The invention relates to a colouring composition in dry form and its application in lacquers intended for coating various pharmaceutical forms and foodstuffs.

Legislation concerning food and food additives used, including permissible types of colorants and their permissible contents, is constantly changing. In recent years, limits relating to azo dyes (Commission Regulation (EU) No. 1129/201 1 of 11 November 201 1 amending Annex II to Regulation (EC) No. 1333/2008 of the European Parliament and of the Council by establishing a Union list of food additives, and Commission Regulation (EU) No. 232/2012 of 16 March 2012 amending Annex II to Regulation (EC) No. 1333/2008 of the European Parliament and of the Council). Colorants with limited use also include quinoline yellow, both in the form of pure dye and a lake of this dye. Azo dyes, including quinoline yellow, are suspected of being carcinogenic, as well as of having an influence on activity and concentration in children.

Quinoline yellow is a dye frequently present in food and food additives, as well as in additives of a medicinal character. As a result of the aforementioned legal regulation, it is permitted to use quinoline yellow in a significantly smaller amount, and in case of use of any amount, special labelling of the packaging is required, warning consumers of the content of quinoline yellow in the product and the possibility of an adverse effect on activity and concentration in children. Use of this colorant has become undesirable in the food industry, particularly in products intended for children.

Colouring of food or pharmaceutical products or dietary supplements is usually carried out in a process of coating with properly prepared lacquer and application of the proper coating layer onto the surface of tablets, capsules, pellets. Dyes or their lakes are added to the lacquer in solid form, most often in the form of a previously prepared mixture of dry raw materials, which are then suspended to the form of water suspension or lacquer.

Quinoline yellow in the form of soluble dye or dye lake, when used in the production of coatings for tablets and food products, provides a lemon yellow shade, very desirable by food and pharmaceutical industries.

Using quinoline yellow in the enforced limits, one cannot achieve a properly intense yellow colour. Thus, other colorants to replace this azo dye have started to be used in the industry. These colorants include: riboflavin, iron oxides and other natural dyes (e.g. biolutein), which would ensure the proper intensity of yellow for coatings for tablets, capsules and pellets. However, these colorants are unstable - they pale under the influence of light and in storage, do not provide proper covering power and are not cost-effective. Colorants such as riboflavin and biolutein have a tendency of migration of the yellow colour to the tablet core.

In the case of colouring compositions, mechanical strength of coatings is of very high importance. Such products as e.g. coated tablets are exposed to abrasive forces during further production stages. The stability of colour is also very important, because of the long shelf life of coated products, such as dietary supplements and pharmaceutical products. Application of a colorant which would not exhibit migration properties to the product's core, e.g. to the tablet core, is a very important aspect when coating pharmaceutical and food products.

It is known that quercetin and rutin, being a quercetin glycoside, as natural compounds of plant origin, belonging to flavonoids, are characterised by a yellow colour. This feature has been used e.g. for colouring tobacco products (DE3142707 Al), for colouring hair (CN1478459A) and for colouring noodles (JPH10108646A).

The goal of the invention was to provide a stable and completely non-toxic colouring composition with yellow colour, intended for application in food and pharmaceutical products.

The colouring composition according to the invention is characterised in that it consists of: quercetin in its free form and/or in the form of glycoside, in a micronized form below 100 micrometres, preferably below 10 micrometres, in the amount of 0.2÷70% by wt.; at least one polymerising substance selected from among: HPMC, HPC, agar, xanthan gum, arabic gum, gelatin, PVP, carboxylmethylcellulose sodium salt, starch derivatives, polysaccharides, modified cellulose derivatives, pectins or their derivatives, individually or as a mixture, in the amount of 5÷80% by wt., and optionally an opacifier in the amount of 0.2%÷35% by wt., while contributions of the individual components are related to the dry contents of the composition. Additionally, the composition may contain plasticisers such as: polyethylene glycol, sorbitol, propylene glycol, vegetable oils, MTC, triacetin, glycerine in the amount of 0.5%÷18% by wt., individually or as a mixture. Additionally, the composition may also contain an antiadhesive and antiaggregation substance, preferably talc or mica, or other known antiadhesives, in the amount of 0.5%÷10% by wt.

Most preferably, the composition contains rutin as the quercetin glycoside. As the opacifier, the composition preferably contains: titanium dioxide, calcium carbonate, microcrystalline cellulose, starch, mica and other known substances, which may be dispersed, individually or as a mixture.

Micronized quercetin or its glycoside form, such as rutin, plays the role of a dye in the colouring composition, and the substance being dispersed, most preferably titanium dioxide and/or calcium carbonate, is an optional component of the composition, used as an opacifier. The opacifier provides a proper colour intensity and the opacity effect to the coating and affects its covering power. In case opacifiers are present in the composition, quercetin or rutin may be used in a smaller amount, up to 50% by wt.

Use of quercetin with the recommended micronization degree and a proper quantitative and qualitative selection of the composition components, ensuring adequate mechanical strength, are important for the stability and appearance of the coating. Quercetin, both in its free form and in glycoside form, is insoluble in water and other solvents, thus it does not migrate to the core of the product being coated. Proper saturation with the colour may be achieved with a quercetin content below 1% by wt.

The invention also includes application of the composition defined above for coating of pharmaceutical preparations and/or foodstuffs. The composition containing quercetin or its glycoside, preferably rutin, or their mixtures according to the invention, may be used as a component of the envelope used for coating of products (such as: tablets, minitablets, granulates, pellets, powders, hard gelatin capsules) with a colour film.

The composition according to the invention is prepared by mixing all the components included in its constitution. Such a mixture is a finished commercial product, which may be stored for a very long time. In order to use the composition, it is solubilised or dispersed in a solvent, such as water or other solvent permissible in the given application, in order to obtain lacquer in the form of a suspension. For coating, a suspension containing from 4% to 25% by wt. of the composition according to the invention is used. The lacquer is used in the process of coating of external surfaces of tablets, minitablets, granulates, pellets, powders and hard gelatin capsules. Preferably, the coating process is realised by spraying, using spray-guns which produce aerosol. After application of the lacquer on the surface, the coated product is dried.

Additions of polymers, such as HPMC and PVP, allow for adjustments of the utility parameters of the coating, such as stability, non-abrasiveness and elasticity.

Colouring compositions according to the invention allow for obtaining envelopes with Friability below 0.08%, resistant to light, with a yellow colour. In case of application of a glycoside form of quercetin, such as rutin, a lemon yellow colour is obtained with such intensity of yellow as when using a large, legally impermissible amount of quinoline yellow lake in the colouring coating. Application of quercetin in its free form provides a slightly different colouring effect, depending on the raw material origin, i.e. a surface coated with lacquer containing quercetin provides a yellow-orange colour. Mixtures of free quercetin and its glycoside form allow for creating coatings with a broad range of yellow shades.

In the products coated with the composition according to the invention, migration (diffusion) of the dye from the surface to the core was not observed, and the colour is resistant to light. Combinations of components may increase the covering power or deepen the colour of the surface covered with the lacquer.

The subject of the invention is presented in more detail in the following examples. Example 1.

Preparation of colouring compositions.

Mixtures with compositions shown in Table 1 were prepared using quercetin and rutin with a micronization degree below 10 micrometres. The mixtures were prepared in a way described below.

Proper amounts of raw materials were weighted then mixed in a totalising mixer for 20 minutes. After mixing, the obtained mixture was calibrated on a calibrator using a sieve with a mesh size of 0.3 mm, in order to homogenise the mixture. The so-obtained mixtures were marked according to Table 1.

Preparation of lacquer for application onto the surface of tablets.

15% suspensions were prepared in separate containers by pouring the obtained composition to cold, purified water with a temperature of 18÷22°C and stirring vigorously for 2 hours.

Coating of tablets.

A coating drum with a capacity of 50 litres was filled with tablet cores in the amount of approx. 2 kg; the tablets were heated to 35°C.

The lacquer was sprayed using a pressure spray-gun, with simultaneous inflow of air with a temperature of 45÷50°C. The process of film application was carried out till a 3% increase of the tablet mass was obtained. Weight of the tablets was measured every 5 minutes.

Using the method described above, finished tablets coated with the compositions according to the invention, with constitutions shown in Table 1, were obtained.

The surfaces of the tablets were investigated with respect to the intensity of the obtained colour and Friability. Colour intensity was evaluated visually, comparing the colour with the colour of standard, and classifying the intensity using a five-degree scale from -5 to +5. The zero value refers to a standard constituted by an envelope containing known colorants - colouring compositions Nos. 1 and 2. The comparison was also carried out using commonly available Pantone colour patterns.

The value of Friability was studied measuring weight loss of the coated tablets after intense abrasion using the method of tablet Friability according to the European Pharmacopoeia. Approx. 6.5 g of tablets was weighed for the test with a precision of 0.1 mg. The tablets were abraded in a drum with a diameter of 156 mm at 25±1 rpm; the number of revolutions was 100. After the abrasion test, the tablets were weighed with a precision of 0.1 mg, and Friability was calculated according to the following formula: S= Δ m/mass of the tablets before abrasion. The results are presented in Table 1.

Table 1

No. HPM Titaniu Polydextr Polyeth Talc Quinoline Iron Rutin Quercetin Colour Friability C m ose elene yellow lake oxide % intensity

dioxid glycol % % yellow % %

% e % %

% %

1 35 20 25 10 5 4 1 - - +2 0.08

2 35 20 25 10 5 5 - - - +3 0.08

3 35 20 25 10 5 - - 5 - +3 0.03

4 35 20 25 10 5 - - - 5 +3 0.02

5 35 20 25 10 5 - - 2.5 2.5 +3 0.01

6 35 20 25 10 5 - - 1 4 +2 0.03

7 35 20 25 10 5 - - 4 1 +3 0.02

8 35 10 30 10 5 - - 10 - +4 0.01

9 35 10 30 10 5 - - - 10 +4 0.009

10 35 10 25 10 5 - - 7.5 7.5 +4 0.01

1 1 35 10 35 10 5 - - 5 - +3 0.03

12 35 - 45 10 5 - - 5 - +3 0.01

13 35 - 35 10 5 - - 15 - +4 0.004

14 35 25 10 5 - - 25 - +5 0.005

15 35 - 15 10 5 - - 35 +5 0.004

16 35 — 45 10 5 — — — 5 +3 0.007

17 35 — 35 10 5 — — — 15 +4 0.009 No. HPM Titaniu Polydextr Polyeth Talc Quiiioline Iron Rutin Quercetin Colour Friability C m ose elene yellow lake oxide % intensity

dioxid glycol % % yellow % %

% e % %

% %

18 35 25 10 5 — — — 25 +5 0.004

19 35 — 15 10 5 — — — 35 +5 0.006

Conclusions:

When using rutin, a coating with better strength parameters was obtained than those obtained when using another yellow dye - quinoline yellow. Colour intensity is directly proportional to the amount of rutin in the colouring composition. Rutin may completely replace the opacifier, such as titanium dioxide. When using quercetin, a coating with better strength parameters was obtained than those obtained when using another yellow dye - quinoline yellow. Colour intensity is directly proportional to the amount of quercetin in the colouring composition. Quercetin may completely replace the opacifier, such as titanium dioxide. Mixtures of quercetin and rutin have similar properties; however, the colour obtained when using a mixture is different from the shades obtained when using the individual components.

Example 2.

Through the method described in Example 1, a coating with a composition presented in Table 2 was obtained and applied onto the surface of tablets using an identical method as in Example 1. Studies of colour intensity and Friability were carried out according to the procedure described in Example 1. The results are presented in Table 2.

Table 2.

Envelope 1 Envelope 2 Envelope 3 Envelope 4 Envelope 5

HPMC (%) 40

PVP K25 (%) 35

HPC (%) 25

Agar (%) 15

KMC sodium salt (%) 10

Titanium dioxide (%) 10 10 10 10 10

Polydextrose (%) 25 30 35 40 45

Polyethylene glycol 10 10 10 10 10

(%) Envelope 1 Envelope 2 Envelope 3 Envelope 4 Envelope 5

Talc (%) 5 5 5 5 5

Rutin (%) 10 10 10 10 10

Colour intensity +2 +2 +2 +2 +2

Friability (%) 0.006% 0.006% 0.008% 0.008% 0.005%

Results of the studies:

It was found that application of rutin and quercetin in envelopes containing various polymers allows for obtaining the same intensity of yellow colour. The polymer share in the composition is various and depends on the viscosity of the polymer solution at 20°C. The difference in the amount of polymer is compensated with a proper amount of neutral filler - polydextrose.

Example 3.

Through the method described in Example 1, a composition with the following constitution was obtained:

HPMC - 40% by wt.

titanium dioxide - 10% by wt.

polydextrose - 30% by wt. polyethylene glycol - 10% by wt.

rutin - 10% by wt.

The obtained compositions were applied onto the surface of tablets in the manner described in Example 1. Rutin, with various micronization degrees, was Used for the studies. Studies of colour intensity and Friability were carried out according to the procedure described in Example 1. For evaluation of covering power, dark (containing extracts) tablet cores were used for coating. Covering power was investigated visually by measuring the mass increase during coating, with which the tablet core had a uniform yellow colouring without an odd- colour resulting from a show-through of the core colour.

The results are presented in Table 3.

Table 3.

Rutin break-up Colour Friability Minimum tablet mass degree intensity increase during

% coating, which

ensures covering

%

80% below 2 +3 0.005 1.9

micrometres

100% below 10 +3 0.004 2.4

micrometres

100% below 50 +2 0.006 2.5

micrometres

100% below 100 +2 0.006 3.1

micrometres

10% above 100 +1 0.09 3.8

micrometres