FIELD OF THE INVENTION : The invention deals with fast-dissolving or easily chewable oral products containing unpleasant tasting, water-soluble bio-affecting agents, such as ascorbic acid (Vitamin C). The products are comestible units made from compositions containing a blend of microparticles of the bio-affecting agents along with shearform floss particles.

Methods of making the products are also described.

BACKGROUND OF THE INVENTION : Ascorbic acid is exemplary of the generally water-soluble unpleasant-tasting, bio- affecting agents used herein.

Ascorbic acid, a water-soluble vitamin, is used in the prevention or treatment of scurvy, anemia, gum infections, dental caries, and other ailments. As a dietary supplement, doses of 30 mg to 60 mg per day for children and 60 mg per day for adults are recommended.

Ascorbic acid is readily absorbed into the body. However, oral products for administering ascorbic acid have drawbacks. Among these drawbacks is the acid's astringent taste, which tends to lower patient compliance with recommended dosage levels.

Most products on the market do not dissolve quickly in the mouth's saliva, requiring vigorous chewing or taking the products with water. Such products can stay in the mouth for significant periods of time, resulting in exposure to the undesirable taste of any unpleasant tasting bio-affecting agents therein for significant periods of time.

There is a need for oral products of unpleasant tasting bio-affecting agents, e. g., ascorbic acid, which dissolve quickly in the mouth with or without chewing and minimize the patient's perception of the agent's unpleasant taste.

SUMMARY OF THE INVENTION : Comestible units for the oral delivery of water-soluble, unpleasant-tasting active

agents are made from a composition containing the following components : (a) optionally coated microparticles containing one or more unpleasant-tasting agents ; (b) saccharide-based shearform floss particles ; and (c) suitable excipients selected from lubricants, flavor enhancers, glidants, fillers and colorants.

The method of making these units comprises combining and shaping components (a) - (c), as follows : (1) preparing saccharide-based shearform floss particles, (2) contacting them with a crystallization enhancer, (3) blending the product of step (2) with microparticles containing unpleasant tasting bio-affecting agent (s) and excipients, and (4) shaping to form comestible units.

Applicants believe that in preferred embodiments, the combination of (I) the taste- masking/improved stability coating on the microparticles of unpleasant tasting active agent with (II) the pleasing taste, or sweetness, of the floss particles renders the bio-affecting agents'unpleasant taste almost undetectable, so that tablets containing them have an acceptable taste.

ADVANTAGES : Comestible units made using the compositions and methods of the invention generally dissolve in the consumer's mouth instantaneously, i. e., in 10 seconds or less, based on organoleptic testing, without the need for chewing or drinking water. The saliva in the mouth provides sufficient liquid to cause quick dissolution. The use of fast- dissolving units assures that the water-soluble vitamin or other unpleasant tasting bio- affecting agent (s) spend a minimal amount of time in the mouth, so that their unpleasant taste is barely detected and patient compliance improves.

In another embodiment, the comestible units made using the compositions and methods of the invention generally dissolve in the consumer's mouth upon gentle chewing, (i. e., in 10 seconds or less, based on organoleptic testing, without the need for drinking water).

Also, the optional presence of one or more coatings on the microparticles of agent (s) and the pleasant flavor of the floss and other excipients tends to make any unpleasant taste less noticeable.

DETAILED DESCRIPTION OF THE INVENTION : The invention relates to novel comestible units and the method of making them.

Unless otherwise noted, all parts and percentages recited are weight percentages, based on total composition weight.

THE COMPOSITIONS : Compositions from which the units are made have three principal components : (a) coated or uncoated microparticles of bio-affecting agents, (b) saccharide-based shearform matrix particles, and (c) one or more excipients.

When present, the coatings on the microparticles provide improved stability, taste- masking, or both.

A. Microparticles of Bio-affecting Agents The bio-affecting agents used in the invention include unpleasant tasting water- soluble vitamins or other water-soluble active agents, i. e., agents having biological activity.

Suitable agents include : ascorbic acid, ferrous fumarate, folic acid, niacinamide, pyridoxine hydrochloride, riboflavin, thiamine mononitrate, Vitamin A acetate, Vitamin B,2, Vitamin D (e. g., Vitamin D3) and Vitamin E and its acetate. Ascorbic acid and Vitamin D, along with pharmaceutically acceptable derivatives of same and combinations with other bio-affecting agents, e. g., Vitamin D with calcium carbonate, are preferred.

The microparticles used in the invention are generally particles of about 0. 1 to about 600 microns in size. They need not be coated.

The microparticles preferably have one or more coating layers, with each layer containing one or more materials selected from : mono- and diglycerides ; starch ; or cellulose derivatives, e. g., ethyl cellulose. Other coating materials which impart taste- masking, improved stability, or other properties can be used.

Coated microparticles generally contain from about 50% to about 100%, preferably about 60%, of active agent (s), with the remainder being one or more coating (s).

Preferred coated ascorbic acid particles include"DESCOTE ASCORBIC ACID 60%"sold by Particle Dynamics of St. Louis, MO.

Useful ascorbic acid particles may have no coatings, i. e., be 100% acid. These include"Ascorbic Acid USP 100%"from BASF, Mt. Olive, NJ.

The particles may have low coating levels, such as those bearing about 2% to 4%, preferably 2. 5%, ethyl cellulose coatings. The product sold as Ascorbic Acid 97. 5% by Roche Vitamins of Paramus, NJ is useful.

The particles may be granulated with starch and lactose. The product sold as Ascorbic acid 90% C-90 by Roche Vitamins of Paramus, NJ is useful.

Spherical microparticles, e. g., microspheres, are useful in the invention. However, they are not required. Accordingly, suitably sized microparticles having irregular and/or non-spherical shapes can be used.

While"ascorbic acid"is referred to herein, other bio-affecting agents, as well as mixtures containing same, may be used.

B. Shearform Floss Particles Useful shearform floss particles are particles described in U. S. Applications SN 08/915, 067 and SN 08/915, 068, both filed August 20, 1997, and assigned to Fuisz Technologies Ltd.

Preferred flosses are termed"unifloss"particles. They contain one or more saccharides and two or more sugar alcohols. Suitable particles are made from compositions containing about 80% to 85% sucrose, about 5% to 20% sorbitol, about 5% to 25% xylitol, and about 0 to 10% polyoxyethylene sorbitan fatty acid esters (e. g., TWEEN 80).

Other ingredients, such as one or more of the excipients discussed at section C, infa, may be used as floss constituents. The floss particles dissolve very quickly in the mouth, releasing the sweeteners therein almost instantaneously.

The flosses are made by subjecting blends of sugar (s) and sugar alcohol (s) to flash flow processing in a suitable spinning device, such as that described in U. S. Patent Application Serial No. 08/854, 344, filed May 12,1997.

The spun floss is chopped for about 0. 5 to about 5 minutes, preferably about 1 to 2

minutes, in the presence of 0% to about 2%, preferably about 2%, lactose, using a Littleford Mixer or other suitable mixing/grinding device. The chopped floss particles generally range in size from about 1 to about 1, 000 microns.

Thereafter, the floss is contacted with about 0. 1% to about 10% ethanol or other suitable crystallization enhancer (s). Preferably, ethanol is used in amounts ranging from about 0. 5% to about 5. 0%. The floss is then treated to remove excess ethanol.

Other useful crystallization enhancers include surfacants, such as Tween 80, which are used at concentration levels of about 0. 001% to about 1. 00%.

The amount of floss must be such that the fast dissolving properties and pleasant taste associated with its use are realized in the final comestible units.

C. Excipients A wide variety of excipients conventionally used in comestible units, especially those employed in food and pharmaceutical formulations, can be employed in the invention. They include lubricants, flavors, flavor enhancers (e. g., sweeteners), glidants, fillers, colorants, perfumes and the like.

Lubricants are generally employed in amounts of about 0. 05% to about 5. 0%, with 0. 3% to about 0. 8% preferred. Adipic acid, a preferred lubricant, also functions as a flavor enhancer and a salivation enhancer. Another preferred lubricant is sodium stearyl fumarate. Magnesium stearate is a preferred lubricant for the chewable comestible units.

It is preferred that the lubricant particles be milled to #200 mesh size before they are added.

Flavor enhancers are present in amounts of about 1% to about 10%. Typical flavor enhancers include sweeteners, e. g., mannitol, monoammonium glycyrrhizinate (MAGNASWEET 100 of Mafco Worldwide Corp. , Camden, NJ) and the like. Mixtures can be used.

Flavors include those that are perceived as orange, lemon, fruit punch, or whipped cream flavors and the like. Mixtures can be used.

Conventional colorants for foods and pharmaceuticals, e. g., FD&C Yellow #6 Lake and others can be used. Mixtures are operable.

Glidants, such as fumed silica (e. g., SYLOID 244FP) or talc, are generally used at

levels of about 0. 05% to about 2. 0%.

The following table gives quantities for the ingredients typically used in the invention.

Parts by Weieht Broad Preferred Most Ranze Range Preferred A. Microparticles of Active Agents 10-70 30-60 30-50 B. Shearform Floss Particles 30-90 40-70 45-65 C. Excipients 0-20 20-10 4-10 THE PROCESS : The comestible units of the invention are made by mixing the microparticles, the floss, and the excipients, then shaping the mix, e. g., via compression, into comestible units, preferably tablets.

The overall process involves : (1) preparation of the floss particles ; (2) mixing microparticles of active agent (s) and excipient (s) therewith ; and (3) shaping.

Optionally, the microparticles are coated, using conventional coating techniques prior to step (2).

(1) Preparation of the Floss Particles The floss particles are prepared using procedures described in U. S. Patent Application Serial No. 08/915, 068, filed August 20,1997.

One highly useful type of floss is made as follows : A mixture of sucrose, sugar alcohols and TWEEN 80 is prepared and spun into a floss at about 3, 500 to 4, 000 rpm (50 to 60 Hz) using a suitable spinning device. The floss was chopped in a higher shear mixer/chopper for about 0. 5 to 2. 0 minutes.

About 0. 5% to 5. 0% of ethanol, or another crystallization enhancer, is then contacted with the surfaces of the floss particles via spraying or other suitable methods to initiate crystallization. After contacting with the crystallization enhancer, the floss is

treated to remove excess enhancer and is optionally milled or screened. It is then used in making tablets or other comestible units.

(2) Mixing the Bio-Affecting Agent Particles and Excipients with the Floss Particles In general, any mixing technique can be used which provides a uniform blend of the ingredients while maintaining the structural integrity of the optionally coated microparticle component and the floss component.

The ingredients are typically blended in a Littleford Mixer. They are mixed at speeds of about 60 to about 140 rpm for about 5 to about 15 minutes.

Alternatively, the ingredients may be mixed with a V-blender or other suitable mixing device.

(3) Tableting The blends are tableted using a standard pharmaceutical tablet press, e. g., a Kilian T-200 tablet press.

Tablets are made to thicknesses of about 3 to about 8 millimeters, with 4. 5 to 5. 5 millimeters preferred.

The fast dissolving tablets are compressed to hardnesses of about 0. 5 to about 6. 0 pounds, with about 1. 0 to about 3. 0 pounds preferred. The chewable tablets are compressed to hardnesses of about 6. 0 pounds to 20. 0 pounds, with about 10. 0 to about 12. 0 pounds preferred.

The preparation of tablets is described above. However, the compositions and methods of the invention can also be used to make other comestible units. It is preferred that the units be orally ingestible, e. g., tablets, lozenges, and the like.

EXAMPLES : The following examples illustrate the invention.

Example 1 A floss containing 78. 25% sucrose, 11. 00% sorbitol, 10. 0% xylitol and 0. 75% Tween 80 was prepared as follows : The mix of ingredients (2 kg) was spun into floss at 3600 rpm (60Hz) using a 5" spinning head in the device described in U. S. Serial No. 08/854, 344, filed May 12,1997.

The floss was chopped in a high shear mixer/chopper for 2 minutes.

The chopped floss was treated with 0. 5% ethanol and allowed to dry for 90 minutes.

The ethanol-treated floss particles were then used in the following formulation : Component Weight (%! DESCOTE 60% Ascorbic Acid 30. 77 Floss 63. 00 Milled Adipic Acid 2. 00 Mannitol 3. 00 Natural Orange Flavor 1. 00 SYLOID FP244 0.10 FD & C Yellow #6 Lake 0. 10 MAGNASWEET 100 0. 03 TOTAL 100. 00 The ingredients were mixed in a Littleford Mixer for 10 to 15 minutes. The mix was tableted on a Kilian T-200 press to yield 0. 65g tablets of 2 pounds hardness, and 3. 06% moisture content, having thicknesses of 4. 5mm to 5. 5mm.

Example 2 Using the floss particles and the general procedure of Example 1,250mg tablets of ascorbic acid, weighing 1 gram each, were made from the following formulation : Component Weight (%! DESCOTE 60% Ascorbic Acid 43. 75 Floss 50. 20 Citric Acid 0. 70 Mannitol 3. 00 Natural Orange Flavor 1. 50 SYLOID FP244 0. 25 FD & C Yellow #6 Lake 0. 10 Sodium stearyl fumarate 0. 50 TOTAL 100. 00

Organoleptic tests, used to indicate dissolution, showed that the tablets of Examples 1 and 2 dissolved in the mouth, without chewing or drinking water, in 5 to 10 seconds.

Example 3 For a 500mg chewable tablet of ascorbic acid, the floss was prepared and chopped using the general procedure of Example 1. The chopped floss was treated with 4. 0% ethanol and allowed to dry for 90 minutes. The 4. 0% ethanol-treated floss particles were then used in the following formulation.

Component Weight (%! Descote 60% Ascorbic Acid 50% Floss (4% ethanol-treated) 44. 15 Mannitol 3. 00 Natural Orange Flavor 1. 50 Syloid 244 FP 0. 25 Magnesium Stearate 1. 00 FD&C Yellow No. 6 Aluminum Lake 0. 10 The ingredients were mixed in a Littleford Mixer for 10 to 20 minutes. The mix was tableted on a Kilian T-200 press to yield 1. 75g tablets of 11 pounds hardness, having a thickness of 6. 5 to 7. 5 mm.

Example 4 A chewable calcium carbonate/vitamin D combination product was made as follows : Floss Formulation Sucrose 78. 25% Sorbitol 11% Xylitol 10% Polysorbate 80 0. 75% The sucrose, sorbitol, xylitol, and Polysorbate 80 were blended in a Littleford FKM600 mixer for 10 minutes. The blend was then subjected to Shearform processes at

60Hz and 250°C temperature using the 5"Pharma processing head. The floss manufactured was chopped in the Littleford FKM600 mixer with 2% lactose and treated with ethanol (7% of the floss). The floss was dried at 45°C for 150 minutes. the floss was then milled/sieved through a 20mesh screen using a Fitzmill or Apexmill.

Tablet Formulation Calcium Carbonate Destab SE 95% 47. 85% Vitamin D3 0. 16% Floss 48. 48% N&A Lemon Flavor 1. 00% Citric Acid 1. 00% Syloid 244FP 0. 50% Magnesium Stearate 1. 00% The calcium carbonate was blended with vitamin D3 for 15 minutes at speed 1 in a Diosna 600. The milled floss was added and blended further for 10 minutes. The flavors and flow agent were added and blend for additional 7 minutes. The blend was compressed on a rotary tablet press at 85N hardness, 2. 75g tablet weight, 19mm concave round or 19mm flat-faced radial edge tooling.

Example 5 Vitamin C EZ Chew 500mg Tablet The floss was prepared and chopped using the general procedure of Example 1. the chopped floss was treated 7. 0% ethanol and allowed to dry for 150 minutes at 45°C. The 7. 0% ehanol treated floss was then used in the following formulation.

Component Weight Coated Ascorbic acid (97. 5%) 37. 61% UniFloss (7% ethanol) 53. 54% Orange flavor 2. 00% Mannitol Powder 5. 00% Acesulfame potassium 0. 10% Syloid 244 FP 0. 50%

Magnesium Stearate 1. 00% Color 0. 25% 100% The ingredients were mixed in a Littleford Mixer for 10-20 minutes. The mix was compressed on a Kilian T-200 press to yield 1. 5g tablets at 80N-1OON hardness using 16. 5 flat faced tooling. Tablet includes 10% excess ascorbic acid of label claim.

Reasonable variations, such as those which would occur to a skilled artisan, can be made herein without departing from the scope of the invention.