PROCESS FOR THE CONDITIONED PACKAGING OF HARD GELATIN CAPSULES

Abstract

A method for conditioning a hard gelatin capsule (50) having any moisture content to a dry and non-brittle state when packed for at least one week in a cavity (45) of a blister base (40) closed by a lid film (35) comprising an aluminium foil, wherein the hard gelatin capsule (50) is a hard starch capsule manufactured from collagen and the hard gelatin capsule (50) contains pharmaceuticals and wherein the dry state of the hard gelatin capsule (50) means a relative humidity of less than 50% at room temperature and the non-brittle state means that the hard gelatin capsule (50) does not break when pressed out of the cavity (45) of the blister base (40) through the lid film (35). The lid film (35) and/or the blister base (40) comprise/s a moisture-regulating buffer layer (20) with a predefined humidity. The moisture-regulating buffer layer (20) consists of a polymer or polymer mixture containing 1 to 60 wt. % of an absorber material which is either a hygroscopic salt, a silica gel or a zeolite or a mixture of any of said absorber materials, wherein the absorber material buffers the humidity in the space within the cavity (45) surrounding the hard gelatin capsule (50) to lie in a range between 10 and 50% r.h.

Claims

1. A method for conditioning a hard gelatin capsule (50) having any moisture content to a dry and non-brittle state when packed in a cavity (45) of a blister base (40) closed by a lid film (35), wherein the hard gelatin capsule (50) is a hard starch capsule manufactured from collagen and the hard gelatin capsule (50) contains pharmaceuticals and wherein the dry state of the hard gelatin capsule (50) means a relative humidity of less than 50% at room temperature and the non-brittle state means that the hard gelatin capsule (50) does not break when pressed out of the cavity (45) of the blister base (40) through the lid film (35), characterised in that the method includes the following process steps: a) providing a lid film (35) comprising an aluminium foil (15) and if applicable a sealing layer (30) made of a polyethylene and/or a moisture regulating buffer layer (20), further providing a blister base (40) having at least one cavity (45), the lid film (35) and/or the blister base (40) comprising a moisture regulating buffer layer (20) with a predefined humidity, wherein the moisture-regulating buffer layer (20) consist of a polymer or polymer mixture containing 1 to 60 wt. % of an absorber material which is either a hygroscopic salt, a silica gel or a zeolite or a mixture of any of said absorber materials, wherein the moisture-regulating buffer layer (20), the lid film (35) and/or the blister base (40) comprising the buffer layer (20) or a prelaminate for the lid film (35) and/or the blister base (40) comprising the buffer layer (20) is exposed to a predefined moisture level, wherein the predefined moisture level of the buffer layer (20) is such that it buffers the humidity in the space surrounding the hard gelatin capsule (50) within the cavity (45) closed by the lid film (35) to lie in a range between 10 and 50% r.h.; b) placing the hard gelatin capsule (50) in a cavity (45) of the blister base (40) provided in step (a) and closing the cavity (45) by laminating the lid film (35) provided in step (a) to the blister base (40) comprising the hard gelatin capsule (50); c) Storing the gelatin capsule (50) for at least one week in the cavity (40) closed by the lid film (35).

2. The method according to claim 1, characterised in that the moistening is done by passing the buffer layer (20), the lid film (35) and/or the blister base (40) comprising the buffer layer (20), or the prelaminate for the lid film (35) and/or the blister base (40) comprising the buffer layer (20) through a water bath, splashing it with water, or storing and/or processing it in an atmosphere having the predefined relative humidity.

3. The method according to claim 1, characterised in that the absorber material consists of potassium acetate, magnesium chloride, calcium chloride, silica gel or zeolite, or a mixture of said absorber materials.

4. The method according to claim 1, characterised in that the moisture-regulating buffer layer (20) contains 2 to 20% by weight of the absorber material.

5. The method according to claim 1, characterised in that the lid film (35) and/or the blister base (40) comprise/s an innermost sealing layer (30) directed to the cavity (45), wherein the sealing layer (30) is made of polyethylene (PE), in particular a mixture of a low density polyethylene (LDPE) and a high density polyethylene (HDPE), or another polyolefin, or modified polyolefins, or a cyclo-olefin copolymer (COC), or a ionomer.

6. The method according to claim 1, characterised in that the lid film (35) and/or the blister base (40) is/are a laminate comprising an aluminium foil (10, 15) as a moisture barrier.

7. The method according to claim 6, characterised in that the lid film (35) comprises the moisture-regulating buffer layer (20) between the aluminium foil (15) and a sealing layer (30), which is optionally bonded to the aluminium foil (15) by means of an adhesion promoter layer.

8. The method according to claim 6, characterised in that the blister base (40) comprises the aluminium foil (10) and on its inner side directed towards the cavity (45) the moisture-regulating buffer layer (20), which is optionally bonded to the aluminium foil (10) by means of an adhesion promoter layer (18).

9. The method according to claim 7, characterised in that the optional adhesion promoter layer (18) lying between the aluminium foil (10, 15) and the moisture-regulating buffer layer (20) consists of an ethylene-acrylic acid copolymer (EAA), or an ethylene-methacrylate copolymer (EMA), or a polypropylene (MAH-PP) grafted with maleic anhydride, or a polyurethane (PU) adhesive or an adhesive layer produced with solvent-containing or solvent-free adhesives.

10. The method according to claim 1, characterised in that the blister base (40) and/or the lid film (35) comprising a moisture-regulating buffer layer (20) made of polyethylene (PE), polypropylene (PP), ethylene-acrylic acid copolymer (EAA), ethylene-methacrylate copolymer (EMA), polyethylene terephthalate (PET), polyvinyl chloride (PVC) or a mixture of any of the preceding mentioned polymers is used, wherein the polymer or polymer mixture contains 1 to 60% by weight of the absorber material.

11. The method according to claim 1, characterised in that the blister base (40) comprises on its side opposite to its cavity (45) an outermost polymer film, in particular a film made of oriented polyamide (OPA).

12. The method according to claim 11, characterised in that the outermost polymer film is bonded to its adjacent layer (10) of the blister base (40) via an adhesive layer.

Description

[0068] The invention will now be described by way of examples and with reference to the accompanying drawings in which:

[0069] FIG. 1 shows schematically a structure of a lid film suitable for the inventive method;

[0070] FIG. 2 shows schematically a structure of a blister base suitable for the inventive method;

[0071] FIG. 3 shows the geometry of the blisters used for the pushing tests;

[0072] FIG. 4 shows a push through tool layout;

[0073] FIG. 5 shows a broken hard gelatin capsule;

[0074] FIG. 6 shows a bent hard gelatin capsule.

[0075] FIG. 1 shows schematically a cross-section of a lid film 35 used for the inventive method. The lid film 35 comprises an outer foil 15 made of aluminium and an inner layer 30 made of polyethylene arranged on the side of the aluminium foil directed to the blister base 40, when the lid film 35 is sealed onto the blister base 40. The inner layer 30 of the lid film 35 serves as sealing layer.

[0076] FIG. 2 shows schematically a cross-section of a blister base 40 of a blister package suitable for conditioning a hard gelatin capsule filled with pharmaceuticals in order to keep the hard gelatin capsule in a dry and non-brittle state. The blister base 40 has cavities (not shown) spaced apart from one other, wherein each cavity houses a single hard gelatin capsule (not shown). The blister base 40 comprises an outer aluminium foil 10 and an inner moisture-regulating absorber layer 20 on the side of the aluminium foil 10 directed to the cavities. The moisture-regulating absorber layer 20 shown in FIG. 2 is bonded to the aluminium foil using a bonding or adhesion promoter layer 18. The bonding or adhesion promoter layer 18 is optional. The moisture-regulating absorber layer 20 contains a polymer or polymer mixture and 1 to 60 wt. % potassium acetate.

[0077] FIG. 3 shows the geometry of a blister base 40 used for the pushing tests. The blister base foil is cut into a 190×120 mm.sup.2 sheet. The blister base foil 40 is inserted to the forming station, where at a forming speed of 40 cycles/min 6 cavities 45 are formed per blister. After forming the cavities 45, the blister base 40 is filled with capsules and the lid 35 is sealed at a temperature of 200° C. at a speed of 40 cycles/min. The final dimension of the lid 35 and the blister base 40 is 114×175 mm.sup.2. The shape of the cavities 45 is oval in a topview and the cavities 45 have a length of 40 mm and a width of 23 mm. The distance between two adjacent cavities 45 is 7 mm in the longitudinal side and broadside.

[0078] FIG. 4 shows the push through tool layout 60 and how the push through test is done: the upper part 62 of the tool 60 is moved downwards by a tensile tester machine spindle with a certain speed that varies between 1-800 mm/min. The bottom 63 of said upper part 62 compresses at a certain point the cavity 45 while the lid film 35 surrounding the capsule 50 is supported by the lower part 65 of the tool 60, and the capsule 50 in the cavity 45 is pushed out of the cavity 45 through the lid film 35 when the lid film 35 breaks.

[0079] FIG. 5 shows a broken hard gelatin capsule 50 after a push through test. The hard gelatin capsule 50 is of the type H and the blister where said capsule H was packed was a blister type 1.

[0080] FIG. 6 shows a bent hard gelatin capsule 50 of the type H after a pushing through test. The blister where said capsule H was packed was a blister type 3.