WO2009123732A2 - Démulsifiants et procédés d'utilisation dans des applications pharmaceutiques - Google Patents

Démulsifiants et procédés d'utilisation dans des applications pharmaceutiques Download PDF

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Publication number
WO2009123732A2
WO2009123732A2 PCT/US2009/002056 US2009002056W WO2009123732A2 WO 2009123732 A2 WO2009123732 A2 WO 2009123732A2 US 2009002056 W US2009002056 W US 2009002056W WO 2009123732 A2 WO2009123732 A2 WO 2009123732A2
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WIPO (PCT)
Prior art keywords
demulsifier
ethylene oxide
propylene oxide
surfactant
group
Prior art date
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Ceased
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PCT/US2009/002056
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English (en)
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WO2009123732A3 (fr
Inventor
Ruela Talingting-Pabalan
Manilal S. Dahanayake
Gary Woodward
Herve Adam
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Solvay USA Inc
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Rhodia Inc
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Priority claimed from US12/191,130 external-priority patent/US7671099B2/en
Application filed by Rhodia Inc filed Critical Rhodia Inc
Priority to CA2720290A priority Critical patent/CA2720290C/fr
Priority to EP09727655.4A priority patent/EP2276468A4/fr
Publication of WO2009123732A2 publication Critical patent/WO2009123732A2/fr
Publication of WO2009123732A3 publication Critical patent/WO2009123732A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D17/00—Separation of liquids, not provided for elsewhere, e.g. by thermal diffusion
    • B01D17/02—Separation of non-miscible liquids
    • B01D17/04—Breaking emulsions
    • B01D17/047—Breaking emulsions with separation aids

Definitions

  • the present invention generally relates to demulsifiers for use in industrial applications and, in particular, to demulsifiers comprising one or more anionic surfactants and/or nonionic surfactants for use in pharmaceutical applications.
  • preparing pharmaceuticals involves the extraction of the desired pharmaceutical from a liquid medium, typically a fermentation mixture. Extraction is necessary because the liquid medium may contain not only the desired pharmaceutical, but may also contain contaminants and impurities such as microorganisms, enzymes and other undesirable components. Typically, this process is carried out in industrial bioreactors through batch production or in continuous production.
  • Extraction of the desired pharmaceutical is typically accomplished in a multi-step process.
  • a solvent is added to the liquid medium, typically an organic phase such as amyl acetate, methyl ethyl ketone, amyl alcohol, butyl alcohol, benzyl alcohol or the like.
  • the solvent is added to extract the desired pharmaceutical from the liquid medium to the organic phase.
  • the liquid medium is then separated from the organic phase.
  • this separation may be difficult to achieve as the liquid medium and organic phase often form an emulsion. Over time, the liquid medium and organic phase slowly separate themselves. More often, however, the addition of a demulsifier is desirable to encourage or speed up the separation of the phases .
  • the solvent phase is generally made up of the desired pharmaceutical, solvent, as well as trace amounts of impurities or contaminants.
  • the liquid medium is generally made the remaining impurities, contaminants and other undesirable components. There may also be trace amounts of the desired pharmaceutical remaining/dissolved in the liquid medium.
  • the solvent phase may be purified and decontaminated after separation from the water phase by, for example, the addition of purified water or passing the solvent through active carbon.
  • the desired pharmaceutical can then be extracted from the solvent and into a water phase.
  • a water phase is by a re-adjustment of the pH of the mix. It is sometimes desirable to isolate a particular phase to more effectively isolate the pharmaceutical (e.g., precipitation of the active from water more easily achieved) , among other reasons. Further, separation of the new water and solvent emulsion can be achieved through the similar aforementioned process. Excess solvent or water can be evaporated off, depending on the phase in which the pharmaceutical is maintained.
  • the present invention provides a demulsifier for use in a variety of industrial applications comprising one or more anionic surfactants, one or more non-ionic surfactants, or a combination thereof. It has been unexpectedly found that demulsifiers containing alkylsulfosuccinates, alkylsufonates, alkylphosphonic acids, and their salts work effectively in pharmaceutical applications. In one embodiment, it has been found that a demulsifier comprising dioctyl sodium sulfosuccinate, sold under the trade name PENTEX 99TM (Rhodia Inc., Cranbury, NJ), works effectively in pharmaceutical applications, for example, in the extraction of penicillin and derivates thereof.
  • PENTEX 99TM Rosodia Inc., Cranbury, NJ
  • compositions comprise an agent and a pharmaceutically acceptable carrier.
  • the agent is present in an amount that is therapeutically effective, preferably in purified form.
  • pharmaceutically acceptable means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or similar pharmacopeia .
  • One aspect of the present invention provides a demulsifier comprising: an anionic surfactant selected from the group consisting of alkylsulfosuccinates, alkylsulfonates, alkylphosphonic acids, salts thereof, and combinations thereof; a nonionic surfactant selected from the group consisting of ethylene oxide/propylene oxide copolymers, ethoxylated fatty acids of polyethylene glycol, terpene alkoxylates, modified alkanolmides, and combinations thereof; or a combination of one or more nonionic surfactant and anionic surfactant.
  • an anionic surfactant selected from the group consisting of alkylsulfosuccinates, alkylsulfonates, alkylphosphonic acids, salts thereof, and combinations thereof
  • a nonionic surfactant selected from the group consisting of ethylene oxide/propylene oxide copolymers, ethoxylated fatty acids of polyethylene glycol, terpene alkoxylate
  • demulsifier for use in pharmaceutical applications comprising: an anionic surfactant selected from the group consisting of alkylalkylsulfonates, succinates, alkylphosphonic acids, salts thereof, and combinations thereof.
  • the demulsifier comprises dioctyl sodium sulfosuccinate .
  • the demulsifier comprises an alkylsulfonate, typically an alkylsulfonate having from 5 to 25 carbon atoms, more typically having from 8 to 20 carbon atoms, and most typically having from 10 to 19 carbon atoms.
  • Another aspect of the present invention provides a demulsifier for use in pharmaceutical applications comprising a nonionic surfactant selected from the group consisting of ethylene oxide/propylene oxide copolymers, ethoxylated fatty acids of polyethylene glycol, terpene alkoxylates, modified alkanolmides, and combinations thereof.
  • a nonionic surfactant selected from the group consisting of ethylene oxide/propylene oxide copolymers, ethoxylated fatty acids of polyethylene glycol, terpene alkoxylates, modified alkanolmides, and combinations thereof.
  • the present invention is a method for breaking an emulsion produced in the preparation of pharmaceuticals comprising contacting the emulsion with a demulsifier comprising: (a) an anionic surfactant selected from the group consisting of alkylsulfosuccinates, alkylsulfonate, alkylphosphonic acids, salts thereof, and combinations thereof; (b) a nonionic surfactant selected from the group consisting of ethylene oxide/propylene oxide copolymers, ethoxylated fatty acids of polyethylene glycol, terpene alkoxylates, modified alkanolamides, and combinations thereof; or (c) a combination of (a) and (b) .
  • a demulsifier comprising: (a) an anionic surfactant selected from the group consisting of alkylsulfosuccinates, alkylsulfonate, alkylphosphonic acids, salts thereof, and combinations thereof; (b) a nonionic surfactant selected from the
  • the present invention is a method for breaking an emulsion produced in the preparation of pharmaceuticals comprising contacting the emulsion with a demulsifier comprising dioctyl sodium sulfosuccinate or a Cio - Ci 8 sulfonate.
  • the pharmaceutical is an antibiotic, typically, penicillin or derivatives thereof.
  • a further aspect of the present invention provides a demulsifier formulated with a relatively low surfactant levels compared to polymers for cost-effective performance.
  • the present invention generally relates to demulsifiers for resolving or otherwise "breaking" emulsions that typically form during industrial applications including but not limited to pharmaceutical and home and beauty applications. More specifically, the present invention generally relates to solvent-in-oil demulsifiers having low toxicity and comprising one or more of an anionic surfactant, a nonionic surfactant or a combination thereof.
  • emulsion shall mean a composition, usually liquid or gelled, comprising two or more immiscible phases in which a first phase (the “dispersed phase”) is dispersed in a second phase (the “continuous phase”).
  • Oil and water emulsions include water-in-oil emulsions (water dispersed in oil) and oil-in-water emulsions (oil dispersed in water) .
  • solvent and water emulsions include solvent-in-water emulsions (solvent dispersed in water) and water-in-solvent emulsions (water dispersed in solvent) .
  • any reference to “emulsion” shall be interpreted to apply equally to all aforementioned emulsions.
  • the term “inverse emulsion” refers to an oil-in-water or solvent-in-water emulsion.
  • surfactant and "emulsifier” are interchangeable and generally refer to a wetting agent that lowers the surface or interfacial tension between two liquids. Using surfactants allows obtaining the dispersion of one phase in the other.
  • the term "demulsifier” shall mean a surfactant, combination of surfactants or surfactant systems that inhibit or prevent dispersion in an emulsion, thereby permitting the immiscible substances to be more readily separated from one another.
  • emulsion breaking shall refer to the process of disrupting the stable surface between the continuous phase and dispersed phase of an emulsion. It is generally accepted that high molecular weight surfactants and water soluble polymers will displace lower molecular weight surfactants at a surface boundary. "Emulsion breakers” are designed to be similar in chemistry to emulsifying surfactants but have a significantly higher molecular weight, allowing them to disrupt the surface layer and destabilize the emulsion. See, e.g., Brady, J. E. and G. E. Humiston, General Chemistry, Principles and Structure, John Wiley and Sons, Inc., New York
  • water is used herein to mean water to prepare demulsifiers and water present in oil and water emulsions as well as oil and solvent emulsions.
  • water may contain dissolved organic salts, organic acids, organic acid salts, inorganic salts, or combinations thereof. Examples are potassium chloride, ammonium chloride, and trimethylammonum chloride.
  • Useful surfactants include anionic and nonionic compounds, which may be used separately or as a mixture in a system, as described below in greater detail.
  • Anionic and nonionic surfactants are added in concentrations that range preferably from about 50 parts per million ("ppm") to about 10,000 ppm of the liquid component volume and more preferably from about 125 ppm to about 2000 ppm of the liquid component volume.
  • the surfactants of the present invention may be used individually or in mixtures or systems.
  • the present invention provides, in one embodiment, a demulsifier comprising: an anionic surfactant selected from the group consisting of alkylsulfosuccinates, alkylsulfonate, alkylphosphonic acids, and salts thereof; a nonionic surfactant selected from the group consisting of ethylene oxide/propylene oxide copolymers, ethoxylated fatty acids of polyethylene glycol, terpene alkoxylates and modified alkanolamides; or a combination of one or more anionic surfactants and nonionic surfactants .
  • an anionic surfactant selected from the group consisting of alkylsulfosuccinates, alkylsulfonate, alkylphosphonic acids, and salts thereof
  • a nonionic surfactant selected from the group consisting of ethylene oxide/propylene oxide copolymers, ethoxylated fatty acids of polyethylene glycol, terpene alkoxylates and modified alkanol
  • the anionic surfactant may be present in amounts from about 5% to about 95% by weight of the total surfactant, and the nonionic surfactant may be present in amount from about 5% to about 95% by weight by weight of the total surfactant.
  • the anionic surfactant is present from about 10% to about 80% by weight by weight of the total surfactant and the nonionic surfactant is present from about 10% to about 80% by weight by weight of the total surfactant.
  • Anionic surfactants useful in the demulsifier composition of the present invention include but are not limited to alkylsulfosuccinates, alkylsulfonates, alkylphosphonic acids, and their salts, and combinations thereof.
  • dioctyl sodium sulfosuccinate and systems thereof sold under the trade name PENTEX 99TM (Rhodia Inc., Cranbury, NJ)
  • PENTEX 99TM Rosodia Inc., Cranbury, NJ
  • dioctyl sulfosuccinate and salts thereof including dioctyl sodium sulfosuccinate are effective demulsifiers in the extraction of penicillin.
  • Anionic surfactants, and in particular, sulfosuccinates such as sodium dioctylsulfosuccinate may be used in either powder form or in solution .
  • anionic surfactants include, but are not limited to, aliphatic sulfonates, such as a primary alkane (e.g., C 5 -C 25 ) sulfonates, primary alkane (e.g., C 5 -C 25 ) disulfonates, (C 5 -C2 5 )alkene sulfonates, C 5 -C 25 hydroxyalkane sulfonates, alkyl glyceryl ether sulfonates (AGS) , aromatic sulfonates such as alkyl benzene sulfonates.
  • the anionic surfactant is sodium Ci 0 -C 2O olefin sulfonate, more typically sodium Ci 4 -Ci 6 olefin sulfonate.
  • the anionic surfactant comprises an alkylsulfonate, typically an alkylsulfonate having from 5 to 25 carbon atoms, more typically having from 8 to 20 carbon atoms, and most typically having from 10 to 19 carbon atoms .
  • the anionic surfactant may be octylphosphonic acid, laurylphosphonic acid, salts of octylphosphonic acid, salts of laurylphosphonic acid, and combinations thereof.
  • Suitable anionic surfactants include the following structural formulas:
  • R 1 is alkyl and may be branched or linear; "M" is hydrogen, an alkali metal such as sodium or potassium, or an ammonium salt; R 1 preferably contains 5 to 20 carbon atoms, more preferably 5 to 16 atoms, most preferably 8 to 12 carbon atoms.
  • R 2 is selected from the group consisting of alkyl, -CH 2 CH 2 OH, aryl, alkaryl, alkoxy, alkylarylalkyl, arylalkyl, alkylamidoalkyl and alkylaminoalkyl .
  • the group preferably has about 5 to about 20 carbon atoms and more preferably has about 10 to about 18 carbon atoms.
  • R 2 represents aryl the group preferably comprises a phenyl, diphenyl, diphenylether, or naphthalene moiety.
  • M is hydrogen, an alkali metal such as sodium or potassium, or an ammonium salt.
  • M is preferably an alkali metal such as sodium or potassium, more preferably sodium.
  • Nonionic surfactants for use in the present invention include but are not limited to linear copolymers, block copolymers, and reverse copolymers of ethylene oxide/propylene oxide; ethoxylated fatty acids of polyethylene glycol/polypropylene glycol; fatty acid esters; glycerol esters; ethoxylated fatty acids esters of glycol; ethoxylated fatty acid esters of polyethylene glycol; terpene alkoxylates, modified alkanolamides and sorbitan esters.
  • Typical nonionic surfactants are ethylene oxide/propylene oxide copolymers, ethoxylated fatty acids esters of glycol, ethoxylated fatty acid esters of polyethylene glycol, terpene alkoxylates and modified alkanomides. More typical nonionic surfactants are ethylene oxide/propylene oxide copolymers, ethoxylated fatty acid esters of polyethylene glycol, terpene alkoxylates, and combinations thereof.
  • Suitable non-ionic surfactants include the surfactants having the structural formulas as shown below.
  • Suitable ethylene oxide/propylene oxide copolymers may be selected from the group consisting of ethylene oxide/propylene oxide block copolymers, ethylene oxide/propylene oxide alkoxylates, and ethylene oxide/propylene oxide reverse copolymers.
  • nonionic surfactant is the product sold under the trade name ANTAROX® L- 64 (Rhodia Inc., Cranbury, NJ) .
  • m is from about 10 to 60 and "n” is about 0 to about 15. In one embodiment, "m” is about 27, and “n” is about 8.
  • the nonionic surfactant is the product sold under the trade name ANTAROX® 31Rl (Rhodia Inc., Cranbury, NJ).
  • R 3 is a hydrocarbon chain hydrocarbon chain containing about 1 to about 22 carbon atoms and may be branched or straight-chained and saturated or unsaturated.
  • "d” is about 5 and "e” is about 8.
  • the nonionic surfactant is the product sold under the trade name ANTAROX® BL-14 (Rhodia Inc., Cranbury, NJ) .
  • R 4 is a hydrogen or a hydrocarbon chain containing about 10 to about 22 carbon atoms and may be branched or straight-chained and saturated or unsaturated and is selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, alkaryl, alkylarylalkyl, arylalkyl, alkylamidoalkyl, and alkylaminoalkyl .
  • R 5 is preferably a hydrocarbon chain containing about 1 to about 22 carbon atoms and may be branched or straight-chained and saturated or unsaturated and is selected from the group consisting of alkyl, alkoxy, aryl, alkaryl, alkylarylalkyl, arylalkyl, alkylamidoalkyl, and alkylaminoalkyl.
  • the groups preferably have about 5 to about 20 carbon atoms and more preferably have about 10 to about 18 carbon atoms.
  • the groups preferably comprise a phenyl, diphenyl, diphenylether, or naphthalene moiety.
  • x is from about 1 to about 20.
  • the structures are mono and diesters .
  • the nonionic surfactants are the products of dioleate ester of PEG 400, sold under the trade name ALKAMUS® 400DO (Rhodia Inc., Cranbury, NJ).
  • Terpene alkoxylates are terpene-based surfactants derived from a renewable raw materials such as ⁇ -pinene and ⁇ - pinene, and have a C-9 bicyclic alkyl hydrophobe and polyoxy alkylene units in an block distribution or intermixed in random or tapered distribution along the hydrophilic chain.
  • the terpene alkoxylate surfactants are described in the U.S. Patent Application Publication No. 2006/0135683 to Adam al., June 22, 2006, is incorporated herein by reference.
  • Typical terpene alkoxylates are Nopol alkoxylate surfactants and have the general formula:
  • R is hydrogen, CH 3 , or C 2 H 5 ; 30; "m” is from about 0 to about 20.
  • the “n” and “m” units may be of block distribution or intermixed in random or tapered distribution along the chain.
  • R 6 is CH 3 ; "n" is from about 20 [0053]
  • the nonionic surfactant is the product sold under the trade name RHODOCLEAN® HP (Rhodia Inc., Cranbury, NJ).
  • the demulsifiers of the present invention contain modified alkanolamides as non ionic surfactant.
  • the modified alkanolamide is the product sold under the trade name ANTAROX AG 5 (Rhodia Inc., Cranbury, NJ).
  • Demulsifiers of the present invention may be used alone or in combination with any of a number of additional demulsifiers described herein or known in the art including but not limited to alkylphenol formaldehyde condensation products such as alkylphenol formaldehyde, resin alkoxylates, polyalkylene glycols including polypropylene glycols and cross- linked polypropylene glycols, organic sulfonates, alkoxylated alcohols, alkoxylated polyols, fatty acids, complex resin esters, alkoxylated fatty amines, alkoxylated polymeric amines, and the like.
  • alkylphenol formaldehyde condensation products such as alkylphenol formaldehyde, resin alkoxylates, polyalkylene glycols including polypropylene glycols and cross- linked polypropylene glycols, organic sulfonates, alkoxylated alcohols, alkoxylated polyols, fatty acids, complex resin esters,
  • the demulsifier may comprise an alkylsulfosuccinate such as sodium diisooctylsulfosuccinate and an ethylene oxide/propylene oxide copolymer.
  • the demulsifier may comprise an alkylsulfosuccinate and an ethoxylated fatty acid of ethylene glycol .
  • the demulsifiers of the present invention may also be used in systems in combination with components such as organic solvents, viscosity reducers, and other chemical treatments used in industrial processing.
  • a variety of conventional additives that do not adversely affect the demulsifier performance can be used.
  • a demulsifier composition is prepared by mixing water with a surfactant comprising an anionic surfactant, a nonionic surfactant, or combinations thereof.
  • the water utilized for forming the demulsifier of this invention can be fresh water or salt water.
  • the water may contain dissolved organic salts, organic acids, organic acid salts, inorganic salts, or combinations thereof.
  • the demulsifier may contain one or more organic solvents.
  • a demulsifier composition comprises a surfactant present from about 60% to about 100% by weight of the composition, propylene glycol present from about 0% to about 2% by weight of the composition, isopropyl alcohol present from about 0% to about 2% by weight of the composition, and water.
  • the surfactant is from about 70% to about 80% by weight of the composition.
  • the initial pH of the demulsifier composition may be lowered or raised to impart stability or to aid in the partitioning of the desired pharmaceutical.
  • the decrease of pH may be by brought about by adding acid and/or buffers.
  • it may be suitable to add a base and/or buffers to increase the pH of the demulsifier composition.
  • the present invention further provides a method for breaking an emulsion produced in the preparation of pharmaceuticals.
  • the emulsion typically comprises oil and water or solvent and water.
  • the method includes contacting the emulsion with any of the demulsifiers described herein or any combinations of such demulsifiers .
  • demulsifiers are surprisingly effective in breaking emulsions produced in preparation of certain pharmaceuticals such an antibiotics, including in particular, penicillin or substances obtained from fungus (e.g, streptomycin, efrotomycin) , by fermentation.
  • demulsifiers comprising dioctyl sodium sulfosuccinate have been found to be particularly effective in phase separation with a well defined interface, wherein substantially or substantially all of the desired pharmaceutical was segregated into one of the phases chosen by manufacturer.
  • the phase in which the desired pharmaceutical is maintained depends in large part on manipulation of the pH. For example, a low pH adjustment (i.e., acidic) may cause the desired pharmaceutical to collect in the organic phase, whereas a higher pH adjustment (i.e., neutral or basic) may cause the desired pharmaceutical to collect in the water phase.
  • the method comprises contacting the emulsion with a demulsifier comprising an anionic surfactant selected from the group consisting of alkylsulfosuccinates, alkylphosphonic acids, and salts of alkylphosphonic acids; a nonionic surfactant selected from the group consisting of ethylene oxide/propylene oxide copolymers, ethoxylated fatty acids of polyethylene glycol, terpene alkoxylates, and modified alkanolamides; or a combination of at least one anionic surfactant and nonionic surfactant.
  • a demulsifier comprising an anionic surfactant selected from the group consisting of alkylsulfosuccinates, alkylphosphonic acids, and salts of alkylphosphonic acids; a nonionic surfactant selected from the group consisting of ethylene oxide/propylene oxide copolymers, ethoxylated fatty acids of polyethylene glycol, terpene alkoxylates, and modified al
  • the method may include contacting an emulsion with a demulsifier composed of an alkylsulfosuccinate such as diooctyl sodium sulfosuccinate and an ethylene oxide/propylene oxide copolymer.
  • a demulsifier composed of an alkylsulfosuccinate such as diooctyl sodium sulfosuccinate and an ethylene oxide/propylene oxide copolymer.
  • the method may also include contacting the emulsion with the demulsifier composed of an alkylsulfosuccinate and an ethoxylated fatty acid of ethylene glycol.
  • the demulsifier is comprised of dioctyl sodium sulfosuccinate (sold under the trade name PENTEX 99TM (Rhodia Inc., Cranbury, NJ).
  • pH of the mixture is adjusted to below a pH of 4 using any acceptable acid including but not limited to sulfuric acid and citric acid.
  • an extracting solvent including but not limited to amyl acetate, methyl ethyl ketone, methyl isobutyl ketone, amyl alcohol, butyl acetate, butyl alcohol, benzyl alcohol or the like, is added to extract the desired pharmaceutical from the water phase to the solvent.
  • the process is typically run at a process temperature of between about 5°C to about 50 0 C. At the present stage, most or a substantial part of the pharmaceutical is separated into the solvent.
  • the solvent is optionally cleaned by filtering the solvent through a mixture of activated/active carbon.
  • the next step can be employed by adjusting the pH of the mixture to a neutral or basic pH, which is typically between about 7 to about 9. Water is then added to the solvent with the desired pharmaceutical to form a second emulsion. The desired pharmaceutical can thus be separated from the solvent and into the added water (separation may be accomplished as described above for the first step emulsion) .
  • the demulsifier comprising the present invention can be added at any time during the process, including but not limited to during, before or after the first emulsion and/or second emulsion.
  • the method includes dispersing the demulsifier in a suitable solvent or liquid carrier.
  • Representative solvents and carriers include aromatic hydrocarbons, aliphatic hydrocarbons such as kerosene, glycols, glycol ethers, alcohols, water, hydrocarbons, aromatic solvents, fatty acid methyl esters, similar compounds, and combinations thereof.
  • the liquid carrier may then be applied to the emulsion by any suitable process commonly known in the art.

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Abstract

L'invention porte sur des démulsifiants contenant un agent tensio-actif anionique choisi parmi les alkylsulfosuccinates, les alkylsulfonates, les acides alkylphosphoniques et leurs sels ; sur un agent tensio-actif non ionique choisi parmi les copolymères oxyde d'éthylène/oxyde de propylène, les acides gras éthoxylés de polyéthylène glycol, les alcoxylates de terpène et les alcanolamides modifiés ; ou sur une combinaison d'un agent tensio-actif anionique et d'un agent tensio-actif non ionique, et sur des procédés d'utilisation de ceux-ci dans des émulsions de rupture.
PCT/US2009/002056 2008-04-02 2009-04-02 Démulsifiants et procédés d'utilisation dans des applications pharmaceutiques Ceased WO2009123732A2 (fr)

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CA2720290A CA2720290C (fr) 2008-04-02 2009-04-02 Demulsifiants et procedes d'utilisation dans des applications pharmaceutiques
EP09727655.4A EP2276468A4 (fr) 2008-04-02 2009-04-02 Démulsifiants et procédés d'utilisation dans des applications pharmaceutiques

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US7276808P 2008-04-02 2008-04-02
US61/072,768 2008-04-02
US12/191,130 US7671099B2 (en) 2007-08-13 2008-08-13 Method for spearation crude oil emulsions
US12/191,130 2008-08-13

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WO2009123732A2 true WO2009123732A2 (fr) 2009-10-08
WO2009123732A3 WO2009123732A3 (fr) 2009-12-30

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EP2276468A4 (fr) 2013-05-01
WO2009123732A3 (fr) 2009-12-30
CA2720290A1 (fr) 2009-10-08
CA2720290C (fr) 2017-05-23
EP2276468A2 (fr) 2011-01-26

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