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WO2008144063A1 - Sucralose lyophilisé - Google Patents

Sucralose lyophilisé Download PDF

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Publication number
WO2008144063A1
WO2008144063A1 PCT/US2008/006485 US2008006485W WO2008144063A1 WO 2008144063 A1 WO2008144063 A1 WO 2008144063A1 US 2008006485 W US2008006485 W US 2008006485W WO 2008144063 A1 WO2008144063 A1 WO 2008144063A1
Authority
WO
WIPO (PCT)
Prior art keywords
sucralose
beads
solvent
drying
droplets
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2008/006485
Other languages
English (en)
Inventor
Warren Lee Nehmer
Christopher R. King
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Tate and Lyle Technology Ltd
Original Assignee
Tate and Lyle Technology Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Tate and Lyle Technology Ltd filed Critical Tate and Lyle Technology Ltd
Publication of WO2008144063A1 publication Critical patent/WO2008144063A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
    • C07H5/02—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to halogen
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/30—Artificial sweetening agents
    • A23L27/33—Artificial sweetening agents containing sugars or derivatives
    • A23L27/37—Halogenated sugars

Definitions

  • Sucralose (4,l I ,6'-trichloro-4,l',6'-trideoxygalactosucrose), a high intensity sweetener made from sucrose, can be used in many food and beverage applications.
  • sucralose can be used in cooking and baking with no loss of sweetening power, and various forms of sucralose have been prepared to improve stability, ease handling, or otherwise adapt the use of sucralose to better suit any of a variety of end-use applications. Examples of such forms include needles, micronized (i.e., jet-milled), and agglomerated forms. Each of these has advantages and disadvantages, depending on the application.
  • the invention provides a method of producing sucralose beads.
  • the method includes the steps of a) forming droplets of a mixture including a solvent and dissolved sucralose; b) contacting the droplets with a fluid medium at a temperature low enough to freeze the droplets; and c) while maintaining the droplets in a frozen state, drying the frozen droplets to remove the solvent.
  • the invention provides a method of freeze drying sucralose.
  • the method includes the steps of a) depositing a mixture including a solvent and dissolved sucralose on a cold surface maintained at a temperature low enough to freeze the mixture; and b) while maintaining the mixture in a frozen state, applying a vacuum to remove the solvent.
  • the invention also provides dried sucralose prepared by either of the above methods.
  • the invention provides non-agglomerated solid spheres consisting of sucralose and optionally a buffer.
  • Figures 1, 2 and 3 are photomicrographs of exemplary sucralose beads according to the invention.
  • Figure 4 is a plot of thermogravimetric data for a commercial sucralose sample.
  • Figure 5 is a plot of thermogravimetric data for sucralose beads made from a seeded solution according to the invention.
  • Figure 6 is a plot of thermogravimetric data for sucralose beads made from an unseeded solution according to the invention.
  • Figure 7 is a differential scanning calorimetry plot for a commercial sucralose sample.
  • Figure 8 is a differential scanning calorimetry plot for sucralose beads made from a seeded solution according to the invention.
  • Figure 9 is a differential scanning calorimetry plot for sucralose beads made from an unseeded solution according to the invention.
  • sucralose can be freeze dried to form crystalline sucralose, as opposed to the amorphous/glassy product described by Jenner and Waite.
  • the invention provides methods of producing crystalline sucralose by freeze drying.
  • the invention provides particles that are nearly perfectly spherical and that have an essentially smooth surface, as distinct from products produced by agglomeration, granulation or spray drying.
  • the highly spherical shape provides dry, non-sticky particles having very good flow, very little dusting, and a pleasing appearance.
  • the degree of sphericity of the beads is such that each of at least 90% of them are essentially spherical, meaning that the shortest diameter of the bead is not less than 85% of the longest diameter. In most cases, the beads are even more nearly spherical than that, with at least 90% of them having a shortest diameter that is not less than 90% of the longest diameter.
  • Freeze drying of sucralose may be performed according to the invention by contacting droplets of a sucralose solution with a fluid medium at any temperature cold enough to freeze the droplets, and then drying (typically under vacuum) the still-frozen particles to evaporate the solvent.
  • the temperature for the freezing step will be about -20 0 C or less, more typically -50 0 C or less, and most typically -100 0 C or less.
  • reference to application of vacuum means exposure to reduced pressure.
  • the pressure will be less than 800 millitorr absolute, more typically less than 100 millitorr absolute. A pressure of about 50 millitorr may be used in some embodiments.
  • the solvent is typically water, but admixtures of water with other solvents may also be used.
  • a liquefied gas such as liquid nitrogen is used for the freezing step.
  • other cryogenic liquids may be used instead, such as liquefied natural gas and liquefied refrigerant gases such as fluorocarbons, hydrofluorocarbons, chlorofluorocarbons, and the like.
  • the particle size of the beads can be controlled over a wide range. Particles as large as about 5 mm diameter may be prepared by dispensing droplets of sucralose solution from a large enough dropper. For example, the diameter of the bead shown in Figure 1 is about 4.5mm.
  • Beads as small as about 10 ⁇ m may be desired in some circumstances, and can be made by dispensing the solution from a sufficiently small orifice. More typically, beads in a range of 100 ⁇ m to 700 ⁇ m will be desired, and product in which at least 90 wt% are within this range can be achieved by suitable adjustments to the dispensing apparatus. Freeze drying of the droplets may also be performed by spraying aqueous sucralose droplets into a gas carrier (typically air) at a temperature low enough to freeze the droplets (typically, less that about -50 0 C) and allowing the suspended frozen droplets to dry.
  • a gas carrier typically air
  • Freeze drying according to the invention may also be performed by depositing a sucralose solution (for example, in sheet or droplet form) on a cold surface (such as a conveyor belt) maintained at a temperature cold enough to freeze the solution, and applying vacuum.
  • a sucralose solution for example, in sheet or droplet form
  • a cold surface such as a conveyor belt
  • Continuous freeze dryers for performing such an operation are available commercially from a number of manufacturers.
  • the sucralose solution that is to be freeze dried may be of any concentration.
  • the solution will contain at least 20 wt% dissolved sucralose, more typically at least 30 wt%, and most typically at least 40 wt%.
  • a small amount of buffer may be added to the solution prior to freeze drying to enhance stability.
  • the buffer is typically present at a level of about 0.1 wt% relative to the total amount of sucralose in the mixture, and typically not more than about 2%.
  • Suitable buffers include salts of weak acids.
  • the salts will be alkali metal salts.
  • the weak acids may include phosphoric acid, carbonic acid, and carboxylic acids.
  • Exemplary carboxylic acids include formic, acetic, propionic, maleic, fumaric, and benzoic acid.
  • Suitable specific compounds include sodium citrate or potassium citrate; sodium phosphate or potassium phosphate; amino acid bases such as arginine and lysine; sodium tartrate or potassium tartrate; sodium adipate or potassium adipate; sodium malate or potassium malate; sodium phosphate monobasic and sodium phosphate dibasic.
  • sodium or potassium ascorbate caprylate, gluconate, lactate, and sorbate.
  • the sucralose solution contains essentially no undissolved sucralose, while in other embodiments the solution may be seeded with sucralose crystals, typically contributing no more than 10 wt% of the total sucralose in the mixture. More typically, the amount is no more than 5 wt%, and usually is no more than 2 wt%.
  • the freeze dried sucralose of this invention may be used in any of a variety of applications requiring the use of an artificial sweetener. For example, it may be dissolved in liquid products such as beverages or blended with solid ingredients such as other high intensity sweeteners, maltodextrin, sucrose, binders, and extenders.
  • Freeze dried sucralose was prepared by dropping a sucralose solution into liquid nitrogen and then putting the frozen droplets into a vacuum freeze dryer to remove the moisture.
  • a 50DS (50% dissolved solids) aqueous sucralose solution was prepared and then split into two batches. A small amount of ground sucralose crystals was added to one batch as seed, and the other was left unseeded. Approximately 5ml_ of each batch was slowly dropped into a Dewar flask of liquid nitrogen from a small syringe. The drops froze almost instantly, forming small spherical sucralose "beads.” After all of the solution was dropped into the nitrogen, the excess liquid nitrogen was decanted off.
  • the sucralose in the beads is at least 55% crystalline. More typically, it is at least 85% crystalline, and usually at least 95% crystalline.
  • Figure 1 shows an exemplary sucralose bead produced by freeze drying the unseeded aqueous sucralose solution described above.
  • the spherical, smooth-surfaced bead has a diameter of about 4.5 mm and has been partially fractured, revealing a porous cracked interior having a high internal surface area.
  • the interior has a large number of internal fissures that form voids within the solid sucralose that composes the particle.
  • Each bead is formed from a single droplet of sucralose solution, and the solid sucralose within each bead is formed in place during the freeze drying.
  • the beads consist of solid sucralose or sucralose fragments that form in situ, rather than a cluster of primary particles that have been formed separately and then agglomerated or otherwise bonded or adhered together to form the final beads.
  • noncompound or non-agglomerated sucralose spheres can be prepared according to the invention.
  • Figure 2 shows another, smaller spherical bead having a diameter of about 0.5 mm.
  • Figure 3 shows a bead of about 3.2 mm diameter, essentially spherical but for the presence of a single necked region on the surface, believed to have resulted from freezing that occurred so quickly that the droplet did not have time to fully relax to a spherical shape before freezing. All of Figures 1, 2 and 3 show beads having an essentially spherical shape and a smooth surface marked with hairline fractures.
  • Sucralose beads prepared from seeded and unseeded aqueous sucralose solutions using the liquid nitrogen technique described above were evaluated to determine degree of moisture absorption as a function of relative humidity (% RH).
  • % RH relative humidity
  • a sample of commercial sucralose needles ("neat" sucralose) was also evaluated in parallel, and the results for these runs are shown in Table 1. Each column represents a ramping up of % RH from zero to 80, followed by ramping back down to 20.
  • each of the three samples was significantly different from the others.
  • the neat (commercial) product showed essentially zero moisture absorption until the RH reached 80%, at which the absorption jumped to 0.1 %.
  • the seeded product began absorbing small amounts of moisture even at low RH, but the maximum value was less than half of that seen with the commercial product. In any case, the absorption was no greater than that of the commercial product under the same test conditions.
  • the unseeded product was different from either of these. It showed significantly higher moisture absorption and further, unlike the other two, showed hysteresis in the moisture absorption/desorption behavior. That is, the mass increase values were significantly lower at most locations on the downward RH ramp than they were at the corresponding locations on the upward ramp, indicating that the product had changed in some way during the experiment. Thus, these products are all substantially different in their response to atmospheric moisture.
  • Thermogravimetric analysis was performed on commercial, seeded and unseeded samples made as described above in order to assess stability of the products at high temperature. The results are shown in Figures 4, 5 and 6, respectively.
  • the mass of a sample was followed as a function of time at 90 0 C in nitrogen, recorded as percent of original mass remaining.
  • the vertical lines represent the point of the mass curve representing the halfway point of mass loss, and thus may be used as a measure of how rapidly decomposition set in.
  • the commercial sample was the earliest to show significant decomposition.
  • the seeded product took considerably longer, and the unseeded product was intermediate between the two. This further bears out the fact, noted above in view of the moisture absorption results, that these samples represent three different forms of sucralose.
  • thermograms of the three samples are distinct from each other in a way that again indicates different structure in the particles.

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  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Food Science & Technology (AREA)
  • Nutrition Science (AREA)
  • Polymers & Plastics (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne un procédé de lyophilisation du sucralose comprenant une étape consistant à mettre en contact une solution de sucralose avec une surface froide ou un fluide froid de manière à congeler la solution et une étape consistant à évaporer le solvant afin d'entraîner une dessiccation du sucralose. La solution de sucralose peut comprendre du sucralose cristallin non dissous. Des sphères de sucralose non agglomérées peuvent être produites selon certains aspects de l'invention.
PCT/US2008/006485 2007-05-21 2008-05-21 Sucralose lyophilisé Ceased WO2008144063A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US93131907P 2007-05-21 2007-05-21
US60/931,319 2007-05-21

Publications (1)

Publication Number Publication Date
WO2008144063A1 true WO2008144063A1 (fr) 2008-11-27

Family

ID=39691023

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/006485 Ceased WO2008144063A1 (fr) 2007-05-21 2008-05-21 Sucralose lyophilisé

Country Status (1)

Country Link
WO (1) WO2008144063A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009140345A3 (fr) * 2008-05-15 2010-02-25 Tate & Lyle Technology Ltd Cristaux de sucralose rincés au moyen d'un tampon
WO2011124667A2 (fr) 2010-04-09 2011-10-13 Qiagen Gmbh Procédé de production de lyophilisats sensiblement sphériques

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3672917A (en) * 1969-08-15 1972-06-27 Fmc Corp Method of improving quality and storage stability of dehydrated products
EP0472500A1 (fr) * 1990-08-21 1992-02-26 Warner-Lambert Company Edulcorants type chlordéoxysaccharide stabilisés à l'état solide et procédés de leur préparation
US20030091714A1 (en) * 2000-11-17 2003-05-15 Merkel Carolyn M. Meltable form of sucralose

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3672917A (en) * 1969-08-15 1972-06-27 Fmc Corp Method of improving quality and storage stability of dehydrated products
EP0472500A1 (fr) * 1990-08-21 1992-02-26 Warner-Lambert Company Edulcorants type chlordéoxysaccharide stabilisés à l'état solide et procédés de leur préparation
US20030091714A1 (en) * 2000-11-17 2003-05-15 Merkel Carolyn M. Meltable form of sucralose

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
HINDMARSH ET AL: "Fundamentals of the spray freezing of foods-microstructure of frozen droplets", JOURNAL OF FOOD ENGINEERING, BARKING, ESSEX, GB, vol. 78, no. 1, 1 January 2007 (2007-01-01), pages 136 - 150, XP005558565, ISSN: 0260-8774 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009140345A3 (fr) * 2008-05-15 2010-02-25 Tate & Lyle Technology Ltd Cristaux de sucralose rincés au moyen d'un tampon
WO2011124667A2 (fr) 2010-04-09 2011-10-13 Qiagen Gmbh Procédé de production de lyophilisats sensiblement sphériques

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