WO2009044118A2

WO2009044118A2 - Indelibly marked polymeric films

Info

Publication number: WO2009044118A2
Application number: PCT/GB2008/003298
Authority: WO
Inventors: Stephen Lee; Stephen Jeremy Martin
Original assignee: Bioprogress Technology Limited
Priority date: 2007-10-01
Filing date: 2008-09-30
Publication date: 2009-04-09
Also published as: WO2009044118A3; GB0719095D0

Abstract

The present invention relates to indelibly marked polymeric films and methods of producing the same. The invention also relates to the use of tablet coatings and the walls of capsules. Such means can be employed as a part of a prevention of counterfeiting.

Description

INDELIBLY MARKED POLYMERIC FILMS

The present invention relates to indelibly marked polymeric films and methods of producing the same. The invention also relates to the use of such films as tamper-evident means when applied to substrates such as, for example, tablet coatings and the walls of capsules . Such means can be employed as a part of a prevention of counterfeiting.

BACKGROUND TO THE INVENTION

Printed polymeric films have a wide range of applications. One important application of such printed films is the application of printed films to a substrate, in particular for the provision of tamper evident means. This is made use of, in particular, in the production of pharmaceutical tablets, where a printed film may be applied to a tablet with the intention that it becomes readily visible if the tablet has been tampered with.

However, presently known means for printing onto a film provide a film in which the ink or other printing matter sits on top of, or at most partially embeds into the film. As such, the printing can easily become damaged or entirely removed, for example, by wiping the film with acetone. This is particularly problematic when the films are being used as tamper evident means in, for example, tablets, as once the markings on the film are removed the tamper evident quality may be rendered partially or entirely ineffective. This is because the film will still remain in place, and with no trace of the previous markings, there will be no visible indication of any tampering.

SUMMARY OF THE INVENTION

The present invention provides indelibly marked homogenous polymeric films, the method for producing the same and substrates to which these films have been applied.

One aspect of the invention provides a method of producing an indelibly marked film comprising applying a liquid or a suspension to a preformed polymeric film, said liquid comprising a dye or a lake or a solid, wherein said liquid is at least partially absorbed into said preformed polymeric film, such that said dye penetrates said polymeric film thereby creating an indelibly marked homogenous polymeric film. FIGURES

Figures 1-3 depicts three types of prior art printed films.

Figure 4 depicts the production of a film of the present invention.

Figure 5 depicts a film of the present invention.

Figure 6 depicts a film of the present invention.

Figure 7 depicts a film of the present invention.

Figure 8 depicts a. form of design which the indelible marking may take, being a one dimensional code.

Figure 9 depicts a form of design which the indelible marking may take, being a two dimensional code.

Figure 10 depicts a form of a design which the indelible marking may take, being a code with manufacturing details (for example batch number, date of manufacture and similar).

Figure 11 depicts a form of a design which the indelible marking may take, being the dose weight.

Figure 12 depicts a form of a design which the indelible marking may take, being a company logo.

Figure 13 depicts a form of a design which the indelible marking may take, being a recognisable specific pattern.

DETAILED DESCRIPTION OF INVENTION

This invention relates to indelibly marked homogenous polymeric films. In this instance, homogenous means that the resultant film is a single, indivisible film. It does not mean that the dye is dispersed uniformly through the film, and in fact this is not the case, as the dye may well be dispersed only within precisely defined desired locations within the film, in order to render a desired marking; instead, this means a resultant film is not a composite of multiple, physically distinguishable components, in which one component is primarily or entirely separate from the other (i.e. the dye is entirely separate from, or being adhered to, the film), instead the dye is integral to the film. In this respect the film produced is a single discrete film (although the films of the present invention may be used as part of a multilayer film). It is this homogenous nature of the dye in film which renders the markings provided by the dye indelible.

This is one way in which the films of the present invention are distinguished from prior art films as shown in Figures 1-3. In these figures, three different types of prior art films are shown. In each case a film, 20 has been printed on with printing matter (for example an ink) 10. In Figure 1, the printing matter rests on top of the film, forming a separate layer such that the film comprises two discrete and separate layers, being the film 20 and the printing matter 10. hi Figure 2, the printing matter 10 has partly embedded into the film 20, for example as a result of pressure exerted on the film during the printing process. However, the film of Figure 2 still comprises two discrete and separate layers. The Film of Figure 3 is similar to that of Figure 1 , except that the printing matter has been applied across the entirety of the film such that the printing matter has formed a complete, separate layer from the film. In contrast the films of the present invention are homogenous, as seen in Figures 5-7, in which although the concentration and location of the dye 40 within the film 80 may vary, the film 80 and dye 40 nevertheless provide a single, discrete film, such that a homogenous polymeric film is provided.

The indelibly marked homogenous polymeric film is produced by applying a liquid comprising a dye to the surface of a preformed film. This can be seen in Figure 4, in which a liquid 30 comprising a dye 40 is applied to the surface of a preformed film 20. In this example a stream of liquid 60 is applied to the film 20 via means of an inkjet 50. The liquid 30 facilitates the penetration of the dye 40 into the film 20; this requires a residence time to allow the ink to penetrate into the film, during which time an intermediate film 70 is provided in which the dye is partially absorbed. Ultimately, an homogenous film 80 is produced. Because the dye has penetrated the film 80 to form an homogenous film, the film 80 is indelibly marked.

The extent to which the dye penetrates the film may vary depending upon the nature of the preformed film, dye and liquid used. These variables can be optimised depending upon the desired result. Differences in the types of film produced are shown in Figures 5-7. In Figure 5, the dye 40 has partially penetrated the film 80, the dye 40 being located primarily on the side of the film 80 comprising the surface on which the dye 40 was applied. However, the concentration of the dye 40 remains substantially constant within the penetrated volume of the film 80. The film depicted in Figure 6 is similar to that of Figure 5 in that again the dye 40 is located primarily on the side of the film 80 comprising the surface on which the dye 40 was applied. In this instance though there is a far more pronounced gradient of dye 40 through the film 80, a greater concentration of dye 40 within the penetrated volume of film 80 being present towards the surface to which the dye 40 was applied. Finally, in Figure 7, the dye 40 has penetrated the entire depth of the film 80, with a relatively even concentration of dye 40 existing within the penetrated volume of the film 80.

A further embodiment of the invention is to provide a three dimensional fused layer form which enables more data to be stored within the form. The form applied to the outside of the film is built up in layers through depositing printed material on its self. Each printed layer maybe the same or different pattern as the previous layer. Each layer has a certain thickness and because of the materials selected will fuse with the previous layer. Thus a homogeneous form is created that is three dimensional, is fused to the polymeric film and is of varying pattern in the thickness and planar direction.

The application of the printing material can be applied to the film prior to its use or further processing and employed to the surface in contact with the drug form or externally.

The dye contained in the liquid may be an ink, a pigment, and/or another form of colorant. The precise nature of the dye and liquid used depends upon the desired final product. The dye will be determined by primarily by the desired nature of the indelible marking, as well as by the need to penetrate and exist stably within the preformed film, whilst the liquid carrier will be determined by the need to maintain the dye in a stable solution, as well as the need to facilitate the penetration of the dye into the preformed film. For example, where the preformed film is a water soluble film, the liquid carrier may be a water based carrier, or a hydrophilic organic carrier such as an alcohol based carrier, which will facilitate the penetration of the dye into the film. Alternatively, a preformed water insoluble film, such as an enteric film, may be used. For a liquid to function as a suitable transport medium, compounds containing one or more of the following functional groups or compounds in its molecular structure have been found to be suitable: hydroxy; carboxy; amino; carboxamido; epoxy; oxo; keto; cyano; benzyl; alkoxy; aryloxy; furans, pyrroles; thiophenes; sulfoxide; sulfone; quaternary nitrogen; pyridine; anhydrides; esters; and lactones. With a relatively broad range of polar organic liquid carriers to select from, it is possible to choose. one or more compounds to act as a transport medium for a dye. The liquid optionally comprises one or more fugitive solvents, i.e. solvents which leave the solution, for example by evaporation from the solution. The precise configurations of the dye and liquid carrier will depend upon the precise nature of the preformed film used

One example of a suitable dye for use with a water soluble film such as HPMC is:

Propylene glycol 64.33 %

Triacetin 31.02 %

HPMC (Methocel El 5 LV Premium) 4.60 %

FD&C Blue 1 dye 0.06 %

A wide range of preformed films may be used to produce the indelibly marked homogenous polymeric film. Examples of suitable films are: hydroxypropyl methyl cellulose (HPMC); hydroxypropyl cellulose (HPC); hydroxyethyl methyl cellulose (HEMC); hydroxyethyl cellulose (HEC); methyl cellulose (MC); carboxymethyl cellulose (CMC); sodium carboxymethyl cellulose; cellulose acetate phthalate (CAP); hydroxypropylmethyl cellulose phthalate (HPMC-P); hydroxypropylmethyl cellulose acetate succinate (HPMC-AC); ethyl cellulose (EC); carboxymethyl hydroxyethyl cellulose (CMHEC); and salts and derivatives of the foregoing. For certain embodiments, in which the film is to be applied to an edible substrate, for example a tablet or a capsule, the preformed film should be edible (as should the dye).

To facilitate processing of the films and to increase the apparent flexibility, at least one plasticiser maybe added, such as an edible plasticiser for an oral film. Plasticisers commonly used are polyols, glycols, acetins, carboxylic acids and the esters of these acids, for example polyethylene glycol, glycerin, triacetin. citric acid and triethylcitrate respectively. The plasticisers maybe used individually or in combination and maybe present in any desired amount, particularly from 0 to about 40 percent of the solid film and more particularly from 0 to 20 percent. Optional ingredients may be added to the preformed film including, without limitation, emulsifiers, humectants, defoamers and anti block agents. Such optional components are typically added in minor amounts, to aid the processing of the film and typically are less than 10% total by weight based upon the weight of the cellulose ether component.

The preformed film may be made by a variety of processes, for example by dissolving or dispersing the film components in water or other solvents and drying into film form. Alternatively the film resins could be hot-melt extruded. Additionally a dispersion or solution maybe directly coated or sprayed onto another edible product, such as a tablet or foodstuff and dried to form an edible film. The preferred technique is to have film solution cast and dried to produce a sheet of flexible, thin film.

It is clearly important that the film used is capable of being penetrated by the liquid carrier in dye, and with this in mind, any suitable film may be used.

The liquid may be applied to the surface of the preformed film in any method suitable for rendering the desired design for the indelible marking. Examples of suitable methods comprise extrusion, roller application, pouring and levelling by doctor blade or knife, spraying, brush painting, wiping, screen printing, and inkjet printing.

A particularly preferred method of applying the liquid to the preformed is via means of inkjet printing. This is particularly desirable due to its automated nature, speed and high level of accuracy in rendering the printing. InkJet means for printing are advantageously computer controlled, and may additionally comprise a computer "eye" located above the film proximate to the site of delivery of the liquid in order to precisely monitor the printing. Standard inkjet printing technology may be used, although this may be tailored for the application of particular liquids, for example, if a particularly viscous liquid is to be applied, the inkjet printers may comprise a heater to improve application. Generally, when using inkjet printing, it should be ensured that the viscosity of the liquid and the solvent used are compatible with the irikjet apparatus. When using inkjet printing means, alcohol based liquid carriers are generally preferred.

The advantage of being able to use precise printing techniques, such as inkjet technology, enables the indelible markings to be provided in a very precise design. These designs may comprises one or more of a logo; a word; wording; a dose description; a dose level; a manufacturers name; a characteristic identification pattern; and a bar code. Particularly advantageous is the ability to indelibly mark the films with bar codes such as one dimensional, two dimensional and three dimensional codes, with the ability to provide two dimensional codes such as data matrices in indelible form to a film being particularly advantageous given the high density of data such matrices can impart. One dimensional (90), and two dimensional (100) codes are depicted in Figures 8 and 9 respectively. The use of such codes may be particularly relevant when wishing to apply the films to substrates for means of tracking of batches of substrate, or providing specific instructions. Other advantageous designs include a code with manufacturing details (for example batch number., date of manufacture and similar), as shown in Figure 10, the dose weight 300 (Figure 11), a company logo 310 (Figure 12); or other recognisable specific pattern 320 (Figure 13).

In order to provide the desired design, it may be necessary to provide multiple dyes. The precise nature of the application and absorption of the dyes is that the use of multiple dyes is entirely feasible with this technology, so as to provide complex or more detailed designs.

One way in which the options for providing a design can be increased involves the utilisation of a preformed polymeric film of a particular colour, or alternatively a preformed polymeric film which is transparent, semi-transparent or translucent.

As noted above, the dye may comprise any manner of ink, pigment or colorant. This may include pigments visible to the human eye and/or pigments which are detectible via means of light of a frequency outside that of normal human vision, for example, pigments detectible only under infra-red or ultra violet light. The use of such pigments enables the homogenous polymeric film to be indelibly marked in such a way that the marking is invisible to the naked eye but can be detected under certain conditions. This may be of particular use in the manufacture of films for use in certain security based applications.

The indelibly marked homogenous polymeric films may in themselves constitute a product for the delivery of an active substance. For example, they may be used to provide a medicament, a breath freshener, or simply a pleasant flavouring. If an active material is to be included, it may be provided in the preformed film prior to application of the liquid; further or alternatively, an active material may be included in the liquid and applied to the film such that the active material, as with the dye, is absorbed into the film, penetrating the film so as to ensure that the film remains a homogenous polymeric film. If an active material is to be provided by means of a liquid carrier, this may be the same liquid in which the dye is suspended, or may be an additional liquid applied separately to the film. Potentially, a wide range of active materials may be used as desired, examples of which comprise hypnotics, sedatives, anti-epileptics, awakening agents, psychoneurotropic agents, neuromuscular blocking agents, antispasmodic agents, antihistaminics, antiallergenics, cardiotonics, antiarrhymics, diuretics, hypotensives, vasopressors, antitussive expectorants, thyroid hormones, sexual hormones, antidiabetics, anti tumor agents, antibiotics, chemotherapeutics, narcotics, breath freshening agents like menthol, or other flavours of fragrances used for oral hygiene and or actives used for dental and/or oral cleansing like quaternary or ammonium bases. The effect of flavours may be enhanced using flavour enhancers like tartaric acid, citric acid, vanillin, and the like.

Where films of the present invention are used for the delivery of an active substance, such delivery may optionally be topical or intra-cavity. Controlled delivery of the active material via the skin, (e. g. in skin care or cosmetics), gynaecological, vaginal, cranial, abdominal, optic, uterine, nasal, sinus, rectal, buccal, oral, or ophthalmic cavity can be achieved by the use of such embodiments of the present invention

The films of the present invention find particular use when applied to substrates, particularly for the purpose of providing a tamper evident means. In these instances, the film is applied to the substrate in such a way that the film must be damaged or destroyed if the substrate is tampered with, the destruction (wholly or partial) of the film providing a readily visible indication of the tampering.

This is of particular use where the substrate is a medicament such as a tablet or a capsule, film potentially being used to partially or entirely enrobe the substrate. Unlike in previously known methods of providing tamper evident means to tablets and capsules, the indelible nature of the marking of the film means that the marking cannot be removed without destroying the film. The destruction of the film is readily evident, thereby rendering making the tampering of the substrate easily visible to an observer.

One particularly advantageous form of tamper evident means provided by the films of the present invention requires the use of a transparent, semi-transparent or translucent preformed film. The liquid is applied to one surface of this film such that the dye penetrates from the surface into the film. Consequently, the greatest concentration of dye is contained at the surface at which the liquid was applied. When applying the film to a substrate for use as a tamper evident means, the film may be applied to the substrate in such a way that the surface of the film to which the liquid was applied is the surface in direct contact with the substrate. As such, the surface of the film which is in closest proximity to the indelible marking is the surface in contact with said substrate. The indelible marking remains visible due to the transparent, semi-transparent or translucent nature of the preformed film. However, because the greatest concentration of the dye is located in direct contract with the substrate, it is impossible to remove the indelible marking by eroding the film without destroying the film entirely.

Claims

What is claimed is:

1. A method of producing an indelibly marked film comprising applying a liquid or a suspension to a preformed polymeric film, said liquid comprising a dye or a lake or a solid, wherein said liquid is at least partially absorbed into said preformed polymeric film, such that said dye penetrates said polymeric film thereby creating an indelibly marked homogenous polymeric film.

2. A method according to claim 1, wherein said dye is applied to said preformed polymeric film in a predetermined design, such that the dye forms an indelible marking corresponding to said predetermined design.

3. A method according to claim 2, wherein said predetermined design comprises one or more of a logo; a word; wording; a dose description; a dose level; a manufacturers name; a characteristic identification pattern; and a bar code.

4. A method according to claim 3, wherein said bar code comprises one or more of a one dimensional code, a two dimensional code, and a three dimensional code.

5. A method according to claim 4, wherein said two dimensional or three dimensional code comprises a data matrix.

6. A method according to any of claims 1-5, wherein multiple liquids comprising multiple dyes are applied to said predetermined film.

7. A method according to any of claims 1-6, wherein said dye or dyes are applied to said film by means of one or more of extrusion, roller application, pouring and levelling by doctor blade or knife, spraying, brush painting, wiping, screen printing, and inkjet printing.

8. A method according to claim 7, wherein said means of applying said liquid is inkjet printing.

9. A method according to any of claims 1-8 wherein said liquid comprises an alcohol based carrier.

10. A method according to any to any of claims 1-9, wherein said dye comprises a visible pigment.

11. A method according to any of claims 1-10, wherein said dye comprises a pigment invisible to the human eye but detectible via means of light outside the frequency of normal human vision.

12. A method according to claim 11, wherein said light outside of the frequency of normal human vision is infra-red light.

13. A method according to claim 11, wherein said light outside of the frequency of normal human vision is ultra-violet light.

14 A method according to any of claims 1-13 wherein said preformed polymeric film comprises one or more of: hydroxypropyl methyl cellulose (HPMC); hydroxypropyl cellulose (HPC); hydroxyethyl methyl cellulose (HEMC); hydroxyethyl cellulose (HEC); methyl cellulose (MC); carboxymethyl cellulose (CMC); sodium carboxymethyl cellulose; cellulose acetate phthalate (CAP); hydroxypropylmethyl cellulose phthalate (HPMC-P); hydroxypropylmethyl cellulose acetate succinate (HPMC-AC); ethyl cellulose (EC); carboxymethyl hydroxyethyl cellulose (CMHEC); and salts and derivatives of the foregoing.

15. A method according to claim 16, wherein said preformed polymeric film comprises hydroxypropyl methyl cellulose (HPMC).

16. A method according to any of claims 1-15, wherein said indelibly marked homogenous polymeric film is edible.

17. A method according to any of claims 1-16, wherein said film is selected from a film comprising one or more of water soluble film, solvent-based film and enteric film..

18. A method according to any of claims 1-17, wherein said preformed polymeric film comprises an active material.

19. A method according to any of claims 1-18, wherein said liquid comprises an active material.

20. A method according to claim 19, wherein said active material is at least partially absorbed into said preformed polymeric film.

21. A method according to any of claims 1-20, wherein said preformed polymeric film is transparent, semi-transparent or transluscerit.

22. A method according to any of claims 1-21, further comprising the step of applying said indelibly marked homogenous polymeric film to a substrate.

23. A method according to claim 22, wherein said application of said film comprises using said indelibly marked homogenous polymeric film to at least partially enrobe said substrate.

24. A method according to claim 23 wherein said substrate is completely enrobed by said indelibly marked homogenous polymeric film

25. A method according to claim 22, 23 or 24, wherein said substrate is a tablet.

26. A method according to claim 22, 23 or 24, wherein said substrate is a capsule.

27. A method according to any of claims 22-26, wherein said substrate is enrobed or partially enrobed with said indelibly marked homogenous polymeric film such that the surface of said film to which said liquid was applied is the surface in contact with said substrate.

28. An indelibly marked homogenous polymeric film, wherein the dye which renders said film as indelibly marked penetrates said film such that said film is a homogenous polymeric film.

29. An indelibly marked homogenous polymeric film according to claim 28, wherein said indelible marking corresponds to a predetermined design.

30. An indelibly marked homogenous polymeric film according to claim 29, wherein said predetermined design comprises one or more of a logo; a word; wording; a dose description; a dose level; a manufacturers name; a characteristic identification pattern; and a bar code.

31. An indelibly marked homogenous polymeric film according to claim 30, wherein said bar code comprises one or more of a one dimensional code, a two dimensional code and a three dimensional code.

32. An indelibly marked homogenous polymeric film according to claim 31, wherein said two dimensional code comprises a data matrix.

33. An indelibly marked homogenous polymeric film according to any of claims 27-32, wherein said indelible marking comprises a visible pigment.

34. An indelibly marked homogenous polymeric film according to any of claims 27-33, wherein said dye comprises a pigment invisible to the human eye but detectible via means of light outside the frequency of normal human vision.

35. An indelibly marked homogenous polymeric film according to claim 34, wherein said light outside of the frequency of normal human vision is infra-red light.

36. An indelibly marked homogenous polymeric film according to claim 34, wherein said light outside of the frequency of normal human vision is ultra-violet light.

37. An indelibly marked homogenous polymeric film according to any of claims 27-36, wherein said indelibly marked homogenous polymeric film comprises a single, discrete film.

38 An indelibly marked homogenous polymeric film according to any of claims 27-37 wherein said preformed polymeric film comprises one or more of: hydroxypropyl methyl cellulose (HPMC); hydroxypropyl cellulose (HPC); hydroxyethyl methyl cellulose (HEMC); hydroxyethyl cellulose (HEC); methyl cellulose (MC); carboxymethyl cellulose (CMC); sodium carboxymethyl cellulose; cellulose acetate phthalate (CAP); hydroxypropylmethyl cellulose phthalate (HPMC-P); hydroxypropylmethyl cellulose acetate succinate (HPMC- AC); ethyl cellulose (EC); carboxymethyl hydroxyethyl cellulose (CMHEC); and salts and derivatives of the foregoing.

39. An indelibly marked homogenous polymeric film according to claim 38, wherein said preformed polymeric film comprises hydroxypropyl methyl cellulose (HPMC).

40. An indelibly marked homogenous polymeric film according to any of claims 27-39, wherein said indelibly marked homogenous polymeric film is edible.

41. An indelibly marked homogenous polymeric film according to any of claims 27-40, wherein said indelibly marked homogenous polymeric film comprises an active material.

42. An indelibly marked homogenous polymeric film according to any of claims 27-41, wherein said preformed polymeric film is transparent, semi-transparent or transluscent.

43. A substrate to which a film as defined in. any of claims 27-42 has been applied.

44. A substrate according to claim 43, wherein said substrate is at least partially enrobed by said film.

45. A substrate according to claim 44 wherein said substrate is completely enrobed by said film

46. A substrate according to claim 43, 44 or 45, wherein said substrate is a tablet.

47. A substrate according to claim 43, 44 or 45, wherein said substrate is a capsule.

48. A substrate according to any of claims 43-47, wherein said film is applied to, enrobes or partially enrobes said substrate such that the surface of said film which is in closest proximity to said indelible marking is the surface in contact with said substrate.

49. A method of producing an indelibly marked polymeric film comprising a three dimensional fused layer structure, said method comprising applying a liquid wherein said liquid is at least partially absorbed into a preformed polymeric film and wherein said three dimensional fused layer structure comprises a plurality of layers at least one of which fuses with a previous layer and said liquid is applied in a predetermined design to each layer.

50. A method according to claim 49 wherein said liquid is selected from one or more of a dye, a lake and a solid.

51. An indelibly marked three-dimensional fused layer structure comprising a plurality of layers at least one of which fuses with a previous layer wherein said indelible marking corresponds to a predetermined design.

52. A method or structure according to claim 49-51, wherein fuses means at least partially absorbed into a previous layer such that said absorption occurs in a direction substantially perpendicular to the plane of the layer.

53. The method or structure according to claim 49-51, wherein there is substantially no absorption in the direction parallel to a layer.