BR112019010874B1 - MATRIX FOR A MULTI-CHAMBER SOFTGEL CAPSULE, MATRIX ROLL, ROTARY MATRIX ENCAPSULATION MACHINE, PAIR OF COUPLED MATRIXES AND APPARATUS - Google Patents

Abstract

The invention provides a matrix suitable for producing a multi-chamber softgel capsule. The matrix comprises a matrix pocket defined by a matrix pocket wall and a bottom surface. The matrix comprises one or more dividing walls dividing the matrix pocket into two or more chambers. The top of the area of the dividing walls has a lowest point that is less than the plane formed by the top of the area along the perimeter of the matrix pocket wall by a gap. Also provided is a die roll comprising a plurality of dies, as well as a rotary die encapsulation machine comprising the die roll.

Description

BACKGROUND OF THE INVENTION 1. Field of Invention

[001] The invention generally relates to a matrix and process for the manufacture of softgel capsules. In particular, the invention relates to a matrix and process for manufacturing softgel capsules with two or more chambers, where each chamber is suitable for encapsulating a different fill material.

2. Description of Related Technology

[002] In recent years, softgel capsules have become a popular dosage form for therapeutic agents and cosmetic products. Softgel capsules are typically filled with a liquid containing therapeutic agents or cosmetic substances. Furthermore, other products such as dietary supplements or veterinary products can also be used in softgel capsule fill materials. Due to their soft and elastic character, patients often find these capsules easier to swallow than conventional tablets or hard gelatine capsules. Softgel capsules are also preferred for bulk liquids because they are easier to transport and avoid the need for patients or users to measure a prescribed amount of liquid before use.

[003] Softgel capsules are commonly produced by a rotary die process, which was described in detail in Ebert, W.R., "Soft elastic gelatin capsules: a unique dosage form", Pharmaceutical Tech., October 1977; Stanley, J.P., "Soft Gelatin Capsules," in The Theory and Practice of Industrial Pharmacy (Lachman, Lieberman, and Kanig, Editors), 3rd edition, published by Lea &Febiger; and Patent Nos. US 1,970,396, 2,288,327 and 2,318,718, the teachings of all of which are hereby incorporated by reference in their entirety.

[004] A typical rotary die encapsulation machine for making softgel capsules is illustrated in FIG. 1. There are a plurality of dies 5, 5' on the die roll 3, 3'. As the die roll 3, 3' rotates in the directions shown by the arrows in FIG. 1, two gel ribbons 2, 2' are fed onto the matrix roll 3, 3' where the gel ribbons 2, 2' are deposited in the matrix pockets 5, 5'. The settled gel ribbons are gathered on the die roll 3, 3' to form the capsules 1. The filling material is injected into the capsule pocket 7 of the forming capsule 1 through an injection channel 4 of the filling wedge 6. The filled capsules are then pinched from the remaining 2, 2' gel strips.

[005] The capsule shell must be compatible with the filling material, especially the pharmaceutical agent or cosmetic substance contained in a liquid vehicle. In addition to liquids, US Patent No. 4,935,243 suggests that the filler material can also be a semi-solid, solid or gel. Conventional tablets or lozenges containing an active ingredient are examples of solid fill materials that can be encapsulated within a softgel capsule.

[006] A softgel capsule may contain two or more active ingredients. The ability to encapsulate two or more active ingredients in a single softgel capsule offers several advantages including convenient delivery of multiple drugs/products, avoidance of potential user error if multiple drugs/products are taken at the same time, increased user acceptance, obtaining possible synergistic effects and possible controlled delivery. However, in some cases, the two or more active ingredients in a softgel may be chemically incompatible. For example, chemical reactions can occur between active ingredients or between an active ingredient and a vehicle in the filler material.

[007] Attempts have been made to separate incompatible active ingredients in the same softgel capsule to avoid chemical incompatibilities and to maintain the chemical integrity of the active ingredients. Physical barriers can be used in a softgel capsule to separate incompatible active ingredients in different chambers. For example, a divider can be used to divide a softgel capsule into separate chambers with each chamber containing a filler material with a different active ingredient.

[008] EP 0 211 079 A1 describes multi-chamber softgel capsules and an apparatus for making the softgel capsules. The multi-chamber softgel capsule consists of at least one divider for dividing its internal space into a plurality of chambers. The multi-chamber softgel capsule is manufactured by feeding a first film to form the first coating, a second film to form the second coating, and a third film positioned between the first and second films to form the divider, between a pair of rollers. die in a capsule molding apparatus. Separate filler materials are introduced into the space between the partition and the first film and the space between the partition and the second film. These films are then joined together by compressing the three films together, except for their capsule-forming portions, to form multi-chamber softgel capsules containing the fill materials.

[009] US Patent No. 7,490,456 describes an apparatus for making two-compartment softgel capsules from films of a polymeric material. The apparatus comprises a pair of rotating weld die rolls defining recesses, means for supplying the films to the weld die rolls to be deformed to form recesses, and means for filling the resulting recesses in the films with a filler material, and means for applying high frequency electrical signals between the welding die rolls so that the films are welded by dielectric welding to form multiple compartments containing the fill material and means for cutting the filled capsules from the remaining films. The apparatus also comprises a transfer roller and a kiss cut roller for cutting the filled capsules between the transfer roller and the kiss cut roller. When three films are supplied to the apparatus, where the two outer films form recesses and the middle film forms the divider between the two compartments.

[0010] Document US 2005/0191346 discloses softgel capsules containing at least two separate chambers. The softgel capsule includes a dividing wall that separates the capsule into two chambers. The dividing wall is formed by two layers of wall material glued together. An encapsulation apparatus for manufacturing such capsules comprises a means for supplying two films to an encapsulation unit, a means for plastically deforming each film to form suitably shaped capsule portions, a means for supplying the respective filling material to be encapsulated in the respective capsule portions, means for supplying a film of dividing wall material to each of the filled capsule portions, and means for adhering the capsule portions and dividing wall material together to produce a capsule having at least two separate chambers.

[0011] Patent No. US 8,361,497 describes a multi-compartment capsule. The capsule comprises a first receiving chamber containing at least one ingredient having a first physical state, with the ingredient selected from a nutraceutical, a vitamin, a dietary supplement and a mineral; and a second receiving chamber containing at least one other ingredient having a second physical state, with the other ingredient selected from a nutraceutical, a vitamin, a dietary supplement and a mineral. The ingredient in the first receiving chamber is different from the other ingredient in the second receiving chamber. The first physical state in the first receiving chamber is different from the second physical state in the second receiving chamber.

[0012] WO 00/28976 discloses softgel capsules with a plurality of chambers separated by barriers. An apparatus for making such gel capsules comprises first gel tape dispensing means for dispensing a first gel tape between a first wedge and a first roll, second gel tape dispensing means for dispensing a second gel tape between a second wedge and a second roller, at least one barrier material delivering means for distributing a barrier material between the first and second wedges where the barrier material forms barriers to divide the capsule into at least two chambers, and an active agent releasing means for delivering at least one active agent to at least one of the chambers. The barrier material is substantially non-permeable to any components contained in the chambers.

[0013] Making these multi-chamber softgel capsules requires significant modifications of the rotary die encapsulation machines that were used to make a softgel capsule filling capsule or an extra step in adhering two chambers into a single softgel capsule. These modifications will incur significant costs and an extra tack step will also incur additional costs to the production process. The present invention provides a new die that can be used in traditional rotary die encapsulation machines with minor modifications for the production of multi-chamber softgel capsules without any additional steps. The new matrix allows efficient production of multi-fill/chamber softgel capsules at a reasonable cost.

SUMMARY OF THE INVENTION

[0014] In one embodiment, a matrix suitable for producing a multi-chamber softgel capsule is disclosed. The matrix includes at least: a matrix pocket defined by a matrix pocket wall and a bottom surface; and one or more partition walls dividing the matrix bag into two or more chambers and wherein the matrix bag wall and one or more partition walls have their respective upper sections defined as areas, an upper part of the area along the perimeter of the wall of the matrix enclosure is in a plane, and a lower point of the upper part of the area of one or more dividing walls being lower than the plane by a gap.

[0015] In each of the foregoing embodiments, one or more matrix divider walls may be perpendicular to the plane comprising the upper part of the area along the perimeter of the matrix pocket wall.

[0016] In each of the above embodiments, at least one of the areas of one or more dividing walls of the array may have a recess in the upper part.

[0017] In each of the foregoing embodiments, one or more dividing walls of the matrix may be, for example, a straight line or a curved line, when viewed from a top view of the matrix.

[0018] In each of the foregoing embodiments, at least one of the one or more dividing walls may have a decreasing thickness from the proximity of the bottom surface of the matrix to the area of the at least one dividing wall.

[0019] In each of the foregoing embodiments, at least one of the one or more dividing walls may have a thickness that increases from the lower surface of the matrix to the upper part of the area of the at least one dividing wall.

[0020] In each of the foregoing embodiments, a size of the gap formed between the lowest point of the upper part of the areas of the one or more partition walls and the plane of the upper part of the wall area of the matrix bag may be in a range from about 0.0508 mm (0.002 inch) to about 2.54 mm (0.1 inch), or from about 0.508 mm (0.02 inch) to about 2.032 mm (0.08 inch), or from about 0.508 mm (0.02 inch) to about 1.524 mm (0.05 inch) or from about 0.762 mm (0.03 inch) to about 1.27 mm (0.05 inch).

[0021] In each of the foregoing embodiments, the gap may be less than about 95%, or less than about 90%, or less than about 85%, or less than about 80%, or less than about 80% 75%, or less than about 70%, or less than about 65%, or less than about 50%, or less than about 45%, or less than about 40%, or less than about 30% , or less than 20% the thickness of a gel strip suitable for use with the matrix.

[0022] In each of the foregoing embodiments, at least one of the two or more chambers may have a different size from another of the two or more chambers.

[0023] In each of the foregoing embodiments, the matrix can be constructed with one or more high-strength materials selected from aluminum, brass, hardened steel, stainless steel, bronze, iron and cast zinc.

[0024] In each of the foregoing embodiments, the die can be constructed with a high wear resistance and hot strength alloy selected from Co, Ni or Mo based alloys.

[0025] In another embodiment, a die roll having a surface comprising a plurality of dies of any one of the foregoing embodiments is disclosed.

[0026] In another embodiment, a rotary die encapsulation machine comprising at least one die roll having a plurality of dies of any one of the foregoing embodiments is disclosed.

[0027] In another embodiment, there is disclosed a multi-chamber softgel capsule made using the matrices of any of the foregoing embodiments, wherein the multi-chamber softgel capsule has two or more chambers separated by one or more barrier seals.

[0028] In the above embodiment, the multi-chamber softgel capsule may have a capsule shell comprising at least one softgel, water-soluble cellulose derivatives, seaweed-derived polymers, pectin, polyethylene oxide, polyvinyl alcohol, alginate, polycaprolactone and gelatinized starch-based materials.

[0029] In each of the foregoing embodiments of the multi-chamber capsule, the softgel capsule can encapsulate at least two different fill materials selected from pharmaceutical formulations, dietary supplements, cosmetic products and industrial applications (for example, two-part epoxy systems or two-part polyurethane systems).

[0030] In each of the foregoing embodiments of the multi-chamber capsule, the multi-chamber softgel capsule can separately encapsulate at least two different materials which, when used, combine to make a single product.

[0031] In another embodiment, a pair of coupled matrices is described which is suitable for producing a multi-chamber softgel capsule, each of the pairs of matrices (10) comprising: a matrix pocket defined by a pocket wall and a bottom surface; and one or more partition walls dividing the matrix pocket into two or more chambers and wherein the matrix bag wall and one or more partition walls have their respective upper sections defined as areas, the partition walls of the coupled matrix pair have heights such that there is a gap between the area(s) of one or more partition walls of one of the arrays and the area(s) of one or more partition walls of the other array.

BRIEF DESCRIPTION OF THE DESIGNS OF CERTAIN MODALITIES

[0032] FIG. 1 is a prior art rotary die encapsulation machine typically used in a conventional rotary die process to make a single fill softgel capsule.

[0033] FIG. 2 is a diagrammatic top view of a die for making a multiple fill softgel capsule.

[0034] FIG. 3 is a cross-sectional view of the die of FIG. 2 is a side view of the die in cross section A-A of FIG. two

[0035] FIG. 4 is another cross-sectional view of the die of FIG. 2 is a side view of the die in cross section A-A of FIG. two

[0036] FIG. 5 is a photo of the matrix of FIG. 4

[0037] FIG. 6 is a diagrammatic top view of a die for making a multi-fill softgel capsule with a twist cap. The location of the A-A cross section is indicated.

[0038] FIG. 7 is a cross-sectional side view of the blank of FIG. 6 in cross section A-A of the matrix, as shown in FIG. 6.

[0039] FIG. 8 is a diagrammatic top view of the same matrix in FIG. 6, showing the location of the B-B cross section near the twist cap.

[0040] FIG. 9 is a cross-sectional side view of the blank of FIG. 8 in cross section B-B of the matrix, as shown in FIG. 8.

[0041] FIG. 10 is a photo of the matrix of FIGS. 6 and 8.

[0042] FIG. 11 is a series of diagrams showing different features of the matrix of FIG. 6 in separate diagrams.

[0043] FIG. 12 is a diagram of a die for manufacturing a multi-fill softgel capsule with a separating tab.

[0044] FIG. 13 is a top view of a die for making a multi-fill softgel capsule, as shown from a side view.

[0045] FIG. 14 is a photo of the arrays of FIG. 1 on a die roll for use in a rotary die encapsulation machine.

[0046] FIG. 15 is a matrix diagram of FIGs. 6 and 8 on a die roll for use in a rotary die encapsulation machine.

[0047] FIG. 16 is a photo of multi-fill softgel capsules produced by the die of FIGs. 5 and 14.

[0048] FIG. 17 is a photo of a multi-fill softgel capsule produced by the die of FIGs. 6 to 8 and 10.

[0049] FIG. 18 is a photo of the multi-fill softgel capsule of FIG. 17 and the two liquid filling materials sprayed onto a piece of paper.

[0050] FIG. 19 shows two alternative multi-fill softgel capsules that may be produced by the die in accordance with some embodiments of the present invention.

[0051] FIGs. 20A-20B are cross-sectional side views of the pouch walls with an upper section thereof called the area. The area may have a smooth top surface (FIG. 20A) or a crescent-shaped recess in its top surface (FIG. 20B).

[0052] FIGs. 21A to 21B are cross-sectional side views of dividing walls with an upper section of the same so-called area. The area may have a smooth top surface (FIG. 21A) or a crescent-shaped recess in its top surface (FIG. 21B).

DETAILED DESCRIPTION OF CERTAIN MODALITIES

[0053] For illustrative purposes, the principles of the present invention are described with reference to various exemplary embodiments. While certain embodiments of the invention are specifically described herein, a person skilled in the art will readily recognize that the same principles are equally applicable to, and can be used in, other systems and methods. Before explaining in detail the disclosed embodiments of the present invention, it should be understood that the invention is not limited in its application to the details of any particular embodiment shown. Additionally, the terminology used here is for the purpose of description and not limitation. Furthermore, although certain methods are described with reference to steps which are presented herein in certain order, in many cases these steps may be carried out in any order, as would be appreciated by a person skilled in the art; the new method is therefore not limited to the particular arrangement of steps disclosed herein.

[0054] It should be noted that, as used herein and in the appended claims, the singular forms "a", "an", and "the/the" include plural references, unless the context clearly dictates otherwise. In addition, the terms "a" (or "a"), "one or more" and "at least one" may be used interchangeably in this document. The terms "comprising", "including", "having" and "constructed from" can also be used interchangeably.

[0055] It will be understood that each feature, component, compound, substituent or parameter disclosed herein shall be construed as being disclosed for use alone or in combination with one or more of each and every other feature, component, compound, substituent or parameter disclosed herein.

[0056] The present description provides a die 10, 100, 200 for producing multi-chamber softgel capsules. The matrix 10, 100, 200 has its matrix pocket 20 defined by a matrix pocket wall 12 and a bottom surface 11. The matrix pocket 20 is divided into a plurality of chambers 14, 16 by one or more dividing walls 18, as shown in FIGS. 2, 6 and 8. The matrix pocket wall 12 and the one or more divider walls 18 have their respective upper sections defined as areas 29, 39 (FIGS. 20A to 20B and 21A to 21B). The upper part of the area 29 along the perimeter of the matrix pocket wall 12 is in the same plane. The upper part of the area(s) 39 of one or more partition walls 18 has a lowest point that is lower than the plane by a gap as shown from a side view in FIGs. 3, 4, 7 and 9. A difference between the matrix 10, 100, 200 of this disclosure and the matrix 5, 5' of FIG. 1 is that the die 10, 100, 200 of this disclosure has multiple chambers 14, 16 in its die pocket 20, which allows the die 10, 100, 200 to produce a multi-chamber softgel capsule with the multiple chambers 14', 16 ' separated by one or more barrier seals 18' (FIGS. 16 to 17).

[0057] The wall area 29 of matrix pocket 12 is shown in FIGs. 20A to 20B. In one embodiment, the upper surface of area 29 is smooth (FIG. 20A). In other embodiments, the area 29 has a recess 19 in its upper part (FIG. 20B). In still other embodiments, the recess 19 has a crescent shape when viewed from a side view (FIG. 20B). It is understood that the upper part of the areas 29 can have different shapes, such as rounded, flat, curved, flat or angular. In one embodiment, the upper portion of areas 29 may be recessed forming a semicircular curve with a radius.

[0058] Similarly, areas of partition wall 18 are shown in FIGs. 21A to 21B. In one embodiment, the top surface of area 39 is smooth (FIG. 21A). In one embodiment, area 39 has a recess 19 at its top (FIG. 21B). In certain embodiments, the recess 19 has a crescent shape from a side view (FIG. 21B). It is understood that the upper part of the areas 39 have a shape that is independent of the shape of the area 29, and may be rounded, flat, curved, flat or angled. In another embodiment, the upper part of the areas 39 can be recessed forming a semicircular curve with a radius.

[0059] In certain embodiments, area 29 and area 39 are not separate pieces adhered to matrix pocket wall 12 and divider wall 18, respectively. Rather, area 29 is a section of matrix pocket wall 12 and area 39 is a section of divider wall 18.

[0060] In one embodiment, the upper part of the area 39 of at least one or more partition walls 18 is curved as seen from the chamber 14, 16. In another embodiment, the upper part of the area 39 of at least one of a or more divider walls 18 is flat as seen from chamber 14, 16. In yet another embodiment, the top area 39 of at least one or more divider walls 18 is serrated as seen from chamber 14, 16.

[0061] As used herein, a "softgel capsule" refers to a softgel capsule, such as a gelatin-based capsule, that is supplied as a single-use form. In some examples, the softgel capsule includes a liquid filler, such as a solution, suspension or semisolid, which is encapsulated by two halves of a capsule shell to form a single, hermetically sealed capsule. In some aspects, the capsule shell can comprise softgel, a plasticizer and water. The capsule shell may also include other ingredients, such as preservatives, coloring, flavoring, opacifying agents, sweetening agents, acids, salts, medicaments or other agents to achieve a desired dosage effect. The filler material may be a pharmaceutical formulation, a dietary supplement, a veterinary product, a cosmetic product or a product for industrial applications (e.g. epoxy or two-part polyurethanes). Industrial applications can include two industrial materials that can be used at the point of use to produce a desirable industrial product.

[0062] In some aspects, the matrix 10 of this disclosure is shown in FIG. 2, which has a matrix pocket 20 divided by a dividing wall 18 into two chambers 14, 16. The matrix pocket 20 is defined by a matrix pocket wall 12 and a bottom surface 11. The upper part of the area 29 of the bag wall 12 is in the same plane. In each chamber 14, 16 there is an air hole 15, 17 in the bottom surface 11 to let air out when a gel tape covering the matrix 10 settles in the chamber 14, 16 to form recesses for receiving the filler material. The two chambers 14, 16 comprise almost the entire volume of matrix pocket 20 in FIG. 2. As shown in the cross-sectional view of the die 10 in FIG. 3, the upper part of the area 39 of the partition wall 18 is lower than the plane formed by the upper part of the area 29 of the wall of the matrix pocket 12 by a gap.

[0063] In the operation of some aspects, a gel ribbon is fed and placed on top of a first matrix 10, with the gel ribbon settling in the chambers 14, 16, for example, by suction in the chambers 14, 16 through the air holes 15, 17 or by the pressure of the filling material. The seated gel tape defines recesses that will become halves of each of the two chambers 14', 16' of a softgel capsule. The gel strip also sits in the area 39 of the partition wall 18. A mated die 10 also has a gel strip seated and forms the nested recesses. After the two paired arrays 10, each with the gel ribbon seated and forming complementary halves of the chambers 14', 16', are pressed together, the gel ribbons are fused under heat along the area 29 of the wall of the matrix pouch 12 and partition wall area 39 18 to form a softgel capsule with two chambers 14', 16'. Because the area 39 of the divider wall 18 is lower than the area 29 of the wall of the matrix bag 12, the molten gel along the area 39 of the divider wall 18 will form a barrier seal 18' to separate the two chambers 14 ', 16' of the softgel capsule further connecting the two chambers 14', 16' together. On the other hand, the gel ribbons along the area 29 of the wall 12 of the matrix pocket are pressed together tightly in such a way that the softgel capsule can be easily separated from the remaining gel ribbons. The two chambers 14', 16' of the softgel capsule can be injected with different filling materials, thus resulting in a softgel capsule having two chambers 14', 16' filled with two different filling materials.

[0064] The softgel capsules can be cut from the remaining gel strips by punching. Alternatively, the softgel capsules can be easily pushed out of the remaining gel ribbons when the coupled matrices 10 are pressed sufficiently tightly together along the wall area 29 of the matrix pocket 12 so that the gel ribbons surrounding each capsule are thin enough. In one aspect, the two-chamber softgel capsules produced from the matrix 10 of FIG. 4 are shown in FIG. 16

[0065] In some aspects, the top surface of area 39 of partition wall 18 may itself have a recess 19 at the top along the length of area 39 of partition wall 18, as shown in FIGS. 4 and 5. The recess 19 at the top of the area 39 of the divider wall 18 will create a thick area along the barrier seal 18' between the two softgel chambers 14', 16'. The thick area can strengthen the 18' barrier fence. A photo of matrix 10 of FIG. 4 is shown in FIG. 5.

[0066] In some other aspects, the die 100 has an area forming a twist cap 25 (FIG. 6) as shown above the die. The two chambers 14, 16 of this matrix 100, each in fluid connection with a discharge channel 22, 23 respectively. The two chambers 14, 16 comprise most of the volume of the matrix pocket 20. The discharge channels 22, 23 and the twist cap area 25 comprise a small portion of the volume of the matrix pocket 20. extends from between the chambers 14, 16 to between the discharge channels 22, 23. The discharge channels 22, 23 are separated from the twist cap 25 by a channel wall 13, which connects to the matrix pocket wall 12 and divider wall 18. The cross-sectional view of die 100 of FIG. 6 at location A-A is shown in FIG. 7. The chambers 14, 16 are semi-circular in shape with air holes 15, 17 at or near the center of the respective chambers 14, 16. The lowest point of the upper part of the area 39 of the dividing wall 18 is less than the plane with the upper part of the wall area 29 of the matrix pocket 12 by a gap (FIG. 7).

[0067] FIG. 9 is a B-B cross-sectional view of die 10, as indicated in FIG. 8, providing a better view of the twist cap 25 and the adjacent area with the two discharge channels 22, 23. The dividing wall 18 extends to the twist cap 25 and separates a small, shallow filling area into two channels of outlet 22, 23. The outlet channel 22, 23 is in fluid connection with respective chambers 14, 16. The channel wall 13 and the matrix pocket wall 12 define a shallow space for forming the twist cap 25. twist cap 25 will be filled with the gel to form the soft gel capsule twist cap 25', which contains no filler material.

[0068] In one aspect, both areas 39 of partition wall 18 and channel wall 13 are lower than area 29 of matrix pocket wall 12 (FIG. 9). Particularly, the area 39 of the divider wall 18 has a greater clearance than the channel wall 13 compared to the plane having the top of the area 29 of the wall 12 of the matrix pocket (FIG. 9). Die 100 of this aspect produces a softgel capsule (FIG. 17) having discharge channels 22', 23' fluidly connected to chambers 14', 16'. In other words, the discharge channels 22', 23' can be filled with the same filling material as the respective connected chambers 14', 16'. Barrier seal 18' (separating chambers 14', 16' and discharge channels 22', 23') is thicker than channel seal separating channels 22', 23' from twist cap 25' . This is because area 39 of divider wall 18 has a greater clearance than channel wall 13, for the plane having the top of area 29 of wall 12 of the matrix pocket. After the twist cap 25' of such a capsule is twisted, the channel seal connected to the twist cap 25' is broken, which exposes the discharge channels 22', 23'. Filler materials can then be released/sprayed from chambers 14' and 16' through discharge channels 22', 23'.

[0069] A photo of matrix 100 of FIGs. 6 and 8 is shown in FIG. 10. The channel wall 13 connects to the divider wall 18 in the middle and to the matrix pocket wall 12 on either side, near the neck area of the twist cap 25. The discharge channels 22, 23 are each at fluid connection with chambers 14, 16 respectively. FIG. 11 shows top view of individual features of matrix 100 of FIG. 6 into separate diagrams 1 to 5, with all individual features merged into diagram 6. Particularly, diagram 1 of FIG. 11 shows the two chambers 14, 16 and the dividing wall 18 separating them. Diagram 2 of FIG. 11 shows the two air holes 15, 17 in the two chambers 14, 16. Diagram 3 of FIG. 11 shows the two discharge channels 22, 23, separated by the dividing wall 18, and the matrix pocket 20. Diagram 4 of FIG. 11 shows twist cap 25 and matrix pouch 20. Diagram 5 of FIG. 11 shows a shoulder area around partition wall 18 and discharge channels 22, 23. Diagram 6 of FIG. 11 shows all features from Diagrams 1 to 5 together in the same diagram.

[0070] The matrix 100 of FIG. 6 can produce a two-chamber softgel capsule with a twist cap 25' and each of its chambers 14', 16' can contain a different filling material (FIG. 17). Before use, the softgel cap twist cap (25') can be twisted away from the softgel main body (FIG. 18). Separating the twist cap 25' exposes the discharge channels 22', 23' which allows the filler materials in both chambers 14', 16' to be released. The softgel capsule can be compressed to spray the two fill materials into each of the chambers 14', 16' through discharge channels 22', 23' (FIG. 18).

[0071] In another aspect, a variation of matrix 100 of FIG. 6 is shown in FIG. 12 with a matrix 200. The dividing wall 18 in this regard is not a straight line, but rather a curved line which also separates the two chambers 14, 16. Furthermore, the air holes 15, 17 can be located at remote locations from the center of the respective chambers 14, 16.

[0072] FIG. 13 shows another variation of matrix 100 of FIG. 6 with a die 200. The die 200 of this variation has a release tab 27 in the form of a bar, which at least partially separates the two discharge channels 22, 23. The discharge channels 22, 23 are in fluid connection respectively with the two chambers 14, 16.

[0073] In some aspects, the bottom surface 11 of the matrix pocket 20 may be flat. In another aspect, the flat bottom surface 11 has rounded junctions with the matrix pocket wall 12, rather than angular junctions. In yet another aspect, bottom surface 11 is curved (rather than flat) with its deepest portion near the center of matrix pocket 20. In yet another aspect, bottom surface 11 is a continuous curve near or up to the bottom surface. upper part of the matrix pocket wall 12 thereby forming a matrix pocket 20 which is one half or one portion of a sphere, one half or one portion of an oval, or one portion of a heart.

[0074] In some aspects, the matrix pocket 20 may have the general shape of a portion of a shape selected from non-limiting examples of sphere, oval, cube or rounded cube, cuboid or rounded cuboid, heart, water drop , animals like fish or bear, triangle or pear.

[0075] In some aspects, the matrix pocket 20 has a bottom surface 11 that is a single point or a line (straight or curved), with the matrix pocket wall 12 extending into the matrix pocket 20 and extending joining at the point or line. For example, the matrix pocket 20 may be cone or pyramid shaped with the tip point at the bottom of the matrix pocket 20 as the bottom surface 11. The pyramid shape may be a three-sided pyramid, a four-sided pyramid, five-sided, six-sided, eight-sided, or ten-sided. In another aspect, the matrix pocket 20 may be in the form of a ridge with the tip being a line on the underside of the matrix pocket 20, and where the line is the bottom surface 11.

[0076] The matrix 10, 100, 200 of this description has a lower point of the upper part of the area 39 of the partition wall 18 less than the plane of the upper part of the area 29 of the perimeter of the wall of the matrix pocket 12 by a gap . The upper part of the area 29 of the wall 12 of the matrix pouch is in one plane, which allows the production of the softgel barrier seal 18' between the two chambers 14', 16' (FIGS. 3 to 4 and 7 ). In some aspects, a gap size is smaller than the thickness of the gel strip used to make the gel caps so that the gel strips are pressed tightly together by the areas 39 of the dividing walls 18 of the coupled dies 10 and fused under heat to make 18' barrier seal. In one aspect, the gap is less than about 95%, or less than about 90%, or less than about 85%, or less than about 80%, or less than about 75%, or less than about than 70%, or less than about 65%, or less than about 60%, or less than about 55%, or less than about 50%, or less than about 45%, or less than about 40 %, or less than about 30%, or less than about 20% of the thickness of the gel strips. Therefore, in this regard, the gap can be adjusted according to the thickness of the gel strips to produce the softgel capsules.

[0077] In one aspect, a gap size is in the range of about 0.0508 mm (0.002 inch) to about 2.54 mm (0.1 inch), or from about 0.508 mm (0.02 inch) ) to about 2.032 mm (0.08 inch), or from about 0.508 mm (0.02 inch) to about 1.524 mm (0.06 inch), or from about 0.762 mm (0.03 inch) to about 1.27 mm (0.05 inch), or about 1.016 mm (0.04 inch).

[0078] In some aspects, the partition wall 18 is perpendicular to the plane at the top of the wall of the matrix bag 12. The thickness of the partition wall 18 can be in the range of about 0.254 mm (0.01 inch) to about 2.54 mm (0.1 inch), or from about 0.508 mm (0.02 inch) to about 2.032 mm (0.08 inch), or from about 0.508 mm (0.02 inch) to about 1.524 mm (0.06 inch), or from about 0.762 mm (0.03 inch) to about 1.27 mm (0.05 inch), or about 1.016 mm (0.04 inch). In certain other aspects, the thickness of divider wall 18 may be greater than 2.54 mm (0.1 inch), or greater than 5.08 mm (0.2 inch), or greater than 7.62 mm (0.2 inch). 3 inch).

[0079] In some aspects, the dividing wall 18 has a different thickness in a different portion of the dividing wall 18. In one example, the dividing wall 18 may have a greater thickness in the portion near the bottom surface 11, but a smaller thickness in a portion near the top of the partition wall 18. In another aspect, the partition wall 18 has a thickness that decreases, preferably continuously, from the near bottom surface 11 to the area of the partition wall 18 such that it is more easy to disengage dividing wall 18 from the softgel capsule produced.

[0080] In some other aspects, the matrix 10, 100, 200 of this disclosure has two or more chambers 14, 16. In one aspect, the matrix 10 may have two or more parallel dividing walls 18, thus dividing the matrix pocket 20 in three or more chambers 14, 16 as seen in a top view above the array. In another aspect, the matrix 10, 100, 200 has multiple divider walls 18 that intersect at the same point and form a star shape, for example, the center of the star being at the center of the matrix pocket 20. The star can have three arms or four arms or five arms or six or more arms, thus dividing the base bag 20 into three or four or five or six or more chambers 14, 16. In yet another aspect, the matrix 10, 100, 200 has walls dividers 18 that are a grid shape that can divide the matrix pocket 20 into multiple chambers 14, 16. In still another aspect, the matrix 10, 100, 200 has divider walls 18 that are intersecting curves, that can also divide the matrix bag 20 into multiple chambers 14, 16. A person skilled in the art would understand that different configurations of the matrix bag 20 will require appropriate modifications to the injection pump.

[0081] In yet other aspects, the chambers 14, 16 of the matrix 10, 100, 200 of this disclosure have different sizes that can encapsulate different amounts of filler materials in one or more of the chambers 14, 16. For example, a chamber 14 can be larger than the other chamber 16, thus producing softgel capsules with a large chamber 14' and a small chamber 16'. The large chamber 14' can contain a greater amount of a filler material than the other filler material in the small chamber 16'. Therefore, a single softgel capsule produced by the matrix 10, 100, 200 of this disclosure can contain two pharmaceutical formulations in different amounts, changing the volumes of their respective chambers, or two cosmetic products can be included in different amounts, changing the volumes of their respective chambers. In some other aspects, the amount of ingredients in each of the chambers can be varied using different concentrations in the respective fillers, so that the volume of their respective chambers need not vary.

[0082] In one aspect, the matrix 10 of FIG. 4 has a depth of from about 2 to about 18 mm, or from about 3 to about 15 mm, or from about 4 to about 12 mm, or from about 5 to about 10 mm, or from about from 6 to about 8 mm.

[0083] In another aspect, the recess 19 of the die 10 of FIG. 4 has a thickness of from about 0.4 to about 4 mm, or from about 0.6 to about 3 mm, or from about 0.8 to about 2 mm, or from about 0.8 to about 3 mm. about 1.5 mm.

[0084] In one aspect, the matrix 10 of FIG. 4 has chambers 14, 16 of 6.604 mm (0.260 inch) depth. The gap between the lowest point of the upper part of the area 39 of the partition wall 18 and the plane having the upper part of the area 29 of the wall 12 of the matrix pocket is 1.016 mm (0.040 inch). The recess 19 at the top of the divider wall 18 has a thickness of 1.016 mm (0.04 inch).

[0085] In another aspect, the matrix 100 of FIG. 6 has chambers 14, 16 of 0.25 inch depth. The gap between the lowest point of the upper area 39 of the dividing wall 18 and the plane formed by the upper area 29 of the wall perimeter of the matrix pocket 12 is 1.016 mm (0.040 inch). The thickness of partition wall 18 is 1.016 mm (0.04 inch). Discharge channels 22, 23 have a depth of 3.048 mm (0.12 inch). The air holes 15, 17 are circular with a diameter of 3.302 mm (0.13 inch).

[0086] In yet another aspect, the air holes 15, 17 have a diameter in the range of from about 1 to about 5 mm, or from about 1.5 to about 4 mm, or from about 2 to about 4 mm, or from about 3 to about 4 mm.

[0087] In still other aspects, the matrix 10, 100, 200 of this disclosure can be a variety of shapes to make softgel capsules of different shapes (FIG. 19). In diagram 1 of FIG. 19, the softgel capsule has an overall oval shape and its two chambers 14', 16' are separated by a barrier seal 18' across the capsule near the middle of the softgel capsule. In diagram 2 of FIG. 19, the softgel capsule has two circular or oval shaped chambers 14', 16' connected by a barrier seal 18'.

[0088] In some aspects, to make the array 100 of FIG. 6 with two chambers 14, 16 and a twist cap 25, a five step process can be used. 1. Design chambers 14, 16 (this area contains the most filler materials). 2. Place air hole 15, 17 in each chamber 14, 16 (allowing air flow into or out of chambers 14, 16). 3. Create the twist cap area 25 (this area is separate from chambers 14, 16 and goes down deep. This area has a specially designed recess that twists the 25' cap and creates a precise hole diameter to release the softgel capsule filling materials). 4. Design channel wall 13 (this creates a wall to prevent filler material from leaking into twist area 25). 5. Create the shoulder area (this area is around the partition wall 18 and the discharge channel area 22, 23, which can be 0.05 inch deep, causing the gel to seal properly).

[0089] In some aspects, this disclosure provides a pair of coupled matrices 10, 100, 200 suitable for producing a multi-chamber softgel capsule, each of the pairs of matrices 10, 100, 200 comprising a matrix pocket 20 defined by a matrix pocket wall 12 and a bottom surface 11, and one or more partition walls 18 that divide the matrix pocket 20 into two or more chambers 14, 16. The matrix pocket wall 12 and the one or more partition walls 18 have their respective upper sections defined as areas 29, 39. The dividing walls 18 of the pair of coupled dies 10, 100, 200 have heights such that when the pair of dies 10, 100, 200 is fitted, there is a gap between the area 39 of each of the dividing walls 18 of the pair of coupled arrays 10, 100, 200.

[0090] In one aspect, a gap size between the top of the area 39 of the partition walls 18 of the pair of coupled arrays 10, 100, 200 is in a range of about 0.508 mm (0.02 inch) to about 5.08 mm (0.2 inch), or from about 1.016 mm (0.04 inch) to about 4.064 mm (0.16 inch), or from about 1.016 mm (0.04 inch) to about 3.048 mm (0.12 inch), or from about 1.524 mm (0.06 inch) to about 2.54 mm (0.1 inch).

[0091] In another aspect, the gap between the top of the area 39 of the partition walls 18 of the pair of coupled arrays 10 is less than about 95%, or less than about 90%, or less than about 85%, or less than about 80%, or less than about 75%, or less than about 70%, or less than about 65%, or less than about 50%, or less than about 45%, or less of about 40%, or less than about 30%, or less than about 20%, of the total thickness of a gel ribbon located between the pair of coupled matrices 10.

[0092] The die 10, 100, 200 of this disclosure is suitable for producing softgel capsules that encapsulate two or more fill materials in separate chambers 14', 16'. The two or more fillers are not mixed in the softgel, thus avoiding any mismatch issues between the fillers. For example, the softgel capsule can be filled with two cosmetic products in two separate chambers 14', 16' for single use. A customer can twist the twist cap 25' and apply the encapsulated cosmetic products, which can then be mixed after being released from the softgel.

[0093] In some aspects, a plurality of dies 10, 100, 200 of this disclosure are placed in a die roll 30 which are suitable for use in a rotary die encapsulation machine (FIGS. 14 to 15). In one example, a plurality of arrays 10 of FIG. 2 are on die roll 30 (FIG. 14). In another example, a plurality of the arrays 100 of FIG. 6 are on die roll 30 (FIG. 15).

[0094] As used herein, a "die roll" refers to a roll with dies 10, 100, 200 on the surface of the roll that are suitable for making and filling softgel capsules on a rotary die encapsulation machine that combines the dies from one die roll to another die roll. Each matrix roll 30 of the coupled pair contains on its surface a series of coupled matrices 10, 100, 200 for forming softgel capsules. The array of dies 10, 100, 200 on the surface of each die roll 30 are arranged, for example, in rows extending along the axial length of the die roll 30, with the series of rows also extending around the die roll 30. In certain examples, the lines may be configured in a pattern, such as an offset pattern, to maximize the number of dies 10, 100, 200 on the surface of a die roll 30.

[0095] The die roll 30 may be substantially cylindrical and rotate about a fixed axis of the die roll 30. Alternatively, the die roll 30 may have a substantially polygonal cross-section, for example octagonal. The axes of two coupled die rolls 30 can be spring loaded with respect to each other. The die rolls 30 can be arranged to form one softgel capsule at a time using the plurality of dies 10, 100, 200 in succession as the die rolls 30 rotate. Alternatively, the dies 10, 100, 200 can be arranged to form a plurality of softgel capsules at once, side by side across the width of the softgel ribbons. In certain embodiments, a heater is associated with the matrix cylinders 30 to provide heating to the gel ribbons to soften them such that they are deformed for sedimentation in chambers 14, 16 and the contacting gels are melted to form softgel capsules. .

[0096] The die roll 30 may be any suitable end-to-end width - as well as any suitable diameter - that is adaptable and configurable for use on conventional rotary die encapsulation machines known in the art. In certain examples, the width of the die roll 30 may be about 25 cm, such as from about 23 to about 27 cm, or from about 24 to about 26 cm, or from 25 to about 26 cm in length. length. In some other examples, the diameter of the die roll 30 can be about 15 cm, such as from about 13 to about 17 cm, or from about 14 to about 16 cm, or from about 15 to about of 16 cm.

[0097] In some aspects, the die roll 30 may include from about 5 to about 30 rows of dies 10, 100, 200, with each row including from 25 to 50 dies 10, 100, 200. In one example, die roll 30 can include from about 7 to about 22 rows of dies 10, 100, 200, with each row including from 30 to 46 dies 10, 100, 200. In one aspect, the shape of dies 10, 100 , 200 can determine the most efficient arrangement of the dies 10, 100, 200 on the surface of the die roll 30. In one example, the dies 10, 100, 200 are arranged on the surface so as to maximize the number of dies 10, 100, 200 on the die roll 30. This allows a maximum number of softgel capsules to be produced by the die roll 30 for each rotation.

[0098] A pair of mated die rolls 30 with mated rows of dies 10, 100, 200 on the surfaces of respective die rolls 30 can be used and/or adapted for use in conjunction with a variety of softgel encapsulation machines. In one example, the die rolls 30 can be adapted for use on conventional rotary die encapsulation machines similar to those known in the art. The two coupled die rolls 30 rotate in opposite directions as part of the encapsulating machine. As the gel ribbons pass through the coupled die roll 30, the coupled die rolls 30 cut and fill the softgel capsule chambers 14', 16' with filling materials. The rotary die encapsulation machine can include any other components for use in making a softgel capsule, such as a heating wedge, nip, injection pump, gelatin film presses, feeders, guide rollers and the like.

[0099] In some aspects, the die 10, 100, 200 or die roll 30 of this disclosure may be constructed of one or more high strength materials. Some examples of suitable materials include aluminum, brass, hardened steel, stainless steel, bronze, iron, cast zinc, etc. Stainless steel includes those steels that contain enough chromium to make them corrosion resistant, generally at least about 10% chromium by weight. For example, the stainless steel used can be selected from the series including Types 309, 414, 440 and 446.

[00100] The die 10, 100, 200 or die roll 30 of this disclosure can also be constructed using an alloy of high wear resistance and heat resistance, such as alloys based on Co, Ni or Mo. Examples include zinc, magnesium, aluminum, brass or bronze alloys, which have excellent physical properties of hardness and high tensile strength.

[00101] In some other aspects, the die 10, 100, 200 of this disclosure, especially when a plurality of dies 10, 100, 200 are on a die roll 30, are suitable for use with the multi-fluid injection pump and filing of Patent Application No. US 15/049,961, filed February 22, 2016, which is incorporated herein by reference. The multi-fluid injection pump can be used to inject different fillers into different chambers 14', 16' of the same softgel capsule produced by the matrix 10, 100, 200 of this disclosure.

[00102] The gel tape suitable for use with the matrix 10, 100, 200 to produce softgel capsules can be made of gelatin, or a water-soluble cellulose derivative such as hydroxypropylmethyl cellulose or hydroxypropyl cellulose, which are approved for use with pharmaceuticals and food. Other gel materials suitable for gel strips include polymers derived from edible algae such as sodium alginate (E401), propylene glycol alginate (E405) or agar-agar (E406). Some suitable cellulose derivatives are hydroxypropyl cellulose (E463) and methyl ethyl cellulose (E465).

[00103] Other gel materials suitable for gel tape include pectin, polyethylene oxide, polyvinyl alcohol, alginate, polycaprolactone and gelatinized starch-based materials. The gel strips can be coated with gum arabic, pectin, alginate or sodium alginate to modify their properties. For example, gum arabic, pectin and alginate have a slight retarding effect on the gel solubility of the gel strip (i.e. the capsule shell), the extent of the effect varying according to the thickness of the coating. Furthermore, both pectin and alginate can be cross-linked, for example with calcium, to make the gel strip (i.e. capsule shell) sensitive to pH such that it does not dissolve in the mouth, but dissolves in the stomach where the pH is lower. Further examples of suitable gel materials and coating materials are given in WO 97/35537 and WO 00/27367, the disclosures of which are incorporated herein by reference in their entirety.

[00104] In some aspects, any materials suitable for making films that can be sealed by a rotational process can be used in the present invention.

[00105] The matrix 10, 100, 200 of this disclosure is suitable for making softgel capsules with two or more incompatible pharmaceutical formulations. Active ingredients in pharmaceutical formulations may be incompatible with each other, or the active ingredient in one formulation may be incompatible with an excipient in another formulation, or pharmaceutical formulations may have excipients that are incompatible with each other. Encapsulating the two or more pharmaceutical formulations in separate chambers 14', 16' allows delivery of the pharmaceutical formulations in the same softgel capsules.

[00106] Multi-chamber softgel capsules with two or more pharmaceutical formulations can provide combined or even synergistic therapeutic effects. Separation of pharmaceutical formulations provides much-needed flexibility in formulating a wide range of active ingredients, regardless of their compatibility. Furthermore, incompatible excipients may be used in the same softgel capsules. This also provides the ability to encapsulate pharmaceutical formulations with different release profiles in the same softgel capsule. For example, a pharmaceutical formulation in one chamber 14' of the softgel capsule may be an immediate release formulation while the pharmaceutical formulation in the other chamber 16' of the same softgel capsule may be a delayed release formulation.

[00107] In some respects, multi-chamber softgels allow half-dosing, which is a significant demand in animal health care, since animals can vary dramatically in size. For example, dogs can weigh over a hundred pounds, or as little as a few pounds, and half dosing, or even quarterly dosing is possible with the multi-chamber softgel capsule produced by matrix 10, 100, 200 of this disclosure.

[00108] In addition to pharmaceutical formulations, the matrices 10, 100, 200 of this disclosure are also suitable for the production of softgel capsules containing two or more cosmetic products for a single use. Encapsulated cosmetic products can be in lotion, cream or paste forms. These products can be anhydrous, aqueous or in emulsion form. The form of emulsion can be oil-in-water or water-in-oil emulsions.

[00109] Cosmetic products usually contain a vehicle or carrier that is inert and an active or performance ingredient. The amount of carrier can range from about 5 to about 99%, or from about 25 to about 80% by weight of the total fillers.

[00110] Various types of active ingredients can be present in cosmetic products. Active ingredients are defined as skin or hair benefiting agents other than emollients and other than just ingredients that enhance the physical characteristics of fillers. Non-limiting examples of active ingredients in cosmetic products include sunscreens, tanning agents, anti-wrinkle skin agents, anti-dandruff agents, anti-acne agents and hair growth stimulants.

[00111] Sunscreens include materials commonly used to block ultraviolet light. Exemplary compounds include 4-aminobenzoic acid (PABA), cinnamate and salicylate derivatives. Some examples of octyl methoxycinnamate and 2-hydroxy-4-methoxy benzophenone (also known as oxybenzone) can be used. The exact amount of sunscreen used in a sunscreen can vary depending on the desired degree of protection from the sun's UV radiation.

[00112] Tanning agents are materials that are capable of coloring the skin through a chemical reaction; in particular, darkening the skin so that it resembles the darkening effect achieved by exposing the skin to the sun's rays (ie a natural tan). Some examples of tanning agents include dihydroxy acetone (DHA), erythrulose and derivatives thereof. Similarly, imidazole and imidazole derivatives may be preferred and may also be used.

[00113] Anti-wrinkle agents can be 2-hydroxyalkanoic acids, prostaglandins, retinoic acids, ceramides and derivatives thereof.

[00114] Anti-dandruff agents are chemicals that are effective in treating dandruff and/or the symptoms associated with it. Anti-dandruff agents are well known in the art (see, for example, US 2004/0202636 (in particular paragraphs 0041 to 0053), US 2003/0003070 (in particular paragraph 007) and US 6,284,234 (in particular, column 13, lines 14 to 33.) Exemplary anti-dandruff agents include, but are not limited to, pyridinothione salts, such as pyridinothione calcium, magnesium, barium, strontium, zinc, and zirconium salts, azoles, such as scalphazol, ketoconazole and itraconazole; pyroctone olamine (octopirox), undecylenamidopropyl betaine, undecylenamidopropyl betaine, coal tar (Neutrogena T/gel), salisylic acid (Ionil T), selenium sulfide (Selsun Blue), tea tree oil, and mixtures thereof.

[00115] Anti-acne agents are any chemical and/or biological agents (i.e., an antimicrobial peptide) which, when administered topically to the acne site, lead to a visible reduction in symptoms associated with the epithelial condition of acne vulgaris. Exemplary anti-acne agents include salicylic acid, sulfur, glycolic acid, pyruvic acid, resorcinol, N-acetylcysteine, picolinic acid, picolinic acid derivatives, picolinic acid analogues, benzoyl peroxide, and retinoids such as retinoic acid and derivatives thereof ( e.g. cis and trans, esters).

[00116] Hair growth stimulants may include benzalkonium hydrochloride, benzethyl hydrochloride, phenol, estradiol, diphenhydramine hydrochloride, cloifeniram maleate, chlorophyll derivatives, cholesterol, salicylic acid, cysteine, methionine, red pepper tincture, benzol, D-menthol, peppermint oil, calcium pantothenate, panthenol, castor oil, hmokitiol, prednisolone, resorcinol, monosacchandes and estenfied monosacchandes, chemical activators of kiase C protein enzymes, inhibitors of cellular uptake of the glycosamoglycan chain, inhibitors of the activity of glycosidase, glycosarmonoglycanase inhibitors, pyroglutamic acid esters, hexosaccharide acids or acylated hexosaccharide acids, aryl-substituted ethylenes and N-acylated amino acids.

[00117] Vitamins can also be included in cosmetic products, such as vitamin A palmitate (retinyl palmitate) and vitamin E linoleate (tocopheryl linoleate). Other esters of vitamins A and E can also be used.

[00118] Many cosmetic products, especially those containing water, ideally include some protection against the growth of potentially harmful microorganisms, often using preservatives. Suitable preservatives include p-hydroxybenzoic acid alkyl esters, hydantoin derivatives, propionate salts and a variety of quaternary ammonium compounds. Particularly preservatives are methyl paraben, propyl paraben, imidazolidinyl urea, sodium dehydroxyacetate and benzyl alcohol.

[00119] Powders can be incorporated into cosmetic products encapsulated in multichamber softgel. Exemplary powders include chalk, talc, Fuller's earth, kaolin, starch, smectite clays, chemically modified magnesium aluminum silicate, organically modified montmorillonite clay, hydrated aluminum silicate, fumed silica, aluminum starch octenyl succinate and mixtures thereof .

[00120] In some other aspects, the matrix 10 of this disclosure can be used to produce softgel capsules containing a pharmaceutical formulation and a dietary supplement, or two different dietary supplements, or different epoxy systems, or different multi-component polyurethane systems. Dietary supplements can be vitamins, minerals, fiber, fatty acids, proteins, amino acids, herbs and bodybuilding supplements. Specific examples of dietary supplements include iron, sodium, calcium, magnesium, carbohydrates, proteins, sugars (glucose), zinc, molybdenum, copper, potassium, manganese, chlorides, bicarbonate and carbonate, aluminum, arsenic, bromine, cadmium, chromium, chlorine , cobalt, fluorine, iodine, manganese, nickel, molybdenum, phosphorus, selenium, silicon, vanadium, zinc, amino acids, vitamin A, vitamin D, vitamin E, vitamin K, vitamin C, vitamin B complex, thiamine (vitamin 31) , riboflavin (vitamin 132), niacin (vitamin B3), pyridoxine (vitamin B6), biotin, pantothenic acid and pantethine, folic acid, vitamin B12, "unofficial" B vitamins, including choline and inositol, vitamin P (bioflavonoids) and other vital nutrients, plus various homeopathic/alternative substances.

[00121] The epoxy systems encapsulated in different chambers can be used in industrial applications, where the epoxy systems are mixed and the reaction will occur to produce a desired product. For example, two-part epoxy systems can be included in the multi-chamber softgel capsule by incorporating an epoxy resin in one chamber and a hardener or curing agent in a second chamber.

[00122] In some embodiments, the epoxy resin comprises a curable epoxide, such as liquid polyglycidyl ethers of polyhydric phenols. In certain embodiments, epoxy resins include both monoepoxides and polyepoxides. Examples of monoepoxides include propylene oxide, allylglycidyl ether, phenylglycidyl ether, pentachlorophenylglycidyl ether, tetrabromophenylglycidyl ether and glycidyl methacrylate. Polyepoxides can average more than 1.0 1,2-epoxy groups per average molecular weight. Among the polyepoxides that can be used herein are the polyglycidyl ethers of polyphenols, such as bisphenol A. These can be obtained, for example, by etherification of a polyphenol with epichlorohydrin or dichlorohydrin in the presence of an alkali. The phenolic compound can be 2,2-bis(4-hydroxyphenyl)propane, 4,4'-dihydroxybenzophenone, 1,1-bis(4-hydroxyphenyl)ethane, 2,2-bis(4-hydroxy-tert- butylphenyl)propane, bis(2-hydroxynaphthyl)methane or 1,5-dihydroxynaphthalene. The polyphenol can also be a Novolak resin.

[00123] In some embodiments, the hardener or curing agent is an amine-based hardener or curing agent, which are compounds having a primary or secondary amino functional group. Examples of suitable curing agents include diethylenetriamine, triethylenetetramine, isophoronediamine, diaminodiphenylmethane, diaminodiphenyl sulfone, polyamides, dicyandiamide, hexahydrophthalic anhydride, methyltetrahydrophthalic anhydride, methyl nadic anhydride, tertiary amines, imidazoles, and the amine complexes of boron trifluoride.

[00124] It should be understood, however, that although numerous features and advantages of the present invention have been set forth in the foregoing description, along with details of the structure and function of the invention, the disclosure is illustrative only, and changes may be made in detail , especially in matters of shape, size and arrangement of parts within the principles of the invention, to the fullest extent indicated by the general meanings of the terms in which the appended claims are expressed.

[00125] The following examples are illustrative, but not limiting, of softgel capsules made by a process in accordance with the present disclosure. Other suitable modifications and adaptations to the variety of conditions and parameters commonly encountered in the field, and which are obvious to those skilled in the art, are within the scope of the disclosure.

EXAMPLES Example 1

[00126] The matrix 10 of FIG. 5 was made and used to produce two-chamber softgel capsules encapsulating combination Peg 400/Peg 400 formulations, with each formulation having visual separation of two fill materials (FIG. 16). The hydrophilic/lipophilic softgels were produced without any problems. The softgels were dried for about 4 days and both sides of the capsules had a hardness value in the range of 9 N. No appearance issues were identified for the softgels after drying. For example, no leakage was observed for softgel capsules. There was also no leakage between the chambers, checking the sealing of the barrier as expected. In general, the softgels had all the normal properties of a "regularly" produced softgel.

Example 2

[00127] The matrix 10 was used to produce two-chamber softgel capsules with one chamber 14', 16' containing a liquid formulation of Labrasol® (surfactant) and the other chamber 14', 16' containing a semi-solid formulation of Gelucire® . Encapsulation of the two formulations using matrix 10 was successful with no problems noted. This example shows an advantage of being able to form softgel encapsulation with liquid and semi-solid formulations in separate chambers of the same capsules. The successful encapsulation of the two formulations suggested that any combination of active ingredients or excipients can be encapsulated in a multi-chambered softgel capsule using matrix 10 of this disclosure, examples including dietary, nutritional, animal health, cosmetics.

Example 3

[00128] The matrix 100 of FIG. 10 was manufactured and used to produce softgel capsules with a 25' twist cap for use in the cosmetic industry. Softgel capsules were successfully produced (FIG. 17). The twist cap 25' and the application of the contents in the two chambers 14', 16' were tested (FIG. 18). The matrix 100 of this disclosure fulfilled the cosmetic industry's requirements for the production of disposable softgel capsules containing two or more cosmetic products.

Example 4

[00129] The matrix 100 of the present invention is used to make softgel capsules with two chambers, encapsulating retinol and vitamin C, respectively. Retinol and Vitamin C are known incompatible ingredients.

Claims (31)

1. Matrix (10, 100, 200) for a multi-chamber softgel capsule, the matrix (10, 100, 200) comprising: a matrix pocket (20) defined by a matrix pocket wall (12) and a lower surface (11); and one or more partition walls (18) dividing the matrix pocket (20) into two or more chambers (14, 16), wherein the matrix pocket wall (12) and the one or more partition walls (18) have their respective upper sections defined as areas (29, 39), an upper part of the area (29) along the perimeter of the wall of the matrix bag (12) is in the same plane, and a lower point of the upper part of the area (39) of the one or more dividing walls (18) is lower than the plane by a gap, characterized in that at least one of the one or more dividing walls (18) has a recess (19) in the upper part of its area (39). 2. Array (10, 100, 200), according to claim 1, characterized in that the upper part of at least one of the areas (29, 39) has a shape selected from flat, round, curved, plateau and angled. 3. Matrix (10, 100, 200), according to any one of claims 1 or 2, characterized in that it additionally comprises at least one air hole (15, 17) in each chamber (14, 16). 4. Array (10, 100, 200), according to any one of claims 2 or 3, characterized in that the one or more dividing walls (18) are perpendicular to the plane. 5. Matrix (10, 100, 200), according to any one of claims 1 to 4, characterized in that it additionally comprises a twist cap (25). 6. Matrix (10, 100, 200), according to claim 5, characterized in that it additionally comprises at least two discharge channels (22, 23), in which each discharge channel is in fluid connection with each chamber (14, 16). 7. Die (10, 100, 200) according to claim 6, characterized in that the discharge channels (22, 23) are separated from the torsion cap (25) by a channel wall (13). 8. Matrix (10, 100, 200), according to claim 7, characterized in that the height of the wall of the channel (13) is less than the height of a highest point of the wall of the matrix pocket wall (12), and is greater than a height of the one or more dividing walls (18). 9. Array (10, 100, 200), according to any one of claims 1 to 8, characterized in that each of said one or more dividing walls (18) has a shape selected from a straight line and a curved line when viewed from above the matrix (10, 100, 200). 10. Array (10, 100, 200), according to any one of claims 1 to 9, characterized in that it has two or more dividing walls (18) configured in parallel to each other. 11. Array (10, 100, 200), according to any one of claims 1 to 9, characterized in that it has two or more dividing walls (18) that intersect each other to form four or more chambers (14 , 16). 12. Matrix (10, 100, 200), according to any one of claims 1 to 11, characterized in that the one or more dividing walls (18) have a thickness of 0.254 mm to 2.54 mm, or from 0.508 mm to 2.032 mm, or from 0.508 mm to 1.524 mm, or from 0.762 mm to 1.27 mm. 13. Array (10, 100, 200), according to any one of claims 1 to 12, characterized in that at least one of the one or more dividing walls (18) has a thickness that decreases from a portion close to the lower surface (11) to the area of at least one dividing wall (18). 14. Array (10, 100, 200), according to any one of claims 1 to 13, characterized in that it includes a plurality of partition walls (18) that intersect to form a star shape or a grid when viewed from above. 15. Array (10, 100, 200), according to any one of claims 1 to 14, characterized in that a gap size is in a range from 0.254 mm to 2.54 mm, or from 0.508 mm to 2.032 mm, or from 0.508 mm to 1.524 mm, or from 0.762 mm to 1.27 mm. 16. Array (10, 100, 200), according to any one of claims 1 to 15, characterized in that the gap is less than 95%, or less than 90%, or less than 85%, or less than 80%, or less than 75%, or less than 70%, or less than 65%, or less than 50%, or less than 45%, or less than 40%, or less than 30%, or less than 20 %, of a gel tape thickness suitable for use with the matrix (10, 100, 200). 17. Matrix (10, 100, 200), according to any one of claims 1 to 16, characterized in that the matrix pocket (20) has the shape of a half or part of a sphere, an oval , a cuboid, a cube, a rounded cuboid, a rounded cube, a heart, a drop of water, an animal such as a fish or a bear, or a pear. 18. Matrix (10, 100, 200), according to any one of claims 1 to 16, characterized in that the matrix pocket (20) is shaped like a cone or pyramid, and the pyramid is selected from among three-sided, four-sided, five-sided, six-sided, eight-sided, and ten-sided pyramids. 19. Array (10, 100, 200), according to any one of claims 1 to 18, characterized in that at least one of the two or more chambers (14, 16) has a different size from the other of the two or more chambers (14, 16). 20. Array (10, 100, 200), according to any one of claims 1 to 19, characterized in that the recess (19) in the upper part of the area (39) of the dividing wall (18) has a shape crescent, as seen in a side view. 21. Matrix (10, 100, 200), according to any one of claims 1 to 20, characterized in that it is constructed with one or more high-strength materials selected from aluminum, brass, hardened steel, stainless steel, bronze, iron and cast zinc. 22. Matrix (10, 100, 200), according to any one of claims 1 to 20, characterized in that it is constructed with a high wear resistance and hot resistance alloy selected from Co-based alloys, Ni or Mo. 23. Die roll (30) characterized in that it has a surface comprising a plurality of dies (10, 100, 200) as defined in any one of claims 1 to 22. 24. Die roll (30) according to claim 23, characterized in that the plurality of dies (10, 100, 200) are arranged in one or more rows on the surface. 25. Die roll (30), according to any one of claims 23 or 24, characterized in that the plurality of dies (10, 100, 200) are arranged in from 5 to 30 rows, or from 7 to 22 queues. 26. Rotary die encapsulation machine characterized in that it comprises at least one die roll (30) as defined in any one of claims 23 to 25. 27. Rotary die encapsulation machine, according to claim 26, characterized in that it comprises two or more die rolls (30) as defined in any one of claims 23 to 25. 28. Pair of mated matrices (10, 100, 200) for producing a multi-chamber softgel capsule, each pair of mated matrices (10, 100, 200) comprising: a matrix pocket (20) defined by a matrix pocket wall (12) and a bottom surface (11); one or more partition walls (18) dividing the matrix bag (20) into two or more chambers (14, 16), the matrix bag wall (12) and the one or more partition walls (18) have their respective sections upper defined as areas (29, 39); and an upper area part (29) of a perimeter of the wall of the matrix bag (12) is in a plane, and a lower point of the upper area part (39) of one or more dividing walls (18) is lower than the plane by a gap, characterized in that at least one of the one or more dividing walls (18) has a recess (19) in the upper part of its area (39), and the dividing walls (18) of the pair of coupled matrices (10, 100, 200) have heights such that there is a gap between an upper part of the area (39) of a said dividing wall (18) of one of the matrices (10, 100, 200) and the area (39) of at least one of the dividing walls (18) of the other matrix (10, 100, 200). 29. Pair of coupled matrices (10, 100, 200), according to claim 28, characterized in that a size of the gap between the upper part of the area (39) of the dividing walls (18) of the pair of coupled matrices (10, 100, 200) is in the range from 0.508 mm to 5.08 mm, or from 1.016 mm to 4.064 mm, or from 1.016 mm to 3.048 mm, or from 1.524 mm to 2.54 mm. 30. Pair of coupled matrices (10, 100, 200), according to claim 28, characterized in that the gap between the upper part of the area (39) of the dividing walls (18) of the pair of coupled matrices (10 , 100, 200) is less than 95%, or less than 90%, or less than 85%, or less than 80%, or less than 75%, or less than 70%, or less than 65%, or less than 50%, or less than 45%, or less than 40%, or less than 30%, or less than 20%, of a total thickness of a gel tape located between the pair of coupled matrices (10, 100, 200) . 31. Apparatus characterized in that it comprises a pair of die rolls (30) as defined in any one of claims 25 to 27, wherein the apparatus is configured to rotate the pair of die rolls (30) to bring at least a die (10, 100, 200) from a first die roll (30) in mating contact with at least one die (10, 100, 200) from a second die roll (30).