BACKGROUND OF THE INVENTION

The present invention relates to powders/granulates, and more particularly colored powders/granulates, and the use of a fluid bed drying apparatus (with a spraying apparatus) for applying a suitable coloring agent to said powders/granulates.

Various fluid bed drying apparatus (with a spraying apparatus) are well- known in the pharmaceutical art [including, for example the Glatt (Model GPCG5) and the Aeromatic (Model S-7/1100L)] and are typically utilized to prepare granulates ("pellets") for use in preparing tablets or powders/granulates for oral suspension.

The spraying apparatus of fluid bed drying apparatus have been used to spray a binder liquid (e.g. starch paste) or coating liquid (e.g waxes, fats and oils) from a nozzle for granulating or coating while they are fluidized by a fluidizing gas introduced from the bottom of the apparatus of a fluid bed machine. The basic design of a typical fluid bed drying machine is center around the product container. The product container is an inverted truncated cone which has a reinforced screen in its bottom. The purpose of the screen is to allow sufficient air flow through the product bed without product passing down through into the inlet plenum, or air handling section. Directly above the product container is a cylindrical deceleration zone called expansion chamber. As air bubbles pass through the product bed, particles are carried upwards into the expansion chamber where the air velocity quickly diminishes to the point where it can no longer entrain particles. The material travels toward the walls of the expansion chamber, drops back into the product container and continue its cycling. At some height in the expansion chamber a nozzle is placed for application of the spraying liquid. The liquid is sprayed at a controlled rate into the randomly fluidized powder.

The application of a colorant by means of the spray apparatus in a fluid bed drying machine has not been previously described.

SUMMARY OF THE INVENTION It has been surprisingly discovered that the use of the spray apparatus in a fluid bed drying machine provides a suitable means of preparing an elegant uniform fine powder having a color appearance of the sprayed excipient which is essentially the same in both solid and reconstituted form. The present invention provides a means of producing a colored excipient with a surprising color intensity and color uniformity with a small quantity of FDC approved color. The present invention includes methods of making colored excipients by means of spray drying of a colorant solution (can be a natural or synthetic FDC color, such as caramel, FDC Blue #1, Blue #2, Yellow #5, Yellow #6 and Red #40) to food and pharmaceutical excipients. DETAILED DESCRIPTION OF THE INVENTION The process of the present invention can be utilized to spray a solution of a colorant (preferably a color approved for use with foods, drugs and/or cosmetics; for example caramel, beta carotene, FDC Blue #1, Blue #2, Yellow #5, Yellow #6 and Red #40), compatible with the excipient(s) to which it is to be applied. The process variables of the present invention include:

1) Atomization air pressure

2) Liquid Spray rate

3) Product temp, inlet temperature 4) Nozzle pore size

5) Nozzle position

6) Batch size and will vary depending upon the particular fluid bed machine utilized and the particle size of the particular excipient (powder/granulate) to be colored. The particle size of the excipient may vary from about 500 to 40 microns, preferably from about 500 to 40 microns. A person skilled in the art can readily determine the appropriate process variables so as to produce an elegant colored product.

The top spray apparatus of the fluid bed drying machine is positioned as low as possible above the bed of the machine in such a manner as to produce a uniform spray pattern.

The process parameters of the present invention, are typically: Spray rate: production scale 200 Gm/min to 3000 Gm/min

Inlet temperature: 60 degree C to 100 degree C

Outlet temperature: 25 degree to 60 degree C

Atomization air: 1 bar to 7 bars, preferably greater than 3 bars

Batch temperature: above 45 degree C

The following Examples further illustrate the subject invention.

Example 1) Pink Electrolyte Powder Formula: Part A: Dextrose USP Anhydrous 3.36 Kg

Sodium Citrate Hydrous USP 490 Gm

Sodium Chloride USP Powder, 150 mesh 195.3 Gm

Potassium Chloride USP Granule 252 Gm

Part B: Aspartame NF Powder 28 Gm

FDC Red #40 Dye 0.35 Gm

Water 1000 Ml

Description of Process: 1) Weigh and screen through a #12 mesh screen all the ingredients.

2) dissolve the red #40 into the water, then suspend aspartame in the colored solution with agitation.

3) To the product container of a Glatt GPC5G fluid bed processor add all of ingredients of Part A.

3) Turn on the turbine, heat the batch until the bed temperature reaches 50 degree C. Start spraying the color/aspartame solution in accordance with the following parameters: Spray rate: 32 Gm/min Atomization air: 3 bar nozzle pore: 1.8 mm inlet air temp: 80 degree

product temp: 48-52 degree C Outlet temp: 36-40 degree C

Nozzle position: lowest (about 10 inches above bed). 4) after spaying all of the liquid, dry the batch to 60 degree C in the fluid bed dryer.

If desired, a bubble gum flavor (e.g. Robertet NV16508; 150 mg/unit dose) can be added to the colored formulation prepared above.

The flavored/unflavored electrolyte formulation can be packaged in unit-of-use packets containing about 6180 mg (each containing about 279 mg. NaCl, 700 mg. Sodium Citrate, 360 mg. KCl, 4800 mg dextrose, 40 mg aspartame and 0.5 mg FDC Red #40). Each packet can be dissolved in about eight ounces of water and taken orally for electrolyte replacement.

Example 2) Pink Bubble Gum Dextrose

Formula:

Part A:

Dextrose USP (Anhydrous) 492.8 Kg

Part B: FDC Red #40 dye 51 Gm

Purified Water 40 liter

Description of Process:

1) Dissolve dye into water. 2) To the Aeromatic S7 (1100L) product container add the

Dextrose [preferably the dextrose having been delumped through a Comil model 196 with #2F083R037/42 screen; impeller number 2F 1601 175 or 2F 1601 221J. 3) Turn on the turbine, heat the batch until the exhaust temperature reaches 50 degree C. Start spraying as the colorant according to following parameters: spray rate: 800 Gm/min

Atomization air: 5-6 bars inlet air temp: 100 degree C outlet air temp: 50 degree C - 60 degree C

Nozzle pore: 1.8 mm nozzle head: triple head

Nozzle position: lowest possible The position of spray arms is such that the nozzle head is at the same height or just below the rolled "V" groves (bottom of the exhaust filter.

10

Note: a dehumidification system is utilized and the dew point allowed to stabilize at about -5 to about -20 degrees C or below.

4) After spraying all of the solution, dry the product

15 65 degree C. in the fluid bed dryer.

If desired, a bubble gum flavor (e.g. Robertet NV16508) and/or aspartame can be added to the pink colored dextrose.

An electrolyte replacement product can be prepared utilizing the pink 20 colored/flavored dextrose of this Example by adding milled salts to an Alma Blender: Sodium Chloride USP Powder 52.9 Kg

Potassium Chloride 68.3 Kg

Sodium Citrate Hydrous USP 132.7 Kg

Aspartame NF Powder 7.6 Kg

25 and 910 KG. of colored/flavored dextrose.

The colored/flavored dextrose is delumped through a Comil Model 196 (with #2F045R031 \37 screen and impeller number 2F 1601 175 or 2F 1601 221).

The salts are premilled by a Comil Model 196 (with #2F024R018\23 screen and impeller number 2F 1601 175 or 2F 1601 221) before blending into the batch for 30 30 minutes.

The electrolyte replacement product can be packaged in unit-of-use packets containing about 6180 mg (each containing about 279 mg. NaCl, 700 mg. Sodium

Citrate, 360 mg. KCl, 4800 mg dextrose, 40 mg aspartame and 0.5 mg FDC Red #40). Each packet can be dissolved in about eight ounces of water and taken orally for electrolyte replacement.

Example 3) Grape Colored Dextrose Formula: Part A:

Dextrose USP Anhydrous 441.3 Kg

Part B: FDC Red #40 55 Gm

FDC Blue #1 18 Gm

Purified water 40 Kg

Description of Process: 1) Dissolve color in purified water.

2) To the product container of a Aeromatic S7 (1100L) add dextrose [preferably the dextrose is delumped through a Comil model 196 with #2F045R031/37 screen].

3) Turn the turbine on, heat the batch to 60 degree C and start spraying as following spray rate : 800 gm min atomization air: 5-6 bars inlet air: 100 degree C outlet air: 50 - 60 degree C nozzle pore; 1.8 mm nozzle head: triple heads nozzle position: lowest possible

4) After all of the liquid is sprayed, dry the batch to 65 degree C. in the fluid bed dryer.

If desired, a grape flavor (e g Florasynth WL-26112, 300 mg/unit dose) and/or aspartame can be added to the grape colored dextrose

An electrolyte replacement product can be prepared utilizing the grape colored/flavored dextrose of this Example by adding milled salts to an Alma Blender Sodium Chloride USP Powder 51 3Kg

Potassium Chloride USP Granule 66 5 Kg

Sodium Citrate Hydrous USP 129 Kg

Aspartame NF Powder 14 7 Kg and 883 KG of colored/flavored dextrose The colored/flavored dextrose is delumped through a Comil Model 196 (with

#2F045R031/37 screen and impeller number 2F 1601 175 or 2F 1601 221) and then added into the blender

The salts are premilled by Comil Model 196 (with #2F024R018/23 screen and impeller number 2F 1601 175 or 2F 1601 221) before blending into the batch for 30 minutes

The electrolyte replacement product can be packaged in unit-of-use packets containing about 6180 mg (each containing about 279 mg NaCl, 700 mg Sodium Citrate, 360 mg. KCl, 4800 mg dextrose, 40 mg aspartame and 0 5 mg FDC Red #40) Each packet can be dissolved in about eight ounces of water and taken orally for electrolyte replacement