WO2004103338A1 - Adhesifs et compositions modifiant des films - Google Patents

Adhesifs et compositions modifiant des films Download PDF

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Publication number
WO2004103338A1
WO2004103338A1 PCT/GB2004/002167 GB2004002167W WO2004103338A1 WO 2004103338 A1 WO2004103338 A1 WO 2004103338A1 GB 2004002167 W GB2004002167 W GB 2004002167W WO 2004103338 A1 WO2004103338 A1 WO 2004103338A1
Authority
WO
WIPO (PCT)
Prior art keywords
films
composition according
film
previous
hpmc
Prior art date
Application number
PCT/GB2004/002167
Other languages
English (en)
Inventor
Edward Zbygniew Nowak
Jason Teckoe
Original Assignee
Bioprogress Plc
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
Priority claimed from GB0311440A external-priority patent/GB0311440D0/en
Application filed by Bioprogress Plc filed Critical Bioprogress Plc
Publication of WO2004103338A1 publication Critical patent/WO2004103338A1/fr

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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2893—Tablet coating processes
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/282—Organic compounds, e.g. fats
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2886—Dragees; Coated pills or tablets, e.g. with film or compression coating having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer
    • 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
    • A61K9/4891—Coated capsules; Multilayered drug free capsule shells

Definitions

  • This invention relates to surface modifiers, or film modifiers, adhesives or glues and their applications and more particularly their use in connection with non gelatin polymeric materials or their derivatives or mixtures thereof.
  • the subject matter includes materials and processes by which modified cellulosic films can be bonded together using e.g. solvents and/or film plasticizers to achieve strong, tamper proof and leak free welds. Capsules, pouches and other packaging constructions can be successfully fabricated using the materials according to the present invention. Also, tablets, powders and compacted powders may be enrobed by film which is bonded by adhesives in accordance with the present invention.
  • Adhesives according to the present invention may be used to bond or associate e.g. HPMC, HPC, PEO, PEO-PEG graft copolymers or PVOH materials or their derivatives or mixtures thereof.
  • HPMC is a synthetic plastics material, which is a chemically modified form of the naturally occurring polymer, cellulose.
  • Films, (or sheets or membranes) of HPMC are available commercially and have various uses, including proposals for use as wall materials for delivery capsules i.e. capsules designed to retain and protect their contents until an intended site of delivery or conditions of delivery are encountered, at which the contents of the capsule are released.
  • HPMC is suitable for ingestion by humans, so delivery capsules with HPMC walls find the potential use as ingestible capsules, e.g. for the delivery of accurately metered doses of pharmaceutical preparations and dietary supplements, as a possible replacement for gelatin based capsules. See for example, WO 97/35537, WO00/27367 and WO01/03676.
  • HPMC can be used to encapsulate substances, such as pharmaceuticals or food supplements like fish oils.
  • PVOH is also a synthetic plastics material and can be used, for example to encapsulate non-ingestible materials such as detergents or can be used for making dissolvable ostomy bags.
  • modified cellulose such as Hydroxy Propyl Cellulose (HPC) and Methyl Cellulose (MC) and particularly Hydroxypropyl methyl cellulose (HPMC) can be cast from aqueous solution to produce films.
  • These films possess thermoplastic properties that vary in degree depending in the substitution of the polymeric molecules.
  • the fact that the polymers have these thermoforming properties enables the material to be welded together at the appropriate melting range to produce various packaging items such as sachets and capsules.
  • the use of relatively high temperatures >200 degrees centigrade and the risk of weld failure due to surface contamination with any fill material means that current processes are less than acceptable and this is especially true where only low failure rates can be tolerated, such as in the construction of medical devices, e.g. ostomy pouches, and in the manufacture of drug related products, e.g. pharmaceutical capsules, enrobed tablets or (compressed) powders.
  • the present invention can assist in overcoming certain problems by reducing and in some cases eliminating the need for excessive bonding temperatures.
  • Such high temperatures can denature and damage the film and may also result in damaging and releasing the product contents previously packaged within a film, e.g. a heat or air sensitive active ingredient maybe exposed to the external atmosphere resulting in oxidation or it may be denatured by heat in the production process (both oxidation and denaturation could well result in completed destruction of the active ingredient thus rendering e.g. the previously active contents of an enrobed tablet, inactive, and so making the dosage form completely useless and ineffective.
  • fluid tight bonds can be achieved when the films themselves have been contaminated with a liquid or a solid (particulate or otherwise), such contamination may well interfere with the fabrication of such intended fluid tight bonds. Instances of such possible interference of the bonding process can be found in the manufacture of liquid or suspension filled capsules used for dietary supplements or pharmaceutical preparations.
  • compositions of adhesive solutions according to the present invention can be used to make
  • the present invention relates to (liquid) compositions that can cause polymeric materials to associate or bond with one another.
  • the compositions may result in glues, adhesives or surface modifiers/film modifiers.
  • soluble, biodegradable or ingestible films can be brought together and bonded or welded using the compositions according to the present invention.
  • a surface modifier may be applied to one or more surfaces of one or more films to be associated with one or more further films . Such an association may result in a bond or a seal.
  • the surface modifier may typically contain e.g. a polar organic hydrocarbon, which may penetrate into the film or film surfaces of e.g cellulosic films and modify e.g. the film's surface characteristics.
  • these liquid polar hydrocarbons can be placed on the surface of 2 films, which are then pressed together to form, e.g. a fluid tight bond ( e.g. after some curing time).
  • the process of film bonding can be accelerated by the careful application of heat to the (surface of) the films. It is important to note that bonding in this instance, may then be achieved at well below the glass transition temperatures of the films themselves, and so there is less chance of damage to the film or the product associated with the film.
  • melting and fusion of the two cellulosic films may be achieved within a very short period of time (this can be normally be between 1 and 3 seconds).
  • a weld can be achieved at a much lower temperature and a shorter period of time as compared to a film which has not been treated with a surface modifier containing polar hydrocarbons. Additionally, using such surface modifiers, a weld can be achieved which is much stronger and far less prone to fatigue.
  • a further embodiment of the present invention is the formulation of compositions to form (viscous) liquids, so that their application, or more particularly, their surface application (e.g. to a film), can be controlled.
  • Most surface application of liquids e.g. to films are performed by the use of rollers, pads, slot coaters, Mayer bars or baths. If the viscosity of the liquid is too low, then surface 'run-off can occur which can result in an inconsistent surface for bonding.
  • Viscosity of compositions can be increased by e.g. dissolving small amounts of the modified cellulose to the polar hydrocarbon. If necessary, (small) amounts of water can also be used to aid the dissolution of the cellulose so that a single- phase solution is obtained.
  • the same/similar/different polymer(s) to the polymer(s) which make up e.g. a film may be added to an organic solvent and/or water to produce a suitable adhesive.
  • a polar hydrocarbon with a much lower polarity or affinity for the cellulosic surface may be added to the formulation. This may well result in less aggressive migration of the polar hydrocarbon (into a film) with the corresponding lesser effects.
  • adhesive formulations can be customised to meet all conventional methods and applications for processes for the bonding and welding of cellulosic films.
  • modified cellulosic films which appear to be most suited to encapsulating materials be it drugs, oils, foodstuffs, dyestuffs etc, may be based on e.g. hydroxy propyl methyl cellulose (HPMC), hydroxy propyl cellulose (HPC), methyl cellulose (MC), or carboxymethyl cellulose (CMC).
  • HPMC hydroxy propyl methyl cellulose
  • HPC hydroxy propyl methyl cellulose
  • HPC hydroxy propyl cellulose
  • MC methyl cellulose
  • CMC carboxymethyl cellulose
  • the films can be plasticised with glycerin, triacetin and triethyl citrate. These are frequently used plasticisers.
  • the currently most preferred cellulose derivative for film formation is HPMC.
  • Films of HPMC can be cast from aqueous solutions and dried to thicknesses ranging from between e.g. 20-150 microns, preferably 70-120 microns when used in capsules, e.g. 80 microns when encapsulating tablets and e.g. 70-130 microns when encapsulating powders
  • the two halves of the film used e.g. either need to be butt welded or overlapped and welded/bonded.
  • one aspect of the invention relies on the application of an adhesive, to the two mated surfaces of the film, followed by the application of pressure or a combination of heat and pressure.
  • An important aspect in the formation of capsules from PVOH or HPMC is the adhesive glue that is used and the way that it is applied to the materials.
  • a single uniform coat of glue can be applied to the film materials, e.g. by a slot coater, whereby a uniform film of glue is applied under pressure, through a narrow slot, e.g. of width less than 50 microns.
  • the slot is positioned, at a specific distance above the travelling film, and the quantity of glue supplied is dictated by tne viscosity of the glue, the pressure behind the glue introduced into the slot, and the speed of the travelling film under the slot.
  • viscosity of glue is often dependent on temperature, it follows that the temperature of the glue supplied in the apparatus, is a very important factor.
  • the slot coater method has been, in certain circumstances, synonymous with producing capsules with superior strength. It has been suggested that one of the reasons for this may be attributed to 'conditioning' of the film, effected by the uniform layer of (hot) glue, whereby the film, in general, not just simply at the point of seam formation, is adapted form superior capsule formation.
  • the film has, under these circumstances may have greater elasticity and may be in a more advanced stage of 'melt', such to produce a stronger capsule, with a seam which is more continuous and (more) associated, with the film material itself.
  • Polar organic hydrocarbons which suitably modify the surface of the cellulose films, and which may or may not have OH or hydroxyl groups, include:
  • Alcohols are preferably low molecular weight alcohols such as ethanol, propanol, butanol, benzyl alcohol and furfuryl alcohols. Some preferred alcohols may include benzyl alcohol or isopropyl alcohol.
  • Carboxylic acids may preferably be low molecular weight carboxylic acids and alpha hydroxy acids, for example, formic cid, acetic acid, lactic and citric acid. The latter two of the acids mentioned may preferably be applied as aqueous solutions.
  • Polyols may preferably include propylene glycol, hexylene glycol and polyethylene glycols (with a molecular weight preferably lower than 600).
  • the currently most preferred alcohol is propylene glycol.
  • Acetins These preferably include mono-, di- and tri- acetins or mixtures thereof.
  • Lactones An example being gamma valerolactone.
  • a concentration of HPMC between ) 0.5 and 15% in weight can be added and dissolved in the hydrocarbon.
  • a co-solvent such as water
  • water at 50% of the total weight of the adhesive formulation, or greater than 50% in the case of a solid polar hydrocarbon (e.g. citric acid).
  • Typical materials used are, for example:
  • Triacetin glyceryl triacetate
  • the balance of chilled water is then added to make up the total water content of 30.0% and also all the propylene glycol (chilled) is added.
  • the mixture is continually stirred until all components are thoroughly dissolved .
  • the temperature of the mixture is then brought ⁇ 20 deg c. using a water bath if necessary.
  • PROPAN-2-OL (TECHNICAL GRADE)
  • the propylene glycol is heated to 80 deg c whilst stirring. HPMC is slowly added whilst continually stirring and heating (avoid charring), until all the HPMC is dissolved.
  • the mixture whilst still being stirred, is then allowed to cool and triacetin is added when the mixture has reached about 40 deg c. It must be noted that triacetin will not dissolve HPMC and it is important not to add triacetin until all the HPMC has completely dissolved in the propylene glycol.
  • Lactic acid was heated to 90 deg c whilst stirring. HPMC was slowly added and the mixture was continually stirred until the HPMC is completely dispersed
  • the lactic acid is heated to 80/90 deg c whilst stirring.
  • HPMC is slowly added whilst continually stirring and heating (avoid charring), until all the HPMC is dissolved.
  • Balance of chilled lactic acid is slowly added followed by the further addition of balance of chilled triacetin.
  • An ice bath is used to further reduce mixture temperature to ⁇ 20 deg c.
  • triacetin will not dissolve HPMC and it is important not to add triacetin until all the HPMC has completely dissolved.
  • Viscosity Brookfield spindle 3 30 rpm 1800+/- 150 cps @ 21 deg c
  • any one of the above compositions is charged into the adhesive feed reservoir of an encapsulating device. Suitable films are then fed into the device and, under appropriate conditions, (heat etc) are brought (close) together and adhesive applied in the appropriate way and amount, the film being formed to produce capsules of sufficient integrity, e.g. for pharmaceutical use.
  • the adhesive formulations can be applied using a variety of techniques, namely glue baths, rollers Mayer bar, slot and extrusion coaters. Typically, the adhesive formulation will be applied at a level of between 5-200grams per square meter (GSM) preferred concentrations between 10-30gsm
  • a higher level of adhesive can be applied, for example, between 20-50gsm.
  • an even higher level of adhesive may be used, e.g. between 50-100gsm.
  • the adhesive formulations themselves are also good solvents, e.g. for dyestuffs, flavours and fragrances and can be used as vehicles to carry these minor constituents into the inner surface of the film e.g. to impart desirable aesthetic characteristics to the encapsulated product.
  • Solutions containing HPMC, acid and water can be used to form an internal adhesive which when the film is used for encapsulating oils, said solutions have the advantage of chasing the oil from the surface of the film, thereby allowing the film(s) to bond together more effectively, which in an encapsulation process, can aid the sealing and cutting of capsules made from e.g. HPMC film, to produce capsules possessing superior properties.

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)
  • General Preparation And Processing Of Foods (AREA)

Abstract

Cette invention concerne un modificateur de surface, un modificateur de film, un adhésif ou une colle qui s'utilisent conjointement avec des films sans gélatine pour l'obtention de robustes soudures inviolables et hermétiques. Sont ainsi produits des capsules, pochettes et autres emballages, ainsi que des comprimés, des poudres et des poudres tassées enrobées dans des films et utilisant les adhésifs/compositions modifiant les films. Ces films, adhésifs et compositions modifiant les films peuvent être ingérés sans danger pour l'homme et conviennent comme matériau d'enveloppe pour gélules à avaler renfermant une dose de composition pharmaceutique.
PCT/GB2004/002167 2003-05-19 2004-05-18 Adhesifs et compositions modifiant des films WO2004103338A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB0311440A GB0311440D0 (en) 2003-05-19 2003-05-19 Glue compositions
GB0311440.2 2003-05-19
GB0318654.1 2003-08-08
GB0318654A GB0318654D0 (en) 2003-05-19 2003-08-08 Improvements in glues

Publications (1)

Publication Number Publication Date
WO2004103338A1 true WO2004103338A1 (fr) 2004-12-02

Family

ID=33477755

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2004/002167 WO2004103338A1 (fr) 2003-05-19 2004-05-18 Adhesifs et compositions modifiant des films

Country Status (1)

Country Link
WO (1) WO2004103338A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1752140A1 (fr) * 2005-08-12 2007-02-14 Warner-Lambert Company LLC Procédé de fermeture de capsules dures utilisant une composition à base d'hydroxypropylméthyl cellulose (HPMC)
WO2022128905A1 (fr) 2020-12-14 2022-06-23 Capsugel France SAS Fluide d'étanchéité pour sceller des capsules

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3281876A (en) * 1963-05-28 1966-11-01 Eastman Kodak Co Method of assembling a shoe upper
EP0262422A1 (fr) * 1986-09-01 1988-04-06 Teikoku Seiyaku Kabushiki Kaisha Forme de dosage à libération prolongée
US5213811A (en) * 1991-09-13 1993-05-25 Sterling Drug Inc. Oral sustained-release drug compositions
US5258436A (en) * 1989-12-19 1993-11-02 Fmc Corporation Film-forming composition; method of producing same and use for coating pharmaceuticals and foods and the like
EP0629402A1 (fr) * 1993-06-15 1994-12-21 Bayer Ag Compositions pharmaceutiques à base de ipsapirone
WO1997035537A1 (fr) * 1996-03-26 1997-10-02 Bioprogress Technology Limited Ameliorations en matiere d'encapsulation
WO2000027367A1 (fr) * 1998-11-11 2000-05-18 Bioprogress Technology International Incorporated Systeme d'administration de medicaments a base de gelules
WO2001003676A1 (fr) * 1999-07-09 2001-01-18 Bioprogress Technology International, Inc. Perfectionnements apportes aux capsules a liberation
US6228400B1 (en) * 1999-09-28 2001-05-08 Carlsbad Technology, Inc. Orally administered pharmaceutical formulations of benzimidazole derivatives and the method of preparing the same
US6620431B1 (en) * 2000-04-17 2003-09-16 Charles Signorino Shellac film coatings providing release at selected pH and method
US6723337B1 (en) * 1997-09-26 2004-04-20 Samyang Corporation Transdermal drug delivery system for anti-inflammatory analgesic agent comprising diclofenac diethylammonium salt, and the manufacturing method thereof

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3281876A (en) * 1963-05-28 1966-11-01 Eastman Kodak Co Method of assembling a shoe upper
EP0262422A1 (fr) * 1986-09-01 1988-04-06 Teikoku Seiyaku Kabushiki Kaisha Forme de dosage à libération prolongée
US5258436A (en) * 1989-12-19 1993-11-02 Fmc Corporation Film-forming composition; method of producing same and use for coating pharmaceuticals and foods and the like
US5213811A (en) * 1991-09-13 1993-05-25 Sterling Drug Inc. Oral sustained-release drug compositions
EP0629402A1 (fr) * 1993-06-15 1994-12-21 Bayer Ag Compositions pharmaceutiques à base de ipsapirone
WO1997035537A1 (fr) * 1996-03-26 1997-10-02 Bioprogress Technology Limited Ameliorations en matiere d'encapsulation
US6723337B1 (en) * 1997-09-26 2004-04-20 Samyang Corporation Transdermal drug delivery system for anti-inflammatory analgesic agent comprising diclofenac diethylammonium salt, and the manufacturing method thereof
WO2000027367A1 (fr) * 1998-11-11 2000-05-18 Bioprogress Technology International Incorporated Systeme d'administration de medicaments a base de gelules
WO2001003676A1 (fr) * 1999-07-09 2001-01-18 Bioprogress Technology International, Inc. Perfectionnements apportes aux capsules a liberation
US6228400B1 (en) * 1999-09-28 2001-05-08 Carlsbad Technology, Inc. Orally administered pharmaceutical formulations of benzimidazole derivatives and the method of preparing the same
US6620431B1 (en) * 2000-04-17 2003-09-16 Charles Signorino Shellac film coatings providing release at selected pH and method

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1752140A1 (fr) * 2005-08-12 2007-02-14 Warner-Lambert Company LLC Procédé de fermeture de capsules dures utilisant une composition à base d'hydroxypropylméthyl cellulose (HPMC)
WO2007020529A3 (fr) * 2005-08-12 2007-04-26 Warner Lambert Co Procede de fermeture de capsules dures au moyen d'hydroxypropylmethyl cellulose (hpmc) utilisee comme base
US9579290B2 (en) 2005-08-12 2017-02-28 Capsugel Belgium Nv Method for banding hard capsules using hydroxypropylmethyl cellulose (HPMC) as a base
WO2022128905A1 (fr) 2020-12-14 2022-06-23 Capsugel France SAS Fluide d'étanchéité pour sceller des capsules

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