MXPA96006373A - Process and apparatus for doing dosing units of quick dissolution and product apparatus of the - Google Patents

Abstract

The present invention relates to a method of preparing fast-dissolving edible units: comprising: subjecting a feedstock containing a carrier material to flow-by-run processing to provide a matrix of unhardened shear-form, macerating said matrix in the form of uncured, macerated shear and an additive, molding the mixture of the matrix in the form of unhardened shear and the additive resulting from the previous step, to provide a unitary dosage form having bridging between crystallized matrix material when curing, and curing said matrix in a shear form to produce a stable structure

Description

PROCESS AND APPARATUS TO MAKE DOSING UNITS OF QUICK DISSOLUTION AND PRODUCT FROM THEM 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. 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 pressure roll 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. Dr. Fuisz 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 volume housed of the final product is less than 30%, and preferably less than 15%, of the yarn volume as such 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. None of the methods described above provides a technique for forming a rapidly dissolving dosage unit that can be manufactured, shipped and sold to consumers. Therefore, it is an object of the present invention to provide a method for preparing such a dosage unit. Other and additional objectives will be achieved 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 dissolves rapidly by mixing unreacted shear form matrix and an additive, molding the mixture to form a unit dosage form, and curing the matrix in the form of shear strength. Preferably, the shear form matrix includes a crystallization enhancer and / or a ligation aid. The present invention also includes a fast dissolving edible unit which is characterized by a three dimensional crystal lattice bonded together to form a porous structure. Preferably, a "deformation modifier" of tabletting is incorporated into the mixture before molding. The deformation modifier may be part of a feedstock used to prepare the matrix in a shear form or may be added to the mixture prior to molding.

The shearing form matrix used to form dosage units according to the invention can be made with flavors and / or sweeteners included in the feedstock used to make the matrix. Flavors of natural and synthetic flavor liquids can be selected. Sweeteners are those materials that provide sweetness to the matrix in addition to the sweetness that is contributed by the carrier material used to form the matrix, for example sucrose. The present invention also includes an interim product used to make the unit dosage of rapid dissolution. The interim product includes matrix of shear stress, preferably yarn, and a deformation modifier. The mixture can be molded by introducing it into a unit dosage cavity and tampering the mixture therein. Generally, the shear form matrix is molded by compacting the matrix, e.g. fibers, to provide sufficient surface contact with surface for ligation and network formation. Surprisingly, the present invention allows the technician to achieve sufficient compaction by tamping. "Tamping", as used herein, means that the mixture is subjected to compression pressure of less than about 500 pounds per square inch (psi), preferably less than 250 psi, and with the greatest preference of around 20 to about 100 psi. The rammed mixture is then cured by subjecting it to environmental conditions of heat, humidity and pressure that induce crystallization. For example, the unit can be cured by increasing the heat under substantially constant moisture conditions. The heat can be increased by subjecting the tamped unit to microwave energy. In any case, the matrix is preferably cured in the presence of moisture. The additive, of course, is preferably an active ingredient such as a medicament. 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 feedstock 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. Another method of identifying the compression force required to mold uncured matrix according to the present invention is by identifying the density that results from tamping. The product of the present invention must be compressed in its uncured condition at a density no greater than about 1.2, preferably no greater than about 0.8, and most preferably no greater than about 0.65. In a preferred embodiment, the density of the finished product is between 0.25 and 0.40. It has been found that tablet formation is considerably improved by the use of strain modifiers. The tablet resistance can be increased without loss of porosity. The units prepared according to the invention have high porosity, ie from about 0.35 to about 0.75, and preferably from about 0.45 to about 0.65 (as used herein, porosity is defined as: 1 - (bulk density / true (or true) density) material without porosity.) The product prepared according to the aforementioned method can dissolve in the mouth of the consumer in less than 10 seconds, usually a product well made according to this process will dissolve in less than 5 seconds, and most preferably less than 3 seconds.The most highly dissolvable units have been described as literally "exploiting" in the mouth.The present invention also includes a composition for delivering an active ingredient, wherein the active ingredient is incorporated into a Said molded crystalline structure The composition also includes the saccharide-based structure which has a bi-dimensionally stabilized crystalline 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 United States patent application Serial No. 08 / -133,669, filed on 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 mass of shear stress * 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. Another embodiment of the present invention is an apparatus that implements the process of mixing and filling, tamping and curing in a continuous manufacturing process. The apparatus elements include filling, tamping and curing stations. Preferred embodiments of the apparatus of the invention include a mixer adjacent to, or in combination with the filling station. In another preferred embodiment, the apparatus also has packing capacity. This may include a continuous feed packing substrate and a forming station that provides the tamping cavities that are subsequently filled with the product in a mixed shear and additive form. And, in a further preferred embodiment, the apparatus may include a sealer that seals the final packaged product followed by a station that separates the continuous packing cavities, for example, by a die punch. The entire apparatus can be tracked in line by a box filling station to prepare boxes and loads, such as loads on pallets, for shipping. 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 process and apparatus described herein, an edible unit Rapidly dissolvable can be manufactured in a continuous way and even prepared for shipment to the consumer in a single manufacturing line. The product can be made to provide the surprising sensation of exploding in the oral cavity when ingested by the consumer. 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, wherein: Figure 1 is a microphotograph of a three-dimensional crystal lattice of an acetaminophen sample of the present invention, cured in a sealed environment for a period of time, and represented at 125 increases; Figures 2 and 3 are microphotographs of the same sample shown in Figure 1, taken at 250 and 500 magnifications, respectively; Figures 4,5 and 6 are photomicrographs of a three-dimensional crystal lattice of an acetaminophen sample of the present invention cured immediately after molding and taken at 125, 250 and 500 magnifications, respectively; Figure 7 is a block diagram of the process and apparatus of the present invention; and Figure 8 is a schematic representation of a preferred embodiment of a process and apparatus according to the present invention. Detailed Description of the Invention The present invention is a method of making edible units that dissolve rapidly in the consumer's mouth. The units produced according to the present invention have the ability to dissolve instantaneously in the mouth of the consumer. However, tablets can be produced, packaged and distributed for sale without deterioration during any step of the process all the way. In the past, tablets have been made primarily by compressing the feedstock under extremely high pressure in order to provide the necessary hardness for packing and dispensing. Accordingly, the prior art tablets thus produced are limited in that their high density reduces the ability to make them rapidly dissolvable in the mouth. The high density packing that results from the high compression of the tablet prevents the disintegration and wetting of the inner portion of the tablet. This aspect of the prior art has been improved by the technology described in United States Patent Application Serial No. 194,682, filed on February 10, 1994. However, as a result of the present invention, a Significant step forward in the field of preparation of edible units that are destined to dissolve in the mouth. The tablets produced by the present invention dissolve in a matter of seconds. The product is prepared by a unique combination of processing steps. The present invention also includes apparatuses for making tablets, as well as tablets (or dosage units) in themselves. The first step of the process is to mix a matrix of uncured shear form and an additive, such as an active ingredient, to prepare a unitary dosage for molding. "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. A preferred apparatus for implementing a heat runoff process is a "cotton candy" type machine. 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 shear force form matrix 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 upon application of a shear force of fluid. 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.

As previously mentioned, each of the carriers is used mainly in combination with sugars, and not as a total replacement. 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 a further embodiment of the present invention includes the use of an effervescent decay 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 mixtures thereof, 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. Acid salts may include sodium dihydrogen phosphate, dihydrogen dihydrogen pyrophosphate, salts acid citrate 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 of incorporating an effervescent disintegrating agent is to include all of 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 crystallization modifiers. 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 bound. 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. Any agents that positively affect the rate and / or the resistance of crystalline development can be used. For example, it has been found that certain alcohols are crystallization enhancers. 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%. A non-limiting list of other crystallization improvers is as follows: C-C5 alcohols, benzoyl alcohol, ethylene glycol, and propylene glycol. It is believed that the hydroxyl-bearing compounds are useful as crystallization modifiers mainly due to the interaction between amorphous izugar and hydroxyl groups. Hydrophilic, non-saccharide organic materials (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. Likewise, the 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 which 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 applicant intends to include all of those additional crystallization modifiers within the scope of the invention claimed herein. Another component that improves the final product of the present invention is a tabletting "deformation modifier". The value of deformation is the elastic limit of the material that is being tabletted. When a material is subjected to tableting pressure, there is a point of pressure beyond which the material loses memory, that is, it is permanently deformed and does not return to occupy a previous volume. At this point, ie the point of deformation, the material undergoes a permanent change of porosity in relation to the applied pressure. Other phenomena occur beyond the point of deformation, including ligation of ingredients and fracturing of materials that are being tabletted. The ligation occurs as a result of forced surface contact with surface that causes welding of the ingredients to occur together. When the tabletting material consists of fibers, the welds are spot welds that hold the network together. Fraction or rupture are the result of the pressure transmitted from a die press to and through the material that is being tabletted. For example, crystallized sucrose fibers fracture easily. It is desirable to obtain maximum ligation with minimum fracturing to achieve high porosity dosage units. In this way, it is desirable to improve the characteristics of plasticity and self-ligature of the material subject to the tabletting press. Tableting deformation modifiers contribute this characteristic. Tableting "deformation modifiers" are agents that can be added to the matrix of shear strength, especially fibers, to improve the integrity of the edible dosage units. The improvement usually occurs by improving the structural formation at a given pressure. In a sense, this improvement may simply mean reducing the pressure required to obtain the point of deformation. However, in another sense, the improvement occurs due to the fact that product formation is obtained structurally more suitable or "tighter" under the same pressure. This last improvement can be achieved because the pressure required to obtain the deformation point has been reduced. The improvement of the integrity seems to be achieved because the plasticity of the matrix is increased, again especially fibers, and the ability to adhere the matrix to itself is also increased, for example, spot welding the fibrous matrix at contact points . The strain modifiers can be added (1) to the feed material that is used to form the matrix, or (2) to the matrix after it is formed but before the tabletting. The deformation modifiers appear to affect the dissolution characteristics of the matrix. It has been found that carbohydrates having glass transition temperatures greater or less than the glass transition temperature of a carrier material in the feedstock are useful. For example, in the case of sucrose, strain modifiers include, but are not limited to the following: maltitol, xylitol, sorbitol, maltose, d-xylose, x-lactose, corn syrup solids, dextrose, polydextrose, lactitol, fructose, mannitol, palatinit and their combinations. Strain modifiers may be included in the mixture in an amount sufficient to improve the point of deformation. Preferably deformation modifiers are incorporated in an amount of not more than about 50% by weight, more preferably between about 5.0 and 40.0%, and most preferably between about 10.0 and about 25.0% by weight. It is also preferred to use the strain modifiers indicated in the aforementioned amounts where the shear-form matrix includes sucrose primarily as a carrier. The process of the present invention requires mixing an additive with the matrix in an uncured shear form.

When the shearing form matrix is in the form of a yarn, it is preferably first cut to reduce the volume of the product, without compressing it. The additive may be any ingredient or ingredients necessary to supply the required characteristics to the dosage unit. The main ingredients are 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-cholesterollemis, anti-lipid agents , anti-arrhythmic, antipyretic, 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-diarrhea preparations, anti-anginal drugs, vasodilators, anti-hypertensive drugs, vasoconstrictors, migraine treatments, anti-biotic, tranquilizers, anti-psychotic, anti-tumor drugs, anti -coagulants, anti-thrombotic medications, hypnotics, anti-emetics, anti-nausea agents, anti-convulsants, neuromuscular drugs, a hyper and hypoglycemic people, thyroid and anti-thyroid preparations, diuretics, anti-spasms, uterine relaxants, mineral and nutritional additives, anti-obesity drugs, anabolic medications, erythropoietic drugs, anti-asthmatics, cough suppressants, mucolytics cos, 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, antitussives, 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, mifenti-dine, 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 ingredients include binders that contribute to the ease of training and the overall quality of the tablet. Binders include starches, pre-gelatinized starches, gelatin, polyvinylpyrrolidone, methylcellulose, sodium carboxymethylcellulose., ethylcellulose, polyacrylamides, polyvinyloazolidone, and polyvinyl alcohols. Lubricants can also be used to help tamping and compaction. 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, sulfate lauryl magnesium, and light mineral oil. Further, disintegrants can be used to improve the dispersibility of the compressed tablet in an aqueous environment. Dispersants may include starch, alginic acid, polyvinyl pyrrolidones, guar gum, kaolin, bentonite, purified wood cellulose, sodium starch glycolate, isoamorph silicate, and microcrystalline cellulose. In view of the highly dissolvable nature of the product of the present invention, there is little need for disintegrants. Another useful ingredient in tabletting is the gliders, which adhere to the cohesive material in order to improve the flow properties by reducing inter-particle friction. Glidants that may be used include starch, talc, magnesium stearate and calcium, zinc stearate, calcium dibasic phosphate, magnesium carbonate, magnesium oxide, calcium silicate and silica aerogels. Color additives useful in the preparation of tablets 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. In a preferred embodiment, the present invention is particularly useful for preparing antacid 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 aluminosilicon, magnesium carbonate, magnesium glycinate, hydroxide of magnesium, magnesium oxide, magnesium trisilicate, milk solids, mono-ordibasic calcium aluminum phosphate, tricalcium phosphate, potassium bicarbonate, sodium tartrate, sodium bicarbonate, magnesium aluminosilicates, tartaric acids and salts. After the ingredients of the "additive" have been mixed with the matrix in an uncured shear form, the result of the mixture must be "molded" as a unit dosage form. It is used in the present "molding" to mean to associate matrix material in an uncured shearing (ie, without crystallizing) form sufficiently narrowly to provide bridging between the crystallized matrix material upon cure. Generally, this requires sufficient strength to provide intimate contact of the fibers before curing, followed by crystallization to form a continuous crystalline structure, bound through the entire tablet. Unlike conventional tableting, which is based primarily on compression to provide the structure, the present process uses the curing process to help form the final product. Consequently, faint compression forces, which can be referred to as compaction, can be used to mold the product. In a preferred embodiment, the compression required to mold uncured matrix material is referred to as "tamped". "Tamping" means compressing with a force less than that required in compression tabletting, which is generally considered to be in the order of thousands of pounds per square inch (psi). The maximum pressure used in the present invention is only 500 psi, but in most cases it will never exceed about 250 psi, and in the most preferred embodiments, no more than 80 psi (e.g., 40 to 80) psi). These lower pressures are called "tamped". Another method of measuring the compression force required to "mold" uncured matrix is by the density of the product. The product of the present invention must be compressed in an uncured condition at a density no greater than about 1.20, preferably no greater than 0.8, and most preferably no greater than 0.65. Yet another preferred feature of a product prepared according to the present invention is high porosity. When the shear force form matrix used in the present method is a fiber, a three-dimensional network is formed, which results in a "stable porous structure". "Stable porous structure" means, in the present, that the edible unit has (1) a strength capable of supporting manufacture and transportation associated with a commercial dosage unit, and (2) a porosity that accommodates the additives, such as active ingredients. , and facilitates rapid dissolution characteristics without excessive deterioration of the strength of the structure. The porosity can be determined by reference to the ratio of the true or actual density of the product, / i, to the absolute or bulk density, / 1. The porosity, e, has been expressed mathematically as e = 1- (pVp) • A porous product according to the present invention has a porosity greater than 0.1, preferably between about 0.35 and about 0.75, and with the highest preference between about 0.45 and about 0.65. While the present invention requires extremely low pressures for molding, it is possible to mold directly into plastic product cavities that can be used as packaging for sales. Accordingly, the present invention includes the concept of molding uncured matrix materials clearly in product cavities such as depressions in plastic blister packs. After preparing the matrix in the form of shear and mold the uncured matrix, the product must be cured. Cure means to ligate and crystallize the matrix material substantially simultaneously. The curing is carried out by subjecting the product to sufficient heat and moisture to provide controlled crystallization. Controlled crystallization occurs when contact points of uncured matrix material become crystalline development points and the crystallization of the material proceeds to provide crystalline structures. The ligation occurs at the contact points, and the simultaneous crystalline development is such as to maintain structural integrity.

The "curing" process of the present invention involves a transformation from amorphous to crystalline state. The transformation must take place while the amorphous matrix of shear force remains linked. Moreover, curing requires that the transformation take place without collapsing the structural integrity of the matrix in its "shaped" condition. As the amorphous shear-form product is hygroscopic, this transformation can be difficult. When the points of contact between pieces of the matrix can become points of crystalline development during the curing, structural integrity is established and conserved. One way to promote the occurrence of this phenomenon is to include crystallization enhancers, for example surfactants, any alcohol, polyethylene glycol, polypropylene glycol, etc. Without being bound by theory, it is believed that the control of the propagation of crystalline development, as outlined above, is significantly improved by the use of crystallization enhancers. Prior to curing, the mixture of the matrix of shear form and active ingredient is maintained at a temperature and a humidity lower than the glass transition temperature of the matrix material in shear form. Suitable conditions for curing may include environmental conditions of heat and humidity or modified environmental conditions. For example, it has been found that curing can be conducted at a temperature of 0 to 90 ° C and a relative humidity of 25 to 90%. In one case, curing has been found to take place in 15 minutes at 40 ° C and 85% relative humidity. In other cases, it has been found that the optimal temperature range is 20-50 ° C. Microwave energy can be used to accelerate curing in a controlled manner. Generally, crystallization is carried out in an environment in which the tableted material is cured at a water content of less than 5% by weight, and preferably less than 1% by weight, based on the weight of the tablet. In this way, the curing environment, for example chamber or enclosure, is maintained at a relative humidity that allows water to be taken in no more than 5%, and preferably less than 1%. It has been found that curing the product in a packing cavity results in shrinkage of the tablet from the walls of the cavity. This feature is particularly advantageous for the purpose of manufacturing individual dosage units, since molding and curing can be carried out in the package used for commercial sales. As a result, several transfer steps can be eliminated. The crystal base network formed in the present invention is outlined in Figures 1-3. These figures show a product that has been prepared with acetaminophen as an additive. The product was cured over time, ie 24-36 hours in a sealed product cavity. The microphotographs, which are taken at 125, 250 and 500 magnifications, respectively for figures 1, 2 and 3, clearly show a network. The net, which appears as a nest, provides a porous structure where the active ingredient, acetaminophen, is held. The network is crystalline based, which means that at least 10%, preferably 30%, and most preferably at least 50% of its structure is crystalline. In most cases, substantially the entire structure is crystalline. Figures 4, 5 and 6 also sketch a three-dimensional crystal base network, in a sample prepared according to the invention. The sample of Figures 4, 5 and 6 was cured immediately after molding, while the sample of Figures 1, 2 and 3 was cured some time after molding, for example 24-36 hours, in a controlled environment provided by a sealed product cavity. It has been found that the products prepared according to the present invention have densities from about 0.20 to about 0.90 g / cc, and some preferred embodiments have densities from about 0.40 to about 0.65 g / cc. Another ingredient that can be included in the matrix in the form of shear is a coadjuvant or agglutination agent or ligature. An agglutination agent is used to assist in the molding step and, in some cases, it contributes to the dissolution capacity of the finished product. Ligation agents useful herein include low glass transition temperature materials. Some agents that were found useful include, but are not limited to, sorbitol, mannitol, lactose, etc. Agglutination or ligation agents also help to keep the matrix material in place for curing. In some cases, portions of the binder become part of the matrix material. Referring to Figure 1, a schematic representation of the process and apparatus according to the present invention is shown. In particular, a mixing station 10 is shown in combination with a forming station 12 and a curing station 14, which are located in series and downstream of the mixing station 10. The mixing station 10 can receive feed material of a shear-shaped product source 22. The shear-form product source may be a run-off flow processing apparatus such as previously described herein. The source of the product in the form of shear can also include an apparatus for weighing. The pre-mixer apparatus may also include a maceration (or cutting) station 22, in which the product in the form of shear in the form of thread can be cut. The mixing station 10 may also receive additive material from a station 30. The station 30 may also include an apparatus for weighing and mixing so that the additive can be prepared in an appropriate manner before being mixed with the product in a shear-off manner in the station 10. In the training station 12, dosage units are formed by tamping. The dosage units formed in station 12 are then transferred to a curing station 14, which may include heat, pressure and humidity control means to provide the desired type of curing. Optionally, the process of the present invention can also include a packaging station 40. In order to demonstrate a preferred form of the invention, reference will be made to Figure 2. In Figure 2, an online apparatus and a process are sketched. schematic, wherein the plastic material can be continuously provided from the roll of material 9. The plastic material can then be formed into a continuous tray having product cavities 6 by means of vacuum forming in the vacuum forming station 8. Each one of the cavities 6 can be filled in the filling and forming station 11. The filling and forming station 11 in Figure 2 includes stations 10 and 12 of the schematic process shown in Figure 1. That is, both product form Shear stress as an additive can be mixed, delivered to each of the cavities 6, and formed by tamping at the station 11 shown in Fig. 2. Continuing to l After the process of Figure 2, the product can then be cured in the curing station 13. Cover material, such as continuous sheet material, can be fed from a roll of material 41, and securely attached ( such as by adhesion) to the upper part of the continuous material of plastic tray 9, thereby sealing product cavities 6. In order to obtain packages of units suitable for sale to individual customers, the continuous sheet can then be separated into lengths of size of the consumer by a die punch 43. Finally, the consumer size packages can then be stored in a box in the packing station 45. The boxes can then be loaded for shipping as, for example, in a palletized configuration. It has been found that the present invention is ideally suited for preparation of anti-acid tablets and tablets in which they are used as an ingredient to alleviate acidic conditions in the body in order to help drugs that do not tolerate acidic conditions. In the case of the anti-acids themselves, the instant dispersion of the tablet in the mouth prevents the residual gis taste of a conventional anti-acid tablet. In the case of ingredients that do not tolerate acidic conditions, it is desirable to include the anti-acids plus the "acid sensitive" pharmaceutical product in a dosage unit prepared according to the invention. For example, didanosine is an anti-viral agent that does not tolerate an acidic environment well. Accordingly, the use of didanosine in combination with an antacid such as calcium carbonate in the same drug delivery system is an ideal method of introducing the drug into the body. The present invention includes the combination of an "acid sensitive" ingredient and an anti-acid in a dosage unit. Actual tests have been conducted to show the effectiveness of the present invention. These examples have been set forth herein for purposes of illustration and demonstration. However, the scope of the invention should not be limited by the examples in any way. The shear force matrix material used in the following examples is an amorphous sugar. Amorphous sugar is used herein as a sugar material that contains a high percentage of amorphism, ie more than 50% by weight, and preferably more than 70% by weight of the sugar material is amorphous. In all the examples, the matrix of shear stress was analyzed by differential scanning calorimetry (DSC) and polarized light under a microscope. In each case, the matrix was formed in shear form to be substantially amorphous before the active ingredient was added. EXAMPLES Example of Anti-Acid A matrix of shear form for use in the process of the present invention was prepared. The matrix was prepared by subjecting a physical mixture of appropriate ingredients to flow-by-flow processing in a cotton candy type apparatus. The combination included saccharide-based carrier material, sucrose, sorbitol as an agglutination agent, and a surfactant known as Tween 60, provided by ICI. The physical mixture was provided according to the formula indicated below in Table 1 of the Strain Endeavor Form Matrix. Cutting Effort Form Matrix Table 1 Quantity in Weight Percentage Sugar (sucrose) 84.75 g 84.75% Binding agent (sorbitol) 15.00 g 15.00% Surfactant (Tween 60) 0.25 g 0.25% 100.00 g 100.00% The sorbitol, the sucrose and the surfactant were mixed by hand, then mechanically in a mixing apparatus.

The resulting mixture was introduced to an Econo Flmachine and processed by runoff at approximately 3,600 rpm. The shear form matrix resulting from the processing was an uncured white yarn of reduced volume per cut. After preparation of the shear-form matrix, an additive was mixed with uncured matrix material. The total combination is indicated below in Table 2 of Unit Dosage. Table 2 Unit Dosage Ingredient Percentage Shaft of shear form (thread of Table 2) 46, .70% Calcium carbonate (CaC03) 50, .00% High intensity sweetener (aspartame) 0, .30% Flavoring 2, .50% Polyethylene glycol ( PEG 300) 0, .50% 100.00% The ingredients mentioned above were mixed in order to prepare them for formation and curing. The resulting mixture of Unit Dosage Table 2 was weighted in samples of 0. 75 g and introduced in molds of approximately 0.75 in diameter. Tablets were formed by tamping the ingredients at pressures of both 60 and 80 psi. The tablets formed were cured in an oven at 40 ° C and a relative humidity of 85% for approximately 15 minutes. The resulting tablets were very attractive looking, with a smooth and shiny surface. Tablets were also prepared in a smaller mold having a diameter of about 0.65 in. Similarly, the smaller tablets were molded at 60 and 80 psi and cured according to the procedures outlined above. The resulting product also had an attractive appearance, with a smooth and shiny surface. The tablets that result from this procedure were melted very quickly. They do not have a gis sensation in their mouth during their consumption. The taste was excellent. Example of Anti-Acid 2 The procedures outlined above were repeated with a different anti-acid formulation. The new formulation also used the cut or macerated yarn prepared according to Table 1 of the Strain Endeavor Form Matrix. The new formulation is indicated in Table 3 of Unit Dosage. Table 3 of Unit Dosage Ingredient Porc enta e Matrix of shear form (thread of Table 1) 46. . 20% Calcium carbonate (CaC03) 50,. 00% High intensity artificial sweetener (aspartame) 0. . 30% Flavoring 2,. fifty%" Polyethylene glycol (PEG 300) 0,. 50% Pigment (Red FD &C No. 40) 0,. 50% 100.00% Tablets were similarly made to the process established with respect to Unit Dosage Formula 2, both with large and small molds and both at 60 and 80 psi. The colored tablets produced according to the third unit dosage formula were similar to those produced with the first formula. The tablets made with the third formula were very fast dissolving and had a smooth and shiny surface. After four days, the tablets had set. They do not manifest a gis sensation in their mouth when they are consumed. The tablets retained structural stability while in the product cavities.

Tablets prepared according to formula 2 and formula 3 had sufficient hardness for subsequent handling and distribution to consumers. Example of Ibuprofen A matrix material was prepared in shear form according to the formula set forth in Table 4 of Cutting Effort Form Matrix. Table 4 Cutting Strain Form Factor Ingredient Percentage Sugar (sucrose) 84.75% Binder (sorbitol) 12.00% Binder (alpha-lactose) 3.00% Surfactant (Tween 80) 0.25% 100.00% Sucrose, sorbitol and lactose were first mixed by hand and then by machine until a homogenous physical mixture was produced. To this mixture, surfactant was added and mixed by hand. The physical mixture was then subjected to flow-through processing in an Econo Floss No. 7025 machine at approximately 3,600 rpm at a high temperature reading. The spun material was collected as yarn and macerated in a mixing machine for about 45 seconds. The resulting material was a matrix of shear force form of reduced volume, in uncured condition. A mixture of ibuprofen was prepared according to the present invention, in accordance with the formula set forth below in Table 5 of Ibuprofen.

Ibuprofen Table 5 Ingredient Amount * ad Weight Percentage Cutting force form matrix (thread of Table 4) 54.41 g 60.46% Ibuprofen (microcapsules) 28.88 g 32.09% Flavor 5.40 g 6.00% High intensity artificial sweetener (aspartame) 0.72 g 0.80% Lecithin (Yelkin DS) 0.32 g 0.35% Silica (Syloid 244) 0.23 g 0.25% Orange color 0.05 g 0.05% 90.01 g 100.00% 'Lecithin and ibuprofen were mixed and added to the ground yarn material. The ingredients were mixed in a mechanical mixing apparatus for 15-20 seconds. The flavors, the high intensity sweetener, and silica were then added and mixed mechanically for an additional 10-15 seconds. Finally, color was added and mixed until the physical mixture became a homogeneous orange color. The ingredients were well mixed on a large scale. / The mixture had a homogeneous density and excellent flow characteristics. The mixture was added in portions of 0.75 g to a die having a diameter of 0.65 in. The ingredients were then rammed at a pressure of 80 psi. The tamped dosage units were then cured. Some of the tablets were cured for one day at room temperature and then the packages were sealed for testing at a later date. In general, the resulting tablets after curing were smooth and easy to handle, without disintegration of the tablet units. Moreover, the tablets quickly dispersed in the mouth and produced little or no unpleasant sensation in the mouth. The ibuprofen product included highly desirable unit dosages for ingestion by consumers. Example of Aspirin "A shear-form matrix was prepared according to the same formula and the same procedures as noted above with respect to the ibuprofen example.An aspirin sample formulation was prepared according to the amounts indicated below in Table 6 of Aspirin Table 6 of Aspirin Ingredient Quantity Weight Percentage Cutting force form matrix (thread of Table 4) 17.10 g 62.18% • / Aspirin 9.00 g 32.73% Flavor 1.00 g 3.64% High intensity artificial sweetener (aspartame) 0.25 g 0.91 ' Wetting agent-lecithin (Yelkin DS) 0.10 g 0.36 Flow agent (Syloid 244 FP) 0.05 g 0.18? 27.50 g 100.00% Aspirin and lecithin were mixed and then added to the matrix in the form of shear shear. These ingredients were mixed and then the high intensity flavors and sweeteners were added, and mixing was continued. Finally, the flow agent and the colors were added and the mixing was continued until a homogeneous mixture was obtained. The physical mixture was introduced into product cavities and then rammed at 80 psi to form dosage units containing aspirin. The tablets were then cured, allowing them to remain at room temperature for about a day. These samples were tested and it was found that the dosage units dissolved in the mouth in less than 5 seconds. The taste was good and there was no residue or feeling of chalk in the oral cavity. Another example of aspirin was prepared according to the table indicated below. Table 7 of Aspirin Ingredient Quantity Weight Percentage Cutting force form matrix (thread of Table 4) 14, .60 g 58.40% Aspirin 9, .00 g 36.00% High intensity artificial sweetener (aspartame) 0, • 25 g 1.00% Taste 1, .00 g 4.00% Wetting agent-lecithin (Yelkin DS) 0, .10 g 0.40% Flow agent (Syloid 244 FP) 0, .05 g 0.20% 25.00 g 100.00% 20 tablets were prepared according to the procedure indicated above with respect to the first examples of aspirin. That is, the unit dosages were ramped to 80 psi and allowed to cure overnight at room temperature and humidity. The resulting tablets were attractive and had a good flavor and texture. They melted very quickly in the mouth, that is, generally in less than 5 seconds. Acetaminophen Example The yarn used in the acetaminophen preparations is the same yarn prepared according to Table 4 of the Matrix of Form of Cutting Effort. A physical mixture of ingredients was prepared according to the formula set forth in Table 8 of Acetaminophen. Table 8 Acetaminophen Ingredient Quantity Weight Percentage Cutting force form matrix (thread from Table 4) 11.01 g 44.04% Acetaminophen 12.19 g 48.76% Flavor 1.50 g 6.00% High intensity artificial sweetener (aspartame) 0.20 g 0.80% Wetting agent-lecithin (Yelkin DS) 0.09 g 0.35 % 24.99 g 100.00% The spun and cut shear form matrix was mixed with acetaminophen and lecithin to coat the medication. Cutting shear form matrix, additional was mixed, until a uniform mixture was obtained. The remaining ingredients were added and physically mixed until a uniform mixture was obtained. Tablet samples were introduced into the molds for tablets. 0. 90 g of the mixture for tablets. The tablets were formed by tamping at 60 psi. Half of the tablets were cured at 40 ° C and a relative humidity of 80% for 15 minutes, in order to cure. The remaining half of the tablets were allowed to cure at room temperature for about a day. The tablets produced by both curing methresulted in rapidly dispersible, high quality units, having excellent mouthfeel and good taste. It is considered that these products are commercially valuable because it is known that the taste of acetaminophen is quite astringent and unpleasant to the consumer. 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 (66)

1. CLAIMS 1. A method of preparing fast dissolving edible units, comprising: mixing uncured shear form matrix and an additive; molding a unit dosage form; and curing said matrix in the form of shear stress.
2. 2. The method of preparing fast-dissolving edible units, according to claim 1, wherein said shear-shaped form matrix further comprises a crystallization enhancer.
3. 3. The method of preparing fast-dissolving edible units, according to claim 1, wherein said shear-shaped form matrix comprises a binder.
4. 4. The method of preparing fast dissolving edible units, according to claim 1, wherein said molding comprises introducing the mixture resulting from the mixing step into a unit dosage cavity and compacting to provide sufficient surface contact with surface of said matrix for agglutinate said matrix for network formation when curing.
5. The method of claim 4, wherein said compaction comprises tamping.
6. 6. The method of preparing fast-dissolving edible units, according to claim 1, wherein the curing comprises subjecting to environmental conditions of heat, humidity and pressure that induce crystallization.
7. 7. The method of preparing fast-dissolving edible units, according to claim 6, wherein said heat is increased under substantially constant moisture conditions.
8. 8. The method of preparing fast-dissolving edible units, according to claim 7, wherein said heat is increased by subjecting to microwave energy.
9. 9. The method of preparing fast-dissolving edible units, according to claim 1, wherein said additive comprises an active ingredient.
10. The method of preparing fast-dissolving edible units, according to claim 9, wherein said active ingredient is selected from the group consisting of anti-tress, 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, medications anti-thrombotic, hypnotic, anti-emetics, anti-nausea agents, anti-convulsants, neuromuscular drugs, hyper and hypoglycemic agents, thyroid and anti-thyroid preparations, diuretics, anti-spasmodics, uterine relaxants, mineral and nutritional additives, anti-drugs -obesity, anabolic drugs, erythropoietic drugs, anti-asthmatics, cough suppressants, mucolytics, anti-uricémics and their mixtures.
11. The method of preparing fast dissolving edible units, according to claim 10, wherein said active ingredient comprises an anti-acid and a pharmaceutical ingredient that is adversely affected by an acidic environment.
12. 12. The method of preparing fast-dissolving edible units, according to claim 5, wherein said tamping is carried out at a pressure of less than about 500 psi.
13. The method of preparing fast-dissolving edible units, according to claim 12, wherein said pressure is less than about 250 psi.
14. 14. The method of preparing fast-dissolving edible units, according to claim 13, where said pressure is around 20 to about 100 psi.
15. 15. The method of preparing fast dissolving edible units, according to claim 1, which further comprises incorporating an effervescent decay agent into said unit.
16. 16. The method of preparing fast-dissolving edible units, according to claim 1, wherein said curing provides a porous network of three-dimensional crystalline base, bonded to form a stable structure.
17. 17. The method of claim 16, wherein said network is not less than about 10% crystalline.
18. 18. The method of claim 17, wherein said network is not less than about 30% crystalline.
19. 19. The method of claim 18, wherein said network is not less than about 50% crystalline.
20. The method of claim 1, which further comprises adding a deformation modifier prior to molding.
21. The method of claim 20, wherein said deformation modifier is added by one of the following steps: (i) including said modifier in the feed material used to form said die in the form of shear stress; (ii) incorporating said modifier as part of said mixing step; and (iii) both by the inclusion of (i) and the incorporation of (ii).
22. The method of claim 21, wherein said deformation modifier is selected from carbohydrates having glass transition temperatures either greater or less than the glass transition temperature of a carrier material included in the feed material used to form said matrix of shear stress.
23. The method of claim 22, wherein said strain modifier is selected from the group consisting of maltitol, xylitol, sorbitol, maltose, d-xylose, x-lactose, corn syrup solids, dextrose, polydextrose, lactitol, fructose , mannitol, palatinit and their combinations.
24. 24. An edible unit of rapid dissolution, comprising: a porous network of crystalline, three-dimensional base, linked to form a stable structure.
25. 25. The unit of claim 24, wherein said unit further comprises a crystallization enhancer.
26. 26. The unit of claim 24, wherein said unit further comprises a binder.
27. 27. The unit of claim 24, which further comprises an additive.
28. 28. The unit of claim 27, wherein said additive comprises an active ingredient.
29. 29. The unit of claim 28, 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 -cholesterolemic, anti-lipid agents, anti-rheumatic, anti-pyrimic, analgesic, appetite suppressants, expectorants, anti-anxiety agents, anti-ulcer agents, anti-inflammatory substances, coronary dilators, brain 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, anti-nausea agents , 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 medications, erythropoietic drugs, anti-asthmatics, suppressants of cough, mucolytics, anti-uricémicos medicines and their mixtures.
30. 30. The unit of claim 29, wherein said active ingredient comprises an anti-acid and a pharmaceutical ingredient that is adversely affected by an acidic environment.
31. 31. The unit of claim 24, which further comprises an effervescent disintegrating agent.
32. 32. The unit of claim 24, wherein said network is not less than about 10% crystalline.
33. 33. The unit of claim 32, wherein said network is not less than about 30% crystalline.
34. 34. The unit of claim 33, wherein said network is not less than about 50% crystalline.
35. 35. The unit of claim 24, which has a porosity of about 0.35 to about 0.75.
36. 36. The unit of claim 35, wherein said porosity is from about 0.45 to about 0.65.
37. 37. The unit of claim 24, which further comprises a deformation modifier.
38. 38. The unit of claim 37, wherein said strain modifier is selected from the group consisting of maltitol, xylitol, sorbitol, maltose, d-xylose, x-lactose, corn syrup solids, dextrose, polydextrose, lactitol, fructose. , mannitol, palatinit and their combinations.
39. 39. Apparatus for the preparation of rapidly dissolving edible units, comprising: a mixing station for physically mixing untreated shear form matrix and an additive; a molding station, wherein said mixture of matrix of shear stress and an additive is subjected to compression of molding substantially less than that required for the formation of a tablet by compression, said molding station connected to receive a mixture of said mixing station; and a curing station wherein said uncured shear form matrix that has been formed is crystallized in a controlled manner.
40. 40. The apparatus of claim 39, further comprising a run-through flow processing apparatus that is connected to said mixing station for transferring the die in the form of shear to it.
41. 41. The apparatus of claim 39, wherein said mixing station further comprises an apparatus for macerating matrix yarn material in shear form.
42. 42. The apparatus of claim 41, wherein said macerating apparatus further includes means for weighing said matrix in the form of sheared shear.
43. 43. The apparatus of claim 39, wherein said mixing station further comprises means for introducing an additive to said mixing station.
44. 44. The apparatus of claim 43, wherein said means for introducing an additive includes weighing means for measuring the amount of said additive.
45. 45. The apparatus of claim 43, wherein said forming station comprises means for delivering a quantity of mixture to a product cavity and compressing said mixture therein.
46. 46. The apparatus of claim 45, wherein said means for compressing comprises a ramming machine delivering a force not greater than 500 psi.
47. 47. The apparatus of claim 39, wherein said curing station comprises means for controlling the ambient heat of the curing environment, means for controlling the ambient pressure of the curing environment, and means for controlling the ambient humidity of the curing environment.
48. 48. The apparatus of claim 39, which further comprises a packaging apparatus.
49. 49. The apparatus of claim 48, wherein said packaging apparatus comprises a source of plastic, continuous packing material and a vacuum forming station that provides product cavities in said continuous material, said source of material and said forming apparatus. vacuum placed upstream of and capable of continuously providing material provided with product cavities.
50. 50. The apparatus of claim 49, wherein said mixing station further comprises means for filling each of said product cavities resulting from said vacuum forming station.
51. 51. The apparatus of claim 50, wherein said curing station comprises a chamber through which said material is passed provided with product cavities for continuous curing.
52. 52. The apparatus of claim 49, wherein a source of cover material is provided to join said continuous material formed with product cavities.
53. 53. The apparatus of claim 49, further comprising a separator separating said continuous seal product containing material in units for consumer sales.
54. 54. The apparatus according to claim 49, further comprising a separator separating said continuous material containing sealed product into units for consumer sales.
55. 55. The apparatus according to claim 48, which further comprises means for packaging containers with multiple units for sale to the consumer. 56. A composition for delivering an active ingredient, comprising: an active ingredient; and a crystalline structure based on saccharides, comprising a stabilized crystalline matrix produced by means of (i) forming amorphous sugar masses in shear form, (ii) molding said masses to form a unit dosage having a porous network, and (iii) subsequently converting portions of said doughs into a fully crystalline structure substantially that is bonded and stabilized to form a porous network, said active ingredient mixed with said doughs before molding, whereby said active ingredient is incorporated into said dough. crystalline structure based on saccharides.
56. 56. The composition of claim 55, wherein said masses are bi-dimensionally monodisperse.
57. 57. The composition of claim 55, wherein said shear force masses comprise an additive, whereby said additive is co-crystallized in said crystalline product.
58. 58. The composition of claim 56, wherein said stabilized, monodisperse masses are microcrystalline.
59. 59. The composition of claim 56, wherein said amorphous shear-shaped product is substantially rod-shaped, said two dimensions lying in a cross-sectional plane of said bar and a third dimension extending along the linear axis of said bar.
60. 60. The composition of claim 59, wherein the structurally stabilized, monodisperse cross section does not exceed 50 μm.
61. 61. The composition of claim 60, wherein said cross section does not exceed 10 μm.
62. 62. A method of administering an active ingredient to a human host, comprising: ingesting a rapidly dissolving edible unit prepared by the method comprising: (i) mixing matrix in an uncured shear form and an active ingredient; (ii) molding a unit dosage form, and (iii) curing said matrix in shear form; 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 into said oral cavity while said unit is retained therein, thereby speeding up the dissolution of said unit significantly.
63. 63. An edible fast-dissolving unit prepared by the method comprising: mixing untreated shear form matrix and an additive; molding a unit dosage form; and curing said matrix in the form of shear stress.
64. 64. An intermediate product for making a fast-dissolving edible unit, comprising: a shear-form matrix and a deformation modifier.
65. 65. The product of claim 64, wherein said shear-form die is a yarn.
66. 66. The product of claim 64, wherein said deformation modifier is added to feed material used to make said die in shear form.