Colored Medicinal Tablet, Natural Color Pigment and Method for Using the Pigment in Coloring Food, Drug and Cosmetic Products

This invention relates to dry edible, natural color pigments that at the present time do not require certification by the Food and Drug Administration since they utilize natural ingredients. These natural dye pigments simulate and are substitutes for FD&C and D&C lakes that are used for coloring food, drugs and cosmetics. Such lakes, and the color coating of pharmaceuticals, confectionery, and food, are discussed in Colorcon Incorporated U.S. Pat. Nos. 3,909,284 issued Sept. 30, 1975, and 3,576,663 issued Apr. 27, 1971, and the references cited therein, all of which are incorporated herein by reference.

With the Food and Drug Administration re-examining its listed and approved FD&C and D&C lakes and withdrawing approval, considering withdrawing approval or introducing restrictions and new regulations for such lakes, there has been a demand in the food, drug and cosmetic industries for pigments that simulate closely and may be substituted for any lakes that the Food and Drug Administration may de-list or restrict. Since such de-listing may occur without very much advance notice, it is also desirable to provide a suitable substitute that may be used immediately, and that does not require submission to the Food and Drug Administration for certification.

Natural dyes such as curcumin and grape skin extract have been used for a very long time. However, they have not been used successfully to form pigments useful for coloring food, drug and cosmetic products. For example, it is not practical to use them to make the lakes employing an alumina hydrate slurry in accordance with the method of U.S. Pat. No. 3,909,284 since at best only very weak colors are obtained. Unexpectedly, the use of natural dyes together with the substrate powders of the invention and dyeing aids produce excellent pigments for their intended purpose. Not only are the pigments of high intensity but they do not bleed in water. Further, the invention has an advantage not heretofore achieved with natural pigments in that FD&C and D&C lakes can be closely simulated.

A pharmaceutical tablet has a substrate containing a medicament and may be coated, said coating including a pigment comprising a natural edible powder dyed with an edible natural dye. The pigment for coloring the tablet, or other pharmaceutical products, as well as food and cosmetics, is made by suspending a natural water insoluble edible powder in an aqueous vehicle and dyeing the suspended powder with an edible natural dye. The liquid is removed to obtain the dry pigment powder of the invention which then can be suspended in a suspending medium and used for coating products to be colored such as food, drug and cosmetic products.

In carrying out the method of the invention, a natural water insoluble edible powder is suspended in a liquid. Exemplary of the powders are water insoluble powders of cellulose, microcrystalline cellulose, cellulose derivatives, for example, ethyl cellulose, and starch and starch derivatives.

Advantageously the particles of powder will be in the range of from about 1 to about 50 microns. While the amount of powder for a given amount of water will vary widely, it is preferred that the powder be from about 2% to about 15% (W/V).

Advantageously, the liquid suspending medium may be water, or an aqueous solution, for example, an acid or a best to achieve a specific pH.

The suspended powdered substrate is then dyed with an edible natural dye, for example, curcumin, turmeric, or an anthocyanin such as those contained in commercial grape skin extract. The dye may be added directly to the liquid in which the powder is suspended or may be first placed in a solvent to form a dye solution which is then added to the suspended powder. Typically the solvent will be water but other solvents such as, for example, methyl alcohol, or ethyl alcohol may be used.

Advantageously an agent is employed to fix the dye onto the powder. Exemplary of these agents are metal salts such as sodium chloride, aluminum chloride, and aluminum sulfate. Inorganic acids such as, for example, hydrochloric acid may also be employed. Except in the case of the inorganic acids, the fixing agent may be in an amount equal to from about 0.1 to about 10% by weight of the powder in suspension. Where the acidity of the suspension is relied upon to fix the dye to the powder through the use of an inorganic acid, it is preferred to have the pH from about 1.0 to about 5.0.

The dye per se or in solution is advantageously added to the suspension of the powder slowly while the suspension is stirred. The stirring is continued after all of the dye has been added for a sufficient period of time to fix the dye to the powder, generally from about 1 to 2 hours, depending on the particular dye. The suspension is then filtered and the recovered powder washed with water and dried to obtain the powdered natural dye pigment which has a particle size in the range of from about 1 micron to about 50 microns. While the powdered pigment can be air dried it is advantageous to carry out the drying in a mechanical convection oven at an elevated temperature of, for example, from about 40.degree. C. to about 50.degree. C.

Following the above method, FD&C and D&C lakes can be closely simulated using one or a mixture of pigments.

A pigment made in accordance with the above method is normally placed in a suspending medium to form a stock suspension which is further diluted prior to application to the product to be colored. Typically the suspending medium is an aqueous medium containing simple syrup U.S.P. and the pigment is present in an amount of from about 10% to about 25% (W/V). The dilution before coloring the selected product may be carried out with any standard syrup, for example, simple syrup, U.S.P., the amount of dilution depending upon the intensity of color desired. Advantageously the diluted suspending medium contains pigment in the amount of from about 1% to about 5% (W/V). Then, for example, tablets are readily coated by placing the tablets in a coating pan and rotated. The diluted stock solution containing the pigment is added in a quantity sufficient to cover the tablets. The covered tablets are dried and the operation repeated until the tablets have the desired color.

The invention will be further clarified by the following specific examples:

100 g of finely powdered microcrystalline cellulose is suspended in 1800 ml of water. 50 g of a 30% (W/V) aluminum chloride in solution in water is added to the cellulose suspension and the suspension heated to 50.degree. C. 10 g of curcumin is dissolved in 800 ml of water containing 3.2 g of sodium hydroxide to form a dye solution. The dye solution is then added in a fine stream to the microcrystalline cellulose suspension while stirring the suspension rapidly. Stirring is continued until all the curcumin is attached to the microcrystalline cellulose particles (60 minutes). The slurry is filtered, washed with water to remove any free dye not attached to the cellulose particles, and dried at 50.degree. C. in a hot air oven to obtain a powdered natural dye pigment that simulates and may be substituted for FD&C Yellow No. 5 Aluminum Lake.

100 g of finely powdered cellulose is suspended in 1800 ml of water. 15 g of aluminum sulfate powder is dissolved in the cellulose suspension and the suspension is then heated to about 50.degree. C. 5 g turmeric is dissolved in 800 ml ethyl alcohol forming a dye solution. The turmeric dye solution is then added in a fine stream to the cellulose suspension while stirring the suspension rapidly. Stirring is continued until all the turmeric is attached to the cellulose particles (60 minutes). The slurry is filtered, washed with water and dried at 50.degree. C. in a hot air oven, to obtain a powdered natural dye pigment of yellow-orange color.

100 g of finely powdered cellulose is suspended in 1800 ml of water. 10 g of water soluble annatto powder is dissolved in 800 ml of water and added to the cellulose suspension. The mass is heated to boiling and 25 g of sodium chloride is added to aid in the dyeing of the cellulose. The suspension is stirred for ten minutes, filtered, the cake washed with water and then washed with dilute acetic acid. The cake is then dried at 50.degree. C. in a hot air oven to obtain a powdered natural pigment of red-orange color suitable for substitution for FD&C Yellow No. 6 Aluminum Lake.

100 g cellulose is suspended in 1500 ml of water at room temperature. 25 g of a grape skin extract (anthocyanins) is added and the pH adjusted to 1.2 with hydrochloric acid. The suspension is then stirred for one hour, filtered and washed with pH 1.2 water. It is then air dried at room temperature to obtain a powdered natural pigment of bluish-red appearance.

100 g of finely powdered corn starch is suspended in 1800 ml of water. 50 g of a 30% (W/V) aluminum chloride solution in water is added to the corn starch suspension and the suspension heated to 50.degree. C. 10 g of curcumin is dissolved in 800 ml of water containing 3.2 g of sodium hydroxide to form a dye solution. The dye solution is then added in a fine stream to the corn starch suspension while stirring the suspension rapidly. Stirring is continued until all the curcumin is attached to the corn starch particles (60 minutes). The slurry is filtered, washed with water, and dried at 50.degree. C. in a hot air oven to obtain a powdered natural dye pigment that simulates and may be substituted for FD&C Yellow No. 5 Aluminum Lake.

Pharmaceutical tablets are made in accordance with the invention by placing pharmaceutical forms comprising a substrate containing a medicament into a coating pan, making a color dispersion by mixing 15 g of natural dye pigment of Example I and 10 g of titanium dioxide with 75 g of simple syrup, U.S.P., further diluting the dispersion by adding 900 g of simple syrup, U.S.P., rotating the coating pan, repeatedly adding portions of the diluted color dispersion to the coating pan to coat the substrates, and drying and polishing the coated tablets.