AUTHOR OF THIS BLOG

DR ANTHONY MELVIN CRASTO, WORLDDRUGTRACKER

Spray drying

 drugs, GENERIC, SYNTHESIS  Comments Off on Spray drying
Jun 042015
 

Laboratory-scale spray dryer.
A=Solution or suspension to be dried in, B=Atomization gas in, 1= Drying gas in, 2=Heating of drying gas, 3=Spraying of solution or suspension, 4=Drying chamber, 5=Part between drying chamber and cyclone, 6=Cyclone, 7=Drying gas is taken away, 8=Collection vessel of product, arrows mean that this is co-current lab-spraydryer

Spray drying is a method of producing a dry powder from a liquid or slurry by rapidly drying with a hot gas. This is the preferred method of drying of many thermally-sensitive materials such as foods and pharmaceuticals. A consistent particle size distribution is a reason for spray drying some industrial products such as catalysts. Air is the heated drying medium; however, if the liquid is a flammable solvent such as ethanol or the product is oxygen-sensitive then nitrogen is used.[1]

All spray dryers use some type of atomizer or spray nozzle to disperse the liquid or slurry into a controlled drop size spray. The most common of these are rotary disks and single-fluid high pressure swirl nozzles. Atomizer wheels are known to provide broader particle size distribution, but both methods allow for consistent distribution of particle size.[2] Alternatively, for some applications two-fluid or ultrasonic nozzles are used. Depending on the process needs, drop sizes from 10 to 500 µm can be achieved with the appropriate choices. The most common applications are in the 100 to 200 µm diameter range. The dry powder is often free-flowing.[3]

The most common spray dryers are called single effect as there is only one drying air on the top of the drying chamber (see n°4 on the scheme). In most cases the air is blown in co-current of the sprayed liquid. The powders obtained with such type of dryers are fine with a lot of dusts and a poor flowability. In order to reduce the dusts and increase the flowability of the powders, there is since over 20 years a new generation of spray dryers called multiple effect spray dryers. Instead of drying the liquid in one stage, the drying is done through two steps: one at the top (as per single effect) and one for an integrated static bed at the bottom of the chamber. The integration of this fluidized bed allows, by fluidizing the powder inside a humid atmosphere, to agglomerate the fine particles and to obtain granules having commonly a medium particle size within a range of 100 to 300 µm. Because of this large particle size, these powders are free-flowing.

The fine powders generated by the first stage drying can be recycled in continuous flow either at the top of the chamber (around the sprayed liquid) or at the bottom inside the integrated fluidized bed. The drying of the powder can be finalized on an external vibrating fluidized bed.

The hot drying gas can be passed as a co-current or counter-current flow to the atomiser direction. The co-current flow enables the particles to have a lower residence time within the system and the particle separator (typically a cyclone device) operates more efficiently. The counter-current flow method enables a greater residence time of the particles in the chamber and usually is paired with a fluidized bed system.

Alternatives to spray dryers are:[4]

  1. Freeze dryer: a more-expensive batch process for products that degrade in spray drying. Dry product is not free-flowing.
  2. Drum dryer: a less-expensive continuous process for low-value products; creates flakes instead of free-flowing powder.
  3. Pulse combustion dryer: A less-expensive continuous process that can handle higher viscosities and solids loading than a spray dryer, and that sometimes gives a freeze-dry quality powder that is free-flowing.

Spray dryer

Spray drying nozzles.

Schematic illustration of spray drying process.

A spray dryer takes a liquid stream and separates the solute or suspension as a solid and the solvent into a vapor. The solid is usually collected in a drum or cyclone. The liquid input stream is sprayed through a nozzle into a hot vapor stream and vaporised. Solids form as moisture quickly leaves the droplets. A nozzle is usually used to make the droplets as small as possible, maximising heat transfer and the rate of water vaporisation. Droplet sizes can range from 20 to 180 μm depending on the nozzle.[3] There are two main types of nozzles: high pressure single fluid nozzle (50 to 300 bars) and two-fluid nozzles: one fluid is the liquid to dry and the second is compressed gas (generally air at 1 to 7 bars).

Spray dryers can dry a product very quickly compared to other methods of drying. They also turn a solution, or slurry into a dried powder in a single step, which can be advantageous for profit maximization and process simplification.

 

The Spray Drying Process

The spray drying process is older than might commonly be imagined.  Earliest descriptions date from 1860 with the first patented design recorded in 1872. The basic idea of spray drying is the production of highly dispersed powders from a fluid feed by evaporating the solvent. This is achieved by mixing a heated gas with an atomized (sprayed) fluid of high surface-to-mass ratio droplets, ideally of equal size, within a vessel (drying chamber), causing the solvent to evaporate uniformly and quickly through direct contact.
Spray drying can be used in a wide range of applications where the production of a free-flowing powder is required. This method of dehydration has become the most successful one in the following areas:

  • Pharmaceuticals
  • Bone and tooth amalgams
  • Beverages
  • Flavours, colourings and plant extracts
  • Milk and egg products
  • Plastics, polymers and resins
  • Soaps and detergents
  • Textiles and many more

Almost all other methods of drying, including use of ovens, freeze dryers or rotary evaporators, produce a mass of material requiring further processing (e.g. grinding and filtering) therefore, producing particles of irregular size and shape. Spray drying on the other hand, offers a very flexible control over powder particle properties such as density, size, flow characteristics and moisture content.

 

Spray drying dia

Design and Control

The challenges facing both designers and users are to increase production, improve powder quality and reduce costs. This requires an understanding of the process and a robust control implementation.

 

Spray drying consists of the following phases:

 

  • Feed preparation: This can be a homogenous, pumpable and free from impurities solution, suspension or paste.
  • Atomization (transforming the feed into droplets): Most critical step in the process. The degree of atomization controls the drying rate and therefore the dryer size. The most commonly used atomization techniques are:

1. Pressure nozzle atomization: Spray created by forcing the fluid through an orifice. This is an energy efficient method which also offers the narrowest particle size distribution.
2. Two-fluid nozzle atomization: Spray created by mixing the feed with a compressed gas. Least energy efficient method. Useful for making extremely fine particles.
3. Centrifugal atomization: Spray created by passing the feed through or across a rotating disk. Most resistant to wear and can generally be run for longer periods of time.

  • Drying: A constant rate phase ensures moisture evaporates rapidly from the surface of the particle. This is followed by a falling rate period where the drying is controlled by diffusion of water to the surface of the particle.
  • Separation of powder from moist gas: To be carried out in an economical (e.g. recycling the drying medium) and pollutant-free manner. Fine particles are generally removed with cyclones, bag filters, precipitators or scrubbers.
  • Cooling and packaging.

 

A control system must therefore provide flexibility in the way in which accurate and repeatable control of the spray drying is achieved and will include the following features:

 

  • Precise loop control with setpoint profile programming
  • Recipe Management System for easy parameterisation
  • Sequential control for complex control strategies
  • Secure collection of on-line data from the system for analysis and evidence
  • Local operator display with clear graphics and controlled access to parameters

Micro-encapsulation

Spray drying often is used as an encapsulation technique by the food and other industries. A substance to be encapsulated (the load) and an amphipathic carrier (usually some sort of modified starch) are homogenized as a suspension in water (the slurry). The slurry is then fed into a spray drier, usually a tower heated to temperatures well over the boiling point of water.

As the slurry enters the tower, it is atomized. Partly because of the high surface tension of water and partly because of thehydrophobic/hydrophilic interactions between the amphipathic carrier, the water, and the load, the atomized slurry forms micelles. The small size of the drops (averaging 100 micrometers in diameter) results in a relatively large surface area which dries quickly. As the water dries, the carrier forms a hardened shell around the load.[5]

Load loss is usually a function of molecular weight. That is, lighter molecules tend to boil off in larger quantities at the processing temperatures. Loss is minimized industrially by spraying into taller towers. A larger volume of air has a lower average humidity as the process proceeds. By the osmosis principle, water will be encouraged by its difference in fugacities in the vapor and liquid phases to leave the micelles and enter the air. Therefore, the same percentage of water can be dried out of the particles at lower temperatures if larger towers are used. Alternatively, the slurry can be sprayed into a partial vacuum. Since the boiling point of a solvent is the temperature at which the vapor pressure of the solvent is equal to the ambient pressure, reducing pressure in the tower has the effect of lowering the boiling point of the solvent.

The application of the spray drying encapsulation technique is to prepare “dehydrated” powders of substances which do not have any water to dehydrate. For example, instant drink mixes are spray dries of the various chemicals which make up the beverage. The technique was once used to remove water from food products; for instance, in the preparation of dehydrated milk. Because the milk was not being encapsulated and because spray drying causes thermal degradation, milk dehydration and similar processes have been replaced by other dehydration techniques. Skim milk powders are still widely produced using spray drying technology around the world, typically at high solids concentration for maximum drying efficiency. Thermal degradation of products can be overcome by using lower operating temperatures and larger chamber sizes for increased residence times.[6]

Recent research is now suggesting that the use of spray-drying techniques may be an alternative method for crystallization of amorphous powders during the drying process since the temperature effects on the amorphous powders may be significant depending on drying residence times.[7][8]

Spray drying applications

Food: milk powder, coffee, tea, eggs, cereal, spices, flavorings, starch and starch derivatives, vitamins, enzymes, stevia, colourings, etc.

Pharmaceutical: antibiotics, medical ingredients, additives

Industrial: paint pigments, ceramic materials, catalyst supports, microalgae

Nano spray dryer

The nano spray dryer offers new possibilities in the field of spray drying. It allows to produce particles in the range of 300 nm to 5 μm with a narrow size distribution. High yields are produced up to 90% and the minimal sample amount is 1 mL.

 

Pharmaceutical Spray drying is a very fast method of drying due to the very large surface area created by the atomization of the liquid feed. As a consequence, high heat transfer coefficients are generated and the fast stabilisation of the feed at moderate temperatures makes this method very attractive for heat sensitive materials.

Spray drying provides unprecedented particle control and allows previously unattainable delivery methods and molecular characteristics. These advantages allow exploration into employing previously unattainable delivery methods and molecular characteristics.

Five things you might not know about spray drying

  1. Spray drying is suitable for heat sensitive materials
    Spray drying is already used for the processing of heat sensitive materials (e.g. proteins, peptides and polymers with low Tg temperatures) on an industrial scale. Evaporation from the spray droplets starts immediately after contact with the hot process gas. Since the thermal energy is consumed by evaporation, the droplet temperature is kept at a level where no harm is caused to the product.
  2. Spray drying turns liquid into particles within seconds
    The large surface of the droplets provides near instantaneous evaporation, making it possible to produce particles with a crystalline or amorphous structure. The particle morphology is determined by the operating parameters and excipients added to the feed stock.
  3. Spray drying is relatively easy to replicate on a commercial scale
    GEA Niro has been producing industrial scale spray drying plants for well over half a century. Our process know-how, products and exceptional facilities put us in a unique position to advise and demonstrate how products and processes will behave on a large scale.
  4. Spray drying is a robust process
    Spray drying is a continuous process. Once the set points are established, all critical process parameters are kept constant throughout the batch. Information for the batch record can be monitored or logged, depending on the system selected.
  5. Spray drying can be effectively validated
    The precise control of all critical process parameters in spray drying provides a high degree of assurance that the process consistently produces a product that meets set specifi cations.

The spray drying process

Spray drying is a very fast method of drying due to the very large surface area created by the atomization of the liquid feed and high heat transfer coefficients generated. The short drying time, and consequently fast stabilisation of feed material at moderate temperatures, means spray drying is also suitable for heat-sensitive materials.

As a technique, spray drying consists of four basic stages:

  1. Atomization: A liquid feed stock is atomized into droplets by means of a nozzle or rotary atomizer. Nozzles use pressure or compressed gas to atomize the feed while rotary atomizers employ an atomizer wheel rotating at high speed.
  2. Drying: Hot process gas (air or nitrogen) is brought into contact with the atomized feed guided by a gas disperser, and evaporation begins. The balance between temperature, flow rate and droplet size controls the drying process.
  3. Particle formation: As the liquid rapidly evaporates from the droplet surface, a solid particle forms and falls to the bottom of the drying chamber.
  4. Recovery: The powder is recovered from the exhaust gas using a cyclone or a bag filter. The whole process generally takes no more than a few seconds.

 

References

  1.  A. S. Mujumdar (2007). Handbook of industrial drying. CRC Press. p. 710. ISBN 1-57444-668-1.
  2.  http://www.elantechnology.com/spray-drying/
  3.  Walter R. Niessen (2002). Combustion and incineration processes. CRC Press. p. 588. ISBN 0-8247-0629-3.
  4.  Onwulata p.66
  5.  Ajay Kumar (2009). Bioseparation Engineering. I. K. International. p. 179. ISBN 93-8002-608-0.
  6. Onwulata pp.389–430
  7.  Onwulata p.268
  8.  Chiou, D.; Langrish, T. A. G. (2007). “Crystallization of Amorphous Components in Spray-Dried Powders”. Drying Technology 25: 1427. doi:10.1080/07373930701536718.

Bibliography

Further reading

External links

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Enzymatic resolution of antidepressant drug precursors in an undergraduate laboratory

 drugs, spectroscopy, SYNTHESIS  Comments Off on Enzymatic resolution of antidepressant drug precursors in an undergraduate laboratory
Apr 012015
 

Enzymatic resolution of antidepressant drug precursors in an undergraduate laboratory

EducaçãoQuim. Nova 2015, 38(2), 285-287

Enzymatic resolution of antidepressant drug precursors in an undergraduate laboratory

Luís M. R. SolanoI; Nuno M. T. LourençoII,*
This paper describes a multi-step chemo-enzymatic synthesis of antidepressant drug precursors.

http://dx.doi.org/10.5935/0100-4042.20140306

Publicado online: novembro 13, 2014
Quim. Nova, Vol. 38, No. 2, 285-287, 2015
Educação http://dx.doi.org/10.5935/0100-4042.20140306
*e-mail: nmtl@tecnico.ulisboa.pt
ENZYMATIC RESOLUTION OF ANTIDEPRESSANT DRUG PRECURSORS IN AN UNDERGRADUATE LABORATORY
Luís M. R. Solanoa and Nuno M. T. Lourençob,* a Faculdade de Farmácia da Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal b Departamento de Bioengenharia, Instituto de Biotecnologia e Bioengenharia, Instituto Superior Técnico, Av. Rovisco Pais, 1, 1049-001 Lisboa, Portugal
Recebido em 07/07/2014; aceito em 17/09/2014; publicado na web em 13/11/2014
The use of biocatalysts in synthetic chemistry is a conventional methodology for preparing enantiomerically enriched compounds. Despite this fact, the number of experiments in chemical teaching laboratories that demonstrate the potential of enzymes in synthetic organic chemistry is limited. We describe a laboratory experiment in which students synthesized a chiral secondary alcohol that can be used in the preparation of antidepressant drugs. This experiment was conducted by individual students as part of a Drug Synthesis course held at the Pharmacy Faculty, Lisbon University. This laboratory experiment requires six laboratory periods, each lasting four hours. During the first four laboratory periods, students synthesized and characterized a racemic ester using nuclear magnetic resonance spectroscopy and gas chromatography. During the last two laboratory periods, they performed enzymatic hydrolysis resolution of the racemic ester using Candida antarctica lipase B to yield enantiomerically enriched secondary alcohol. Students successfully prepared the racemic ester with a 70%-81% overall yield in three steps. The enzymatic hydrolysis afforded (R)- secondary alcohol with good enantioselectivity (90%–95%) and reasonable yields (10%–19%). In these experiments, students were exposed to theoretical and practical concepts of aromatic acylation, ketone reduction, esterification, and enzymatic hydrolysis. Keywords: sec-alcohols; esters; lípase; enantiomers; resolution.
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– See more at: http://organicsynthesisinternational.blogspot.in/#sthash.6AgqWtpw.dpuf

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The structure of Omeprazole in the solid state: a 13C and 15N NMR/CPMAS study

 drugs  Comments Off on The structure of Omeprazole in the solid state: a 13C and 15N NMR/CPMAS study
Feb 172015
 

 

 

ARKIVOC Volume 2006
Part (v): Commemorative Issue in Honor of 
Facilitator: Luba Ignatovich
Scientific Editor: Mikael Begtrup

2. The structure of Omeprazole in the solid state: a 13C and 15N NMR/CPMAS study (EL-1719AP)
Rosa M. Claramunt, Concepción López and José Elguero
Full Text: PDF (193K)
pp. 5 – 11

The structure of Omeprazole in the solid state: a 13C and 15N NMR/CPMAS study

Rosa M. Claramunt,a Concepción López,a and José Elguero b *

a Departamento de Química Orgánica y Bio-Orgánica, Facultad de Ciencias, UNED, Senda del Rey 9, E-28040 Madrid, Spain

b Instituto de Química Médica, CSIC, Juan de la Cierva, 3. E-28006 Madrid, Spain E-mail: iqmbe17@iqm.csic.es

To our friend Professor Edmunds Lukevics on his 70th anniversary

 Edmunds Lukevics

Abstract

The 13C and 15N CPMAS spectra of a solid sample of Omeprazole have been recorded and all the signals assigned. The sample consists uniquely of the 6-methoxy tautomer. For analytical purposes, the signals of the other tautomer, the 5-methoxy one, were estimated from the data in solution (Magn. Reson. Chem. 2004, 42, 712).

Keywords: Omeprazole, NMR, 13C, 15N, CPMAS, tautomerism, benzimidazole

see at

http://www.arkat-usa.org/arkivoc-journal/browse-arkivoc/2006/5/graphical-abstracts/

http://www.arkat-usa.org/get-file/22955/

 

 

Edmunds LUKEVICS

(14.12.1936 – 21.11.2009)

lukevics.jpg (11249 bytes) Professor Edmunds LUKEVICS
Latvian Institute of Organic Synthesis,
Head of the Laboratory of Organometallic ChemistryAizkraukles iela 21,
Riga, LV-1006
Latvia

 

Born: December 14, 1936, Liepaja, Latvia
Departed: November 21, 2009, Riga, Latvia

Interests:

  • Organometallic Compounds
  • Heterocyclic Compounds
  • Biological Activity of Organic Compounds

Main Research:

Development of methods for the synthesis of organosilicon and -germanium derivatives of furan, thiophene and nitrogen-containing heterocycles ; study of the influence of organosilicon ,-germanium and -tin substituents on the direction of substitution and addition reactions of furan and thiophene derivatives ; study of hydrosilylation and hydrogermylation reactions, synthesis and investigation of properties of penta- and hexacoordinated organosilicon and -germanium derivatives; application of alkenyl silanes and germanes in the synthesis of nitrogen-containing heterocycles; application of phase-transfer catalysis and ultrasonic irradiation in organometallic synthesis; synthesis of biologically active organosilicon and organogermanium compounds and studies of their properties.

Education:

  • University of Latvia (Faculty of Chemistry), 1958
  • Dr.chem. (Candidate of Science in former USSR, Ph.D. in Western countries), Latvian Academy of Sciences, Riga, 1966
  • Dr.habil.chem. (Doctor of Science in former USSR), Latvian Academy of Sciences, Riga, 1973

Experience:

Latvian Institute of Organic Synthesis –

  • Junior Researcher, 1958-1967
  • Senior Researcher, 1968-1970
  • Head, Laboratory of Organometallic Chemistry, 1970 – 2009
  • Vice-director, 1980-1982
  • Director, 1982 – 2003

Honours and Awards:

  • Corresponding Member, Latvian Academy of Sciences , 1982
  • Full Member, Latvian Academy of Sciences , 1987
  • Member, New York Academy of Sciences, 1993
  • The Latvian Academy of Sciences Gustavs Vanags Prize (in Chemistry), 1986
  • Latvian SSR State Prize, 1974, 1989
  • S.Hiller Medal (Latvian Institute of Organic Synthesis), 1990
  • G.Vanags Medal (Riga Technical University), 1991
  • D.H.Grindel Medal (company ‘Grindex’, Latvia), 1995
  • L.Liepina Medal (Institute of Inorganic Chemistry, Riga), 1996
  • The Latvian Academy of Sciences Grand Medal, 1996
  • Silver Medal of Milan University, 1996
  • Schmiedebergs Medal (Latvian Pharmacological Society), 1998
  • The Latvian Academy of Sciences and Company “GRINDEX” Prize, 1999
  • Paul Walden’s Medal (Riga Technical University), 2000
  • Latvian Academy of Sciences Presidium Award, 1971, 1973, 1977, 1981, 1982, 1985,1987, 1989, 1992
  • International Man of the Year (The International Biographic Centre of Cambridge, England), 1992-1993, 1994-1995
  • Man of the Year (The American Biographical Institute), 1994, 2005
  • The first-level Badge of Honour of the Order of Three Stars, 1997
  • Company “Grindex” gold badge of honour, 2001
  • The Cabinet of Ministers of the Republic of Latvia Prize , 2004
  • American Medal of Honor (ABI), 2005
  • Gold Medal for Latvia (ABI), 2006
  • The Plato Award (IBC), 2006
  • Man of Achievement (ABI), 2007

Professional Activities:

    • Member of Presidium and Senate, Latvian Academy of Sciences, 1987-1991
    • Member of Board, Division of Chemical and Biological Sciences, Latvian Academy of Sciences, 1983-1993
    • Member, Latvian Academy of Sciences Commission on Terminology, 1987- 1999
    • Chairman, Habilitation and Promotion Council (Chemistry and Pharmacy), Latvian Institute of Organic Synthesis, 1994 -1999
    • Member (Chairman,1991-1993, 1997-2002), Latvian Council of Science Expert Committee for Chemistry, 1991 – 2006

    • Vice-chairman, Habilitation and Promotion Council (Chemistry), University of Latvia, 1998- 2009

    • Member of Editorial Board for:

Khimiya Geterotsikicheskikh. Soedinenii (Chemistry of Heterocyclic Compounds, Springer), 1980-1985; Editor-in-chief, 1985 – 2009
Proceedings of Latvian Academy of Sciences, 1982-1990
Latvian Journal of Chemistry, 1991 – 2009
Bioorganicheskaya Khimiya, 1989 – 1993
Applied Organometallic Chemistry, 1990 – 2009
Main Group Metal Chemistry, 1992 – 2009
Metal-Based Drugs, 1993 – 2003
Mendeleev Communications, 1994 – 2009
Advances in Heterocyclic Chemistry, 1994 – 2009
Silicon Chemistry, 2001-2007
Arkivoc, 2001 –  2009
Bioinorganic Chemistry and Applications, 2003 – 2006
Heterocyclic Communications, 2005 –  2009
Molecules, 2008 –  2009
Journal of Organic and Pharmaceutical Chemistry (Ukraine), 2009 – 2009

  • Chairman, Scientific Council “Chemistry and Technology of Sulfur Organic Compounds”, USSR State Committee of Science and Technics, 1982-1987
  • Chairman, Council “Application of Organometallic Compounds in National Economy”, USSR (Russian) Academy of Sciences, 1984-1992
  • Member, United Libraries Informative Council, USSR Academy of Sciences, 1985-1990
  • Member, Scientific Council “Physiologically Active Compounds”, USSR Academy of Sciences, 1986-1992
  • Member, Scientific and Technical Council, USSR Ministry of Medical and Microbiological Industry, 1987-1990
  • Member, Soviet National Committee on collecting and estimating information in science and technics “CODATA”, 1987-1990
  • Member of Council for Coordination of scientific work, Department of Biochemistry, Biophysics and Physiologically Active Compounds, USSR Academy of Sciences, 1988-1991
  • Member of International Organizing Committees
    – International Conference on the Coordination and Organometallic Chemistry of Germanium, Tin and Lead, 1992, 1995, 1998, 2001
    –  International Symposium on Organosilicon Chemistry, 1993, 1996, 1999, 2002, 2005, 2008.

Memberships:

  • Member of Organometallic Chemistry Division, Federation of European Chemical Societies, 1995-2005
  • Member of Organometallic Chemistry Division, European Association for Chemical & Molecular Sciences, 2006
  • Member, Latvian Chemical Society, 1995
  • Member, American Chemical Society, 1997
  • Member, National Geographic Society, 1997
  • Honorary Member,  Pharmacological Society of Latvia, 1998

Lectures

Invited Lectures at Universities

  • Indian Institute of Science, Bangalore (India), 1989
  • Indian Institute of Technology, Bombay (India), 1989
  • University of Dresden (Germany), 1989
  • Universities of Bordeaux, Tolouse, Montpellier, Marseilles (France), 1990, 1994
  • University of Lund (Sweden), 1992
  • University of Alcala de Henares ( Spain), 1993
  • Tohoku University (Sendai, Japan), 1991, 1992
  • Tokyo University of Science (Japan), 1997
  • Kyoto University (Japan), 1997
  • Universities of Kyoto and Kanagawa, Japan, 2002.

Invited Lectures and Symposium’s Plenary Lectures:

  • 40th Nobel Symposium (Lidingö, Sweden), 1977
  • VI Symposium on Chemistry of Heterocyclic Compounds (Brno, Czechoslovakia), 1978
  • 7th International Symposium on Organosilicon Chemistry (Kyoto, Japan), 1984
  • VI FECHEM Conference on Organometallic Chemistry (riga, Latvia), 1985
  • II Soviet-Indian Symposium on Organometallic Chemistry( Irkutsk, Russia), 1989
  • 17th DDR-Poland Colloquy on Organometallic Chemistry (Holzhau, Germany), 1989
  • 6th International Conference on Organometallic and Coordination Chemistry of Germanium, Tin and Lead (Brussels, Belgium), 1989
  • Huang Minlon Symposium on Organic Chemistry (Shanghai, China), 1989
  • International Chemical Conference on Silicon and Tin ( Kuala Lumpur, Malaisia), 1989
  • 9th International Symposium on Organosilicon Chemistry (Edinburgh, UK), 1990
  • 1st Meeting of the European Society of Sonochemistry, Autrans (Grenoble, France), 1990
  • 11th International Symposium on Medicinal Chemistry (Jerusalem, Israel), 1990
  • S.Hiller Memorial Lectures (Riga, Latvia), 1990
  • 1st Meeting of Japanese Germanium Discussion Group (Tokyo, Japan), 1991
  • International Conference on Environmental and Biological Aspects of Maingroups Organometals (Padua, Italy), 1991
  • 3rd Swedish-German workshop: Nucleic Acid Synthesis, Structure and Function (Uppsala, Sweden), 1992
  • 2nd ANAIC Conference on Materials Science and Environmental Chemistry of Main Group Elements (Kual Lumpur, Malaysia), 1993
  • Todai Symposium “Ge-Sn-Pb Tokyo’93”: International Symposium on Organic, Bioorganic and Bioinorganic Chemistry of Compounds of higher row Group 14-elements (Tokyo, Japan), 1993
  • 10th International Symposium on Organosilicon Chemistry (Poznan, Poland), 1993
  • 3rd Meeting of the European Society of Sonochemistry (Figueira da Foz, Portugal), 1993
  • 14th Nordic Meeting of Structural Chemists (Helsinki, Finland), 1993
  • 8th International Conference on the Organometallic Chemistry of Germanium, Tin and Lead (Sendai, Japan), 1995
  • 8th IUPAC Symposium on Organometallic Chemistry Directed Towards Organic Synthesis (Santa Barbara, USA), 1995
  • 8th Symposium Heterocycles in Bioorganic Chemistry (Como, Italy), 1996
  • 9th International Conference on the Coordination and Organometallic Chemistry of Germanium, Tin, and Lead (Melbourne, Australia), 1998
  • 12th International Conference on Organosilicon Chemistry (Sendai, Japan), 1999
  • International Conference on Organic Synthesis “Balticum Organicum Sinteticum-2000″(Vilnius, Lithuania), 2000
  • X International Symposium “Jubilee Krka Prizes” (Novo Mesto, Slovenia), 2000

Recent/Representative Publications:

  • E.Ya. Lukevits, M.G.Voronkov. Organic Insertion Reactions of Group IV Elements, 1966, New York: Consultants Bureau, 413 pp.
  • S.N.Borisov, M.G.Voronkov, E.Ya.Lukevits. Organosilicon Heteropolymers and Heterocompounds, 1970, NewYork: Plenum Press, 633 pp.
  • S.N.Borisov, M.G.Voronkov, E.Ya.Lukevits. Organosilicon Derivatives of Phosphorus and Sulfur, 1971, NewYork; London: Plenum Press, 343 pp.
  • M.G.Voronkov, G.I..Zelchan, E.Ya.Lukevits. Silizium und Leben, 1975, Berlin: Akademie-Verlag, 370 pp.
  • E.Lukevics, O.Pudova, R.Sturkovich. Molecular Structure of Organosilicon Compounds, 1989, Chichester: Ellis Horwood Ltd., 359 pp.
  • E.Lukevics, T.Gar, L.Ignatovich, V.Mironov. Biological Activity of Germanium Compounds, 1990, Riga: Zinatne, 191 pp. (in Russian).
  • E.Lukevics, A.Zablocka. Nucleoside Synthesis: Organosilicon Methods, 1991, Chichester: Ellis Horwood, 496 pp.
  • E.Lukevics,  L.Ignatovich. Biological activity of organogermanium compounds. – In: The Chemistry of Organic Germanium, Tin and Lead Compounds/Ed. Z.Rappoport/, Wiley, Chichester, 2002, vol. 2, pt. 2, pp. 1653-1683.
  • E.Lukevics,  O.Pudova. Biological activity of organogermanium compounds. – In: The Chemistry of Organic Germanium, Tin and Lead Compounds/Ed. Z.Rappoport/, Wiley, Chichester, 2002, vol. 2, pt. 2, pp. 1685-1714.
  • E.Lukevics, O.Pudova. Silyl imidic esters. – In: Science of Synthesis, Thieme, 2002, vol. 4, pp. 305-315.
  • E. Lukevics, P. Arsenyan, S. Belyakov, O. Pudova. Synthesis, structure and chemical transformations of ethynylgermatranes – Eur. J. Inorg. Chem., 2003, Iss.17, pp.3139-3143.
  • R. Abele, E. Abele, M. Fleisher, S. Grinberga, E. Lukevics. Novel fluoride ion mediated synthesis of unsymmetrical siloxanes under phase transfer catalysis conditions. – J. Organomet. Chem., 2003, vol.686, N 1/2, pp.52-57.
  • E. Lukevics, L. Ignatovich, I.Shestakova. Synthesis, psychotropic and anticancer activity of 2,2-dimethyl-5-[5-trialkylgermyl(silyl)-2’-hetarylidene]-1,3-dioxane-4,6-diones and their analogues. – Appl.Organomet. Chem., 2003, vol. 17, N 12, pp.898-905.
  • P. Arsenyan, K. Rubina, I. Shestakova, E. Abele, R. Abele, I. Domracheva, A. Nesterova, J. Popelis, E. Lukevics. Synthesis and cytotoxicity of silylalkylthio-substituted N-heterocycles and their hydroselenites. – Appl. Organomet. Chem., 2003, vol. 17, N 11, pp.825-830.
  • E. Lukevics, L. Ignatovich, T. Shul’ga, S. Belyakov. The crystal structure of 2-benzo[b]thienylgermatrane. – Appl. Organomet. Chem., 2003, vol. 17, N 9, pp.745-746.
  • K. Rubina, E. Abele, P. Arsenyan, M. Fleisher, J. Popelis, A. Gaukhman, E. Lukevics. The role of palladium catalyst and base in stereoselective tranformations of (E)-2-chlorovinylsulfides. –Tetrahedron, 2003, vol.59, N 38, pp.7603-7607.
  • I. Iovel, L. Golomba, J. Popelis, S. Grinberga, E. Lukevics Catalytic hydrosilylation of furan, thiophene, and pyridine aldimines. – Chem. Heterocycl. Comp., 2003, vol.39, N 1, pp.49-55.
  • G. Veinberg, M. Vorona, I. Shestakova, I. Kanepe, E. Lukevics. Design of ß-lactams with mechanism based nonbacterial activities. – Current Medicinal Chemistry, 2003, vol.10, N 17, pp.1741-1757.
  • E. Lukevics, P. Arsenyan, O. Pudova. Methods for the synthesis of oligothiophenes. – Heterocycles, 2003, vol.60, N 3, pp.663-687.
  • V.Dirnens, V.Klusa, J.Skuyins, S.Svirskis, S.Germane, A.Kemme, E.Lukevics. Synthesis and pharmacological activity of silyl isoxazolines-2. – Silicon Chemistry, 2003 (publ. 2004), vol. 2, N 1/2, pp. 11-25.
  • I.Iovel, L.Golomba, M.Fleischer, J.Popelis, S.Grinberga, E.Lukevics. Hydrosilylation of (hetero)aromatic aldimines in the presence of Pd(I) complex. – Chem.Heterocycl. Comp., 2004, vol. 40, N 6, pp. 701-714.
  • P.Arsenyan, O.Pudova, J.Popelis, E.Lukevics. Novel radial oligothienylsilanes. – Tetrahedron Lett., 2004, vol. 45, N 15, pp. 3109-3111.
  • E.Lukevics, L.Ignatovich, S.Belyakov. Crystallographic report: 2-furfurylgermatrane. – Appl. Organomet. Chem., 2004, vol. 18, N 4, p. 203.
  • G. Veinberg, I. Shestakova, M. Vorona, I. Kanepe, E. Lukevics.  Synthesis of antitumor 6-alkylidenepenicillanate sulfones and related 3-alkylidene-2-azetidinones. –   Bioorg. Med. Chem. Letters, 2004, vol. 14, No 1, 147-150.
  • E.Lukevics, L.Ignatovich, T.Shulga, S.Belyakov. 1-[4-(2-Thienyl)phenyl]germatrane. –   Appl. Organomet. Chem., 2005, vol. 19, N 1, pp. 167-168.
  • E.Lukevics, L.Ignatovich. Biological activity of organosilicon compounds. – In:  Metallotherapeutic Drugs and Metal-Based Diagnostic Agents. The Use of Metals in Medicine / Eds. M.Gielen, E.R.T.Tiekink/, 2005, J.Wiley & Sons, Ltd. Chichester, pp. 83-107.
  • E.Lukevics, L.Ignatovich. Biological activity of organogermanium compounds. – In:  Metallotherapeutic Drugs and Metal-Based Diagnostic Agents. The Use of Metals in Medicine / Eds. M.Gielen, E.R.T.Tiekink/, 2005, J.Wiley & Sons, Ltd. Chichester, pp. 279-295.
  • Yu.Melnik, M.Vorona, G.Veinberg, J.Popelis, L.Ignatovich, E.Lukevics. Synthesis and stereoisomerization of 2-(1-alkoxyimino-2,2,2-trifluoroethyl)-5-trimethylsilylfurans. –   Chem. Heterocycl. Comp., 2005, vol. 41, N 6, pp. 718-721.
  • L.Ignatovich, J.Popelis, E.Lukevics. Synthesis and NMR spectra of diaryl-  and dihetarylsilacycloalkanes. – In: Organosilicon Chemistry VI / Eds. N.Auner and J.Weis/, Wiley-VCH Weinheim, 2005, vol. 1, pp. 559-562.
  • L.Ignatovich, D.Zarina, I.Shestakova, S.Germane, E.Lukevics. Synthesis and bological activity of silicon derivatives of 2-trifluoroacetylfuran and their oximes. – In: Organosilicon Chemistry VI / Eds. N.Auner and J.Weis/, Wiley-VCH Weinheim, 2005, vol. 1, pp. 563-568.
  • E.Lukevics, L.Ignatovich, I.Sleiksha, I.Shestakova, I.Domrachova, J.Popelis. Synthesis and cytotoxic activity of silacycloalkylsubstituted heterocyclic aldehydes. –  Appl. Organomet. Chem., 2005, vol. 19, N 10, pp. 1109-1113.
  • S.Belyakov, E.Alksnis, V.Muravenko, I.Turovskis, J.Popelis, E.Lukevics. Crystal structure and conformation of 8-(2-hydroxyethylamino)-  and 8-(pyrrolidin-1-yl)adenosines. – Nucleosides, Nucleotides & Nucleic Acid, 2005, vol. 24, N 8, pp. 1199-1208.
  • A. Zablotskaya, I.Segal, S.Belyakov, E.Lukevics. Silyl modification of biologically active compounds. 11. Synthesis, physico-chemical and biological evaluation of N-(trialkoxysilylalkyl)tetrahydro(iso,silaiso)quinoline derivatives. Appl. Organomet. Chem. 2006, vol.20, N 2, 149-159.
  • A.Zablotskaya, I.Segal, J.Popelis, E.Lukevics, S.Baluja, I.Shestakova, I.Domracheva. Silyl modification of biologically active compounds. 12. Silyl group as true incentive to antitumour and antibacterial action of choline and colamine analogues. – Appl. Organomet. Chem. 2006, vol. 20, N 11, 721-728.
  • E.Lukevics, L.Ignatovich, I.Sleiksha, V.Muravenko, I.Shestakova, S.Belyakov, J.Popelis. Synthesis, structure and cytotoxic activity of 2-acetyl-5-trimethylsilylthiophene(furan) and their oximes. – Appl. Organomet. Chem. 2006, vol 20, N 7, 454-458.
  • L.Ignatovich, V.Muravenko, S.Grinberga, E.Lukevics. Novel reactions to form an Si-O-Ge group. – Chem.Heterocycl. Comp., 2006, vol. 42, N 2, 268-271.
  • E.Lukevics, I.Shestakova, I.Domrachova, A.Nesterova, Y.Ashaks, D.Zaruma. Synthesis of complex compounds of methyl derivatives of 8-quinolineselenol with metals and their cytotoxic activity. – Chem.Heterocycl. Comp., 2006, vol. 42, N 1, 53-59.
  • E.Lukevics, L.Ignatovich, I.Sleiksha, V.Romanov, S.Grinberga, J.Popelis, I.Shestakova. A New method for the synthesis of silicon- and germanium-containing 2-acetylfurans and 2-acetylthiophenes. –Chem.Heterocycl. Comp., 2007, vol. 43, N 2, 143-150.
  • V.Dirnens, I.Skrastina, J.Popelis, E.Lukevics. Synthesis of isoxazolinylxanthines. – Chem.Heterocycl. Comp., 2007, vol. 43, N 2, 193-196.
  • E.Lukevics, L.Ignatovich, S.Belyakov. Disordering in the crystal structure of thienylgermatranes. – Chem.Heterocycl. Comp., 2007, vol. 43, N 2, 243-249.
  • E.Lukevics, I.Shestakova, I.Domrachova, E. Yashchenko, D.Zaruma. Y.Ashaks. Cytotoxic di(8-quinolyl)disulfides. – Chem.Heterocycl. Comp., 2007, vol. 43, N 5, 629-633.
  • V.M.Vorona, I.Potorocina, G.Veinberg, I.Shestakova, I.Kanepe, M.Petrova, E. Liepinsh, E.Lukevics. Synthesis and structural modification of tert-butyl ester of 7a-chloro-2-(N,N-dimethylaminomethylene)-3-methyl-1,1-dioxoceph-3-em carboxylic acid.- Chem.Heterocycl. Comp., 2007, vol. 43, N 5, 646-652.
  • A.Zablotskaya, I.Segal, E.Lukevics, S.Belyakov, H.Spies. Tetrahydroquinoline and tetrahydroisoquinoline mixed ligand rhenium complexes with the SNS/S donor atom set.- Appl.Organomet.Chem.,2007, vol.21, N 4, 288-293.
  • A.Zablotskaya, I.Segal, M. Maiorov, D. Zablotsky, A. Mishnev E.Lukevics, I.Shestakova, I. Domracheva. Synthesis and characterization of nanoparticles with an iron oxide magnetic core and a biologically active trialkylsilylated aliphatic alkanolamine shell. J. Magn. Magn. Mater. 2007, 311, pp. 135-139.
  • Zablotskaya A., Segal I., Lukevics E., Maiorov M., Zablotsky D., Blums E., Shestakova I., Domracheva I.  Synyhesis, physico-chemical and biological study of trialkylsiloxyalkylamine coated iron oxide/oleic acid magnetic nanoparticles for the treatment of cancer. – Appl. Organomet. Chem. 2008, vol. 22, pp. 82-88.
  • E.Lukevics, E.Abele. Four-membered rings with three heteroatoms not including oxygen, sulfur or nitrogen atom. – In: Comprehensive Heterocyclic Chemistry III., 2008, 2.   Four-membered heterocycles together with all fused systems containing a four-membered heterocyclic ring (Exec. Ed. A. Katritzky, FRS: Eds Ch.A. Ramsden, E.V.Scriven, R.J.Taylor), pp. 973-989.     
  • Soualami S., Ignatovich L., Lukevics E.,Ourari A., Jouikov V. Electrochemical oxidation of benzylgermatranes. – J. Organomet. Chem., 2008, vol.693 (7), pp. 1346-1352.
  • Lukevics E.,   Ignatovich L., Shul’ga T., Belyakov S. Synthesis and crystal structure of 1-(4-fluorophenyl)- and 1-(4-dimethylamino)phenylgermatranes. – Chem. Heterocycl.Comp. (Engl.Ed.), 2008, vol. 44 (5), pp. 615-620.
  • Abele E., Lukevics E. Synthesis of Heterocycles from Oximes. – In: The Chemistry of Hydroxylamines, Oximes and Hydroxamic Acids. (Eds. Z.Rapoport, J.F.Liebmann ), J.Wiley, Chichester, 2009,  Part I, pp. 233-302.
  • Erchak N., Belyakov S., Kalvinsh I., Pypowski K., Valbahs E., Lukevics E. Two polymorphic modifications of 1-(N-morpholiniomethyl)spirobi(3-oxo-2,5-dioxa-1-silacyclopentan)ate hydrate. –Chem.Heterocycl. Comp.(Engl. Ed.), 2009, vol. 45, N 9, pp.1137-1143..
  • Zablotskaya A.,Segal I., Lukevics E., Maiorov M., Zablotsky D., Blums E., Shestakova I., Domracheva I.  Water-soluble magnetic nanoparticleswith biologically active stabilizers. – J.Magn.Mater.,2009, 321, pp. 1428-1432.
  • Ignatovich L., Muravenko V., Shestakova I., Domracheva I, Popelis J., Lukevics E. Synthesis and Cytotoxic activity of new 2-[(3-aminopropyl)- dimethylsilyl]-5-triethylsilylfurans. –  Appl. Organomet. Chem. 2009, DOI 10.1002, aoc, 1538.
  • Vorona M., Veinberg G.,Liepinsh E., Kazoka H., Andrejeva G., Lukevics E. Enzymatic synthesis of amoxycilloic acids. – Chem.Heterocycl. Comp.(Engl. Ed.), 2009, vol. 45, N 6, pp.782-754.
  • Zablotskaya A.,Segal I., Lukevics E. Iron oxide-based magnetic nanostructures bearing cytotoxic organosilicon molecules for drug delivery and therapy. – Appl. Organomet. Chem. 2010, vol. 24, N 3, pp. 150-157.
  • Ignatovich L., Muravenko V., Shestakova I., Domracheva I, Popelis J., Lukevics E. Synthesis and Cytotoxic activity of new 2-[(3-aminopropyl)- dimethylsilyl]-5-triethylsilylfurans. –  Appl. Organomet. Chem. 2010, vol. 24, N 3, pp. 158-161.
  • Segal I., Zablotskaya A.,Lukevics E., Maiorov M., Zablotsky D., Blums E., Mishnew A., Georgieva R., Shestakova I., Gulbe A. Preparation and cytotoxic properties of goethite-based nanoparticles covered with decyldimethyl(dimethylaminoethoxy)silane metoxyde. –  Appl. Organomet. Chem. 2010, vol. 24, N 3, pp. 193-197.
  • Ignatovich L., Muravenko V., RomanovsV,  Sleiksha I., Shestakova I., Domracheva I, Belyakov S., Popelis J., Lukevics E. Synthesis, structure and cytotoxic activity of new 1-[5-organylsilyl(germyl)-2-furyl(thienyl)]nitroethenes. –  Appl. Organomet. Chem. 2010, vol. 24, N 12, pp. 858-864.
  • Lukevics E., Abele E., Ignatovich L. Biologically Active Silacyclanes. – Adv. Heterocycl. Chem., 2010, vol. 99, pp. 107-141.
  • Abele E., Lukevics E. Synthesis, structure and reactions of organometallic derivatives of oximes. – In: The Chemistry of Hydroxylamines, Oximes and Hydroxamic Acids. Eds. by Zvi Rapoport, J.F.Liebman. 2011, Vol.2, Part 1 (Chapter 4), pp. 145-203.
  • Katkevics M., Kukosha T., Lukevics E. Heterocycles from hydroxylamines and hydroxamic acids. –  In: The Chemistry of Hydroxylamines, Oximes and Hydroxamic Acids. Eds. by Zvi Rapoport, J.F.Liebman. 2011, Vol.2, Part 1 (Chapter 5), pp. 205-293.

Research Projects:

  • E.Lukevics (Head of Project). Silylheterocycles in Organic Chemistry. Latvian Council of Science (1993-1995).
  • E.Lukevics (Head of Project). Bifunctional Organosilicon Compounds. Latvian Council of Science (1993-1995).
  • E.Lukevics (Head of Project). Synthesis of Heterocyclic Organosilicon and Organogermanium Compounds, Investigation of their Physical and Chemical Properties. Latvian Council of Science (1997-2000 ).
  • E.Lukevics (Head of Project). Asymmetric and Catalytic Synthesis of Heteroaromatic Compounds. Latvian Council of Science (1997-2000 ).
  • E.Lukevics (Head of Program). The Development of Modern Methods of Organic Chemistry Directed towards the Development of Pharmaceutical Industry in Latvia. Latvian Council of Science (1997-2000 ).
  • E.Lukevics (Head of Project). Experimental and Theoretical Aspects of the Catalytical Synthesis of Heteroaromatic Compounds. Latvian Council of Science (2001 –2004 ).
  • E.Lukevics (Head of Project). Comparative Study of the Structure and Biological Activity of Organosilicon and Organogermanium Compounds. Latvian Council of Science (2001 – 2004).
  • E.Lukevics (Head of Project). Heterocyclic Derivatives of Tetra- and Hypercoordinated Germanium and Silicon. Latvian Council of Science (2005 -).
  • E.Lukevics ( Programme Director). Development  of Organic Synthesis Methods for  Obtaining of Biologically Active Compounds. Latvian Council of Science (2002 -2005 ).
  • E.Lukevics ( Programme Director). Development  of  Heteroatom Chemistry for Preparation of Biologically Active Compounds. Latvian Council of Science (2006 – 2009 ).
  • E.Lukevics (Head of Project). Carbofunctional Silylheterocycles. Latvian Council of Science (2009 ).

Hobbies:

Opera, Basketball, Mountains.

 

Edmunds LUKEVICS

 Edmunds LUKEVICS 
Head of Laboratory of Organometallic Chemistry

Latvian Institute of Organic Synthesis
Aizkraukles iela 21,
Riga, LV-1006
http://www.lza.lv/scientists/lukevics.htm

Born: December 14, 1936, Liepaja, Latvia
Departed: November 21, 2009, Riga, Latvia

Interests in inventing:

  • Development of medicament synthesis and technology
  • Development of the synthesis and technology of agricultural chemicals

Main invention:

In the sphere of medicament synthesis:

  • Acylete derivatives of aminobenzylpenicillin with antimicrobe activity.
    Co-authors: G.Veinbergs, G.Kvitsors a.o.
    Authors’ certificate of USSR Nr.1829360, 1992
  • Substituted 3-hydrazinopropionates and their pharmaceutically available salts with antiarythmic activity.
    Co-authors: G.Bremanis, I. Kalvins, I.Ancena a.o.
    Authors’ certificate of USSR Nr.1247012, 1986.
    Patent of USA Nr. 4633014
    Patent of England Nr. 2144121
    Patent of France Nr. 2549050
    Patent of Italy Nr.1175577

In the sphere of the synthesis of agricultural chemicals:

  • 2,2 –dimethyl-6-alkyl–1,3-dioxa-6-aza-2-silacyclooctanes with antiinsect activity.
    Co-authors: V.Markina, N.Smirnova a.o.
    Authors’ certificate of USSR Nr.687855, 1978.
  • Lucerne productivity stimulator.
    Co-authors: L.Sermans, V.Janisevska, G.Zelcans a.o.
    Authors’ certificate of USSR Nr. 1161056, 1985

Selection of patent documents:

Totally: 104 authors’ certificates of USSR, 11 patents of Latvia, 3 patents of Germany, 3 patents of Canada, 3 patents of France, 3 patents of Italy, 1 patent of Japan, 1 patent of Switzerland, 4 patents of Great Britain, 5 patents of USA.

Patents of Latvia:

  • E.Lukevics, D.Feldmane, H.Kazoka, I.Turovskis. Method for obtaining metoxi-alpha-methylbenzyl alcohol. Patent of Latvia Nr. 11864, C 07 C 29/58, 1997;
  • E.Lukevics, V.Slavinska, Dz.Sile, M.Katkevics, E.Korcagova. Method for obtaining 2-oxo-4-phenylbutane acid ethylester. Patent of Latvia Nr. 11891, C 07 C 69/716, 1998;
  • E.Lukevics, V.Slavinska, Dz.Sile, M.Katkevics, E.Korcagova, V.Belikovs. Method for obtaining 2-oxo-4-phenylbutane acid ethylester. Patent of Latvia Nr. 11892, C 07 C 69/716, 1998;
  • E.Lukevics, I.Kalvins, A.Birmans. Cardioprotector “Mildronate”. Patent of Latvia Nr. 5402, A 61 K 31/205, 1994;
  • E.Lukevics, G.Veinbergs, I.Sestakova, I.Kalvins. Cephalosporin derivatives with citostatic activity. Patent of Latvia Nr. 11953, C 07 D 501/02, 1998.

 

Riga latvia

 

    1. Map of riga

The building of the Brotherhood of Blackheads is one of the most iconic buildings of Old Riga (Vecrīga)

RIGA

RIGA

 

RIGA

RIGA

Cook in traditional latvian dress serving local food for tourists Riga Latvia

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Piece by Piece A guide to fragment-based drug discovery

 DRUG DESIGN, drugs  Comments Off on Piece by Piece A guide to fragment-based drug discovery
Dec 222014
 

DESIGNING A BETTER DRUG: The combination of chemical groups from three different fragments that bind weakly to an enzyme produce a potent new enzyme inhibitor (center) that binds in the nM range.COURTESY OF RODERICK HUBBARD

In search of better drugs and therapies, researchers are constantly looking for new ways to identify compounds that selectively block disease pathways. Industrial labs have relied on high-throughput screening to finger promising new molecules, but most academic labs lack the equipment and resources to scan many thousands, even millions, of compounds. For a long while this shut academic labs out of such searches, but a related technique, fragment-based drug discovery (also called fragment-based lead discovery), offers another way to develop small-molecule drugs and chemical probes for investigating biological processes. And this approach relies on instruments and expertise available at many academic institutions.

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Piece by Piece

A guide to fragment-based drug discovery

http://www.the-scientist.com/?articles.view/articleNo/35711/title/Piece-by-Piece/

 

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Drug Discovery: Researchers optimize syntheses by adapting coupling reactions in array format

 drugs  Comments Off on Drug Discovery: Researchers optimize syntheses by adapting coupling reactions in array format
Nov 242014
 
09247-notw8-amine

The Merck group used arrays of coupling reactions to optimize the microgram-scale C–N coupling of an aryl halide (left) with an amine (over arrow) to give an arylamine. They then scaled up the process to gram level.
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Direct Route To Natural Products, Drug Discovery: Technique zeroes in on microbes that biosynthesize specific compound families

 drugs  Comments Off on Direct Route To Natural Products, Drug Discovery: Technique zeroes in on microbes that biosynthesize specific compound families
Oct 062014
 
09240-notw8-pcr_18276322-690

SETTING PRIORITIES
A real-time PCR technique saves time and energy in natural product drug discovery by screening microbes for those that biosynthesize desired compound families.
Credit: J. Nat. Prod.

Direct Route To Natural Products

Drug Discovery: Technique zeroes in on microbes that biosynthesize specific compound families
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Drug development, approval, manufacturing, and post-marketing…..Japan’s journey of a pharmaceutical product

 drugs, japan, Uncategorized  Comments Off on Drug development, approval, manufacturing, and post-marketing…..Japan’s journey of a pharmaceutical product
Sep 042014
 

Drug development, approval, manufacturing, and post-marketing

  • Development of a new drug involves a complicated process that requires a lot of time and enormous amounts of funding. In order to create one drug, you would need to evaluate approximately 700,000 candidates1). Of them, just one reaches the patients. Here, we will share how a new drug begins its journey, from the research and development of candidate compounds, to a product, to the patients, and how we are involved with drugs once the physician prescribes a drug to patients. We will explain what pharmaceutical companies call “the lifecycle of a drug.”
    1) from Japan Pharmaceutical Manufacturers Association DATABOOK 2013

The journey of a pharmaceutical product

1. Basic research

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  • Conduct a research to discover new drug candidate substances and components and create new compounds. Most requires 2 to 3 years. This process also functions as an opportunity to research the yet-to-be-defined mechanisms of diseases, where the basic research conducted may not directly lead to a new drug. Discovering a seed for a new drug is like looking for a piece diamond on the bottom of the deep ocean, where these highly uncertain basic research and drug development research could become the base in identifying several million candidate elements. After this process, a screening method to narrow down potential substances will be developed, and several of the candidate substances move on to the next process.
  • There are two types of research, collaborative research and sponsored research, where pharmaceutical companies and others provide funding support.
    The research is conducted after an official contract is exchanged with universities and others.
    Collaborative research：(Joint research expenses in the JPMA Transparency Guideline)
    Research institutions such as universities and investigators of pharmaceutical companies and others conduct a research cooperatively.
    Sponsors such as pharmaceutical companies entrust research institutions such as universities to conduct the research, where accomplishments are reported to the sponsors.
    Image result for kiyomizu dera

    The journey of a pharmaceutical product

    2. Development

    1) Non-clinical trial

    • CMC: Quality
      CMC stands for Chemistry, Manufacturing and Control. Design and research for manufacturing procedures, specifications and stability tests are carried out.
    • A process to investigate the efficacy and safety of candidate drug compounds. An animal testing is conducted for pharmacokinetics, pharmacological and toxicity tests. The next trials are conducted based on data obtained from this first process. This process takes about 3 to 5 years.
    • The trial is required to be conducted based on GLP for non-clinical trial regarding safety of pharmaceutical products.

    2) Clinical trial

    • The clinical trial is conducted by pharmaceutical companies and others based on the Pharmaceutical Affairs Law, in order to have a new drug approved or to apply for a new indication for an existing drug. Other than clinical trials conducted by pharmaceutical companies with an objective of approval application, there are trials called investigator-led clinical trials which are conducted by physicians and medical institutions for the purpose of the approval application.
    • The trial process investigates the efficacy and safety of the candidate compound on humans. The clinical trial is conducted mainly in 3 steps, Phase I, Phase II and Phase III. This process takes approximately 3 to 10 years. It is required to conduct the trials based on the GCP.
      Phase I trial (human pharmacology study) :
      Confirms mainly the compound’s safety among healthy people
      Phase II trial (exploratory study) :
      Confirms the drug’s administration method and administration amount among a small number of patients
      Phase III trial (confirmatory trial) :
      Confirms the drug’s efficacy and safety among numerous patients

The journey of a pharmaceutical product

3. NDA and regulatory approval application

  • The enormous amount of data gathered on candidate compounds so far is compiled into an approval application document and submitted to the regulatory authority in each country/region. In Japan, it is submitted to the Ministry of Health, Labour and Welfare (MHLW). The Pharmaceuticals and Medical Devices Agency (PMDA) will conduct a strict review from a scientific standpoint, and once the efficacy and safety of the candidate compound is confirmed, it will obtain approval by the MHLW as a new drug to be manufactured and distributed.
  • The PMDA website provides a detailed explanation on the complicated and wide-ranging process from application to approval.

 

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 The journey of a pharmaceutical product

  • 4. Production, Quality, Information Provision & Product Distribution

    1) Manufacturing of newly approved drugs and the quality control process.

    In every process of the drug development, from manufacturing to shipping and transportation after shipments, there are strict standards in place, ranging from those defined by the Pharmaceutical Affairs Law, those that require approval from regulatory agencies, and unique standards set within companies.

    • Approval and inspection of manufacturing site: Under the Pharmaceutical Affairs Law, a GMP compatibility investigation is required for a new drug to be approved. This is an investigation that also confirms that the manufacturing site has the building, facility and administrative system to constantly manufacture the product which has been guaranteed its efficacy, safety and homogeneity.
      GMP investigation is conducted regularly as well as unscheduled, in addition to the investigation conducted at the time of approval.
    • The manufacturing process begins from the measuring of raw materials: (Chugai Pharmaceutical “Manufacturing of active pharmaceutical ingredient/solid drug factory”)
    • Decision on shipment: Some products, such as vaccines and blood products, require a national test per lot and may take time for it to be shipped out.
      National test process for vaccines

    2) Product distribution and provision of information

 

Image result for golden pavilion kyoto

The journey of a pharmaceutical product

5. Post manufacturing and distribution

  • Conduct surveys and trials on appropriate use, in order to confirm the new drug’s efficacy and safety in a regular and a daily medical setting that cannot be obtained from a clinical trial conducted for the drug’s approval. For example, through post-manufacturing and distribution clinical trials and post-manufacturing and distribution surveys, collect information on adverse reaction and the drug quality, and communicate assessment and analysis results to medical facilities.
  • Making changes to items listed in the application material submitted to obtain marketing approval, requires companies to submit an approval application for partial approval and obtain an approval per the Pharmaceutical Affairs Law.
  • The reporting system of adverse reactions and infectious diseases based on the Pharmaceutical Affairs Law, is for pharmaceutical companies and healthcare practitioners such as physicians and pharmacists to report the MHLW. The objective for this is to appropriately collect adverse reaction, infectious diseases and default information of pharmaceutical products and others in approved medical facilities such as hospitals, and promptly conduct safety measures.
  • Pharmaceutical companies, in order to promote academic research and provide aid for the research, supports research institutions such as universities, hospitals and medical academic conferences. As an academic research aid, it provides scholarship donations to universities and others. For example, in order to promote case reports that communicate product usage experience by expert physicians for products that have been in the market for 3 to 5 years since post-manufacturing and distribution, pharmaceutical companies will bring together a seminar through donations to the medical academic conferences and co-host seminars with academic conferences. Through such activities, it will promote the products’ safety and appropriate usage post-manufacturing and distribution.
  • There are also clinical research and clinical trials that are led by physicians and medical facilities conducted after a product’s post-manufacturing. Some physician-led clinical trials do not have an objective to apply for approval, but rather are conducted by physicians and researchers in order to provide the best treatment to patients and promote evidence-based medicine.

……………………………………………………………………………….

  • The various steps in this process are usually conducted by pharmaceutical companies alone. However, at times accomplishments are made through a cooperative effort with universities and medical institutions. In order for cooperative research with universities and medical institutions to steadily progress, and for new drugs to be created as a result, companies sometimes contribute by providing funding to the research. The types of funding provided are presented in the table below. Also, for certain items an example is illustrated and explained in each process within the “product lifecycle,” and is hyperlinked to the cost items of each member companies’ disclosure target within the JPMA‘s “Transparency guideline for the relationship between corporate activities and medical facilities and others.”
  • The progress of each process within the “product lifecycle” is managed by adhering to various laws and self-regulations. We will explain the process of drug development that at times is considered complicated, to the manufacturing and distribution of new drugs, and related laws and regulations to adhere to. The following table shows one part of the product lifecycle chart.
    Product lifecycle and requirements overviewProduct lifecycle and requirements overview

 

Terminology: Product lifecycle and related laws

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  • PAL：Pharmaceutical Affairs Law
    A Law regulating matters related to the manufacturing, distribution, standards and screening, handling and advertising regulation and others for healthcare products, quasi-drugs, cosmetics and medical devices in Japan. (Law No. 145, Aug. 10, 1960).
  • GLP：Good Laboratory Practice
    A standard for conducting non-clinical studies on the safety of drugs. It is a standard regarding animal studies in non-clinical studies, particularly regulated for toxicity studies.
  • CMC：Chemistry, Manufacturing and Control
    Information regarding Chemistry, Manufacturing and Control. It refers to the integrated concept of researches for drug substance process, drug development, and quality assessment, as well as works related to those researches. The pharmaceutical companies’ CMC includes a wide range of work from non-clinical studies, clinical studies to regulatory approval applications.
  • GCP：Good Clinical Practice
    A standards regarding the implementation of clinical trial for pharmaceutical products.
  • ICH：International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use
    A project that brings together regulatory authorities in Europe, Japan and the United States. The purpose is to make recommendations on ways to achieve greater harmonisation in the interpretation and application of technical guidelines and requirements for product registration.
  • GMP：Good Manufacturing Practice
    A ministry ordinance related to standards for the manufacturing management and quality management of pharmaceutical products and quasi-drugs. It refers to the standard for the manufacturing management and quality management at manufacturing facilities of pharmaceutical products and others.
  • PV：Pharmacovigilance
    Activities related to the safety monitoring of pharmaceutical products. It refers to the careful monitoring and continuous surveillance of the safety of an approved product during its life on the market.
  • GQP：Good Quality Practice
    A standard on the quality management of pharmaceutical products and others.
  • GDP：Good Distribution Practice
    A standard on pharmaceutical product distribution.
  • GPSP：Good Post-marketing Study Practice
    A standard on the implementation of the pharmaceutical products’ post-marketing surveillance and study.
  • GVP：Good Vigilance Practice
    A standard on the safety management of pharmaceutical products and others after manufacturing and distribution.

 

Sources:

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Polyketide Synthase Secrets Revealed Structural Enzymology: Findings could aid engineering of multienzyme complexes for drug discovery

 drugs  Comments Off on Polyketide Synthase Secrets Revealed Structural Enzymology: Findings could aid engineering of multienzyme complexes for drug discovery
Jun 242014
 
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ENZYME FACTORY
During PKS biosynthesis, ACP moves to AT to pick up an extender group and then delivers it to KS. In KS’s active site, the group is added to pentaketide. ACP then takes the fused product to KR, where it is reduced. Finally, ACP offers the extended product to PKS’s next module. Active sites on enzyme domains are yellow.
Credit: Adapted from Nature

Polyketide Synthase Secrets Revealed

Structural Enzymology: Findings could aid engineering of multienzyme complexes for drug discovery
A new study solves long-standing mysteries about how bacterial natural-product-making factories are put together and how they work. The findings could accelerate efforts to engineer these workshops to produce novel bioactive agents for drug discovery.
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