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www.chemicalsknowledgehub.com www.chemicalsknowledgehub.com


Water Treatment


4. Once the salometer readings are stable at less than 2% for three consecutive measurements, record the final reading. 5. Note the time the system changes from brine rinse to fast rinse and record. 6. As soon as the last salometer reading is recorded, measure the level of water in the brine tank with a measuring tape and record.


Using either graph paper or a spreadsheet program like Microsoft


Excel, create a graph of concentration (percent NaCl) on the Y axis and time (in minutes) on the X axis. In a properly functioning regeneration cycle, the data recorded and graphed should indicate at least a 30% saturated brine solution for a minimum of 30 minutes. Higher concentration is acceptable but is wasteful if much higher than 30%or longer than 30 minutes.


Data interpretation and elution curve analysis Dr John Studley, Scientific Director, Scientific Update


dichloromethyllithium at higher temperatures under flow conditions was demonstrated,9 Christian Schuster’s team at Patheon (Thermo Fisher Scientific), in collaboration with a wider group of industry experts,successfully utilized this technology, converting a lab-based model reaction into a continuous manufacturing process run on several-hundred-kilogram scale under full cGMP conditions in yields of 97% .10 The corresponding batch process proved unscalable under laboratory conditions. Ultimately several tonnes of Matteson product were prepared in a process validation flow campaign enabling FDA fast-track approval and facilitating rapid development of Vaborbactam. Key to the success of this work was a detailed investigation into the zinc chloride addition and developing conditions to prevent precipitated solids clogging the system – a mainstay of flow chemistry processes. In early development work, the process flowstream was quenched into a batch vessel containing the pre-cooled zinc Lewis acid.


issues with patients because regular administrations of the drug are not required.


Mechanical data and calculations


Ion exchange specification data can be used for calculating performance in general terms, below are some useful formulas and mechanical information that can help compare field results with actual operation of the ion exchange equipment. For determining resin volume in cubic feet, take an actual measurement of the resin depth in the vessel and use the following formula:


Volume (cu. ft.)= π r2 h π = 3.14


r = radius of the vessel h = height of the resin in the tank


In lieu of physical measuring of the resin height and calculation, consult the softener manual for resin volume. The freeboard area should allow for a 50% expansion of the resin during backflush. The softener is not completely filled with resin.


Nanoencapsulation in cosmetic applications While much of the focus of nanoencapsulation and nanocarriers has been around pharmaceuticals and drug delivery systems, there are some areas within the cosmetics industry where they are also used. Some of the more common examples include delivering moisture in oil-based ointments and creams to increase the hydrating properties of the product. There are a number of commercial products that use nanocarriers to add such hydration properties to formulations and hydrate the skin when applied.


This quickly became a bottleneck for Abstract representation of drugs encapsulated in nanocarriers. (Image © iStock.com / writerfantast)


Plotting the data collected from the elution study and the interpretation of the results can identify irregularities and potential causes of poor softener performance. Simple review of cycle sequence timing, salometer comparisons to manufacturer data, brine tank drawdown volume and review of sodium chloride use can provide further details on the softener operation. Brine draw evaluation is the first step in diagnosing a hard water excursion in a water softener. Small variations in cycle timing, flow rates or salt concentrations can have a significant impact on the softener output quality and can ultimately affect the operation costs of equipment requiring the soft water.


Another common nanoencapsulation approach is to encapsulate fragrances, where the nanocarrier vessel breaks upon application, releasing the fragrance and making it last longer. There are also many unstable cosmetic compounds, such as hydroquinone— a compound that is used to lighten skin — that oxidize rapidly in oxygen and moisture. By encapsulating such molecules, they can be applied on the skin and not undergo any unfavourable chemical reactions before they perform their intended function. There is also a growing trend to use nanocarriers to deliver cosmeceuticals — a cross-over area of pharmaceuticals and cosmetics that applies both therapeutic and cosmetic benefits


increasing throughput, however. Two engineering solutions to this problem were explored, a continuous loop quench (mimicking the batch process) and a continuous stirred tank (CSTR)- based cascade quench. In the loop quench, boronate adduct was fed into a circulating pre-cooled solution of zinc chloride with reaction temperature controlled by heat exchangers. The product solution was pumped out and consumed zinc salt was continuously replenished in the loop reactor to keep the molar ratio constant. In the CSTR approach, zinc chloride solution was constantly fed to the pre-cooled vessel, the product solution exiting the CSTR in a cascade system controlled by an overflow device. The loop reactor system was ultimately selected to move forward and enabled the reaction to be run at a higher temperature and with better diastereometric control.


Flow rates Service flow


Backwash flow Pressure drop


water temperature) Brine draw flow Fast rinse


By leveraging the advantages a continuous process can impart, including increased process control, energy efficiency and reduced processing times, Schuster’s team succeeded in taking a difficult, unscalable organometallic


Life Sciences Focus: Drug Delivery Flow Chemistry


www.chemicalsknowledgehub.com


reaction to full-scale production. Another victory in the ongoing battle against the bacteria!


References: 1) Evolution of antimicrobial resistance among Enterobacteriaceae (focus on extended spectrum -lactamases and carbapenamases, J. Lynch et al, Expert Opin. Pharmacother. 2013, 14, 199-210; Three decades of -lactamase inhibitors, S. Drawz et al, Clin. Microbiol. Rev.2010, 23, 160-201.


2) Meropenem/Vaborbactam: a review in complicated urinary tract infections, S. Dhillon, Drugs 2018, 78, 1259-1270. The first -lactamase inhibitor approved for clinical use was Clavulanic acid in the 1970s.


3) Discovery of a cyclic boronic acid -lactamase inhibitor (RPX7009) with utility vs class A carbapenemases, S. Hecker et al, J. Med. Chem. 2015, 58, 3682-3692; T. Eisenman, FDA approves new antibacterial drug, August 29th2017.


4) Synthesis of biologically active boron-containing compounds, H. Zhou et al, Med. Chem. Commun. 2018, 9, 201-211; The versatility of boron in biological target engagement, A. Yudin et al, Nature Chem. 2017, 9, 731-742. The first boron-containing drug, Bortezomib (Velacade), was approved in 2003.


Distributors for larger softeners will have a spider web design under the resin and covered with bed support material. Small water softeners may have a different distributor design.


Typical specifications for cation resin Resin capacity


have the lower capacity) Salt use (NaCl) 6-10 lbs per cubic foot of resin (8-9 lbs. is common)


Further information: www.kuritaamerica.com


About the Author Paul Sharpe is an industry consultant at Kurita America, specializing in boiler and cooling water and has over 30 years of water treatment experience including chemical treatment formulations, sales, marketing, and technical product applications.


to the surface they are applied on. A range of nanocarriers are in use in this interdisciplinary field, including liposomes and other lipid-based carriers, niosomes and nanoemulsions, to name a few. These nanoencapsulation methods play a wide role in the cosmeceutical area, including hair care products for treating grey hair and hair loss (as well as other hair serums), anti-wrinkle creams,and in sunscreens. Identik, Origem, Nirvel, Chanel, Dior, Estée Lauder, Decorte and Sesderma are just a few of the big-name brands that currently utilize nanoencapsulation technologies to enhance their products.


In summary Overall, a number of companies


Author details: Dr John Studley, Scientific Director Scientific Update Limited Maycroft Place, Stone Cross Mayfield TN20 6EW UK E: johns@scientificupdate.com


NEW! Connecting industry across the globe


Enquire now! info@ckhglobal.org


Summer 2020 April/May 2020


58 March/April 2021 • Issue 2 37 21 2-4 gpm/cubic foot of resin Author:


5) Homologation of boronic esters to -chloro boronic esters, D. Matteson et al, Organometallics, 1983, 2, 1529-1535; -halo boronic esters: intermediates for stereodirected synthesis, D. Matteson Chem. Rev. 1989, 89, 1535-1551.


6) Stability and reactivity control of carbenoids: recent advances and perspectives, V. Gessner, Chem. Commun. 2016, 52, 12011-12023.


22-28 kilograins/cubic foot of resin (older resin will


7) Lithiation-borylation methodology and its application in synthesis, V. Aggarwal et al, Acc. Chem. Res. 2014, 47, 3174-3183.


8) Flow technology for the genesis and use of (highly) reactive organometallic reagents, R. Luisi et al, Chem. Eur. J. 2020, 26, 19-32; A perspective on continuous flow chemistry in the pharmaceutical industry, M. Baumann, M. Smith et al, Org. Process Res. Dev. 2020, ASAP 10.1021/ acs.oprd.9b00524.


9) Dichloromethyllithium: synthesis and application in continuous flow mode, J. Sedelmeier et al, Org. Lett. 2017, 19, 786-789.


10) Development of a continuous flow process for a Matteson reaction: from lab to full-scale production of a pharmaceutical intermediate, C. Schuster et al, Org. Process Res. Dev.2019, 23, 1069-1077.


1.5 – 2.5 gpm/cubic foot of resin 1 psi per linear foot of resin


in: https://www.linkedin. com/in/liam-critchley- nanowriter/ t: https://twitter.com/LC_ nanowriter


6 gpm/square foot of resin (dependent on 0.5-1.0 gpm/cubic foot of resin


Liam Critchley Freelance Chemistry and Nanotechnology Writer E: liam_critchley@hotmail. com


across the pharmaceutical and cosmetic sectors are now starting to utilize and reap the benefits of nanoencapsulation methods, and nanotechnology in general. It is likely that this trend will continue, and there will be more products in both sectors utilizing nanoencapsulation methods and other nanotechnology-based systemsin the years to come.


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