Phasex Corp. (New Web site is educational platform for supercritical fluid technology)

Chemical Market Reporter

Phasex Corp. has designed a new Web site to provide an educational platform for supercritical fluid (SCF) technology and to improve interactive communication, located at www.phasex4scf.com.The company has re-engineered its business processes to strengthen customer relationships and to deliver a more complete package of SCF processing services, says a company spokesperson.

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Chemical Specialties

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Nutritional Outlook

Phasex Deal is Latest in SCF for Lavipharm. (Lavipharm Laboratories Inc. acquires rights to supercritical fluids technology from Phasex Corp.)

Chemical Market Reporter

LAVIPHARM LABORATORIES Inc. has acquired exclusive and perpetual rights to Phasex Corporation’s supercritical fluids (SCF) technology, patents, trademark and know-how for use in the pharmaceutical and cosmetics fields. Lavipharm has also acquired a 30 percent equity stake in Phasex, with the right to purchase the remainder of the company.

Lavipharm Laboratories is a particle and formulation design company with expertise in molecular transport.  Located in East Windsor, N.J., it is the research and development arm of the Lavipharm Group.

The Phasex deal caps a busy autumn for Lavipharm.  In October, Lavipharm announced plans to buy another SCF business, France-based Separex.

Lavipharm Laboratories Inc. Acquires Exclusive Rights to Phasex Corporation; Technologies for Use in the Pharmaceutical and Cosmetic Fields.

PR Newswire

EAST WINDSOR, N.J., Dec. 6/PRNewswire

Lavipharm Laboratories Inc. announced today that it has acquired exclusive and perpetual rights to Phasex Corporation's supercritical fluids (SCF) technology, patents, trademark, and know-how for use in the pharmaceutical and cosmetic fields, together with a thirty-percent (30%) equity stake in Phasex Corporation.

Phasex, based in Boston, Massachusetts, applies SCF technology to the development of separation, purification, and recrystallization processes, with particular emphasis on particle design of small and bio-molecules, including proteins and peptides.

"Lavipharm continues to expand and strengthen its position in the drug delivery industry by constantly adding to its technology platform. The SCF technology licensed from Phasex is a great example of this initiative," said Dr. A. Lavidas, Chairman of Lavipharm Laboratories Inc. "The founder and president of Phasex, Dr. Val Krukonis, is a highly regarded scientist, opinion leader and author in the supercritical fluids and particle design of small and bio-molecules, Val will provide to us a strong knowledge base in polymers and polymer processing, which he has acquired through twenty five years of research," continued Dr. Lavidas.

"The Agreement between Phasex and Lavipharm is the culmination of a long term goal that I have had to take the Phasex technology to another level," said Dr. Krukonis. "This arrangement combines the strengths of the two companies to fully exploit the potential for supercritical fluids in the pharmaceutical and cosmetic arenas. I feel that Lavipharm's commitment to Phasex, its technology, and to its future has been further demonstrated through Lavipharm's acquisition of the thirty percent equity interest in, and the right to purchase the remaining shares of Phasex Corporation," said Dr. Krukonis.

Earlier this fall, Lavipharm announced its acquisition of Separex S.A., based in France. Separex is a world leader in formulation of proteins/peptides and small molecules, particle design, extraction and fractionation, utilizing its environmentally friendly and flexible SCF technology, which is rapidly gaining acceptance as an attractive and improved alternative to solvent based processes used in the pharmaceutical and biotech industries.

"By combining Lavipharm's existing expertise in drug delivery, with its newly obtained expertise through the Separex acquisition and this arrangement with Phasex, we have become a world leader in the application of supercritical fluids technology to traditional pharmaceuticals, proteins and peptides. Lavipharm can now deliver "one-stop shopping" to its clients by providing early stage research and development services, design and manufacturing of highly specialized GMP/CIP equipment, and commercial manufacturing services," said Zsolt Lavotha, President and CEO of Lavipharm Laboratories Inc.

"Lavipharm's capabilities as a trouble shooter for pharmaceutical and biotech companies, addressing common drug delivery issues such as poor solubility, low bio-availability, inadequate adsorption and dosing frequency issues, are greatly enhanced through this expanded and strengthened technology platform. We have now put ourselves in the position where our combined expertise in the field of formulation and particle design utilizing this environmentally friendly "green" SCF technology will undoubtedly provide significant value to our clients. Indeed, Lavipharm will now be able to satisfy the every-increasing demand in the pharmaceutical industry for developing superior new formulations or improving existing products, under a quicker development schedule and at substantially lower costs.  There is no doubt, that this is the technology platform of the future for the pharmaceutical and biotech industries," said Mr. Lavotha.

Lavipharm Laboratories is the research and development engine of the Lavipharm Group of Companies, founded in Greece in 1911.  Lavipharm Group's sales last year were $250 million.  For more information, visit Lavipharm's Web site at www.lavipharm.com.

Lavipharm Buys Phasex. (Lavipharm Laboratories licenses)

Chemical Week

LAVIPHARM LABORATORIES (EAST WINDSOR, NJ) SAYS IT HAS ACQUIRED the exclusive rights to Phasex’s (Lawrence, MA) supercritical fluids (SCF) technology, patents, and trademark for use in pharmaceuticals and cosmetics. Lavipharm has also acquired 30% equity stake in Phasex and has the right to purchase the remaining shares.

Phasex applies SCF technology to the development of separation, purification, and recrystallization processes, targeting biomolecules including protein and peptides. Phasex will continue to develop SCF technology for Nutraceuticals, polymers, surfactants, and other specialty chemicals.

Lavipharm Laboratories is the R&D arm of Lavipharm S.A. (Attica, Greece), a drugs and cosmetics maker with sales of $250 million. Lavipharm recently bought Separex (Champignuelles, France), a proteins and peptides formulator in November.

Supercritical Fluids Inch Toward Credibility the $40-million.

Chemical Week

Author/s: Samuel K. Moore

Fluoropolymers pilot plant at DuPont's Fayetteville, NC site, announced this spring, will constitute the largest application of supercritical carbon dioxide (scCO₂) as a chemical reaction medium to date. Supercritical fluids are popular solvents for large-scale extraction processes, but even proponents acknowledge that they will never become the environmentally friendly wonder-solvents once promised.

"Overly optimistic forecasts and technical announcements have rendered potential users rather skeptical," says Michel Perrut, president of scCO₂ process developer

Separex (Champigneulles, France). Chemists are churning out an increasing stream of reactions to perform in supercritical fluids, but few combine the efficiency, selectivity, and environmental or regulatory benefit needed to entice industry investment.

Industrial use of scCO₂ and other supercritical fluids-including propane, butane, and water-has advanced farthest in separations such as extraction of natural ingredients and deasphaltization of petroleum. scCO₂ has flourished in separations because of pressure to replace organic solvents. It has supplanted trichloro-ethylene in coffee decaffeination and is favored for extracting high-value fine chemicals such as pharmaceutical actives. scCO₂ is challenging perchloroethylene in dry cleaning, helped by technology from Micell Technologies (Raleigh, NC), which was founded by University of North Carolina at Chapel Hill chemist Joseph DeSimone in 1997. DeSimone invented DuPont's fluoropolymers process (CW, Dec. 24, 1997, p. 30).

Compared to extraction, the adoption of scCO₂ as a reaction medium has been "incredibly slow," says Joan Brennecke, professor of chemical engineering at Notre Dame University (Notre Dame, IN). Brennecke says that solvent replacement is not a sufficient driver for the chemical industry: scCO₂ must also offer cost reductions or other benefits, such as improved selectivity.

Part of the delay stems from an incomplete understanding of the details of certain reactions, such as selectivity and reaction rates. "There are many things people don't fully understand," Brennecke says. "That makes them worry."

Efforts to apply the technology to production of high-volume chemicals failed, reorienting supercritical fluids researchers towards niche, high-value applications. "What people were trying to achieve a decade ago and what they are trying to achieve now are quite different," says Erdogan Kiran, a chemical engineering professor at the University of Maine (Orono, ME) and editor of The Journal of Supercritical Fluids.

The expense of reactors is also helping steer supercritical fluids toward high-value products. "Pressure costs money," says Brennecke. However, development of continuous processes should reduce costs compared to batch operations. Supercritical lab- and pilot-scale reactor makers, such as Applied Separations (Allentown, PA), are also lowering research costs. Lab-scale supercritical reactors have fallen from about $60,000 to $15,000 over the past decade, says Applied Separations president Rolf Schlake.

Specialty chemicals maker Thomas Swan (Consett, U.K.) is one of the few companies committed to scCO₂ reactions, hoping to accelerate their expansion into pharmaceutical intermediates. The company teamed with Degussa-Huls and Nottingham University (Nottingham, U.K.) chemist Martyn Poliakoff to design continuous scCO₂ hydrogenation and alkylation processes. Swedish process engineering firm Chematur is building a 500 m.t.-1,000 m.t./year pilot reactor for Swan to test the technology (CW, Dec. 2, 1998, p. 58).

Toll processing firm Phasex (Lawrence, MA) has used scCO₂ for separations and extractions, but president Val Krukonis says the company is also using the fluids to replace conventional solvents in two reactions. One, the formation of a reactive multi-acrylate monomer, also offers improved yield.

DuPont's scCO₂ process for fluoropolymers including polytetrafluoroethylene will replace hydrofluorocarbon solvents, which are potent greenhouse gases. (Previously, DuPont's process used ozone- depleting chlorofluorocarbon solvents.) "We also believe the operating costs will be lower," says Everett Baucom, technical manager/fluoropolymers. "How much lower is yet to be determined."

In the scCO₂ process, fluoropolymers fall out of solution as they polymerize.

DeSimone says that the technology is attractive partly because fluoropolymer synthesis has unusual reactants. "The active species in the process is a radical so reactive that the polymerization can't be done in a solvent with any hydrogen present," he says. "There's a short list of those solvents."

But DeSimone maintains that scCO₂ holds potential for other large-scale polymerizations that require an energy-intensive drying step, including polyvinyl chloride (PVC) and polyacrylic acid (PAA), because scCO₂ can be driven out of the polymer far easier than water. He estimates that PVC makers could save 1 trillion btu/year using scCO₂.

However, several polymer producers say efforts to apply the technology have fizzled. Geon says it considered PVC polymerization in scCO₂ but decided not to pursue it because of an unattractive preliminary economic analysis.

Dow Chemical did some research on supercritical PAA processes but has since dropped the project. Ciba Specialty Chemicals explored supercritical fluids to extract residual monomers from PAA and other water-soluble polymers but discovered that the monomers were insufficiently soluble. "There was not much done on polymerizing directly in scCO₂ mainly because of the monomer solubility problem," says Ian Johnson, Ciba's U.K. director/polymer technology.

Chemists have taken two paths to solve scCO₂'s solubility problem. DeSimone champions the use of surfactants to dissolve the reactants, while the other method uses a mixture of scCO₂ and organic solvents such as toluene or ethanol. "At the end of the process you can drive off the unwanted solvent and unreacted monomer by decompressing the scCO₂," says Kiran.

  Another potential scCO₂ extender may be ionic liquids, molten salts that have been hyped as alternative reaction media. Ionic liquids can dissolve many of the polar compounds scCO₂ rejects, and Brennecke recently demonstrated that scCO₂ can extend the use of ionic liquids to the synthesis of hydrophobic products (CW, May 12, p. 47).

Brennecke says companies including fluoropolymers giant Elf Atochem and UOP have shown interest in combined ionic liquid-scCO₂ systems. However, commercial use of ionic liquids as reaction media is at least five to 10 years off, she says.

"It wasn't until 1992 that the first air- and water-stable liquids were developed," says Brennecke. "You can't even buy these things commercially yet."

Using Supercritical Fluids to Provide Useful Information

Chemical Week - Polypropylene Review

Phasex Riding New Wave of SCF As Technology Awareness Grows.

Chemical Market Reporter

Author/s: Clay Boswell

THE PROCESS CHEMICAL industry is at a turning point in its relationship to supercritical fluids (SCF), says Val Krukonis, president of Phasex Corporation, a Lawrence, Mass., company specializing in SCF developmental work and toll processing.

SCF has been used since the late 1970s for the large-scale decaffeination of coffee and tea and the extraction of flavors from hops and other natural sources. But Dupont's recent announcement that it will construct a $40 million pilot plant to explore the commercial feasibility of Teflon manufacture in supercritical CO₂ reflects a growing awareness of the technology's broader applicability.

Supercritical fluids are gases that have been heated above their critical temperature and compressed. The resulting fluid, which is not a true liquid, has a dissolving power that is pressure-dependent. This property can be used for the extraction, fractionation, or purification of complex chemical mixtures based on the differential solubility of their components.

Environmental friendliness is a major driver in SCF, but Phasex has always had a different emphasis, says Mr. Krukonis. Rather than sell SCF for what it doesn't do, Phasex sells SCF for what it can do- especially to improve an existing product or produce a product that cannot be achieved by any other technology.

One example he offers is the formation of nanoparticles of the anticancer agent paclitaxel. Extracted from the yew tree, it must be administered intravenously in a hospital setting due its large particle size.

Precipitation from SCF, however, allows for the careful control of particle size to yield uniform nanoparticles that can be injected intramuscularly at a doctor's office.

The same principle can be applied to many other drugs, and Phasex is working with a Montreal company, RTP Pharma, on the production of nanoparticles of hydrophobic drugs.

Another example is the purification of a polymer used in a medical device. The polymer had an impurity deleterious to the body.

"Using SCF, we process tens of thousands of pounds of this polymer to remove the impurity, which is present at only one-tenth of one percent of the total weight," says Mr. Krukonis.

Phasex has also used SCF for many other applications that benefit from selective extraction, fractionation, ultra-fine particle formation or surface modification. It is even possible to run reactions in SCF.

The economics of SCF must be considered case-by-case, says Mr. Krukonis. But he is convinced that its value is finally being recognized, and almost 20 years after founding Phasex, he sees a bright future.

Custom Manufacturers Find Their Niche.(CW Fine and Custom Chemicals Conference and Expo)

Chemical Week

Author/s: Samuel K. Moore

Competition for outsourcing deals, particularly in the fast-growing pharmaceuticals sector, is further stratifying the custom manufacturing industry, according to attendees at the CW Fine and Custom Chemicals Conference and Expo in Baltimore last month.

Large fine chemical firms are becoming as important a customer group as pharmaceutical firms for smaller, niche fine chemicals suppliers. Conference speakers say the large fine chemical companies are beginning to control the flow of contracts to niche producers.

Christian Leemann, business director/bulk pharmaceuticals and intermediates at Algroup Lonza, estimates that the leading 30-40 fine chemical companies compete to make about 15 new pharmaceuticals and pesticides every year. Leemann says that lopsided ratio is accelerating consolidation. "Custom synthesis is still considered a cottage industry," he says. "But size does matter." He suggests $200 million/year as the minimum size for a company to be competitive in fine chemicals for life science.

Cameron Reid, president of Reddy-Cheminor (Hyderabad, India), says consolidation dominates India's fine and custom chemicals industry. "The future of the industry is M&A, and those that are not candidates will become extinct," Reid says.

Major toll and custom producers, particularly those involved in manufacturing for the pharmaceuticals industry, are adding to their capabilities. AlliedSignal has been expanding its newly acquired plants at Arklow, Ireland and Freeport, the Bahamas. At Freeport, Allied is installing a cryogenic reactor to attract drugs business.

Catalytica continues its efforts to become a single source for pharmaceuticals customers. James Cusumano, chairman of Catalytica, says he wants to double sales to $1 billion in the next five years through organic growth and acquisitions. The company recently strengthened its formulation capabilities, adding sterile dosage lines at Greenville, NC. Catalytica also plans to add to its biotechnology and fermentation capabilities (CW, April 21, p. 25).

Mergers and acquisitions have beefed up other custom manufacturers. Dow has pushed Hampshire Chemical, which it purchased two years ago, to aggressively pursue custom contracts, says Leo J. Thielman, leader/corporate development and market research at Hampshire. Thielman says that before the acquisition, Hampshire merely responded to customers seeking suppliers. "We tended to be reactive," he says. "Now we are consciously trying to partner with companies in pharmaceuticals, agrochemicals, and personal care at early stages."

Other recent M&A deals include Laporte's purchase of Inspec last year and this year's purchase of Haltermann by Ascot (London)-parent of Chemoxy International and Pentagon Chemicals.

Still, custom manufacturers intent on building broad technology platforms stress that opportunities remain for a "second tier" of niche suppliers. Leemann says these suppliers will have a regional customer base and will take work outsourced by the industry leaders as these bigger players shift toward services such as process development. Edward Richman, president of Richman Chemicals (Lower Gwynedd, PA), says this model also benefits firms such as his that specialize in outsourcing management.

Small suppliers say they have always benefitted from subcontracting. "We've had some opportunities to do pharmaceutical intermediates on a spot basis," says Frank LaMonica, general manager for custom producer Cymer (Decatur, TN). "We mostly come in to get people out of a jam."

Specialized niche chemistries help small manufacturers survive among giants, according to Val Krukonis, president of Phasex (Lawrence, MA), which specializes in supercritical fluids extraction. Krukonis says there is no danger of large companies getting into his field because it is too small.

Bob Kopki, contract manufacturing manager at Mobil Chemical, says this does not mean large companies cannot compete in custom manufacturing. He says his division acts as a small, entrepreneurial business. "In that regard, we're not all that much different [from smaller companies], though I suspect our equipment is bigger."

Mobil and Lubrizol are among the giants using their excess capacity to form custom manufacturing ventures. Mobil is offering to toll a variety of products, including esters and olefins, at Edison, NJ; Beaumont, TX; and Amsterdam. Lubrizol is tolling organic specialties at Painesville, OH.

More producers may follow. Mallinckrodt Baker (Phillipsburg, NJ) may parlay its analytical chemistry skills into a fine and custom chemicals business, says Herman J. Mitchell, senior business manager/chromatography products. Eui-Won Choe, technology consultant for petrochemical and pharmaceutical intermediates maker ISU Chemical (Seoul), says ISU is looking for a joint venture partner to market its services in the U.S.

Neil A. Burns, v.p./marketing at Pilot Chemical (Red Bank, NJ), says Pilot will commission expansions at its Lockland and Middletown, OH plants by third-quarter 1999. The expansion will triple the company's detergent sulfonation capacity and double its oil solubles sulfonation capacity. Burns adds that Pilot will have to establish manufacturing in Europe within a year-either on its own or through a jv-to keep up with its global customers.