WO2010018591A1

WO2010018591A1 - Multi coloured tablets

Info

Publication number: WO2010018591A1
Application number: PCT/IN2009/000185
Authority: WO
Inventors: Suresh Pareek; Chetan Rajsharad
Original assignee: Ideal Cures Pvt. Ltd.
Priority date: 2008-08-12
Filing date: 2009-03-17
Publication date: 2010-02-18

Abstract

The present invention is directed towards a dry mix composition that can be used to produce multi coloured tablets. The dry mix composition can be used to achieve a multi colour effect for uncoated and coated tablets. Coated tablets include any and all coatings applied over tablets like film coating, enteric coating, polymeric coats and other similar coatings. The dry mix composition comprises of commonly used excipients incorporating a fixing agent and a suitable pigment colour. A process to manufacture multi coloured tablets using the inventive dry mix composition is also described. The invention can be applied to pharmaceutical, food products, confectionery, agricultural seeds, nutritional feeds etc. Furthermore, the application describes the formulation variances by which the invented technology can easily be implemented on commercial levels.

Description

MULTI COLOURED TABLETS

FIELD OF THE INVENTION:

This invention relates to the a dry mix composition used for field of film coating of substrates in the areas of pharmaceuticals, neutraceuticals, food products, agricultural produce and confectionery to have a multi - coloured appearance for better brand identification in the market place and to reduce the possibilities of counterfeiting. The invention can be applied to uncoated tablets, film coated tablets, and enteric coated tablets, coated controlled release tablets, tablets coated for protection to the substrate from environmental conditions like light, humidity, atmospheric gases etc.

BACKGROUND OF THE INVENTION:

This invention is concerned with a method of marking forms such as confectionery products, food, pharmaceutical tablets, and hard and soft gelatin capsules with a dry mix composition comprising a suitable colour. It has always been a dream of almost all pharmaceutical scientists to produce a film-coated tablet with multi - colour look. However, with the known technology, this dream remained an unfulfilled desire. Scientists have tried various approaches but could not succeed even at laboratory scale, not to mention for commercial application. This is the reason for pharmaceutical tablets in market place are available only with a single colour shade on the tablet surface which could be the result of either a single colour or a mixture of more than one colour. There is not a single product in market in which there is more than one distinct colour shades on the tablet surface.

U.S. Pat. No. 3,258,347 issued on Jun. 28, 1966 for "Edible Pharmaceutical Ink"; Roy Y. Sanders, Jr. U.S. Pat. No. 2,948,626 issued on Aug. 9, 1960 for "Edible Pharmaceutical Ink and Process of Using Same"; Chester J. Piotrowski U.S. Pat. No. 3,694,237 issued on Sept. 26, 1972 for "Edible Ink"; and Stuart C. Porter et al. U.S. Pat. No. 4,543,370 issued on Sept. 24, 1985 for "Dry Edible Film Coating Composition, Method and Coating Form" are some of the earlier patents relating to the art. US 5,006,362 assigned to Berwind Pharmaceutical services describes a method of marking forms such as pharmaceutical tablets, capsules, confectionery and food with a water based ingestible ink comprising mixing pigments, a polymer, and optionally a plasticizer into water to form an ink dispersion, and printing the ink dispersion onto said forms to form a trademark, logo, or the like.

Prior art ingestible inks suitable for marking forms such as confectionery products, food, pharmaceutical tablets, and hard and soft gelatin capsules have a shellac base in ethyl alcohol. One of the problems in marking such forms and one of the more important parameters for these inks is drying time. Brown U.S. Pat. No. 3,258,347, which refers to drying time as "set-to-touch- time", states that the optimum transfer characteristics of the ink are obtained when the set-to-touch-time is two to four minutes. When the drying time is too slow, as is discussed in Sanders, Jr. U.S. Pat. No. 2,948,626, a tackiness problem develops resulting in spotting or smudging of the ink. Drying time is also discussed in Piotrowski U.S. Pat. No. 3,694,237 at column 1, lines 57-72 which states: "Prior art edible inks are made with dry shellac, ethyl alcohol, plasticizers and/or detackifiers, pigments, or dyes, and solvents which give a desired drying time, say three minutes. As the ink ages, a process occurs wherein the acid groups of the shellac react with the ethyl alcohol to form an ethyl ester of the shellac. The presence of the shellac ester increases the drying time of the ink, and as the amount or percentage of ester increases, the drying time is increased, eventually to a point where the drying time is too long, causing offset, or pick-off, or transfer of the ink from one printed piece or tablet to another. Accordingly, it has been noted that the drying time of prior art inks increases with age, and this limits the shelf or storage life of the ink."

The machines presently being used to print marks onto pharmaceutical, food or confectionery products use a principle that is best described as offset gravure. An engraved cylinder picks up ink as it rotates in an ink bath. Excess ink is wiped off the engraved cylinder by a doctor blade and the ink remaining in the gravure etch of the cylinder is transferred to a rubber transfer (offset) roller which rotates with its roller surface in contact with the engraved cylinder. The ink on the transfer roller is then deposited onto the end product such as a tablet, or capsule.

The form may have been film coated, sugar coated, or not coated at all. To date, almost all inks used for this purpose have been of a shellac base in ethyl alcohol. While some shellac- based inks have incorporated some water into the formula by the modification of pH, the inks remain alcohol based for the most part. Accordingly, their closed cup flash point is less than lOO.degree. F., and, therefore, they must be labeled as a hazardous flammable liquid.

There is available in the marketplace today, a plethora of pharmaceutical formulations manufactured by various companies, which are generally coloured for identification and to avoid the mix-up of different products during packaging operations and during dispensing to the patients.

However, as the number of colours available to the pharmaceutical industry is limited, every product cannot be coated with different colour. Hence, within a pharmaceutical anufacturing unit as well as at dispensary, one can have several different products (for very different therapeutic application) which look alike because these products may be coated with the same colour.

In order to overcome this kind of situations, pharmaceutical scientists had developed the process of tablet printing by which the product name could be printed on the sugar coated tablets. Once the process of film coating was developed, same printing technology became applicable to the film coated tablets also. Though this technological advancement had helped in preventing the mix-ups and confusion in dispensing the correct product to the patient, but it hampered the productivity at the manufacturing site. The printing process was very slow and setting the printing machine itself was a skillful operation so that each tablet has the print in the centre of the tablet. There were lots of rejection during the printing operation onto the otherwise finish dosage form due to the shift of the printing monogram from the desired location on the tablet surface and the slow drying of the printing inks due to which many times it is not possible to operate the printing machine at the maximum possible speed.

The problem related to tablet printing was solved by embossing the letters on the tablet surface. Such letters were found to be quite stable and there was no compromise on the productivity or the cost of production as the process of embossing was concurrent with the process of tablet compression. The desired letters were engraved on the tip of the compression tooling so that the desired letters were embossed during the compression operation itself. Such embossed tablets could easily be film coated so that even after the coating, the embossed letters are still visible.

With the development of embossed film coated tablets, the problem of mix-ups, identification and correct dispensing were thought to have been solved but in case of very small size tablets reading or identifying very small letters (against coloured background) is very difficult even for a person with normal eyesight. In case of bigger tablets also there is a potential of error in dispensing when the pharmacist is surrounded with similar colour tablets.

Yet another approach has been used where a compressed tablet is enrobed with two different coloured gelatin sheets. In this approach one side of the tablet has one colour whereas the other side of the tablet has another colour. This approach has given two distinct colours to the tablet surfaces but the technology is not user friendly, moreover, the machinery involved is very expensive and skillful operations increase overhead costs making the end product quite expensive.

SUMMARY OF THE INVENTION:

A dry mix edible coating composition for use in pharmaceuticals, confectionery and food forms, such as hard and soft shell gelatin capsules, tablets, candy and the like, comprises about 50 to 95 parts of a filler, 1 to 25 parts of a flow aid , 1 to 25 parts of pigment particles / opacifier, 1 to 10 parts of a humectants and 1 to 10 parts of a fixing agent. Additionally the dry composition may include about 1-25 parts of a binder.

The filler may be lactose, starch, microcrystalline cellulose, calcium phosphate, mannitol, xylitol or mixtures thereof and may include commonly used fillers in the prior art known in the arena of formulation and the like. Preferably, the filler comprises about 70% to about 85% by weight of the dry coating composition of the invention.

The flow aid may be talc which is the most commonly used, but others like aluminum hydrate, glyceryl monostearate, kaolin, or mixtures thereof and is used principally to reduce the incidence of tablet-to-tablet sticking. Preferably, the flow aid comprises about 10% to about 15% by weight of the dry coating composition of the invention.

Examples of pigments include FD&C and D&C lakes, titanium dioxide, magnesium carbonate, talc, pyrogenic silica, iron oxides, channel black, and insoluble dyes or mixtures thereof. Also natural pigments such as riboflavin, carmine 40, curcumin, and annatto. Other examples are listed in Jeffries U.S. Pat. No. 3,149,040 and Butler et al. U.S. Pat. No.

3,297,535, as well as in Signorino U.S. Pat. ^"No. 3,981,984, which are incorporated herein by reference. Preferably, the pigment comprises about 1% to about 10% by weight of the inventive dry coating composition.

The humectants may include glycerin, propylene glycol, Triacetin (Pfizer's glycerin triacetate), acetylated monoglyceride, and Citroflex 2 (triethyl citrate), Citroflex 4 (tributyl citrate), Citroflex A2 (acetyl triethyl citrate), Citroflex A4 (acetyl tributyl citrate), diethyl phthalate, water or mixtures thereof and the like. Preferably, the humectant comprises about 2% to about 6% by weight of the inventive dry coating composition. The fixing agent may include liquid paraffin, a mineral oil or mixtures thereof and the like. Preferably, the fixing agent comprises about 2% to about 6% by weight of the inventive dry coating composition.

In addition, the inventive dry composition may contain additional ingredients like binders, which include povidone, HPMC or mixtures thereof and the like. Preferably, the binder comprises about 5% to about 15% by weight of the inventive dry coating composition As a result of the present invention , several advantages and improvements over the prior art are realized. For example by using the present invention one can manufacture multicoloured tablets wherein there are two different colours on a single tablet and the logos or imprints can be of a different colour. The present dry inventive composition can be used on both uncoated and coated tablets. The problems that a manufacturer faces while overprinting tablets using edible inks are also solved by the present invention. It makes the process of having different coloured base tablets and different coloured logo much easier by using the present invention. In addition investment into machinery used for over printing and or marking tablets is totally eliminated.

Another aspect of the present invention is that the multi colored tablet operation wherein there is a different colour can be achieved in the coating pan itself as a one pot operation after normal coating of tablets as the present inventive dry mix composition need not be reconstituted or sprayed onto the uncoated or coated tablets. This saves the overhead costs and also decreases the total productivity time.

For purposes of the present invention "orally- ingestible substrate" shall be understood to mean any pharmaceutically acceptable dosage form, e.g. tablet, capsule, caplet, etc. or any other veterinary or confectionary product capable of being taken via the oral route of administration. For purposes of the present invention, "dry powder" shall be understood to mean powders which are relatively dry to the touch a rather than powders which are essentially without moisture content.

For purposes of the present invention, "dry mix" shall be understood to mean powders but could include a granulated version of the present dry mix inventive composition which are useful for logo filling in case of deeply engraved embossing on the uncoated or coated tablets.

Another object of the invention is to provide a method so that the invented technology can be implemented on commercial scale and the multi - colour effect remain stable during the packaging operations and shelf life of the finish product.

DETAILED DESCRIPTION OF THE INVENTION: The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated.

In accordance with the invention, the inventive technology can be used to apply another colour to the already coloured film coated tablet or to an uncoated tablet.

Most of the currently produced tablet products are having embossing on the tablet surface.

These tablets when film coated with a coloured polymeric solution give single colour tablet whereas the cavities created on the tablet surface due to letter embossing are still clearly visible. Such cavities provide an opportunity to apply another colour to the tablet surface.

In accordance with the invention, a dry powder blend is formulated which when applied to the tablet surface (by mixing the tablets and the powder blend in a coating pan or a mixer and let the mixer roll for sufficient time), the powder blend gets filled into the cavities available on the tablet surface. The same process when applied to the uncoated tablets, the result was found to be the same that the coloured powder blend gets filled into the cavities available on the tablet surface. As the uncoated tablets generally, are white in colour, the dry powder blend can be prepared with any desired colour shade, thus producing a two colour finish dosage form. Similarly, for film coated tablets, the colour of the dry powder blend can be selected either white or any other suitable colour, depending on the colour of the film coating so that two different colours are distinctly visible.

Thus by following the above process one can practically achieve dual coloured tablets wherein the first colour involves the basic coloured tablet or uncoated tablet (usually white) and the second colour which is achieved by using the dry mix composition of the present invention which can be in the form of a logo filling by incorporating the desired colour pigment in the dry mix composition of the present invention.

The main advantage of the present inventive dry mix composition is that it can be directly applied on the coated or uncoated tablet in powder form. There is no need for any reconstitution on spraying machinery or tablet overprinting machinery, which used edible inks in suspension form to overfill logos on embossed tablets. As there are no solvents like ethyl alcohol or resins like shellac, which are used in edible printing inks the patient is not exposed to these residual solvents. In addition there is no effect on the disintegration time or dissolution profile of the tablets unlike in some cases wherein the shellac used in the edible printing inks may affect disintegration and or dissolution times.

As the finished tablet dosage form has to undergo various stress conditions during further handling, packaging and transportation, the formulation of the dry mix composition to achieve this dual coloured tablet dosage form needs to be selected carefully so that the powder blend which is filled into the cavities, does not come out during such stress conditions. It was found during experimentations that colour blends with lactose provide good opportunities of cavity filling. However, it was found that just a simple blend of colour with lactose, though, provides good cavity filling, but a lot of this powder blend comes out of cavity during further tablet handling. Other commonly used excipients like starch, calcium phosphate, microcrystalline cellulose etc. also gave the similar problems. Further experimentations revealed that the addition of commonly used binders like povidone, HPMC etc. improve the powder retention inside the cavities. It was further observed that further addition of small amount of liquids like water, castor oil or liquid paraffin etc. help in improving the binding properties of the powder and provide much better retention of colour powder blend inside the cavities. Addition of humectants like glycerin further improved the powder retention inside the cavities.

A combination of glycerin and oily substance like liquid paraffin to the powder blend of colour, lactose, povidone, HPMC etc. provided excellent results as it not only helped in better powder retention inside the cavities but also helped in removing the excessive powder from the tablet surface due to the presence of small amount of oily substance in the powder blend.

In a systematic study undertaken to arrive at the present inventive dry mix composition, to ascertain the powder retention capacity, we used the Friability Test, which is described in the United States Pharmacopoeia as an official test for testing uncoated tablets. Friability test was carried out using USP friability test apparatus for 4 minutes (100 revolutions), by using various powder blends filled into the cavities of uncoated and coated tablets. The percentage friability gives an approximate idea of the fixability of the dry mix composition onto the surface of the coated or uncoated tablet.

A simple process of blending prepared the following dry mix compositions and uncoated and coated tablets were coated with this second coloured logo filling powder mix by the following process: The uncoated or coated tablets were placed in a coating pan. The inventive dry mix composition was sprinkled on the tablet bed in the pan and the pan was rotated at a suitable speed and for a time sufficient enough for the coloured dry mix blend to get filled onto the embossed logos. Tablets were off loaded onto a 10-mesh screen, after the logos were filled to remove the excess of the dry mix. These tablets were then evaluated for friability the results of which are given in Table 1 below:

Table 1: Exam les o various dr mix com ositions and the riabilit test values:

From the above Table 1 it can be observed that Dry Mix 9 gives us good friability values for both uncoated and coated tablets. Hence it was further decided to optimize the ingredients that constituted this dry mix. A powder blend formulation as described above provides the desired results as far as the loading of a different colour to achieve multi coloured tablet but may still leave the tablet surface little dusty. This can be cured by either polishing the tablets with a wax-based solution or any polishing system for tablets such as INSTAGLOW (water as well as organic solvent soluble polishing system manufactured by Ideal Cures Pvt. Ltd., Mumbai, India).

Alternatively, a transparent film coating system (either based on low viscosity HPMC, PVA, PVP, Shellac etc) may be used which not only makes the tablet surface smooth but also acts as an additional fixer to the colour powder blend filled inside the cavities.

The following table (Table2) provides an optimized dry mix inventive composition with the ingredients and their percentages, which can easily be used to practice this invention

Table 2: An optimized formula of the inventive dry mix composition

Some examples illustrative of the inventive dry mix composition are given below in Examples 1 to 5

Example 1:

185

12

Process of Preparation of the Dry Mix composition:

In a planetary mixer, take required quantity of Lactose and Colour (Lake colour and / or soluble colour and / or Titanium Dioxide) and blend to produce a homogenous mix.

Dilute Glycerin in water and add to the mix of step 1 ; blend the whole material for 5 minutes in the mixer. Add liquid paraffin (the main advantage of liquid paraffin is that due to its presence, the powder blend does not stick to the tablet surface, otherwise the powder blend leaves colour specs on the tablet surface) to the mix of step 2 and blend for another 5 minutes. Sieve the blend of step 3 through 40-mesh sieve and then lubricate with required quantity of Talc (talc works as glidant and helps in better rotation of tablets in the coating pan during logo filling operation).

The dry blend with other varying compositions can be prepared by the above given process using various other excipients like starch, MCC, calcium carbonate, HPMC, ethyl cellulose, povidone, polyvinyl alcohol, gum acacia, propylene glycol, PEG, castor oil etc.

Example 2:

Example 4:

In order to further enhance the applicability of the invention and obtain a multi coloured physical appearance of the tablet surface, a small amount of coloured granules of size varying between 50 to 500 microns of a different colour was incorporated into the inventive dry mix composition, to obtain a dual coloured dry mix. When this was used for logo filling a multi colored tablet was obtained sue to the presence of the granules in the dry mix composition which by itself had a different colour, thus providing more than two colours on the tablet surface.

Thus, the invention provides a novel technology of making the dull looking tablets very elegant with many colours on the tablet surface which will provide unique way of product identification in market place.

The following example provide the possible composition of the coloured powder blend which can easily be used to practice this invention. While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents (like use of different excipients / binders and the combinations thereof) will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

The ranges of each component of the dry colour powder composition of the invention are as follows, by weight:

Example 6

The dry components of the formulation are blended in a blender for 15 minutes, the liquid components are then added slowly with continuous mixing. Resulting mixture was further blended for another 10 minutes until a homogenous mixture is achieved.

While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents (like use of different excipients / binders and the combinations thereof) will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

Claims

1. A dry powder mixture for use in preparing multi coloured substrates, comprising a filler, a flow aid, pigment particles / opacifier, a humectant and a fixing agent.

2. The powder mixture of claim 1, wherein said filler is selected from lactose, microcrystalline cellulose, starch, calcium carbonate, mannitol or xylitol or mixtures thereof.

3. The powder mixture of claim 2, wherein said filler is present in an amount of from about 50 to about 95% by weight, more preferably from about 70 to about 85% by weight.

4. The powder mixture of claim 1, wherein said flow aid is selected from talc, aluminum hydrate, glyceryl monostearate or kaolin or mixtures thereof.

5. The powder mixture of claim 4, wherein said flow aid is present in an amount of from about 1 to about 25% by weight, more preferably from about 10 to about 15% by weight.

6. The powder mixture of claim 1, wherein said pigment particles / opacifier is selected from FD&C and D&C lakes, titanium dioxide, magnesium carbonate, iron oxides, channel black and insoluble dyes or mixtures thereof.

7. The powder mixture of claim 6, wherein said pigment particles / opacifier is present in an amount of from about 1 to about 25% by weight, more preferably from about 1 to about 10% by weight.

8. The powder mixture of claim 1, wherein said humectant is selected from the group consisting of glycerin, propylene glycol, acetylated monoglycerides, diethyl phthalate, water or mixtures thereof.

9. The powder mixture of claim 8, wherein said humectant is present in an amount of from about 1 to about 10% by weight, more preferably from about 2 to about 6% by weight.

10. The powder mixture of claim 1, wherein said fixing agent humectant is selected from the group consisting of liquid paraffin, mineral oil or mixtures thereof.

11. The powder mixture of claim 10, wherein said fixing agent is present in an amount of from about 1 to about 10% by weight, more preferably from about 2 to about 6% by weight.

12. The powder mixture of claim 1, further comprising an additional binder.

13. The powder mixture of claim 12, wherein the binder is selected from the group of HPMC and its derivatives, povidone and its derivatives or mixtures thereof.

14. The powder mixture of claim 13, wherein said binder pigment is present in an amount of from about 1 to about 25% by weight, more preferably from about 5 to about 15% by weight.

15. An orally ingestible substrate coated with a dry mix composition of claim 1.

16. A method of dry coating using a dry mix composition of claim 1 comprising the steps of a) Placing the uncoated or .coated tablets in a coating pan. b) Sprinkling the dry mix composition on the tablet bed in the pan and rotating the pan at a suitable speed and for a time sufficient enough for the coloured dry mix blend to get filled onto the embossed logos. c) Off loading the logo filled tablets onto a 10 mesh screen, to remove the excess of the dry mix.

17. A coated substrate produced by the process claimed in claim 16

18. A coated substrate produced by the application of dry mix composition of claim 1.