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WO2025219482A1 - Composition de gel constituée de gomme gellane et d'agarose pour la production de capsules ou de films souples, son utilisation et son procédé de production - Google Patents

Composition de gel constituée de gomme gellane et d'agarose pour la production de capsules ou de films souples, son utilisation et son procédé de production

Info

Publication number
WO2025219482A1
WO2025219482A1 PCT/EP2025/060569 EP2025060569W WO2025219482A1 WO 2025219482 A1 WO2025219482 A1 WO 2025219482A1 EP 2025060569 W EP2025060569 W EP 2025060569W WO 2025219482 A1 WO2025219482 A1 WO 2025219482A1
Authority
WO
WIPO (PCT)
Prior art keywords
gel mass
agar
gel
weight
film
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.)
Pending
Application number
PCT/EP2025/060569
Other languages
German (de)
English (en)
Inventor
Christoph HUNDSCHELL
Anja WAGEMANS
Isabel WASMUHT
Martin Hahn
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.)
Technische Universitaet Berlin Koerperschaft Des Oeffentlichen Rechts
Gelita AG
Original Assignee
Technische Universitaet Berlin Koerperschaft Des Oeffentlichen Rechts
Gelita AG
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 Technische Universitaet Berlin Koerperschaft Des Oeffentlichen Rechts, Gelita AG filed Critical Technische Universitaet Berlin Koerperschaft Des Oeffentlichen Rechts
Publication of WO2025219482A1 publication Critical patent/WO2025219482A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4816—Wall or shell material
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds

Definitions

  • the present invention relates to a gel mass for producing soft capsules or films, as well as a process for producing the gel mass.
  • the invention further relates to the use of such a gel mass for producing soft capsules or films, as well as to processes for producing soft capsules or films using such a gel mass.
  • Soft capsules have long been a well-known dosage form for pharmaceutical active ingredients or dietary supplements.
  • the vast majority of soft capsules on the market have a capsule shell based on gelatin as a gel-forming hydrocolloid.
  • These soft gelatin capsules are manufactured using the so-called Scherer process, in which the filling is encapsulated fully automatically using counter-rotating forming rollers (hence the synonymous term "rotary die process").
  • Two gel ribbons made of a gel mass, typically containing approximately 40 to 50 wt.% gelatin, a plasticizer (e.g., glycerin), and water, are passed between the forming rollers at a temperature of approximately 55 to 70°C and sealed around the filling. Upon cooling, the gel mass acquires its required strength through gelation (so-called cold-set gelation) and is then dried.
  • the invention is therefore based on the object of proposing a vegan gel mass from which soft capsules can be produced using the established Scherer process.
  • the gel mass of the type mentioned at the outset in that the gel mass comprises agarose, gellan with a high degree of acylation, one or more fillers, one or more plasticizers and water.
  • the combination of agarose and gellan with a high degree of acylation in particular, enables the production of a gel mass whose rheological properties are highly suitable for the production of soft capsules using the Scherer process.
  • the gel mass according to the invention can be processed using the same equipment used to produce soft gelatin capsules.
  • the agarose in particular, provides the required gel strength, while the gellan with a high degree of acylation is responsible for the required elasticity of the gel mass.
  • the respective advantageous properties of the two polymers, and in particular their gel formation, are surprisingly not negatively affected by this combination.
  • Agarose is a polysaccharide composed of D-galactose and 3,6-anhydro-L-galactose.
  • Agarose is the main component of agar, in which it, along with agaropectin, makes up approximately 70% by weight.
  • Agar is obtained from various algae species, primarily from the red algae of the genera Gelidium and Gracilara.
  • agarose is completely safe. This represents a significant advantage over carrageenan, a hydrocolloid also derived from algae, which, however, has been suspected for some time of causing allergenic effects in humans.
  • the European Food Safety Authority has set a permissible daily intake of 75 mg/kg body weight for carrageenan, whereas there are no such restrictions for agarose or agar.
  • the agarose is present as a component of agar in the gel mass according to the invention.
  • Agar is relatively inexpensive.
  • pure agarose which is obtained by removing the agaropectin from agar, can also be used for the gel mass.
  • the melting point of agar is typically around 92°C and thus higher than that of gellan (approximately 70 to 80°C)
  • the melting point of the gel mass according to the invention is primarily determined by the agar (or agarose). Since it is advantageous in the production of soft capsules if the gel bands can be sealed at the lowest possible temperature, the use of an agar with the lowest possible melting point is preferred within the scope of the invention.
  • the agar comprises partially hydrolyzed agar. Partial hydrolysis of the agar can reduce its melting point, e.g., to below 90°C or below 85°C. Partial hydrolysis can be achieved, in particular, by thermal hydrolysis of the agar, as described below, or by chemical or enzymatic hydrolysis.
  • the gel mass according to the invention comprises gellan with a high degree of acylation as another gel-forming hydrocolloid. that this, in combination with agarose, leads to significantly better rheological properties of the gel mass than gellan with a low degree of acylation.
  • the required proportion of agarose and gellan in the gel mass according to the invention is, as explained in detail below, significantly lower than for gelatin.
  • the gel mass according to the invention also contains one or more fillers.
  • the filler(s) are preferably selected from fructans, especially inulin, and from modified and/or hydrolyzed starches, especially maltodextrin.
  • unmodified starch is not suitable as a filler because it prevents the agarose from gelling.
  • the gel mass according to the invention further contains one or more plasticizers to ensure the required flexibility of the produced soft capsules.
  • the plasticizer(s) are preferably selected from sugar alcohols and non-reducing sugars, in particular from glycerol, sorbitol, sorbitan, mannitol, maltitol, isomalt, isomaltulose, and trehalose.
  • the gel mass further comprises one or more complexing agents for divalent metal ions.
  • the complexing agent(s) are preferably selected from alkali metal salts of polybasic carboxylic acids, particularly sodium or potassium citrate.
  • the gel mass according to the invention preferably comprises a significantly lower proportion of agarose and gellan with a high degree of acylation, typically approximately 5% by weight or less, than the gelatin content of a gel mass for soft gelatin capsules (approximately 40 to 50% by weight).
  • the quantitative composition of the gel mass according to the invention is preferably as follows: about 0.7 to about 2.1% by weight agarose or about 1.0 to about 3.0% by weight agar, preferably about 1.5 to about 2.5% by weight agar, about 1.0 to about 3.0% by weight, preferably about 1.5 to about 2.5% by weight gellan with a high degree of acylation, about 10 to about 25% by weight, preferably 12 to 20% by weight, of one or more fillers, about 10 to about 30% by weight, preferably 20 to 25% by weight of one or more plasticizers, about 0.5 to 2.0% by weight of one or more complexing agents for divalent metal ions, and about 37 to about 78% by weight water.
  • the specific composition of the gel mass is as follows: about 1.5 to about 2.5 wt% agar, about 2.0 to about 3.0 wt% gellan with a high degree of acylation, about 12 to about 20 wt% maltodextrin, about 8.0 to about 15 wt% glycerol, about 2.0 to about 3.0 wt% isomalt, about 0.5 to 1.5 wt% sodium citrate dihydrate, and about 55.0 to about 74.0 wt% water.
  • the concrete composition of the gel mass is as follows: about 1.5 to about 2.5 wt.% agar, about 1.5 to about 2.5 wt.% gellan with a high degree of acylation, about 12 to about 20 wt.% maltodextrin, about 12 to about 20 wt.% glycerol, about 8 to about 15 wt.% isomalt, about 0.5 to 1.5 wt.% sodium citrate dihydrate, and approx. 38.5 to approx. 64.5 wt% water.
  • the concrete composition of the gel mass is as follows: approx. 2 to approx. 3 wt.% agar, approx. 2 to approx. 3 wt.% gellan with a high degree of acylation, approx. 12 to approx. 20 wt.% maltodextrin, approx. 12 to approx. 20 wt.% glycerol, approx. 8 to approx. 15 wt.% isomalt, approx. 0.5 to 1.5 wt.% sodium citrate dihydrate, and approx. 37.5 to approx. 63.5 wt.% water.
  • a higher proportion of agar and gellan typically results in increased elasticity and strength of the soft capsules or films produced from the gel mass.
  • the gelling point of the gel mass according to the invention is, depending on the specific recipe, typically in the range of 50 to 70 °C.
  • the gel mass according to the invention is intended in particular for the production of vegan soft capsules, it preferably does not comprise any components obtained from animal raw materials, in particular no gelatin, collagen or collagen hydrolysate.
  • the gel mass according to the invention does not contain carrageenan.
  • carrageenan is not harmless from a health perspective.
  • To produce the gel composition according to the invention its components can be dissolved in water at elevated temperature, especially at approximately 100°C. The resulting homogeneous solution solidifies upon cooling below the gel point, e.g., in the form of a film.
  • Producing the gel mass by mixing the precursor with gellan with a high degree of acylation, one or more fillers, one or more plasticizers and water.
  • the production and processing of the gel mass according to the invention can be simplified and accelerated.
  • the agar is mixed with the required amount of glycerin to completely hydrate it, preferably at a temperature of approximately 95°C or more. Further processing, when the precursor is mixed with the remaining ingredients, may require additional glycerin addition.
  • the homogeneous agar/glycerin compound gels upon cooling and can be immediately mixed with the other ingredients to produce the inventive to obtain the gel mass according to the invention.
  • the compound is gelled, comminuted, and dried to produce a storable and transportable precursor, which is then further processed at a later time to produce the gel mass according to the invention.
  • the agar/glycerin compound is first gelled by cooling and then formed and/or comminuted using suitable methods, e.g., by extrusion or spheronization.
  • the precursor is obtained in particle form, particularly as granules.
  • the mixture of agar and glycerin can also be first "comminuted” by dripping and then gelled.
  • the comminuted precursor of agar and glycerin is preferably dried to a water content of less than approximately 15% by weight, more preferably less than approximately 10% by weight.
  • Such dried granules are microbiologically stable and have good storage and transport properties.
  • the present invention further relates to the use of the gel mass according to the invention for the production of soft capsules, in particular by means of the rotary die process (Scherer process).
  • the gel mass according to the invention is particularly distinguished by the fact that, due to its rheological properties, it can be used for the production of vegan soft capsules on the same systems used for the production of gelatin soft capsules. Thus, no additional costs arise due to the necessary adaptation of the rotary die systems.
  • the present invention further relates to a process for producing soft capsules, comprising the steps
  • the process according to the invention corresponds in its basic features to the known rotary die process for the production of soft gelatin capsules and, as mentioned, can be carried out on the same rotary die systems.
  • gelatin capsules differ from the production of gelatin capsules.
  • the aging process required for gelatin capsules which involves tempering the gel mass over a period of 6 to 18 hours, is not required for the agarose and gellan-based gel mass according to the invention.
  • the process according to the invention offers significant time savings.
  • the gel mass is typically provided at a temperature between 80 and 100 °C via a so-called spreader box. From this box, the gel mass is transferred to a rotating cooling drum to form the film. Cooling to a temperature below 30 °C can be achieved either passively or by means of active cooling.
  • the capsule filling is preferably enclosed by welding two strips of film at a temperature of approximately 95 °C or more, corresponding to the typical melting point of the gel mass.
  • welding can also be carried out at a temperature of approximately 85 °C or less.
  • the system usually comprises two spreader boxes, cooling drums, etc.
  • the capsule filling is added via a so-called wedge.
  • the film strips are welded around the filling using a rotating forming roller, the actual rotary die, and the capsules are formed.
  • the present invention further relates to a soft capsule produced from a gel composition according to the invention and/or by the process according to the invention. Preferred embodiments and advantages of the soft capsules according to the invention have already been described in connection with the gel composition according to the invention.
  • the soft capsule according to the invention preferably comprises a capsule shell having a thickness in the range of approximately 200 to approximately 1,000 pm, these values relating to the thickness of the capsule shell after drying of the soft capsule.
  • the resulting thickness of the capsule shell can be varied over a relatively wide range.
  • thinner or thicker capsule shells may be preferred, for example, in the range of approximately 200 to approximately 400 ⁇ m, approximately 400 to approximately 700 ⁇ m, or approximately 700 to approximately 1,000 ⁇ m.
  • the gel mass according to the invention is in principle also suitable for other applications, e.g. in the food sector or for technical applications.
  • the invention therefore also relates to the use of a gel mass according to the invention for producing a film, as well as to a film produced from a gel mass according to the invention.
  • Such films can be used, for example, for the production of foodstuffs or as a biodegradable film (e.g., as packaging material).
  • the film according to the invention preferably has a thickness in the range of about 200 to about 1,000 pm.
  • the inventive The gel mass can be applied to a carrier, in particular with an appropriate thickness, e.g., using a doctor blade, and then cooled and dried to gel.
  • the thickness of the film according to the invention can be varied over a relatively wide range, particularly depending on the intended use.
  • the film can have a thickness in the range of approximately 200 to approximately 400 ⁇ m, in the range of approximately 400 to approximately 700 ⁇ m, or in the range of approximately 700 to approximately 1,000 ⁇ m.
  • a special feature of the film according to the invention is that it is transparent after drying, unlike comparable films based on other hydrocolloids.
  • the transparency of the film represents a significant advantage for many applications.
  • Fig. 1 photographic image of a film produced from the gel mass according to the invention in a rotary die system
  • Fig. 2 Photographic image of a film according to the invention after drying.
  • the agar and sodium citrate are first boiled in water while stirring until a clear solution is obtained. Then, the filler maltodextrin and the plasticizer isomalt are mixed and added to the solution while stirring until a clear solution is obtained.
  • the highly acylated gellan is mixed with the plasticizer glycerin and gradually added to the hot solution. The mixture is stirred at 95 °C until a homogeneous gel mass is obtained.
  • crystallization of the isomalt can be prevented by mixing the isomalt with the maltodextrin before adding it to the solution.
  • the gel masses according to Examples 1 to 3 have a gel point of approximately 57 °C, approximately 62 °C and approximately 66 °C, respectively.
  • a film was produced from the gel mass according to Example 1 by pouring the gel mass from the spreader box of a rotary die system onto the cooling drum at approximately 80 °C.
  • the cooled and gelled film has sufficient stability and tensile strength to be able to be drawn over the deflection rollers of the Rotary die system without tearing.
  • Figure 1 shows a photographic image of film 18 running over several pulleys 10, 12, 14, 16.
  • the film Before drying, the film has a thickness of approximately 1,000 ⁇ m. After drying to a water content of approximately 16 wt.%, the thickness of the film according to the invention is approximately 850 ⁇ m.
  • the dried film is transparent.
  • a gel composition according to the invention was prepared according to Example 1.1 above and knife-coated onto a plastic carrier film with a thickness of approximately 1,000 ⁇ m. After cooling and drying, the film according to the invention had a thickness of approximately 700 ⁇ m.
  • Figure 2 shows a photographic image of the dried film 20 on the carrier foil 22, which in turn lies on a metal plate 24.
  • the film 20 is transparent, which can be seen by the clearly translucent colored dots 26 on the metal plate 24.
  • the sealing machine is equipped with a heating plate that is lowered onto the films to perform the welding process.
  • the two films are placed on top of each other, with the first film being formed into a hollow, creating a cavity between them. Pressing the heating plate against the film at a temperature of approximately 96-98 °C, the films briefly melt at the contact point and bond together. In this way, the films according to the invention could be joined together via a stable and permanent seam.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Jellies, Jams, And Syrups (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne une composition de gel pour la production de capsules ou de films souples, ladite composition de gel comprenant de l'agarose, de la gomme gellane ayant un degré d'acylation élevé, une ou plusieurs charges, un ou plusieurs plastifiants et de l'eau. L'invention concerne également un procédé de production de capsules souples, comprenant les étapes consistant à : fournir une composition de gel selon l'invention à une température comprise entre 80 et 100°C, former un film à partir de la composition de gel par refroidissement à une température inférieure à 30°C, fournir un agent de remplissage de capsule, produire les capsules souples en enfermant l'agent de remplissage de capsule avec le film formé à partir de la composition de gel, pour ainsi former l'enveloppe de capsule, et sécher l'enveloppe de capsule jusqu'à obtention d'une teneur en eau d'environ 20% en poids ou moins.
PCT/EP2025/060569 2024-04-19 2025-04-16 Composition de gel constituée de gomme gellane et d'agarose pour la production de capsules ou de films souples, son utilisation et son procédé de production Pending WO2025219482A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102024111019.8 2024-04-19
DE102024111019.8A DE102024111019A1 (de) 2024-04-19 2024-04-19 Gelmasse zur Herstellung von Weichkapseln oder Filmen, deren Verwendung und Herstellungsverfahren

Publications (1)

Publication Number Publication Date
WO2025219482A1 true WO2025219482A1 (fr) 2025-10-23

Family

ID=95480847

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2025/060569 Pending WO2025219482A1 (fr) 2024-04-19 2025-04-16 Composition de gel constituée de gomme gellane et d'agarose pour la production de capsules ou de films souples, son utilisation et son procédé de production

Country Status (2)

Country Link
DE (1) DE102024111019A1 (fr)
WO (1) WO2025219482A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1623757B1 (fr) * 2004-07-10 2009-02-11 Cognis IP Management GmbH Microcapsules (XXXII)
US20220226478A1 (en) * 2019-12-30 2022-07-21 Sirio Pharma Co., Ltd. Film-forming composition containing gellan gum and starch, and application in soft capsule

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK2258349T3 (da) 2004-05-11 2014-10-13 Egalet Ltd Kvældbar doseringsform omfattende gellangummi
WO2019208668A1 (fr) 2018-04-26 2019-10-31 富士カプセル株式会社 Composition de film de capsule molle
AU2020361859A1 (en) 2019-10-11 2022-05-12 Sunsho Pharmaceutical Co., Ltd. Soft capsule
CN113768137B (zh) 2020-12-31 2023-01-20 仙乐健康科技股份有限公司 淀粉成膜组合物及其制备胶囊壳的方法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1623757B1 (fr) * 2004-07-10 2009-02-11 Cognis IP Management GmbH Microcapsules (XXXII)
US20220226478A1 (en) * 2019-12-30 2022-07-21 Sirio Pharma Co., Ltd. Film-forming composition containing gellan gum and starch, and application in soft capsule

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
AMICI E ET AL: "INTERPENETRATING NETWORK FORMATION IN GELLAN-AGAROSE GEL COMPOSITES", BIOMACROMOLECULES, AMERICAN CHEMICAL SOCIETY, US, vol. 1, 1 January 2000 (2000-01-01), pages 721 - 729, XP001183813, ISSN: 1525-7797, DOI: 10.1021/BM000057D *

Also Published As

Publication number Publication date
DE102024111019A1 (de) 2025-10-23

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