11215017, National Key RD Project of China (2018YFE0201603), and Shanghai Municipal Science and Technology Major Project (2017SHZDZX01) (L.S.