CN101365429A

CN101365429A - Sealed tablet

Info

Publication number: CN101365429A
Application number: CNA2006800501719A
Authority: CN
Inventors: J·特克
Original assignee: Bioprogress Technology Ltd
Current assignee: Bioprogress Technology Ltd
Priority date: 2005-10-31
Filing date: 2006-10-31
Publication date: 2009-02-11
Also published as: JP2009513693A; CA2627504A1; WO2007052003A9; GB0522186D0; WO2007052003A1; EP1942876A1

Abstract

The present invention relates to a coated tablet and a method for making a coated tablet and in particular the present invention provides a tablet having a coating formed from at least 2 separate film layers, wherein the film layers overlap and the overlapping film layers are sealed so that there is at least one non-sealed region.

Description

Sealed tablet

The method of the tablet that tablet that the present invention relates to coat (coated tablet) and manufacturing coat.

For example, the absorbed tablet of medicine, vitamin, nutritional supplement or the like is coated with usually and can absorbs material, makes tablet more stable and easier swallowing between the storage life.Described coating is also served as jamproof " bodyguard " (safeguard against tampering).For this purpose, known to being immersed in tablet in the gelatin solution and making the solution drying make tablet coating (enrobe) in gelatin to form coating.Suitable gelatin solution can be colored, and known to coating whole tablet with first coloured coating, then after the drying, coats half of this tablet and prepares double-colored gelatin coating with the gelatin of different colours.This has produced and has disturbed explicit (tamper-evident) tablet.

The additive method of tablet coating has been described among the U.S. Patent application US2004/0161527.In this application, the method for tablet coating has been described, method is included in vacuum formation material film on the tablet surface.In the method, thin film is that vacuum forms around the first surface of tablet, removes unnecessary thin film, and with this tablet upset, the second thin film vacuum is formed on the surface that tablet exposes now, makes tablet by coating fully.Then, any overlapping layer of the thin film that is produced by this method is sealed with glue, and described glue is applied to overlapped surfaces one of at least.

The problem of many tablets is that disintegrate and/or dissolved speed can not easily be changed.Especially, when tablet is ingested, disintegrate and/or dissolved speed will depend on the material that is used for coated tablets at least in part.Therefore, for disintegrate and/or the rate of dissolution that changes tablet, can change the thickness or the composition of coating.It may be time-consuming finishing these changes, and disintegrate and/or rate of dissolution only change and reach lesser extent, and this depends on the kind of the clad material of use.

Thereby the method that changes the disintegrate of tablet and/or rate of dissolution is laser-induced thermal etching to be fallen partial coating and makes medium directly arrive tablet.The tablet that this engraving method requires to utilize expensive laser equipment and can only be used for the coating of some kind.

The invention provides a kind of tablet of coating, it can easily be produced and wherein the disintegrate and/or the rate of dissolution of tablet can change easily.

The invention provides a kind of tablet, it has the coating that is formed by at least 2 independent thin layers, wherein sealed at least one non sealed regions of feasible existence of the overlapping and eclipsed thin layer of thin layer.

Have been found that the disintegrate and/or the rate of dissolution of tablet are improved by sealing this overlapping edge by halves.And, have been found that the disintegrate of this tablet and/or rate of dissolution can by changing how much changing of sealed overlapping layer.Overlapping layer is sealed many more, and dissolution velocity is just slow more.

As the term " tablet " that uses in this article, represent the medicine of any solid form etc., comprise tablet, capsule sheet, capsule etc.For the sake of simplicity, all above-mentioned forms are referred to herein as tablet.This tablet can be any suitable shape, comprises the tablet circular symmetry shape, capsule shape, rectangular, rhombohedral and oval-shaped with cylindrical side wall.

Tablet of the present invention is coated with at least 2 thin film.Preferably, these thin film are hot forming thin film, and its hot forming is on tablet.Hot formed thin film comprises the heating thin film to the temperature that requires on tablet, and it is deformable to make that thin film becomes, so that meet the outer surface of tablet.Preferably, these thin film be water soluble with ingestible.Suitable hot forming thin film is described in U.S. Patent application US 2004/0161527.Suitable hot forming thin-film material comprises cellulosics, as hydroxypropyl emthylcellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl-cellulose (HEC), ethyl cellulose (EC), methylcellulose (MC), carboxymethyl cellulose (CMC) or the like, enteric solubility (enteric) polymer such as HPMC-AS (HPMC-acetas succinate), HPMC-P (HPMC-phthalic acid ester) are and if other glue, polyvinyl alcohol (PVOH) polyethylene glycol oxide (PEO), PEO-PEG graft copolymer, alginate, amylopectin or these any derivants.Preferably, this hot forming thin film is hydroxypropyl emthylcellulose (HPMC) thin-film material.The method of hot forming thin film it is known to those skilled in the art that on tablet.Especially referring to U.S. Patent application US 2004/0161527.

Usually, the first film is forming surpassing slightly on 50% the tablet, and like this, in case this tablet and form second thin film at the opposite side of this tablet of overturning, this tablet is fully coated and first and second film overlaies.

Surface modifying material as adhesive material, can be applied to the surface of tablet before coating with thin film.Can use any suitable surface modifying material, especially, the material on those dissolving films surfaces is as water or alcohol.In some cases, preferably, surface modifying material is applied in whole tablet surface, in order partly thin film to be attached to tablet.This can help to differentiate the interference (tampering with the tablets) with tablet.Applied adhesives is described in U.S. Patent application US 2004/0161527 on the surface of tablet.

This overlapping thin layer seals by surface modifying material is provided, as the binding agent between overlapping thin film.If necessary, heating and/or pressure can be applied to overlapping thin layer to help to form sealing.As discussed above, surface modifying material can be any suitable material.Especially, surface modifying material can be an alcohol, or can have the composition identical with thin layer easily, but has the more plasticizer of vast scale, and 93%-98% plasticizer for example is so that provide the viscosity materials with smaller.Surface modifying material, as binding agent, can be with the thin layer different colours so that provide pattern in the eclipsed place of thin layer.

In order to ensure at least one non sealed regions is arranged, application surface is not material modified at least one zone (zone) of the overlapping region of thin film.This non sealed regions makes medium directly arrive tablet.Suitable medium comprises fluid, contains thing or the like as water, saline solution, individual stomach.Exist non sealed regions to represent that the overlapping layer of thin film does not form sealing completely and guarantees that instead overlapping thin layer does not form sealing waterproof or gas-tight.These non sealed regions can vary in size or be close each other, so that for example, change the size of sealing area or change fluidic capillarity (capillarity) or the degree of wicking (wicking).

The specific application of surface modifying material, particularly binding agent can realize with the whole bag of tricks.Preferably, surface modifying material is by only being applied to thin film with surface modifying material in the sealing area and being applied on the thin film waiting to become.This class is accurately used and can be realized by using any suitable device, as by ink jet printing, indirect gravure (offset gravurewith pattern), impression (pad printing), labelling spraying (mark spray) with cover (blanket coating) method of coating with pattern, as use with the suitable bonded scraper of mask or extrusion die can coat required pattern.Preferably, use ink jet printing to come to the applied as thin films binding agent.

As skilled in the art will appreciate, can change disintegrate and/or the rate of dissolution of size to influence tablet of sealing area and non sealed regions.For example, if tablet will have low rate of dissolution, only the overlapping thin film of sub-fraction (a small part of) will be not sealed (for example, 5%).If tablet will have high rate of dissolution, most (substantial part of) overlapping thin film not sealed (for example, about 40%, preferably about 60%).Particularly preferably, sealing area by equably at interval, makes at least two (individual) layer or thin film remain on tablet to keep together around the overlapping thin film zone of tablet.

The present invention also provides the method with the thin film coated tablets, comprising:

I. hot forming at least two thin layers around tablet make thin layer overlapping; With

Ii. overlapping thin layer is sealed, makes to have at least one non sealed regions.

The suitable method of hot forming thin film is disclosed in U.S. Patent application US2004/0161527 around tablet.As noted before, at least one non sealed regions forms by at least one zone that makes surface modifying material (as binding agent) not be applied to overlapping thin film, thereby prevents that thin film from forming sealing.Preferably, thin film before the hot forming, is applied to thin film with surface modifying material around tablet.Surface modifying material preferably only is applied to such zone of thin film, and described zone will form overlapping and described zone with another thin layer will form sealing.This surface modifying material can be applied to the only one deck that forms eclipsed each thin layer or be applied to this thin film.If this surface modifying material is being applied on the thin film before the hot forming around the tablet at thin film, the position of surface modifying material must be coordinated with the subsequent position of tablet.

According to a second aspect of the invention, provide method, comprising with the thin film coated tablets:

I. hot forming at least two thin layers around tablet make thin layer overlapping; And

Ii. with surface modifying material overlapping thin layer is sealed, described surface modifying material only is applied between the overlapping thin layer.

By only between the thin layer in the overlapping region application surface material modified, as binding agent, the amount of the surface modifying material of use is reduced widely.This will cause that production cost obviously reduces.

As noted before, the appropriate method of hot forming thin film is disclosed in U.S. Patent application US 2004/0161527 around tablet.Surface modifying material preferably is being applied on the thin film before the hot forming around the tablet at thin film.Surface modifying material can be applied to that every layer of forming eclipsed thin film is gone up or monolayer only.If surface modifying material is being applied on the thin film before the hot forming around the tablet at thin film, the position of surface modifying material must be coordinated with the subsequent position of tablet.Surface modifying material will be used by using any suitable technique, as above-mentioned those.As noted before, preferably, surface modifying material will form overlapping areas with another layer film by those that make that this surface modifying material accurately is sprayed on thin film be applied to thin film.Preferably, use ink jet printing to the applied as thin films surface modifying material.

The invention still further relates to the tablet of producing by according to the method for second aspect present invention.

The present invention also provides thin layer, and with discontinuous mode application surface material modified (as binding agent), described thin film is applicable to method of the present invention to this thin layer.Preferably, surface modifying material and thin film are as defined above.

Use term " discontinuous mode " to describe the mode that surface modifying material is applied to thin film.Its presentation surface is material modified not to be to be applied to whole film surface.In fact, surface modifying material only is applied to some zones on surface.As mentioned above, thin film is used to cover tablet.Around thin layer was wrapped in tablet, it and the second layer were overlapping.Application surface is material modified still to stay some zones without any surface modifying material to form sealing between two-layer, so the sealing that forms is not completely.Surface modifying material is applied to thin film discontinuously, makes to stay some non sealed regions.

With reference now to the following drawings, the present invention is only described by way of example.

Fig. 1 shows the tablet with thin film half coating.

Fig. 2 shows the thin film of deposit binder thereon.

Fig. 3 shows the profile of the tablet that coats with two thin layers.

Fig. 4 shows the thin film of deposit binder in the zone that limits thereon.

Embodiment 1

Tablet (1) carries out half coating according to the method that is disclosed in U.S. Patent application US 2004/0161527 with the first hot forming thin film (3), and is maintained at carrier (5) upward (referring to Fig. 1).Then, second hot forming thin film (7) (referring to Fig. 2) hot forming of ring (ring) that has thereon the surface modifying material (binding agent) (9) that forms is on the surface that does not coat of tablet (1), the first film of overlapping (3) that wherein comprises second thin film (7) of surface modifying material (9) makes surface modifying material (9) be positioned between eclipsed first (3) and second thin layer (7).Tablet (1) with overlapping thin film (3,7) is shown among Fig. 3, and wherein this overlapping thin film has the surface modifying material (9) that is placed in therebetween.According to the method that is disclosed among the U.S. Patent application US 2004/0161527, second thin film (7) hot forming is on the tablet (1) that part coats.

The ring of surface modifying material (9) is applied to second thin film (7) by using printing ejector (printing jet).

Those skilled in the art is to be understood that, the ring of surface modifying material (9) can be positioned on the first film layer (3) and second thin film (7) position overlapped, and it can have or the ring of the corresponding surface modifying material (9) that also can not form thereon.

Embodiment 2

Tablet (1) carries out half according to the method that is disclosed in U.S. Patent application US 2004/0161527 with the first hot forming thin film (3) and coats (referring to Fig. 1).Second thin film (7) (referring to Fig. 4) hot forming of surface modifying material (9) that has thereon the plurality of sections (sections) that forms then is on the surface that does not coat of tablet (1), the first film of overlapping (3) that wherein comprises second thin film (7) of surface modifying material (9) makes surface modifying material (9) be positioned between eclipsed first (3) and second (7) thin layer.The tablet (1) that coats has some overlay segments, and it is because the existence of surface modifying material (9) and not sealed overlay segment (that is, unencapsulated section (owing to there not being surface modifying material (9) to produce)) produces.Unencapsulated section makes fluid directly reach tablet (1) to cause tablet (1) disintegrate faster and/or rate of dissolution with respect to the coating of describing in embodiment 1.According to the method that is disclosed in U.S. Patent application US 2004/0161527, second thin film (7) hot forming is on the tablet (1) that part coats.

The surface modifying material of plurality of sections (9) is applied to second thin film (7) by using the printing ejector.

Those skilled in the art is to be understood that, the surface modifying material of plurality of sections (9) can be positioned on the first film layer (3) and second thin film (7) position overlapped, and it can have or also can not form the surface modifying material (9) of corresponding section thereon.

The invention provides the method for tablet and manufacturing tablet, it has different disintegrates and/or rate of dissolution.

It will be apparent to those skilled in the art that and to carry out multiple modification to aforesaid tablet.These modifications are considered to belong to of the present invention in the scope defined in the appended claims.

All above-cited documents are hereby incorporated by.

Claims

1. tablet has the coating that is formed by at least 2 independent thin layers, and wherein thin layer is overlapping and this overlapping thin layer is sealed, makes to have at least one non sealed regions.

2. according to the tablet of claim 1, wherein thin layer is the hot forming thin film, its hot forming around tablet.

3. according to each tablet of front claim, wherein at least one non sealed regions makes fluid directly reach this tablet.

4. according to each tablet of front claim, wherein this overlapping layer is sealed by the surface modifying material that use is positioned between the overlapping layer.

5. according to each tablet of front claim, two thin layers are arranged wherein.

6. according to each tablet of front claim, a plurality of non sealed regions are arranged wherein.

7. with the method for thin film coated tablets, comprising:

8. according to the method for claim 7, wherein overlapping thin layer is sealed by application surface between overlapping layer is material modified, thereby and wherein at least one non sealed regions be by at least one zone of overlapping thin film not the application surface modification prevent that thin film from forming sealing and forming.

9. according to the method for claim 7 or 8, wherein this surface modifying material is being applied to thin film before the hot forming at thin film around the tablet.

10. according to each method of claim 7-9, wherein surface modifying material is applied to and forms eclipsed each thin layer.

11. according to each method of claim 7-10, wherein surface modifying material is applied to thin film by those zones of the thin film that this surface modifying material accurately is applied to will form sealing.

12. the method with the thin film coated tablets comprises:

13. according to the method for claim 12, wherein this surface modifying material is being applied to thin film before the hot forming at thin film around the tablet.

14. according to the method for claim 12 or 13, wherein this surface modifying material is applied to eclipsed each thin layer of formation.

15. according to each method of claim 12-14, wherein surface modifying material is applied to thin film by making this surface modifying material accurately be sprayed at those zones that will form eclipsed thin film with another thin layer.

16. according to each method of claim 7-15, wherein this surface modifying material also is being applied to tablet before the hot forming at thin film around the tablet.

17. by what produce according to each method of claim 7-16

18. a thin layer is material modified to its application surface in discontinuous mode, it is applicable to each method of claim 7-16.