MXPA96006372A

MXPA96006372A - Edible unit of rapid dispersion and produ

Info

Publication number: MXPA96006372A
Application number: MXPA/A/1996/006372A
Authority: MX
Inventors: C Fuisz Richard; E Battist Gerald; L Myers Garry; R Cherukuri Subraman
Original assignee: Fuisz Technologies Ltd
Priority date: 1994-06-14
Filing date: 1996-12-13
Publication date: 1997-12-01

Abstract

The present invention relates to a method of preparing fast dissolving edible units, comprising: a) subjecting to flow processing by runoff a feedstock containing a carbohydrate capable of undergoing processing by flow by runoff in the absence of a solution for provide a matrix of shear stress, b) initiate the crystallization of said matrix in the form of shear, c) form compact micro-particulates, capable of flowing, by combining an additive with said matrix in the form of shear stress; ) compacting said micro-particulates resulting from step c), comprising at least partially crystallized shear form matrix, to form said unit

Description

EDIBLE DISPERSION AND PRODUCT COMFORT UNIT BACKGROUND OF THE INVENTION The present invention relates to the field of manufacturing edible dosage units, such as tablets, which disintegrate rapidly in the mouth. The dosage units in the form of tablets are usually prepared by compressing a formulation containing a medicinal substance or medicament and other ingredients, such as excipients selected by properties that facilitate the production and use of the tablet. There are currently three basic methods known for preparing granulations for tablets. These are wet granulation, dry granulation and direct compression. Both wet granulation and dry granulation involve the formation of an agglomerate for feeding into a die cavity. Direct compression usually involves compressing a physical powder mixture of an active ingredient with suitable excipients. The preparation of formulations for tabletting by wet granulation is the oldest and still the most widely used method. Wet granulation involves many steps, including: grinding medicines and excipients, mixing the ground powders, preparing the binder solution, mixing the binder solution with the powder mixture to form a wet mass, coarsely sieving the wet mass using 6-12 mesh sieves, drying of wet granules, sieving of dry granules through a 14-20 mesh screen, mixing of granules sieved with lubricant and disintegrant, and compression of the tablet. Wet granulation is an expensive process because it requires many processing steps and involves considerable material handling equipment. Consequently, the process requires both energy and considerable space, which must be controlled environmentally. Generally, free water and heat are harmful to the active ingredient. Wet granulation processes involve water and / or heat. Therefore, it is desirable to provide a method for making tablets in the substantial absence of heat and free water in order to improve the survival of active ingredients incorporated in the tablet. Dry granulation refers to the granulation of a powder mixture by compression without the use of heat and solvent. Dry granulation is used when wet granulation is not available because the medicine is sensitive to moisture or heat. Two methods are used for dry granulation. One method is deformation, where the powder is pre-compressed in a press for heavy duty tablets, and the resulting tablets or pieces are milled to give the granulation. The other method is pre-compression of the powder with pressure rollers using a compactor. Dry granulation has many disadvantages. It requires a press for specialized tablets, heavy-duty, to form the piece; does not allow a uniform distribution of color as can be achieved with wet granulation, where the pigment can be incorporated in the binder liquid; The press roller press can not be used with insoluble drugs because this can slow the rate of dissolution; and the process tends to create dust, thereby increasing the potential for cross-contamination. Direct compression tabletting has the least amount of steps. Direct compression is used in a process by which tablets are compressed directly from physical powder mixtures of the active ingredient and suitable excipients (including fillers, disintegrants and lubricants), which are included in the mixture to provide uniform flow into the cavity of Die and form a solid, firm compression tablet. Pre-treatment of the physical powdered mixtures by wet or dry granulation processes is not necessary. Although it has considerably fewer steps than any of the wet or dry granulation processes, direct compression also has many technological limitations. These limitations mainly include obtaining sufficient flux, and obtaining particle binding to form a strongly compressed tablet. The low dose drugs are difficult to physically mix, ie the uniform distribution of the drug is not easily achieved and sometimes separation of the physical mixture occurs during the compression stage. High-dose medications do not lend themselves to direct compression due to poor flowability and poor compressive capacity. A typical example would be some of the anti-acid drugs, such as aluminum hydroxide and magnesium carbonate. When direct compression is used, the choice of excipients is extremely critical. It is desirable that when direct compression is used, the fillers and binders have both compressibility and flowability. In addition to compression failures, the direct compression process also has disadvantages in the area of physical mixing. Direct compression physical mixtures are subject to separation of the mixture in physical post-mixed handling steps. The differences in particle size, due to differences in density between the medicament particles and the excipient, can also lead to separation of the mixture in the hopper or feed frame in the tablet press. A disadvantage of all the processes of the prior art is the production of fine particles, usually associated with the manufacture of compression tablets. In the prior art, the preparation of particles for tablet formulation by compression results in a conspicuous amount of fine particles, ie very small particles in the order of 150 microns and less. These fine particles can interfere with the operation of the apparatus for feeding tableting machines as well as the operation of the tabletting machines. Often, it is necessary to drive the production of tablets in a facility that is environmentally controlled to eliminate or reduce fine particles. This raises the cost of producing the tablets. Moreover, a percentage of the uncompressed particulate material is lost during production because there are fine dispersed particles that can not be re-captured, and because some of the fine particles can not be recovered or recycled. In order to overcome the disadvantages associated with the prior art discussed above, technology has been developed by the assignee of the present and of the United States patent application Serial No. 194,682, filed on February 10, 1994. This case discloses a unique process in which compressed tabletting can be carried out in a simple and precise manner by "melting and compressing" steps. Fusion is achieved by flow-through processing of the tablet ingredients to provide shear-form matrix masses that are subsequently compressed to form edible compression units. This process includes advantages of wet and dry granulation and direct compression, but does not have the disadvantages associated with these prior art processes. In another request from the United States of the same transferee (which has attorney's file No. 447-105), filed on the same date as the request serving as priority claim for this, a rapid unit dosage is disclosed dissolution and a preparation and an apparatus for making the same. The method disclosed in such a case includes mixing matrix material in an uncured shear with an additive, followed by tamping the resulting mixture to form a dosage unit. The tamped unit is subsequently cured by exposure to controlled environmental heat, humidity and pressure. Dr. Fuisz also has different patents that refer to other unique means of delivery. For example, in U.S. Patent No. 4,855,326, Dr. Fuisz discloses a fiber form of drug carrier product that can be compacted to form a sheet-like body. However, he warns that the compact body can not be too tight for fear of breaking the fibrous mass. There is no indication of forming a compressed tablet as a medicinal dosage form. Similarly, in U.S. Patent No. 4,873,085, a spun fibrous cosmetic is disclosed, as well as a compacted form of sugar fibers to form a sheet-like body that can be handled more easily. There is no indication of forming a compressed tablet. In U.S. Patent No. 4,997,856, a wafer-like structure is disclosed in which a medicament is distributed in or through spun fibers which are then cut by passing them through a conventional "food mill" (mill). Hobart burgers). The housed volume of the final product is less than 30%, and preferably less than 15%, of the yarn volume as it is rotated. There is no mention in the disclosure of this patent of the formation of a compressed tablet. The use of spun fibers, compacted in the same sense as the aforementioned patents is also described in U.S. Patent Nos. 5,034,421 and 5,096,492. None of these disclosures suggests the formation of a compressed tablet. Although the methods described above in the application identified in Case 447-105 disclose a technique for making a rapidly dissolving dosage unit, none of the other methods provides a technique for forming a dosage unit that rapidly disintegrates in the mouth of the patient. consumer, but which can be conveniently manufactured for shipment and sale. Therefore, it is an object of the present invention to provide another method for preparing a dosage unit that rapidly disintegrates in the mouth. Other and additional objectives will be foreseen by the technicians in the matter, in view of the following description. SUMMARY OF THE INVENTION The present invention is a method of preparing an edible unit that rapidly disperses in the mouth of the consumer. The method includes initiating the matrix crystallization in a shear form either before or after combination of the matrix in shear form with an additive to form compact, flowable microparticles. The combination, which includes at least partially crystallized shear form matrix, is then compacted to form the edible unit. Preferably, a crystallization / ligation promoter is used to improve the formation of compact, flowable microparticles. The crystallization / ligation promoter can be selected from the group consisting of an alcohol, such as ethanol, polyvinylpyrrolidone and a combination thereof. The promoter can also be a surfactant. The surfactants can be added to the feed material used to form the matrix. Alternatively, polydextrose can be used as a promoter by inclusion in the feed material. In one embodiment, promoter and drug are combined with the matrix in shear form. The additive portion of the mixture preferably includes an active ingredient. The shear force form matrix can be prepared by flow-through processing of feed material, which includes saccharide-based material as a carrier component. Sucrose is a preferred carrier, and may be combined with other carrier components based on saccharides such as dextrose, and sugar alcohols, such as sorbitol, mannitol, etc. The feedstock may also include a crystallization improver such as a surfactant, for example Tweens, Spans, etc. In order to form the edible unit, an average compression force can be used without fear of affecting the disintegration capacity of the unit. The compression force does not need to exceed ten (10) strong Cobb units ("SCU"), and preferably does not exceed average compression forces of between six (6) and eight (8) SCUs. In some embodiments, a low compression force may also be used. In any case, tablets produced according to the invention can be made of low density and easily disintegrated. Another method of identifying the compression force required to mold uncured matrix according to the present invention is by identifying the density resulting from the compaction. The product of the present invention should be compacted at a density of no more than about 1.2, and preferably no more than about 0.8. In a more preferred form of the invention, the active ingredient is an anti-acid and the crystallization / ligation promoter is ethanol. It has also been found that when calcium is included as an active ingredient, the release characteristics of the dosage unit are extremely favorable. In fact, the unit can actually be used as a calcium supplement due to its high calcium release characteristics. In the case of pharmaceutical products, it has been found that pharmaceutical products are not "tied" with the components of the dosage unit. Consequently, pharmaceutical products can be made available to the bio-systems for which they have been administered. Another type of additive that can be used in the present invention is an effervescent disintegrating agent. The term "effervescent disintegrating agent (s)" includes gas releasing compounds. Preferred effervescent agents release gas by means of chemical reactions that take place upon exposure of the effervescent disintegrating agent to saliva in the mouth. The agent or agents can be included in various forms in the units of the present invention. First, the agents can be incorporated into the matrix by mixing with the feed-li material before processing by flow-through. Alternatively, all the effervescent agent can be mixed with the matrix in a shear form after it has been produced by flow-through techniques. As yet a third possibility, a part of the agent can be included in the feedstock that is processed by runoff flow while the other part of the agent can be incorporated after the runoff flow processing. In any case, the effervescent disintegrating agent provides rapid and controlled disintegration of the tablet when placed in the mouth, and provides a positive organoleptic sensation by the effervescent action of the mouth. The texture, velocity and disintegration sensation can be adapted especially for use by children in combination with the taking of one or more medicaments contemplated for use in the present invention. The present invention also includes a composition for delivering an active ingredient, wherein the active ingredient is incorporated into a crystalline structure based on saccharides, molded. The composition also includes the saccharide-based structure having a bi-dimensionally stabilized crystalline sugar. The sugar is produced by forming a crystalline sugar framework from an external portion of a sugar mass in the form of an amorphous shear, and subsequently converting the remaining portion of the mass into a substantially crystalline structure in a complete form. The product is preferably monodisperse and preferably also microcrystalline-flax. For definitions relating to "monodisperse" and "microcris-talin", as well as other definitions relating to the compositional aspects of the present invention, reference is made to U.S. patent application Serial No. 08 / -133,669, filed October 7, 1993, which is incorporated herein by reference. The shear-form mass may also include an additive that is co-crystallized in a crystalline product. The amorphous shear-shaped mass is substantially bar-shaped, and has two dimensions lying in a cross-sectional plane of the bar. The other dimension extends along a linear axis of the bar. Preferably, the structurally stabilized, monodisperse cross section does not exceed 50 μm, and preferably does not exceed 10 μm. Yet another manifestation of the present invention is a method of administering an active ingredient to a human host. The method includes ingesting a rapidly dissolving edible unit prepared by the method of the present invention. The next step requires the host to retain the rapid dissolution unit in the oral cavity for a sufficient time to contact the unit with water while it is in the oral cavity. Finally, the human host introduces water to the oral cavity, while the unit is retained in it, to improve the dissolution of the dosage unit. As a result of the present invention, a rapidly dispersible edible unit can be manufactured for shipment and sale to consumers. The method of the present invention is such that manufacturing can proceed on a continuous basis. As the agglomerate can be compacted with average compaction forces, a unit can be formed that is durable and can withstand the handling associated with packing and dispensing. Moreover, the dispersion capacity of the unit is perceived as almost instantaneous. Consequently, the consumer does not experience unpleasant effects of unpleasant ingredients that remain in the oral cavity. These and other advantages of the present invention will be appreciated from the detailed description and the examples indicated therein. The detailed description and the examples increase the understanding of the invention, but are not intended to limit the scope of the invention. BRIEF DESCRIPTION OF THE DRAWINGS Preferred embodiments of the invention have been selected for purposes of illustration and description, but are not intended in any way to restrict the scope of the present invention. Preferred embodiments of certain aspects of the invention are shown in the accompanying drawings, where: Figure 1 is a schematic representation of the ingredients before forming compact, flowable microparticles.; Figure 2 is a schematic representation of microparticles formed from the mixture shown in Figure 1; and Figure 3 is a schematic representation of the compaction of microparticles in an edible unit according to the invention. Detailed Description of the Invention The present invention is a method of making edible units that rapidly disintegrate in the mouth of the consumer. The units produced according to the present invention disintegrate almost instantaneously. However, these units or tablets are capable of being manufactured so that they can be handled for packaging and distribution without deterioration of the integrity of the edible units. In the past, edible units such as tablets have been mainly made by compressing the feedstock under extremely high pressure in order to provide the necessary hardness for handling required during packing and dispensing. Accordingly, the prior art tablets thus produced are limited in that their high density reduces the ability to make them rapidly disintegrable in the mouth. The high density packing resulting from the high compression prevents disintegration and wetting of the inner portion of the tablet. This aspect of the prior art has been improved by the technology disclosed in United States Patent Application Serial No. 194,682, filed on February 10, 1994. Similarly, another method of overcoming these and other methods has been disclosed. difficulties in the United States patent application identified as case 447-105, referred to above. However, as a result of the present invention, a significant step forward has been achieved in the field of the preparation of edible units that disintegrate very quickly in the mouth. In fact, the tablets produced by the present invention disintegrate in a matter of seconds. The product is prepared by a unique combination of processing steps. The present invention also includes the product that is produced by means of the new process. The first step of the process is to mix shear form matrix and an additive, such as an active ingredient. "Cutting-force form matrix" in the present invention means a matrix produced by subjecting a feed material containing a carrier material to flow-by-run processing. Flow-by-run processing can be accomplished in several ways. Heat due to runoff and shear due to runoff are two processes that can be used. In the process of heat by runoff, the feed material is heated sufficiently to create an internal flow condition that allows part of the feed material to be moved at the sub-particle level with respect to the rest of the mass and outlet openings provided in the perimeter of a spinning head. The centrifugal force created in the spinning head oscillates the feed material that flows out of the head so that it is reformed with a changed structure. The force required to separate and discharge the feed material capable of flowing is the centrifugal force that is produced by the spinning head. An apparatus for implementing a heat run-off process is a machine manufacturing "sweet cotton". The spinning machine used to achieve a run-off heat condition is a cotton candy machine such as the Econo-floss, model 3017, manufactured by Gold Medal Products Company of Cincinnati, Ohio, United States. Any other devices that provide similar temperature gradient and strength conditions can also be used. In the process of shear stress by runoff, a matrix of shear stress is produced by raising the temperature of the feed material, which includes a non-solubilized carrier such as a saccharide-based material, until the carrier undergoes internal flow when a shear force of fluid is applied. The feedstock is advanced and ejected while in the condition of internal flow, and subjected to disruptive force of fluid shear to form multiple parts or masses having a morphology different from that of the original feedstock. The multiple masses are cooled substantially immediately after contact with the shear force of fluid and allowed to continue in a free-flowing condition until solidified. The shear shear process can be carried out in an apparatus having means for increasing the temperature of a non-solubilized feedstock and means for advancing it simultaneously for ejection. A twin screw extruder, with multiple heating zones, can be used to increase the temperature of the non-solubilized feed material. A second element of the apparatus is an ejector that provides the feed material in a condition for shear stress. The ejector is in fluid communication with the means for increasing the temperature and is disposed at a point to receive the feedstock while in the condition of internal flow. The ejector is preferably a nozzle that provides high pressure ejection of the feed material. See U.S. Patent Application Serial No. 965,804, filed October 23, 1992, entitled "Process for Making Shearform Matrix", pending, of the same assignee, which is hereby incorporated by reference .

The feed material for producing a shear-form matrix includes a carrier material. The carrier material can be selected from a material that is capable of undergoing both physical and chemical changes associated with run-off flow processing. The materials useful as matrices can be selected from those carbohydrates that are capable of forming free-form agglomerates when processed. Preferred carrier materials are selected from such classes of sugars or sugar derivatives. "Sugars" are those substances that are based on simple crystalline structures of mono and di-saccharides, that is, based on structures of sugars C5 and C6. "Sugars" include glucose, sucrose, maltose, lactose, arabinose, xylose, ribose, fructose, mannose, pentose, galactose, sorbose, dextrose, sorbitol, xylitol, mannitol, pentathol, maltitol, isomalt, sucralose and mixtures thereof. Preferred combinations of sugars include sugars, as used herein, in combination with other mono, di, tri and polysaccharides up to 50% of the total amount, preferably up to 30%, and most preferably up to 20%. A product is used in the form of shear in the technique of the present invention to obtain the new sugar product. A shear-shaped sugar product is a substantially amorphous sugar that results from subjecting sugar to sufficient heat and shear to transform crystalline sugar (usually granulated) into amorphous sugar without the use of a solution. Thus, in the sense of the present invention, a sugar product of shear stress is characterized as a sugar product resulting from a non-solubilized sugar. It is the initial material to form the unique crystalline product of the present invention. Other carrier materials may be used, but preferably in combination with sugar, not as a total replacement. Maltodextrins are an example of other carrier materials. Maltodextrins include those mixtures of carbohydrates that result from the hydrolysis of a saccharide feedstock that is described as solids having an OD of up to and including 65. The feedstock may also include malto-oligosaccharides produced by selective hydrolysis of starch of corn, followed by removal of high and low molecular weight compounds. The general description of the malto-oligosaccharides contemplated herein is set forth in U.S. Patent Application Serial No. 07 / -847,595, filed Mar. 5, 1992, pending. Polydextrose is also contemplated for use in combination with sugar in the carrier. Polydextrose is an essentially non-nutritive carbohydrate substitute, without sucrose. It can be prepared by polymerizing glucose in the presence of polycarboxylic acid catalyst and polyols. Generally, it is known that polydextrose is commercially available in three forms: polydextrose A and polydextrose K, which are pulverized solids, and polydextrose N, supplied as a 70% solution. Each of these products also contains some low molecular weight components, such as glucose, sorbitol and certain oligomers. With respect to polydextrose, the Applicant hereby incorporates the contents of U.S. Patent Application Serial No. 07 / 881,612, filed May 12, 1992, pending. "Initiating crystallization" in the present invention means inducing crystallization. The shear form matrix used in the present invention contains a substantial amount of amorphous sugar. Crystallization can be initiated in several ways. For example, the crystallization promoters may be included in the feedstock used to make the matrix in shear form. Crystallization promoters include surfactants such as Tweens, Spans, and polydextrose, and their mixtures. Crystallization can also be initiated by adding a crystallization agent to the matrix before or after combining with an additive. Thus, the onset of crystallization in the present invention can occur before or after the combination with the additive. "Combining" an additive with the shear-form matrix to form compact, flowable micro-particulates means adding and mixing an additive before or after initiating the crystallization to form a medium consisting of micro-particulates. Micro-particulates are discrete entities that seem to "roll" easily or "flow" in response to the force of gravity and / or agitation. On a macroscopic scale, the micro-particulates appear as a mass or medium capable of flowing. Consequently, the medium can easily be used in tabletting machinery without plugging or creating undesirable dust in the ambient atmosphere. The shear-form matrix of the present invention is removed from processing, and generally "cut" before being combined with the additive. The additive may be any ingredient or ingredients necessary to supply the required characteristics to the edible unit. Preferably, the primary ingredient of the additive is selected from one or more medicinal substances. The medicinal substances that can be used in the present invention are varied. A non-limiting list of such substances is the following: anti-tresses, anti-histamines, decongestants, alkaloids, mineral supplements, laxatives, vitamins, anti-acids, ion-exchange resins, anti-cholesterol, anti-lipid agents , anti-arrhythmic, antipyretic, analgesic, appetite suppressants, expectorants, anti-anxiety agents, anti-ulcer agents, anti-substances. inflammatory, coronary dilators, cerebral dilators, peripheral dilators, anti-infective, psychotropic, anti-manic, stimulants, gastrointestinal agents, sedatives, anti-diarrheal preparations, anti-anginal drugs, vasodilators, anti-hypertensive drugs, vasoconstrictors , treatments for migraine, anti-biotic, tranquilizers, anti-psychotic, anti-tumor drugs, anti-coagulants, anti-thrombotic, hypnotic, anti-emetics, anti-nausea, anti-convulsant, neuromuscular drugs, hyper and hypoglycemic agents, thyroid and anti-thyroid preparations, diuretics, anti-spasms, uterine relaxants, mineral and nutritional additives, anti-obesity drugs, anabolic drugs, erythropoietic drugs, anti-asthmatics, cough suppressants, mucolytics, anti-uricémicos medicines and their mixtures. Especially preferred active ingredients contemplated for use in the present invention are antacids, H2 antagonists and analgesics. For example, anti-acid doses can be prepared by using the ingredient calcium carbonate alone or in combination with magnesium hydroxide and / or aluminum hydroxide. Moreover, anti-acids can be used in combination with H2 antagonists. Analgesics include aspirin, acetaminophen and acetaminophen plus caffeine. Other preferred medicaments for other preferred active ingredients for use in the present invention include anti-diarrheals such as immodium AD, anti-histamines, antiperspirants, decongestants, vitamins and breath fresheners.

Also contemplated for use herein are anxiolytics such as Xanax; anti-psychotics such as clozaril and Haldol; non-steroidal anti-inflammatories such as Voltaren and Lodine; anti-histamines such as Seldane, Hismanal, Relafen and Tavist; anti-emetics such as Kytril and Cesamet; bronchodilators such as Bentolin, Proventil; anti-depressants such as Prozac, Zoloft and Paxil; anti-migraine agents such as Imigran; ACE inhibitors such as Vasotec, Capoten and Zestril; anti-Alzheimer agents such as Nicergoline; and CAH antagonists such as Procardia, Adalat and Calan. Popular H2 antagonists which are contemplated for use in the present invention include cimetidine, ranitidine hydrochloride, famotidine, nizatidine, ebrotidine, mifentidine, roxatidine, pisatidine and aceroxatidine. Other ingredients that may be included are fragrances, pigments, artificial and natural sweeteners, and other additives. For example, fillers may be used to increase the volume of the tablet. Some of the commonly used fillers are calcium sulfate, both di and tri-basic, starch, calcium carbonate, microcrystalline cellulose, modified starches, lactose, sucrose, mannitol and sorbitol.

Other materials that can be incorporated into the feedstock to improve the shear-form matrix include flavors and sweeteners (other than the carrier itself). The flavors can be selected from natural and synthetic flavor liquids. An illustrative list of such agents includes volatile oils, synthetic flavoring oils, aromatic flavors, oils, liquids, oleoresins or extracts derived from plants, leaves, flowers, fruits, stems and combinations thereof. A representative, non-limiting list of examples includes citrus oils such as lemon, orange, grape, lime and grapefruit and fruit essences that include apple, pear, peach, grape, strawberry, raspberry, cherry, plum, pineapple, apricot or other flavors of fruits. Other useful flavorings include aldehydes and esters such as benzaldehyde (cherry, almond), citral, ie alpha-citral (lemon, lime), neral, ie beta-citral (lemon, lime), decanal (orange, lemon), aldehyde C-8 (citrus fruits), aldehyde C-9 (citrus fruits), aldehyde C-12 (citrus fruits), tolyl aldehyde (cherry, almond), 2,6-dimethyloctanal (green fruits) and 2-dodecenal (citrus, mandarin), their mixtures and the like. Sweeteners can be selected from the following non-limiting list: glucose (corn syrup), dextrose, invert sugar, fructose and their mixtures; saccharin and its various salts, such as sodium salt; dipeptide sweeteners such as aspartame; compounds of dihydrochalcone, glycyrrhizin; Stevia rebaudiana (stevioside); chlorinated derivatives of sucrose such as sucralose; sugar alcohols such as sorbitol, mannitol, xylitol and the like. Also contemplated are the hydrogenated starch hydrolysates and the synthetic sweetener 3,6-dihydro-6-methyl-III, 2,3-oxathiacin-4-one-2,2-dioxide, particularly the potassium salt (acesulfama-K), and its sodium and calcium salts. Other sweeteners may also be used. Yet another embodiment of the present invention includes the use of an effervescent disintegrating agent. Its action can help to mask the objectionable taste of active ingredients such as vitamins, medicines and / or minerals, etc. It is generally believed that the positive organoleptic sensation achieved by the effervescent action in the mouth, the texture, the speed and the sensation of disintegration help to mask undesirable flavor notes in the mouth. In preferred embodiments of the present invention, the effervescent disintegrating agent may include at least one acid selected from the group consisting of citric acid, tartaric acid, malic acid, fumaric acid, adipic acid, succinic acid, acid anhydrides and acid salts and its mixtures, and at least one base selected from the group consisting of carbonate salts, bicarbonate salts and mixtures thereof. As much as the term "effervescent" refers to those agents that release gas, the bubble or gas that generates the action is very often the result of the reaction of a source of soluble acid and a source of carbonate or alkali metal carbonate. . The reaction of these two general classes of compounds produces gaseous carbon dioxide upon contact with the water included in the saliva. Carbonate sources include solid, dry carbonate and bicarbonate salts, such as sodium bicarbonate, sodium carbonate, potassium bicarbonate, and potassium carbonate, magnesium carbonate, and sodium sesquicarbonate, glycine sodium carbonate, carbonate of L- lysine, arginine carbonate and amorphous calcium carbonate. Although the food acids can be those indicated above, acid anhydrides of the acids described above can also be used. The acid salts may include sodium dihydrogen phosphate, dihydrogen dihydrogen pyrophosphate, citrate acid salts and sodium acid sulfite. Other sources of effervescence may be included, and the present invention is not limited to those specifically noted herein. Also as previously mentioned, the effervescent agent ingredients can be included in one of at least three different ways. The first method includes incorporating all the effervescent agent into the feedstock that is used to form the product in shear form. The second way to incorporate an effervescent disintegrating agent is to include all the agent as an additive that is • mixed with the matrix in a shear form after it is formed. The third method contemplates incorporating a portion of the disintegrating agent in the matrix in the form of shear and another portion of the disintegrating agent as an additive after the formation of the matrix material in the form of shear. The technician will determine the best way to preserve the agent by its disintegration and effervescence properties when ingested by the host. The shear force form matrix used in the process of the invention must not be cured before being molded. "Unhealed" means amorphous or having a degree of amorphism that allows the formation of a dosage unit when curing. "Cure" means to transform the matrix from amorphous to crystalline while it is sufficiently linked to produce a stable structure. Curing can be improved by modifiers,. crystallization. Crystallization modifiers can be added to the feedstock before processing by flow-through, such modifiers include, but are not limited to, surfactants (Spans and Tweens), dextrose, polyethylene glycol (PEG), polypropylene glycol (PPG), etc. . These modifiers generally provide controlled acceleration of the crystallization while the matrix is linked. Crystallization modifiers improve the formation of a crystalline framework and the conversion of the remaining mass. "Improvement", as used with respect to the process of the present invention, primarily means acceleration of the process. The improvement also includes contribution to the strength of the crystal structure, and the predictability of the results. Other benefits such as product of reduced size are also achieved through the use of crystallization modifiers. Crystallization modifiers, which are preferably added to the sugars before being processed to an amorphous mass in shear form (or can be coated on the sugar), are used to affect the rate of crystallization. The water itself is a crystallization modifier, and is preferably included in the amorphous sugar mass in the form of shear in an amount of between about 0.5 to about 2.0%. Hydrophilic organic materials, not saccharides (NSHMs) are also used as crystallization modifiers. Even though some NSHMs are surfactants, other materials may be used. The materials that have been found to be most effective have a hydrophilic to lipid balance (HLB) of 6 or more, that is they have the same degree of hydrophilicity as surfactants characterized by the degree of HLB. Such materials include, but are not limited to, anionic, cationic, zwitterionic surfactants as well as neutral materials having an HLB of six (6) or more. Preferred NSHMs are hydrophilic materials having polyethylene oxide bonds. Also, preferred NSHM's have a molecular weight of at least 200, and preferably at least 400. Lecithin is a surfactant for use in the present invention. The lecithin can be included in the feed material in an amount from about 0.25 to about 2.00% by weight. Other surfactants include, but are not limited to, Spans and Tweens, which are commercially available from ICI Americas Inc. Carbowax is still another crystallization modifier that is extremely useful in the present invention. Preferably, Tweens or combinations of surfactants are used to achieve the desired HLB. Through the use of a surfactant, the process and the product of the present invention can be reproduced with a high degree of reproducibility. As additional crystallization modifiers are identified that improve the process and the product of the present invention, the The applicant intends to include all of those additional crystallization modifiers within the scope of the invention claimed herein. Fillers can be used to increase the volume of the tablet. Some of the commonly used fillers are calcium sulfate, both di and tri-basic, starch, calcium carbonate, microcrystalline cellulose, modified starches, lactose, sucrose, mannitol and sorbitol. Other ingredients include binders that contribute to the ease of training and the overall quality of the tablet. The binders include starches, pre-gelatinized starches, gelatin, polyvinylpyrrolidone, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyacrylamides, polyvinyloazolidone, and polyvinyl alcohols. Lubricants are also useful in tableting formulations. Lubricants may include, but are not limited to the following: magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, stereotex, polyoxyethylene, monostearate, talc, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, and light mineral oil. Further, dispersion improvers can be used to improve the breaking capacity of the compressed tablet in an aqueous environment. Dispersants may include starch, alginic acid, polyvinylpyrrolidones, gum ,. guar, kaolin, bentonite, purified wood cellulose, sodium starch glycolate, isoamorfo silicate, and microcrystalline cellulose as high HLB emulsifying surfactants. In view of the ease with which the product of the present invention disintegrates, there is little need for disintegrants. The combination of the shear force form matrix and the additive should be provided as compact, flavourable micro-particulates. The micro-particulates are agglomerates of a type that includes the ingredients of the mixture, but which are relatively low density. The "micro-particulates" of the present invention are capable of withstanding a comparatively high compaction force without experiencing an increase in density. The microparticles can then be compacted under a relatively high compaction force to form a low density dosing unit having high structural integrity, high strength, and excellent appearance. Micro-particulates are preferably formed by combining the mixture with a crystallization / ligation promoter such as ethanol (preferably 200 °), polyvinylpyrrolidone, a combination thereof, as well as other agents that improve micro-particulate formacon without increasing density mix. The microparticles resulting from the previous step can then be compacted, for example to 6-8 SCUs, whereby a structurally resistant tablet can be formed which has excellent appearance and can be handled without deterioration of the surface or structure. "Compact" in the present invention means pressing into an edible unit, for example a tablet, at a generally higher pressure of about 500 psi, but not necessarily as high as the normal tableting pressure, which is of the order of magnitude of thousands of psi (that is, at least about 1,000 psi). In a preferred embodiment, where polydextrose (especially Poly Dex brand polydextrose supplied by AE Staley &Co.) has been included as a crystallization promoter, a compaction pressure as low as 50 psi has been found to be effective. . In all of the present cases, the micro-particulate medium that is being compacted includes a shear-shape matrix that has been at least partially crystallized. Other ingredients may also be used in the present invention, either during the mixing step, during the agglomeration step, or after the agglomeration step. Such ingredients are ingredients that are useful for tabletting such as glidants that adhere to the cohesive material and improve flow properties. The flow property is improved by reducing the inter-particle friction that would otherwise exist. Slides that can be used include starch, talc, magnesium stearate and calcium, zinc stearate, calcium dibasic phosphate, magnesium carbonate, magnesium oxide, calcium silicate and silica arogels. Also, color additives can be used in the preparation of tablets. Such color additives include food colorants, medications and cosmetics (FD &; C), dyes for medicines and cosmetics (D &C), or external dyes for medicines and cosmetics (Ext. D &C). These dyes are pigments, their lacquers, and certain neutral dyes and derivatives. The lacquers are pigments absorbed on aluminum hydroxide. As a result of the process of the present invention, a highly attractive, resistant tablet can be produced having a texture that is relatively open for ease of fracture and ease of solubilization. However, the unit remains of high strength due to the high compaction pressure of each of the units. In a preferred embodiment, the present invention is particularly useful for preparing anti-acid tablets. The anti-acids are conveniently provided in a chewable tablet form to provide a convenient method of delivering the anti-acid to the consumer. The chewable form provides an advantage as the tablet is broken into granules during chewing and mixed with saliva before being swallowed. This creates a suspension. One of the disadvantages of current anti-acid tablets is that the mass of the ingredients that reside in the mouth during and after chewing has an objectionable texture and taste. The present invention overcomes these disadvantages due to the rapid disintegration that occurs in the mouth. The objectionable texture and taste of unpleasant ingredients are reduced because the residence time in the mouth is substantially reduced. Active anti-acid ingredients include, but are not limited to the following: aluminum hydroxide, dihydroxyaluminium aminoacetate, aminoacetic acid, aluminum phosphate, sodium dihydroxyaluminum carbonate, bicarbonate, bismuth aluminate, bismuth carbonate, bismuth subcarbonate , bismuth subgalate, bismuth subnitrate, calcium carbonate, calcium phosphate, citrate ion (acid or salt), aminoacetic acid, hydrous magnesium aluminate sulfate, megaldrate, magnesium aluminosilicate, magnesium carbonate, magnesium glycinate, magnesium hydroxide, magnesium oxide, magnesium trisilicate, milk solids, aluminum calcium mono-ordibasic phosphate, tricalcium phosphate, potassium bicarbonate, sodium tartrate, sodium bicarbonate, magnesium aluminosilicates, acids and tartaric salts. One method of measuring the results of the present invention is the ability to make a product of low density. The micro-particulates are capable of being subjected to high pressure without reducing the density of the resulting product. Accordingly, the product prepared in accordance with the present invention even after high pressure compaction will still remain below 1.2 g per cubic centimeter (g / cc), and preferably below 0.8 g / cc. The pressure required to prepare tablets according to the present invention exceeds that generally required in the accompanying case (identified with file No. 447-105), but is less than previously required with normal tabletting procedures (although some embodiments they do not require compaction pressure greater than that established in case 447-105). As a result of the increased pressure that can be used to form tablets according to the present invention, the strength of the product is increased, and the hardness of the surface is also increased. This results in a confection dosing unit that is capable of being manually handled and machine processed without degradation of structural or surface integrity. With reference to Figures 1-3, the process of the present invention is described in greater detail. In Figure 1, a combination of a shear-shaped form matrix is sketched in the form of yarn material cut in a mixture with a representative of an additive, ie, + s. An anti-acid agent is a preferred additive, +. In figure 1, the combination is shown as yarn and additive particles mixed indiscriminately with each other. There is no fixed relationship between the particles in the mixture shown in Figure 1. The crystallization of the yarn is initiated before or after the combination with an additive is formed. In figure 2, the combination is shown as compact, micro-particulates capable of flowing. The micro-particulates shown in Figure 2 are represented by matrix collections of shear-force form with the additive fixed in it and on it. The transformation is enhanced when the combination shown in Figure 1 is subjected to a crystallization / ligation promoter such as ethanol, polyvinylpyrrolidone, or combinations thereof. Other crystallization / ligation promoters can be used to form the microparticles. It is intended to include all those other agents useful for this purpose. The micro-particulates form a medium that is capable of flowing. Therefore, the medium is easily fed to pigment cavities in tabletting devices without plugging the movable parts. Moreover, the incidence of dust is reduced. Referring now to Figure 3, a schematic representation of the performance of the microparticles during actual compression has been made. In Figure 3, micro-particulates are schematically represented under compaction force. The micro-particles are deformed, but their density is not increased. Basically, the spaces between the micro-particulates are reduced or virtually eliminated, but the micro-particulates themselves retain their low density. The additive particles are retained in and on the surface of the - agglomerates. The micro-particulates retain their individual integrity, and disintegration lines are provided throughout the entire unit. Moreover, since the mass can be subjected to relatively high pressure compaction, the surface of the resulting dosage unit is smooth, and the strength of the tablet is relatively high. Therefore, the resulting units can be easily handled without • deterioration of the surface appearance or destruction of the edible units. In the formation of the micro-particulates, the material preferably contains up to 5% water, and most preferably up to 1% water. The water may be provided by water contained in the ingredients, such as that carried in the sugars or binders. Water may also be provided in small amounts in the alcohol, such as 200 ° alcohol which absorbs moisture rapidly and generally contains small amounts of moisture, for example up to 1% by weight. Additional moisture can be provided by the surrounding environment, such as humidity in the air. EXAMPLES Example of Anti-Acid Shear-form matrices were prepared for use in the process of the present invention. The , -. matrices were prepared by subjecting combinations of carrier material • to processing by flow in a cotton candy type apparatus. The combination included the carrier material based on saccharides, sucrose, as well as other carriers, and surfactants such as Tween 80, supplied by ICI, and lecithin. The isomalt used herein is commonly available as isomalt brand Palatinit. The physical mixtures were provided according to the formulas indicated below in the Cutting Effort Form Matrix Table.

Shape Effort Matrix Table The matrix recovered from each of the physical mixtures indicated above was a light colored yarn, for example substantially white. Each die was then cut to mix with an additive, for example an anti-acid combination. The examples set forth below refer to the matrices recovered from each of the previous physical mixtures as MI, M2, ..., etc. Example of Anti-Acid I The first example of anti-acid was mixed according to the formula indicated below in the Anti-Acid Table I. Anti-Acid Table I Ingredient Percentage Anti-acid agent (CaC03) 36. .55% MI 58, .63% Flavoring 0.35% Vegetable oil 0.50% Flow agent - Syloid 244 1. .00% Cab-0-Sil 0.. 40% Starch 2. .00% High intensity sweetener (aspartame) 0. .07% Lubricant (magnesium stearate) 0.50% _100.00% The ingredients were combined by mixing to provide a mixture as shown in the Figure 1. After the mixture was formed, ethanol (200 °) was added and compact, flowable microparticles were formed. (About 4.0% ethanol was used, based on the weight of the mixture.) The schematic representation of such agglomerates is shown in Figure 2. After a consistency of agglomerate was achieved, tablets were formed by compression under a compression force of around 6 SCU. The weight of each tablet was around 1,500 g. The tablets thus formed had an excellent appearance, and immediately disintegrated in the mouth of the consumer. The calcium release capacity of the dosage unit has been established later in the calcium release table. As can be seen from the release capacity, not only is the dosage unit an excellent source of anti-acid agent, but it can also be classified as a source of calcium for nutritional purposes. Therefore, the dosage unit can be characterized as a nutritional calcium supplement. Example of Anti-Acid II A second example was prepared using the mixture indicated below in the Table of Anti-Acid II. , .r Anti-Acid Table II Ingredient Percentage Anti-acid agent (CaC03) 36.55% M2 58.86% Peppermint flavor (oil of) 0.12% Vegetable oil 0.50% Flow agent - Syloid 244 1.00% Cab-O-Sil 0.40% Starch 2.00% High intensity sweetener (aspartame) 0.07% Lubricant (magnesium stearate) 0.50% 100.00% The above ingredients were mixed together and then subjected to agglomeration in the presence of ethanol (200 °). A compactable micro-particulate was formed, able to flow. (About 4% ethanol was used based on the weight of the mixture.) The resulting agglomerate was directed to a tableting press and compressed at a compression force of about 6 SCU. The resulting tablets were smooth and had a quality appearance. Furthermore, the product disintegrated immediately in the consumer's mouth. Tests were also conducted on two of the samples to determine the release characteristics of calcium. The results of the test are shown in the Release Table as test results lia and IIb. Example of Anti-Acid III Another example of an anti-acid dosage unit was prepared according to the mixture established in the Table of Anti-Acid III. Table of Anti-Acid III Ingredient Percentage Anti-acid agent (CaC03) 36.550% M2 58.630% Flavor 0.350% Vegetable oil 0.500% Flow agent - Syloid 244 1.000% Cab-0-Sil 0.400% Starch 2.000% High intensity sweetener (aspartame) 0.070% Lubricant (stearate magnesium) 0.500% 100.00% The above ingredients were mixed intensively and formed compact, micro-particulates capable of flowing. The agglomerates were formed in the presence of added ethanol in an amount sufficient to form the microparticulate consistency (about 4% by weight of the total mixture). The ethanol was mixed intensely with the ingredients and the agglomeration was formed. The micro-particulate medium was then directed to a tablet-forming press where the tablets were prepared using a compaction pressure of about 6 SCU. The resulting tablets were of high quality appearance, and were able to disintegrate immediately in the oral cavity. Further, the tablets prepared according to this example were subjected to calcium release analysis and the results have been established in the calcium release table below. Example of Anti-Acid IV Another example of an antacid dosage unit was prepared according to the mixture set forth in Table IV Anti-Acid IV. Table of Anti-Acid IV Ingredient Percentage Anti-acid agent (CaC03) 36. .55% M2 58. .59% Flavoring 0.35% Vegetable oil 0. .05% Flow agent - Syloid 244 1. .00% Cab-0-Sil 0.. 40% Starch 2 .. 00% High intensity sweetener (aspartame) 0,. 07% Lubricant (magnesium stearate) 0. . 50% Red dye (FD &C No. 40) 0. . 04% _ 100.00% The above ingredients were mixed intensively until the homogeneous red color appeared throughout the entire mixture. The mixture was then combined in the presence of ethanol (200 °) in order to improve the formation of compactable, micro-particulates capable of flowing. The micro-particulate medium was a consistent red color. The resulting agglomerates were tabletted using a compaction pressure of about 6 SCU. The tablets formed of them had appearance of good quality, including a consistent red color and a smooth surface. Furthermore, the tablets thus prepared immediately disintegrated in the mouth of the consumer. Tablets prepared according to the above-mentioned formula were subjected to calcium release tests and the results have been established later in the calcium release table. Example of Anti-Acid V Another example of an anti-acid dosage unit was prepared according to the mixture established in the Anti-Acid Table V. Table of Anti-Acid V Ingredient Percentage Anti-acid agent (CaC03) 36.55% MI 58 .. 83% Peppermint flavor (oil of) 0. . 15% Vegetable oil 0. . 50% Flow agent - Syloid 244 1. . 00% Cab-0-Sil 0. . 40% Starch 2 . 00% high intensity sweetener (aspartame) 0. . 07% Lubricant (magnesium stearate) 0. . 50% 100.00% The above ingredients were thoroughly mixed and then subjected to agglomeration by addition of ethanol while mixing. (The ethanol was added in an amount of about 4% by weight of the mixture.) The resultant, flowable, compacting, micro-particulate medium was then subjected to tableting by compression in a tableting unit at a compaction pressure. of around 6 SCU. Each tablet weighed 1,500 g. The resulting tablets had a high quality appearance and immediately disintegrated in the oral cavity. Furthermore, the tablets were subjected to three separate tests to determine the characteristics of calcium release. The results have been established in the calcium release table as Va, Vb and Ve. Example of Anti-Acid VI Another example of an antacid dosage unit was prepared according to the mixture set forth in the Table of Anti-Acid VI .

Table of Anti-Acid VI Ingredient Percentage Anti-acid agent (CaC03) 36. .55% M3 58, .83% Mint flavor (physical mixture of mint) 0. .15% Vegetable oil 0.50% Flow agent - Syloid 244 1. .00% Cab-0-Sil 0.40% Starch 2. .00% High intensity sweetener (aspartame) 0. .07% Lubricant (magnesium stearate) 0.50% - 100.00% The above ingredients were mixed until achieved a homogeneous mixture. Compact, flowable micro-particulates were then formed by the addition of ethanol (200 °) and physically mixed until the micro-particulate was formed.

The micro-particulate agglomerates were then used to form tablets under compaction pressure of about 6 SCU. The resulting tablets have excellent taste and good appearance and were easily disintegrated in the consumer's mouth. Calcium release tests were carried out on the tablets and the results have been reported in the calcium release table below. Example of Anti-Acid VII A seventh unit of anti-acid dosage was prepared according to the mixture set forth in Table Anti-Acid VII.

Table of Anti-Acid VII Ingredient Percentage Anti-acid agent (CaC03) 36, .55% M4 58, .73% Flavor 0.25% Vegetable oil 0.50% Flow agent - Syloid 244 1, .00% Cab-0-Sil 0.. 40% Starch 2. .00% High intensity sweetener (aspartame) 0. .07% Lubricant (magnesium stearate) 0, .50% - 100.00% The above ingredients were physically mixed and agglomerated to form compactable microparticles, capable of to flow through the use of 200 ° ethanol. The resulting micro-particulate medium was subjected to tabletting and the tablet press had a compaction pressure of about 6 SCU. The resulting tablets had a smooth surface, excellent appearance and structural integrity. Moreover, the tablets disintegrated immediately in the consumer's mouth. The calcium release characteristics were also excellent and have been reported herein in the calcium release table. Example of Anti-Acid VIII Another example of anti-acid was prepared using the formulation set forth in the Table of Anti-Acid VIII.

Table of Anti-Acid VII Ingredient Percentage Anti-acid agent - CaC03 29.50% Mg (0H) 2 5.79% MI 59.99% Flavor 0.35% Vegetable oil 0.50% Flow agent - Syloid 244 1.00% Starch 2.00% High intensity sweetener (aspartame) 0.07% Lubricant (magnesium stearate ) 0.50% Crystallization promoter / ligation 0.30% (polyvinylpyrrolidone) 100.00% The above ingredients were combined and then subjected to agglomeration by adding ethanol (200 °) and mixing until a compact, flowable micro-particulate medium was formed. It is noted that the polyvinylpyrrolidone and ethanol were combined in the present mixture as a crystallization / ligation promoter. Polyvinylpyrrolidone is included as an ingredient in the Table Anti-Acid VIII. Ethanol was added after the formation of '' mixing in an amount of 4% by weight of the total mixture. The resulting micro-particulate medium was subjected to tabletting under compaction pressure of about 6 SCU. The resulting tablets had excellent appearance, a good surface and high structural integrity. Furthermore, the tablets disintegrated immediately in the mouth of the consumer. The calcium release characteristics have been noted later in the calcium release table. Example of Anti-Acid IX Another example of anti-acid was prepared using the formulation set forth below. Table of Anti-Acid IX Ingredient Percentage Anti-acid agent - CaC03 29.50% Mg (0H) 2 5.79% M2 60.12% Peppermint flavor (oil of) 0.12% Vegetable oil 0.50% Flow agent - Syloid 244 1.00% Cab-O -Sil 0.40% Starch 2.00% High intensity sweetener (aspartame) 0.07% Lubricant (magnesium stearate) 0.50% 100.00% The above ingredients were mixed and subjected to agglomeration to form a compact, flowable micro-particulate medium, in presence of ethanol of 200 °. The ethanol was added and mixed with the ingredients to form the agglomeration. The resulting agglomerate was subjected to a tableting force of about 6 SCU. The resulting tablets had excellent appearance and high structural integrity and good surface quality. The tablets disintegrated immediately in the consumer's mouth. Further, the tablets were subjected to calcium release and were shown to have excellent calcium release characteristics. The results are indicated later in the calcium release table. Example of Anti-Acid X Another example of anti-acid was prepared using the formulation set forth below. Table of Anti-Acid X Ingredient Percentage Anti-acid agent - CaC03 29.50% Mg (0H) 2 5.79% MI 58.89% Flavoring 0.35% Vegetable oil 0.50% Flow agent - Syloid 244 1.00% Cab-O-Sil 0.40% Starch 2.00 % High intensity sweetener (aspartame) 0.07% Lubricant (magnesium stearate) 0.50% Red dye (FD &C No. 40) 0.04% 100.00% The above ingredients were mixed intensively and then agglomerated by using 200 ° ethanol in an amount of about 4% by weight of the total mixture. The resulting micro-particulate medium was subjected to tabletting under a compaction force of about 6 SCU. The resulting tablets had a good appearance on the red surface and good structural integrity. Furthermore, the tablets disintegrated immediately in the mouth of the consumer. The tablets were then subjected to calcium release tests and the results have been reported herein in the calcium release table. Calcium Release Characteristics An assay was conducted in order to determine the calcium release characteristics of the samples prepared as noted above. The calcium release characteristics were prepared according to the protocol established in the Pharmacopoeia of the United States. Various tablets were weighed and powdered, and the weight of each sample tested had a dosage amount of 550 mg. This powder was introduced into water to which 10 mm of IN HCl had been added. It was boiled for 30 minutes, allowed to cool and then transferred to a volumetric matrix of 100 ml with the aid of water. This was diluted with water to volume, mixed and filtered. 20 ml of the filtrate were transferred to a suitable vessel and diluted with 100 ml water. 15 ml of IN NaOH was added together with 5 ml of triethanolamine, and 100 mg of hydroxy naphthol blue trituration, and titrated with 0.05M sodium di-sodium ethylene diamine tetraacetate until the solution is a deep blue color. . Each ml of ethylenediamine 0.05M di-sodium tetraacetate is equivalent to 5,004 mg of calcium carbonate (CaCO3). The assay results have been established later in the calcium release table. Calcium Release Table Shows% Calcium Release I 95 76 Has 95. 21 Hb 95. 76 III 95. 48 IV 94. 93 Go 96.03 Vb @ 93.58 Go 96.03 VI 94.47 VII 87.41 VIII 98.64 IX 95.25 X 94.92 As can be seen, the calcium released at 30 minutes was excellent in all the samples prepared according to the present invention. Examples of Acetaminophen Various examples were prepared using the active ingredient acetaminophen (APAP). It is well known that acetaminophen has an unpleasant impact on the oral cavity. In this way, it is desirable to provide an edible to deliver acetaminophen that masks the taste and minimizes the time the ingredients reside in the mouth. Therefore, these examples were prepared with acetaminophen. All examples were prepared using the MI thread formulation. An additional example was prepared with aspirin. Example of Acetaminophen XI An example of acetaminophen was prepared using the formulation set forth in the Table for Acetaminophen XI.

Acetaminophen Table XI Ingredient Percentage MY 74.305% Acetaminophen (APAP) 21.660% APAP mask 0.160% High intensity sweetener 1.300% Grape flavor 0.500% Hydrol 92 2.000% Blue dye 0.042% Red dye 0.033% 100.00% The previous formulation was physically mixed and then subjected to treatment with a crystallization / ligation promoter, ie 20% of a PVP solution at 0.5% (PVP K-30) in ethanol of 200 °. About 20 ml of the crystallization / ligation promoter were added and combined with the ingredients. A compactable micro-particulate medium, capable of flowing, was formed. The medium was then subjected to tabletting under a compaction pressure of about 6 SCU. The resulting tablets quickly disintegrated in the mouth. The unpleasant impact of acetaminophen in the mouth was considerably reduced. Furthermore, the release of acetaminophen is expected to be quite efficient, especially in view of the high release characteristics reported previously in the calcium release table. Example of i cet > * rn rinffa? XII Another acetaminophen was prepared using the formulation indicated in the Acetaminophen Table XII.

Table of Acetaminophen XII Ingredient Percentage M2 69, .05% Acetaminophen (APAP) 25. .00% APAP mask 0.25% Yellow color (aluminum HT lacquer) 0. .15% Hydro1 92 2. .00% High intensity sweetener 0,. 80% Flavoring 2.25% 100.00% The above ingredients were mixed and then subjected to the formation of compactable micro-particulates, capable of flowing in the presence of ethanol of 200 ° having additionally 20% of a PVP solution at 0.5%. The micro-particulate medium was subjected to tabletting under a pressure of about 6 SCU. The resulting tablets rapidly disintegrated in the oral cavity. They had excellent structural integrity and appearance. Moreover, they are expected to provide excellent release characteristics of acetaminophen. Example of Acetaminophen XIII Another example was prepared using acetaminophen as the active ingredient, according to the formula set forth in the Table of Acetaminophen XIII. Acetaminophen Table XIII Ingredient Percentage MY 74.22% Acetaminophen (APAP) 16.25% APAP mask 0.25% Caffeine 3.25% Caffeine mask 0.25% Hydrol 92 2.00% Red dye 0, .08% Flavor 2, .40% High intensity sweetener 1, .30% ~~ "100.00% The above formulation was physically mixed and then agglomerated using a 10% ethanol solution.The resulting agglomerate was tabletted under a pressure of 35 pounds on a 15/16 inch die.The resulting tablet was a weight tablet The taste was palatable, despite the presence of the highly objectionable acetaminophen, the appearance of the tablet was excellent, and the release of acetaminophen is expected to be truly excellent. Vitamin XIV An example was prepared for a multi-vitamin dosage unit The matrix was a lactose matrix prepared according to the following formulation: Matrix XIV Ingredient Percentage Weight Sucrose 59.35 35 6.10 Dextrose 18.00 108.00 Mannitol 20.00 120.00 Lactose 2.00 12.00 Surfactant (Tween 80) 0.25 2.40 Polydextrose 0.40 2.40 100.00 600.00 g The ingredients were subjected to flow-by-run processing by the use of heat by runoff, i.e. subjected to spinning in a cotton candy machine at about 3,600 rpm. The resulting product was a yarn that was cut in preparation for combination with additives. A micro-particulate medium was prepared according to the process of the present invention, based on the formulation set forth below: Table of Multi-Vitamin XIV Ingredient Percentage Matrix XIV 55.685% High intensity sweetener 0.450% Sweetener mask 0.200% Starch 2.000% Dye 0.250% Oilseed 0.500% Flow agent 1.400% Flavor 3.500% Lubricant 0.750% Multi-vitamin component Vitamin A 1.778% Vitamin D3 0.867% Vitamin E 1.913 % Vitamin B 0.084% Vitamin B2 0.138% Vitamin B6 0.103% Vitamin B12 0.092% Vitamin C 4.792% Bioteno 0.250% Folic acid 0.738% Nicotinamide 1.100% Pantothenic acid 1.163% Calcium carbonate 6.427% Magnesium oxide 0.067% Phosphorus 14.655% Iron 0.570 % Zinc 0.430% Manganese 0.046% Copper 0.052% 100,000% The above ingredients were combined and mixed in the presence of 200 ° ethanol, which was added in an amount of 4% based on the weight of the mixture. As a result of the above procedure, a compactable micro-particulate medium was formed, capable of flowing. The medium was then directed to a tableting and tabletting machine under a compaction pressure of only 35 SCUs to provide an extremely attractive tablet that had excellent dispersibility in the oral cavity. Moreover, the objectionable taste in other circumstances, generally associated with vitamins and minerals, was overcome to the extent that the product was suitable for human consumption. Examples of Micro-Particulate The micro-particulate medium formed as a result of the present invention demonstrates excellent flowability and excellent handling capabilities for use in tabletting. The micro-particulates are extremely small and yet they talk about the flow characteristics, that is to say they "roll" easily in the middle. In the past, it has been a laborious task to obtain small particulates that are able to flow for tableting purposes. The granulation methods known in the art produce a high amount of powder as a by-product of the milling that is required to obtain the small particle size. As a consequence of the present invention, the micro-particulate medium can be produced with little or no dust, and still retain excellent flow characteristics. To demonstrate this characteristic, two formulas were prepared and a sieve analysis was carried out. The media were prepared according to the formulas indicated below in the sieve analysis formulation table. The matrix used for each of the examples, namely sieve XV and sieve XVI, was of a type indicated in the Anti-Acid Examples, especially M2 and M3. Sieve Analysis Formulation Formulation Ingredient Sieve XV Sieve XVI Matrix 58.53% 58.90% CaC03 36.55% 36.55% High intensity sweetener 0.07% Flavor 0.35% 0.15% Vegetable oil 0.50% 0.50% Flow agent 1.40% 1.40% Starch 2.00% 2.00% Color 0.10% Lubricant 0.50% 0.50% _100.00% 100.00% The ingredients were prepared according to the present invention and a sieve analysis was carried out to determine the size of the microparticles that make up the media. The results of the sieve analysis have been indicated in the sieve analysis table. Sieve Analysis Table Sieve Size XV Sieve * XVE Sieve * 10 5.380% 4.415% 7.475% 5.660% 40 5.185% 5.535% 60 4.230% 5.560% 80 4.610% 4.635% 100 13,465% 6,605% Tray 59.655% 67.590% * Percentages represent the amount retained in the screen.

Taking into account that the higher the sieve number, the smaller the opening, it should be noted that 75-85% pass through a sieve of 60 mesh or greater. These micro-particulates are very small in size, but excellent for tabletting. Moreover, the tablets produced therefrom result in excellent disintegration and excellent texture. These tablets overcome the well-known difficulty of retaining a grainy texture in the mouth. In order to emphasize the fineness of the microparticles forming the tabletting medium, it should be noted that 60 mesh screen is no larger than 250 μm. Thus, 75-85% of the micro-particulates are less than only 250 μm. 59-67% of the micro-particulates are less than 150 μm, which is the opening provided by a 100-mesh sieve. These results are quite unexpected, because it has not been possible to produce an excellent disintegration and texture tablet using a micro-particulate medium substantially free of moisture and in the absence of heat. Thus, although those which are currently believed to be the preferred embodiments of the present invention have been described, those skilled in the art will appreciate that other and further embodiments may be made without departing from the spirit of the invention, and are intended to be include all those modifications and additional changes as they fall within the true scope of the claims, as stated herein.

Claims

CLAIMS 1. A method of preparing edible units of rapid dissolution, comprising: a) initiating the crystallization of matrix in the form of shear stress; b) before or after initiating the crystallization, combine an additive with said matrix in a shear form to form compact, flowable microparticles; and c) compacting the combination resulting from step b), which includes at least partially crystallized shear form matrix, to form said unit.
2. The method of preparing fast dissolving edible units, according to claim 1, wherein said combination further comprises subjecting said additive and said matrix to treatment with a crystallization promoter.
3. The method of preparing fast-dissolving edible units, according to claim 2, wherein said promoter comprises an ingredient selected from the group consisting of an alcohol, polyvinylpyrrolidone, and a combination thereof.
4. The method of preparing fast dissolving edible units, according to claim 1, wherein a crystallization / ligation promoter is incorporated in said matrix in a shear form including said promoter in the feedstock from which said matrix is formed .
5. The method of preparing fast-dissolving edible units, according to claim 4, wherein said promoter is a surfactant.
6. The method of preparing fast-dissolving edible units, according to claim 4, wherein said promoter is polydextrose.
7. The method of preparing fast-dissolving edible units, according to claim 1, wherein said additive is an active ingredient.
8. The method of preparing fast-dissolving edible units, according to claim 7, wherein said active ingredient is selected from the group consisting of anti-tresses, anti-histamines, decongestants, alkaloids, mineral supplements, laxatives, vitamins, anti -acids, ion exchange resins, anti-cholesterol, anti-lipid agents, anti-arrhythmic, anti-pyretic, analgesic, appetite suppressants, expectorants, anti-anxiety agents, antiulcer agents, anti-inflammatory substances, dilators of the coronary, cerebral dilators, peripheral dilators, anti-infective, psychotropic, anti-manic, stimulants, gastrointestinal agents, sedatives, anti-diarrheal preparations, anti-anginal drugs, vasodilators, anti-hypertensive drugs, vasoconstrictors, migraine treatments, anti -biotics, tranquilizers, anti-psychotics, anti-tumor drugs, anti-coagulants, medicines ntitrombóticos, hypnóticos, anti-emetics, anti-nausea agents, anti-convulsive, neuromuscular drugs, hyper and hypoglycemic agents, thyroid and anti-thyroid preparations, diuretics, anti-spasmodics, uterine relaxants, mineral and nutritional additives, anti-obesity drugs , anabolic medications, erythropoietic drugs, anti-asthmatics, cough suppressants, mucolytics, anti-uricémicos medicines and their mixtures.
9. The method of preparing fast-dissolving edible units, according to claim 1, wherein said compaction is carried out under a pressure not greater than
10 SCUs. The method of preparing fast dissolving edible units, according to claim 9, wherein said pressure is not greater than 8 SCUs.
11. The method of preparing fast dissolving edible units, according to claim 1, which further comprises the incorporation of an effervescent disintegrating agent.
12. An edible unit that disperses rapidly in the mouth, prepared from the process comprising: a) initiating the crystallization of matrix in the form of shear stress; b) before or after starting crystallization, combine an additive with said matrix in a shear form to form compact, flowable micro-particulates; and c) compacting the combination resulting from step b), which includes at least partially crystallized shear form matrix, to form said unit.
The unit according to claim 12, wherein said combination further comprises subjecting said additive and said matrix to treatment with a crystallization promoter.
The unit according to claim 13, wherein said promoter comprises an ingredient selected from the group consisting of an alcohol, polyvinyl pyrrolidone, and a combination thereof.
15. The unit according to claim 12, wherein a crystallization / ligation promoter is incorporated in said matrix in a shear-force manner including said promoter in the feedstock from which said matrix is formed.
16. The unit according to claim 15, wherein said promoter is a surfactant.
17. The unit according to claim 15, wherein said promoter is polydextrose.
18. The unit according to claim 12, wherein said additive is an active ingredient.
19. The unit according to claim 18, wherein said active ingredient is selected from the group consisting of anti-tresses, anti-histamines, decongestants, alkaloids, mineral supplements, laxatives, vitamins, antacids, ion exchange resins, anti -cholesterolemic, anti-lipid agents, anti-arrhythmic, anti-pyretic, analgesic, appetite suppressants, expectorants, anti-anxiety agents, anti-ulcer agents, anti-inflammatory substances, coronary dilators, cerebral dilators, peripheral dilators, anti-infective, psychotropic, anti-manic, stimulants, gastrointestinal agents, sedatives, anti-diarrheal preparations, anti-anginal drugs, vasodilators, anti-hypertensive drugs, vasoconstrictors, migraine treatments, anti-biotic, tranquilizers, anti-psychotic , anti-tumor drugs, anti-coagulants, anti-thrombotic, hypnotic, anti-emetics, agents to nti-nausea, anti-convulsants, neuromuscular drugs, hyper and hypoglycemic agents, thyroid and anti-thyroid preparations, diuretics, anti-spasms, uterine relaxants, mineral and nutritional additives, anti-obesity drugs, anabolic drugs, erythropoietic drugs, anti-asthmatics, cough suppressants, mucolytics, anti-uricémicos medicines and their mixtures.
20. The unit according to claim 18, wherein said active ingredient is ibuprofen.
21. The unit according to claim 18, wherein said active ingredient is acetaminophen.
22. The unit according to claim 18, wherein said active ingredient is aspirin.
23. The unit according to claim 18, wherein said active ingredient is a H2 antagonist.
24. The unit according to claim 18, wherein said active ingredient is an anti-acid.
25. The unit according to claim 18, wherein said active ingredient is a breath freshener.
26. The unit according to claim 12, wherein said additive is a pharmaceutical product and said combination further comprises subjecting said additive and said matrix to treatment with a crystallization / ligation promoter.
27. The unit according to claim 12, which further comprises an effervescent disintegrating agent.
28. A composition for delivering an active ingredient, comprising: an active ingredient; and a crystalline structure based on saccharides comprising a crystalline sugar stabilized and continuously bound in two-dimensional form, produced by i) initiating the formation of a crystalline sugar framework from an external portion of amorphous sugar masses in the form of shear stress, ii) before or after initiating the formation of said crystalline framework, combining said active ingredient with said matrix in a shear form to form compactable micro-particulates, capable of flowing; iii) compacting said masses to form a unit dose, and iv) subsequently converting the remaining portion of said masses into a substantially fully crystalline structure, which is continuously bound and stabilized, whereby said active ingredient is incorporated into said structure crystalline based on saccharides.
29. The composition of claim 28, wherein said masses are bi-dimensionally monodisperse.
The composition of claim 28, wherein said shear-form masses further comprise an additive, whereby said additive is co-crystallized in said crystalline product.
The composition of claim 29, wherein said monodisperse stabilized masses are microcrystalline.
32. The composition of claim 29, wherein said amorphous shear-shaped product has substantially a bar-like shape, said two dimensions lying in a cross-sectional plane of said bar and a third dimension extending along the linear axis of said bar. said bar.
33. The composition of claim 32, wherein said structurally stabilized, monodisperse cross section does not exceed 50 μm.
34. The composition of claim 33, wherein said cross section does not exceed 10 μm.
35. A method of administering an active ingredient to a human host, which comprises: ingesting a rapidly dissolving edible unit prepared by the method comprising: i) initiating matrix crystallization in shear form; ii) before or after initiating the crystallization, combining an additive with said matrix in a shear form to form compactable micro-particulates capable of flowing, and iii) compacting the combination resulting from step ii), which includes matrix at least particularly crystallized shear stress; retaining said unit in the oral cavity for a sufficient time to contact said unit with water introduced into said oral cavity; and introducing water to said oral cavity while retaining said unit therein, thereby expediting the dispersion of said unit considerably.