COMPOSITIONS OF FILM COATINGS FOR TABLETS WITH INCREASED GLOSS, METHOD FOR PRODUCTION THEREOF AND APPLICATION OF SAME

Abstract

Compositions and procedures for applying pharmaceutical tablet coatings, recognized as film coating wherein it is possible to obtain a final product coated with brightness superior to that achievable with typical compositions. The main difference in the composition is in the inclusion of the product derived from isomaltulose, which is a mixture of 6-O-α-D-glucopyranosyl-D-mannitol dihydrate with 6-O-α-D-glucopyranosyl-D-sorbitol, known as Isomalt, combined with a variety of film-forming polymers such as ethylene glycol and polyvinyl alcohol copolymer, copovidone, polyvinyl alcohol, and cellulosic derivatives, wherein the process conditions are advantageous as it is possible to handle high concentrations of solids in their preparation and wider applying temperature ranges than normally recommended for film coatings.

Claims

1. A coating composition for solid dosage forms, selected from the group consisting of tablets, supplements, pills, lozenges, dragees, caplets or microspheres, comprising: an isomaltulose derivative; adherent polymers; and individual or combined additives.

2. The composition according to claim 1, wherein the isomaltulose derivative is in a percentage from 5% to 85% by weight, relating to the total weight of the composition.

3. The composition according to claim 1, wherein the isomaltulose derivative is preferably in a percentage from 15% to 50% by weight, relating to the total weight of the composition.

4. The composition according to claim 1, wherein adherent polymers are selected from the group consisting of hypromellose, cellulosic derivatives, copovidone, povidone, methacrylate derivatives, polyvinyl alcohol, ethylene glycol and vinyl alcohol graft copolymer, ethylene glycol and vinyl alcohol graft copolymer or combinations thereof.

5. The composition according to claim 1, wherein the adherent polymers are in a percentage from 5% to 60% by weight, relating to the total weight of the composition.

6. The composition according to claim 1, wherein the adherent polymers are preferably in a percentage from 10% to 40% by weight, relating to the total weight of the composition.

7. The composition according to claim 1, wherein the individual or combined additives have functions of opacifying plasticizers or pigments from 5% to 60% by weight, relating to the total weight of the composition.

8. The composition according to claim 1, wherein the individual or combined additives are preferably from 0.1% to 40% by weight, relating to the total weight of the composition.

9. The composition according to claim 1, wherein the final coated product shows increased brightness, ranging from 10 to 30 or more Gloss Units (BU), measured at 60° angle of incidence.

10. The composition according to claim 9, wherein the brightness of coatings of adherent polymer mixtures with isomaltulose derivatives is significantly greater that the brightness generated by any of the individually tested adherent polymers.

11. The composition according to claim 10, wherein the brightness is increased from 100% to 400% and between 10 and 18 GU relating to the brightness of the individually tested adherent polymers.

12. The composition according to claim 1, wherein it is used in an inert coating, in film-shaped for tablets, supplements, pills, lozenges, dragees, caplets or microspheres, used in the food, cosmetic or pharmaceutical industries having the feature of increased brightness, using isomalt.

13. The composition according to claim 1, wherein it is used in the preparation of a dispersion in an aqueous vehicle, with concentrations from 8% to 50% by weight of the composition relating to the total weight of the dispersion.

14. The composition according to claim 13, wherein the preferred concentration of the preparation can be greater than or equal to 35% by weight of the composition relating to the total weight of the dispersion.

15. The composition according to claim 14, wherein it has a viscosity of less than 0.5 Pa s (500 cp) in its preparation.

16. The composition according to claim 15, when applied, reduced process times are needed, due to the decrease in the amount of liquid to evaporate in the process.

17. The composition according to claim 16, wherein one of the options for preparing the dispersion in water comprises the following formulation: TABLE-US-00022 Isomalt 6.00 (%) Hypromellose 5.40 (%) Ethylene glycol-vinyl alcohol graft copolymer 3.60 (%) mixed with polyvinyl alcohol Polyethylene glycol 3.60 (%) Talc 5.10 (%) Titanium dioxide 4.80 (%) Pigment 1.50 (%) Water 70.00 (%) Total 100.00 (%)

18. The composition according to claim 17, wherein it can be applied and dried on cores with a tablet bed temperature in a range of 30° C. to 48° C.

19. The composition according to claim 16, wherein one of the options for preparing the dispersion in water comprises the following formulation: TABLE-US-00023 Isomalt 18.00 (%) Ethylene glycol-vinyl alcohol graft copolymer 4.00 (%) mixed with polyvinyl alcohol Polyethylene glycol 10.0 (%) Talc 5.60 (%) Titanium dioxide 1.60 (%) Sodium lauryl sulfate 0.20 (%) Pigment 0.60 (%) Water 60.00 (%) Total 100.00 (%)

20. The composition according to claim 19, having a concentration of 40% solids or more, and formed as a film with high brightness, where the brightness is greater than 15 Gloss Units measured with a KSJ brand Glossmeter instrument, MG6-SA model with 60° angle of incidence.

21. A coating composition for solid dosage forms, selected from the group comprising tablets, supplements, pills, lozenges, dragees, caplets or microspheres, wherein the composition comprises: an isomaltulose derivative; adherent polymers; and individual or combined additives. wherein the composition resists dissolution in non-polar oily media, selected from the group comprising: vegetable oil and Polaxmer 124.

22. A drug product, food supplement or cosmetic product comprising the composition according to claim 1, wherein a solid coating is required to remain intact in non-polar media, and at the same time maintain solubility in aqueous media.

23. The composition according to claim 1, wherein the components can be added individually in the preparation of aqueous or non-aqueous coating dispersions.

24. The composition according to claim 1, wherein the components can be added as pre-mixes containing the components in the preparation of aqueous or non-aqueous coating dispersions.

25. The composition according to claim 1, wherein the components can be added sequentially or non-sequentially to a solvent or solvent mixture.

Description

DETAILED DISCLOSURE OF THE INVENTION

[0030] The invention disclosed in this document mentions the film coating compositions and the applying procedures with which coated tablets, supplements, pills, lozenges, dragees, caplets or microspheres, used in the food or pharmaceutical industry, can be obtained, by processes recognized as belonging to film coating. The final product obtained with the proposed compositions and procedures consists of a coating for tablets, supplements, pills, tablets, dragees, caplets or microspheres, used in the food or pharmaceutical industry, coated, with finishes that have increased brightness, typically not achievable with film coating compositions and processes described in the state of the art and used to date. The applying procedures can be used in standard coating equipment, such as conventional pans, drilled pans, paddle systems and fluidised beds.

[0031] The film coating compositions obtained are based on the incorporation of a product derived from isomaltulose, in the composition of the coating material. The isomaltulose derivative is an appropriate material for pharmaceutical use due to its properties of being innocuous, inert and not digestible or minimally digestible by humans.

[0032] The brightness provided by coated compositions by the present invention is one of the fundamental properties that are declared as innovative, presenting measurable and differentiating evidence regarding materials prepared for film coating. The key and differentiating component is the use of the isomaltulose derivative, which is a semi-synthetic, harmless, inert, non-human digestible polyalcohol, properties that are considered appropriate and desirable for use as a pharmaceutical excipient. This component has not been previously declared as an ingredient in thin layer coating formulations and although it has been declared to be used for dragee systems, film coatings are differentiable from dragee systems as the process times are much shorter, the thickness of the film is very different, the stages of production processes are different and the equipment is different.

[0033] Meanwhile, the use of the isomaltulose derivative in tablet cores is mainly cited to achieve fluidity and compactness to powder mixtures for the compression operation of pharmaceutical tablets. The properties imparted by the isomaltulose derivative in the thin layer coating formulas are different from those mentioned above for the manufacture of pharmaceutical tablet cores.

[0034] Described below are mixtures of materials useful as film coatings, capable of providing the finished final product with greater brightness, not expected in its intensity, in products of this class.

[0035] The invention encompasses coating compositions that include the isomaltulose derivative in pre-mixed manufactured products, known in the pharmaceutical medium as ready-to-use, as well as compositions that include the isomaltulose derivative in the preparation of film coating dispersions, where the addition of the components where the isomaltulose derivative is included, are added sequentially to a solvent or solvent mixture.

[0036] The isomaltulose derivative is a mixture of 6-O-α-D-glucopyranosyl-D-mannitol dihydrate with 6-O-α-D-glucopyranosyl-D-sorbitol, which is a component not previously used in film coatings, in the manner expressed in the present invention in which differences are presented in relation to the state of the art such as the declared concentrations of the isomaltulose derivative in the coating, the preparation methodology, wherein with the present invention high concentrations of solids can be achieved, the applying process temperature ranges, such as expressed in the described examples, in order to obtain innovatively increased brightness film coatings for this type of film coating compositions.

[0037] Another relevant advantage of the type of innovative coatings described in this document is that the concentration at which they can be prepared in liquid dispersions, prior to their applying by spray, can be significantly higher than that typically prepared by film coatings.

[0038] Depending on the composition, there are coatings that can be prepared in a range of 8-12% solids, as an example of those based on hypromellose

[0039] In a range of 15-18%, as an example those based on hypromellose-carbohydrate mixtures In a range of 20-25%, as an example those based on polyvinyl alcohol as film-forming

[0040] There are reports of up to 35% in compositions including polyvinyl alcohol or ethylene glycol-vinyl alcohol graft copolymers and in low viscosity hypromellose based formulations.

[0041] The film-forming polymer or the adhering polymer may come from non-limiting materials such as hypromellose or cellulosic derivatives, polyvinyl alcohol, ethylene glycol-vinyl alcohol graft copolymer, povidone, copovidone.

[0042] It is noteworthy as a further contribution in the present invention, that some compositions of film coatings for pharmaceutical use, stated in this document, can be prepared to have solids concentrations higher than 35%, maintaining viscosities below 0.5 Pa.Math.s (500 cp), thus decreasing the amount of liquid to evaporate in the process, representing improvements to the preparation concentrations considered for this type of formulations. Within the usual techniques of film coating processes, it is often preferred that the liquid dispersions prepared for its applying have viscosities less than 500 cp, so that the dispersion of the liquid dispersion in the coating process is carried out without problems and so that the appearance of the coated tablets has good quality in terms of having a smooth appearance and a uniform finish.

[0043] Additionally, it has been found as a relevant additional property of some coating films that include the isomaltulose derivative in their composition, the ability to resist dissolution in non-polar oily media such as vegetable oil and Polaxamero 124. This property of resistance to solubility in oily media is not normally found in pharmaceutical-type coatings and can be useful for use in drug products, food supplements or cosmetic products, where the solid coated product is required to remain intact in non-polar media, but that maintains its properties of being soluble in aqueous media.

[0044] To facilitate a better understanding of the present invention, the following examples of certain aspects of some embodiments of the invention are provided. In no way should the following examples be construed to limit, or define, the entire scope of the invention.

[0045] Such examples include compositions of solid mixtures, which can be prepared and subsequently dispersed in water as a vehicle, and compositions in which the vehicle is already included in the preparation are also described. The invention is also encompassed in the case that the components are added individually in the preparation of coating dispersions, or as pre-mixes containing the components.

EXAMPLE 1

Coating Film Formulation 1

[0046]

TABLE-US-00001 No. Description Composition (%) 1 Isomalt 45.00 2 Copovidone 10.00 3 Polyethylene glycol 25.00 4 Talc 10.00 5 Titanium dioxide 10.00 Total 100.00

EXAMPLE 2

Coating Film Formulation 2

[0047]

TABLE-US-00002 No. Description Composition (%) 1 Isomalt 13.50 2 Copovidone 3.00 3 Polyethylene glycol 7.50 4 Talc 3.00 5 Titanium dioxide 3.00 6 Water 70.00 Total 100.00

EXAMPLE 3

Coating Film Formulation 3

[0048]

TABLE-US-00003 No. Description Composition (%) 1 Isomalt 45.00 2 Copovidone 10.00 3 Polyethylene glycol 25.00 4 Talc 10.00 5 Titanium dioxide 7.65 6 Blue Aluminum Lacquer No. 2 2.00 7 Red Aluminum Lacquer No. 40 0.35 Total 100.00

EXAMPLE 4

Coating Film Formulation 4

[0049]

TABLE-US-00004 No. Description Composition (%) 1 Isomalt 13.500 2 Copovidone 3.000 3 Polyethylene glycol 7.500 4 Talc 3.000 5 Titanium dioxide 2.295 6 Blue Aluminum Lacquer No. 2 0.600 7 Red Aluminum Lacquer No. 40 0.105 8 Water 70.000 Total 100.000

EXAMPLE 5

Coating Film Formulation 5

[0050]

TABLE-US-00005 No. Description Composition (%) 1 Isomalt 22.00 2 Hypromellose 5.00 3 Copovidone 5.00 4 Polyethylene glycol 12.00 5 Talc 50.00 6 Titanium dioxide 6.00 Total 100.00

[0051] EXAMPLE 6

Coating Film Formulation 6

[0052]

TABLE-US-00006 No. Description Composition (%) 1 Isomalt 8.80 2 Hypromellose 2.00 3 Copovidone 2.00 4 Polyethylene glycol 4.80 5 Talc 20.00 6 Titanium dioxide 2.40 7 Water 60.00 Total 100.00

EXAMPLE 7

Coating Film Formulation 7

[0053]

TABLE-US-00007 No. Description Composition (%) 1 Isomalt 40.00 2 Acetyl triethyl citrate 5.00 3 Talc 25.00 4 Titanium dioxide 29.00 5 Blue Aluminum Lacquer No. 2 1.00 Total 100.00

EXAMPLE 8

Coating Film Formulation 8

[0054]

TABLE-US-00008 No. Description Composition (%) 1 Isomalt 12.00 2 Talc 9.00 3 Titanium dioxide 8.70 4 Blue Aluminum Lacquer No. 2 0.30 5 Water 70.00 Total 100.00

EXAMPLE 9

Coating Film Formulation 9

[0055]

TABLE-US-00009 No. Description Composition (%) 1 Isomalt 20.00 2 Talc 15.00 3 Titanium dioxide 14.50 4 Blue Aluminum Lacquer No. 2 0.50 5 Water 50.00 Total 100.00

EXAMPLE 10

Coating Film Formulation 10

[0056]

TABLE-US-00010 No. Description Composition (%) 1 Isomalt 45.00 2 Ethylene glycol-vinyl alcohol 6.00 graft copolymer 3 Polyvinyl alcohol 4.00 4 Polyethylene glycol 25.00 5 Talc 14.0 6 Sodium lauryl sulfate 0.50 7 Titanium dioxide 5.50 Total 100.00

EXAMPLE 11

Coating Film Formulation 11

[0057]

TABLE-US-00011 No. Description Composition (%) 1 Isomalt 25.00 2 Ethylene glycol-vinyl alcohol 9.00 graft copolymer 3 Polyvinyl alcohol 6.00 4 Hypromellose 23.00 5 Polyethylene glycol 15.00 6 Talc 9.24 7 Titanium dioxide 7.00 8 Yellow Aluminum Lacquer No. 6 5.00 9 Red Aluminum Lacquer No. 40 0.76 Total 100.00

EXAMPLE 12

Coating Film Formulation 12

[0058]

TABLE-US-00012 No. Description Composition (%) 1 Isomalt 20.00 2 Ethylene glycol-vinyl alcohol 35.00 graft copolymer 3 Polyethylene glycol 13.00 4 Kaolin 16.00 5 Titanium dioxide 15.00 6 Yellow iron oxide 0.50 7 Red iron oxide 0.50 Total 100.0

EXAMPLE 13

Coating Film Formulation 13

[0059]

TABLE-US-00013 No. Description Composition (%) 1 Isomalt 20.00 2 Ethylene glycol-vinyl alcohol 12.00 graft copolymer mixed with polyvinyl alcohol 3 Hypromellose 18.00 4 Polyethylene glycol 12.00 5 Talc 17.00 6 Titanium dioxide 16.00 7 Yellow Aluminum Lacquer No. 10 5.00 Total 100.00

EXAMPLE 14

Coating Film Formulation 14

[0060]

TABLE-US-00014 No. Description Composition (%) 1 Isomalt 6.00 2 Ethylene glycol-vinyl alcohol 3.60 graft copolymer mixed with polyvinyl alcohol 3 Hypromellose 5.40 4 Polyethylene glycol 3.60 5 Talc 5.10 6 Titanium dioxide 4.80 7 Yellow Aluminum Lacquer No. 10 1.50 8 Water 70.00 Total 100.00

EXAMPLE 15

Coating Film Formulation 15

[0061]

TABLE-US-00015 No. Description Composition (%) 1 Isomalt 24.00 2 Ethylene glycol-vinyl alcohol 12.00 graft copolymer mixed with polyvinyl alcohol 3 Hypromellose 12.00 4 Polyethylene glycol 12.00 5 Talc 18.00 6 Titanium dioxide 18.00 7 Carmine aluminum lacquer 4.00 Total 100.00

EXAMPLE 16

Coating Film Formulation 16

[0062]

TABLE-US-00016 No. Description Composition (%) 1 Isomalt 45.00 2 Ethylene glycol-vinyl alcohol 10.00 graft copolymer mixed with polyvinyl alcohol 3 Polyethylene glycol 25.00 4 Talc 14.00 5 Titanium dioxide 4.00 6 Sodium lauryl sulfate 0.50 7 Red Aluminum Lacquer No. 40 1.50 Total 100.00

EXAMPLE 17

Coating Film Formulation 17

[0063]

TABLE-US-00017 No. Description Composition (%) 1 Isomalt 18.00 2 Ethylene glycol-vinyl alcohol 4.00 graft copolymer mixed with polyvinyl alcohol 3 Polyethylene glycol 10.00 4 Talc 5.60 5 Titanium dioxide 1.60 6 Sodium lauryl sulfate 0.20 7 Red Aluminum Lacquer No. 40 0.60 8 Water 60.00 Total 100.00

[0064] The percentages described in Examples 1 to 17 are defined by weight relating to the total weight of the composition.

[0065] In pharmaceutical type film coating processes, it is generally preferred to prepare coverage dispersions for coating not exceeding 0.5 Pa.Math.s (500 cp) in order that, in the applying process, the spraying of the material is carried out without problems to obtain smooth and aesthetically acceptable coated tablets. The table in Example 18 shows the viscosities of a series of coatings in common use and also of some coatings that include Isomalt in their composition. It is evident that some formulations containing Isomalt, can allow its preparation in concentrations from 35% of solids content or higher.

[0066] In the table of Example 18, the viscosities were determined with a Brookfield type viscometer, brand W&J Instrument Co. Model RV-2M. Considering that the dispersions of coatings in general are non-Newtonian type fluids, wherein the measured viscosity depends on the measurement conditions, the needle and the speed of rotation of the needle are shown in square brackets when making the respective measurement.

EXAMPLE 18

Film Coating Product Viscosity Table

[0067]

TABLE-US-00018 Polymeric Base in examples Viscosity (mPa s) at various coverage preparation of film coatings, in typical concentrations/[needle, speed in rpm] formulations 10% 12% 15% 20% 25% 30% 35% 40% Hypromellose 120/ 240/ 680/ [2, 12] [2, 12] [2, 12] Hypromellose + Polydextrose 130/ 140/ 408/ 1050/ [1, 30] [2, 30] [2, 30] [3, 30] Hypromellose + Lactose 90/ 150/ 290/ 1210/ [1, 30] [2, 30] [2, 30] [2, 12] Hypromellose + Xylitol 70/ 100/ 290/ 660/ [1, 30] [1, 30] [2, 30] [2, 30] Polyvinyl alcohol 140/ 340/ 600/ [1, 12] [2, 12] [2, 12] Ethylene glycol and vinyl 80/ 190/ 1160/ alcohol graft copolymer [1, 12] [1, 12] [2, 12] Ethylene glycol and vinyl 70/ 340/ 680/ alcohol graft copolymer [1, 12] [1, 12] [2, 12] with polyvinyl alcohol Ethylene glycol and vinyl 70/ 120/ 170/ 440/ 1020/ alcohol graft copolymer [1, 60] [2, 60] [2, 60] [2, 60] [3, 30] with polyvinyl alcohol + Hypromellose + Isomalt Ethylene glycol and vinyl 20/ 30/ 40/ 100/ 160/ alcohol graft copolymer [1, 60] [1, 60] [1, 60] [1, 30] [1, 30] with polyvinyl alcohol + Isomalt Copovidone + Isomalt 50/ 60/ 90/ [1, 30] [1, 30] [1, 30]

[0068] As a relevant property of the film coating compositions that the present invention includes, there is the high brightness of the films that are obtained by using isomalt as an ingredient in its formulation. The table in Example 19 shows the brightness of films with formulations that do not include Isomalt, compared to the brightness of compositions with film-forming polymers supplemented with Isomalt. Measurements were made with the brand KSJ Glossmeter instrument, model MG6-SA with 60° angle of incidence. It is evident that the inclusion of isomalt promotes increased brightness in films, increasing on average by 15 GU, increasing brightness by more than 300%. In order that the comparisons were objective without intervention of the color factor, the brightness was determined on white films. In the same way, with the aim of making the comparisons impartial, without the intervention of the polishing factor that exists during the coating processes caused by the action of friction between the tablets, the brightness was measured in films applied on inert substrate such as white cardboard. Brightness measurements are reported in Gloss Units (GU).

EXAMPLE 19

Comparison Tables of Applied Film Gloss Measurement

[0069]

TABLE-US-00019 Brightness Brightness excluding including Polymer of reference Isomalt (GU) Isomalt (GU) Mixture of ethylene glycol and 7.2 18.3 vinyl alcohol graft copolymer with polyvinyl alcohol Hypromellose 8.3 26.0 Polyvinyl alcohol 5.3 21.3 Brightness Brightness including including Polymer of reference Xylitol (GU) Isomalt (GU) Mixture of ethylene glycol and 6.0 18.3 vinyl alcohol graft copolymer with polyvinyl alcohol

[0070] The table in Example 20 shows the brightness of composition films where only one film-forming agent is involved. It is appreciated that the Isomalt component alone generates greater brightness, however, when comparing with the results in Table 19, a synergy effect is observed where the brightness of coatings of film-forming mixtures mixed with Isomalt is greater than the brilliance generated by any of the individually tested film-forming agents.

EXAMPLE 20

Comparison Table of Applied Film Gloss Measurement

[0071]

TABLE-US-00020 Film-forming agent of reference Brightness (GU) Polyvinyl alcohol 5.3 Hypromellose 8.3 Mixture of ethylene glycol and vinyl 7.2 alcohol graft copolymer, with polyvinyl alcohol Isomalt 16.5

[0072] Optimal coating processing conditions, i.e. those required to apply a thin layer film to tablets, granules, pellets, or capsules, are dependent on the composition of the film. In the case of compositions that include Isomalt as an ingredient, it has been found that, in some cases, the optimal applying temperature ranges are wider, meaning this is an advantage, given that many substrates due to instability or various causes, can require processing at relatively low temperatures. The table in Example 21 shows optimal applying temperature ranges for various types of film coating formulations. It is noteworthy that some of the compositions that include Isomalt can be applied at moderately lower temperatures than traditional coatings.

EXAMPLE 21

Comparison Table of Optimal Process Temperatures in Coating Applying. Tablet Bed Temperature

[0073]

TABLE-US-00021 Optimal applying temperatures Coating product (tablet bed temperature) Hypromellose base in water 40-45° C. Hypromellose base with carbohydrates 38-45° C. Polyvinyl Alcohol Base in Water 38-44° C. Ethylene glycol and vinyl alcohol 38-44° C. graft base Ethylene glycol and vinyl alcohol 30-48° C. graft base plus polyvinyl alcohol, plus hypromellose plus Isomalt (composition of example 14)

[0074] As used in this document, the term “increased brightness” refers to the gloss shown by the coating film and is in the range of 10 to 30 or more Gloss Units (GU), measured with a brand KSJ Glossmeter instrument, model MG6-SA with 60° angle of incidence.

[0075] In this document, the terms “Isomalt” or “isomaltulose derivative” are used interchangeably and refer to the mixture of 6-O-α-D-glucopyranosyl-D-mannitol dihydrate with 6-O-α-D-glucopyranosyl-D-sorbitol.

[0076] The term film-forming polymer is used interchangeably as film-forming or adherent polymer to denote polyvinyl alcohol, hypromellose, ethylene glycol and vinyl alcohol graft copolymer, with polyvinyl alcohol, copovidone, polyvinyl alcohol, methacrylate derivatives, isomalt and cellulosic derivatives

Additional Observations

[0077] Therefore, the present invention is well adapted to achieve the aforementioned purposes and advantages, as well as those inherent therein. The particular embodiments disclosed above are illustrative only, as the present invention can be modified and practiced in different but equivalent apparent ways for those skilled in the art who have the benefit of the teachings herein. Furthermore, no limitation is intended to the details of the features shown in this document, in addition to those described in the claims that follow. It is therefore evident that the particular illustrative embodiments disclosed above can be altered, combined or modified and that all such variations are considered within the scope and spirit of the present invention.

[0078] The invention disclosed illustratively herein can be suitably practiced in the absence of any item not specifically disclosed herein and/or any optional item disclosed herein. While the formulations and methods are described in terms of “comprising”, “containing”, or “including” different components or steps, the formulations and methods may also “consist essentially of” or “consist of” the different components and steps. The terms formulation, formulations, composition and compositions are used interchangeably and refer to the same. All the numbers and ranges disclosed above may vary by some amount. Whenever a numerical range with a lower limit and an upper limit is disclosed, any number and any included range that falls within the range is specifically disclosed. The terms in the claims have their simple, ordinary meaning unless explicitly and clearly defined otherwise by the patent holder. Furthermore, the indefinite article “one”, as used in the claims, is defined herein to refer to one or more than one of the elements you introduce. If there are any conflicts in the uses of a word or term in this specification and one or more patents or other documents that may be incorporated herein by reference, the definitions that are consistent with this description should be adopted.