KR100823524B1 - Double Convex Rapid Collapse Type - Google Patents

Abstract

The present invention relates to a process for the preparation of rapid disintegrating solid dosage forms molded as both convex tablets with symmetrical top and bottom surfaces, and to the formulations obtainable thereby.

Description

Biconvex Rapid Disintegrating Formulations

The present invention relates to a process for the preparation of rapid disintegrating solid dosage forms molded as both convex tablets with symmetrical upper and lower surfaces, and to the formulations obtainable by the method.

Rapid disintegrating solid formulations filled with an amount of active ingredient are known from GB-A-1,548,022 (US-4,305,502). These solid dosage forms comprise a porous network of matrix materials that carry the active ingredient, which matrix material consists of a water soluble or water dispersible carrier material. Solid formulations are prepared by lyophilization or lyophilization of a solvent from a frozen solution or suspension of the matrix material and the active ingredient.

Various improvements have been developed to prepare formulations by lyophilization. GB-A-2,111,423 and US Pat. No. 4,371,516 disclose methods for producing solid formulations which are rapidly disintegrated by water and in which a network of matrix substances carries a certain amount of active ingredient, in particular pharmaceutical substances. Many applications are found for such formulations, particularly where it is necessary to administer, formulate or vice versa the active ingredient in a unit dose. For example, solids which are used in the form of solutions or suspensions, but which are difficult to transport or store in this form or which are harmful to the user, can be added to the aqueous medium to produce the desired solution or suspension containing a certain amount of the active ingredient. Can be converted into a form. The active ingredient may also be a reagent that can be added to a known amount of an aqueous liquid to produce a standardized liquid composition and then used, for example, for chemical analysis. In addition, the active ingredient may be a diagnostic compound that is added to a biological sample (eg blood, urine) to determine the amount of a particular ingredient present in the sample. However, preferably, the active ingredient is a human or veterinary drug substance. Fast dissolving solid drug formulations are particularly suitable for oral administration. When orally administered, they generally disintegrate rapidly within the oral cavity (eg within 1 or 2 seconds) and thus this formulation is a particularly useful means for administering the drug to humans and animals. Such formulations may be used for patients such as humans and animals that are difficult to swallow these conventional formulations as a separate means for conventional tablets, pills or capsules.

US-4,642,903 teaches a process for preparing lyophilized foam formulations using conventional lyophilization techniques to obtain rapid dissolving pharmaceutical formulations.

In WO-93 / 23017, there is a problem inherent to the conventional freeze-drying method, namely the lack of uniform porosity in the freeze-dried product. Uniform porosity in the lyophilized product is important for post-loading placabo or unfilled formulations with active ingredients. WO-93 / 23017 relates to a process for the preparation of formulations which avoids cracking and remelting, which have moderate strength and porosity and which will exhibit a fast dissolution rate.

Other methods of preparing solid dosage forms that disintegrate rapidly in the oral cavity, namely solid state dissolution techniques, are disclosed in US-5,039,540, US-A-5,215,756, US-A5,330,764 and US-5,298,261.

GB-2,119,246 relates to a process for preparing a solid dosage form using a mold having one or a plurality of sidewalls which diverge outward from the bottom and at an angle of at least 5 ° from the surface of the composition. When lyophilizing this type of underfilled mold, a solid molded product with a more even thickness is obtained and therefore flatter than a product obtained from a less filled mold with sidewalls perpendicular to the base.

Solid dosage forms provided by the prior art are used to dispense an amount of the active ingredient. Since the administration of such products is associated with a number of risks, it is necessary to package them appropriately, for example in blister packaging, and to give them identity.

According to the prior art methods, the packaging of rapid disintegrating solid formulations, in particular produced on an industrial scale, is associated with many specific problems. First, the crushability of such formulations seriously limits how the formulation is shipped and handled. As a result, the reduction in crushability of the fast disintegrating solid formulations will greatly increase the industrial utility by relaxing the manufacturing pressures. A second problem directly related to the form of the fast disintegrating solid formulations prepared according to the methods of the prior art is the fact that the top and bottom surfaces of the formulations are sometimes symmetrical. Typically the bottom will be a flat surface that is somewhat perpendicular to one or a plurality of sidewalls of the formulation, whereas the top surface may be concave or planar depending on the extent of filling the mold. Formulations with different top and bottom formulations may require a process step to direct them to the correct position before filling them into the blister package (this process detects the orientation of each individual form, Selecting and converting the formulations).

1 is a view from above of 0.5 ml oval mold (scale 5: 1),

2 and 3 show two cross-sections of the mold of FIG. 1,

4 is a view from above of 0.1 ml of a circular mold (scale 5: 1);

5 and 6 show two cross-sections of the mold of FIG. 4,

7 is a top view of a square mold with 0.5 ml rounded corners,

8 and 9 show two cross sections of this mold,

FIG. 10 shows the round mold together with the corresponding both convex solid formulations obtainable in the present invention. FIG.

FIG. 11 shows the round mold and the corresponding both convex solid formulations obtainable in the present invention.

The invention is further illustrated by the following examples in which the active ingredient is a pharmaceutical. It will be appreciated that the method according to the invention and the formulation obtainable thereby can be applied to many different forms of active ingredient.

Experiment

Many essential parameters for defining a convex mold in accordance with the present invention are set forth in Table 1 below. The following variables are suggested:

Vt: formulation volume

Sc: surface confined by mold te

Hc: Height of the mold sidewalls perpendicular to Sc

Hm: height of the meniscus (also the depth under the mold convex)

Ht: total height of the formulation = Hc + 2 Hm

Curve 1 (2): Long and small axis values defining an elliptic curve describing the intersection of the top surface of the meniscus with the first (second) cross section along one of the planes of symmetry.

Vc: mold partial volume provided by Sc x Hc

Vm: volume of the meniscus or convex bottom of the mold provided by (Vt-Vc) / 2

Square tablets are shown in FIG. 7, oblate tablets are shown in FIG. 4, elliptical tablets are shown in FIGS. 1 and 10, and round tablets are shown in FIG. 11.

TABLE 1a

Variable / type Square tablets Oblong tablet Vt = _total volume 500 mm ³ 1,000 mm ³ Sc = surface _center Length = 11 mm Rounded corner r = 1.4 mm Area = 119.8 mm ² Length = 20 mm Rounded corner r = 5 mm Area = 178.54 mm ² Hc = height _Zhong 2.00 mm 2.70 mm Hm = height _meniscus 1.80 mm (90%) 2.20 mm (81.5%) Ht = _overall height 5.60 mm 7.10 mm Curve 1 Long axis = 11 mm Small axis = 3.6 mm Long axis = 20 mm Small axis = 4.4 mm Curve 2 Long axis = 14.4 mm Small axis = 3.6 mm Long axis = 10 mm Small axis = 4.4 mm Vc = _middle volume = Sc x Hc 239.6 mm ³ (47.9%) 482.06 mm ³ (48.2%) Vm = volume _meniscus = (Vt-Vc) / 2 130.2 mm ³ (26%) 258.97 mm ³ (25.8%)

TABLE 1b

Variable / type Square tablets Round tablet Vt = _total volume 500 mm ³ 1,000 mm ³ Sc = surface _center Length = 17 mm Rounded corner r = 9.3 mm Area = 124.17 mm ² r = 8.4 mm area = 221.67 mm ² Hc = height _Zhong 2.25 mm 2.34 mm Hm = height _meniscus 1.75 mm (77.8%) 1.85 mm (79.1%) Ht = _overall height 5.75 mm 6.53 mm Curve 1 Long axis = 17 mm Small axis = 3.5 mm Long axis = 16.8 mm Small axis = 3.7 mm Curve 2 Long axis = 9.3 mm Small axis = 3.5 mm Long axis = 16.8 mm Small axis = 3.7 mm Vc = _middle volume = Sc x Hc 279.39 mm ³ (55.9%) 518.71 mm ³ (51.2%) Vm = volume _meniscus = (Vt-Vc) / 2 110.31 mm ³ (22.1%) 240.65 mm ³ (24.1%)

The present invention provides a simple solution to all of these problems, consisting of imparting symmetrical convex top and bottom surfaces to the fast disintegrating solid formulation. First, a formulation with less acute angle between one or more sidewalls and an upper or lower surface that reduces the breakability of the formulation is obtained. Symmetry also means that once the formulation is removed from the mold there is no longer a difference between the bottom and top of the formulation. Both convex forms have the additional advantage that they can easily be arranged to gently rock the formulation to lie on one side of their convex surface. In addition, they are easily picked up by the patient or person administering the formulation during or after manufacture and packaging.

Both convex forms of the solid formulations prepared according to the invention also serve to distinguish them from other prior art formulations and thus assist in the prevention of mistakes by physicians, pharmacists or end users, patients when administering medicaments filled in both convex formulations. can do.

The present invention relates to a process for the preparation of a fast disintegrating solid formulation comprising a porous network of matrix forming materials, the method

Filling the mold with an amount of an aqueous composition comprising a matrix forming material such that convex meniscus is produced on top of the mold;

Freezing the aqueous composition in the mold;

Removing the solvent from the frozen composition by performing lyophilization or solid state dissolution on the frozen composition, thus obtaining a porous network of matrix forming material,

The shape of the lower surface of the mold is a mirror image in the form of an upper frozen meniscus, the mirror-plane being parallel to the plane defined by the rim of the mold, and thus shaped as both convex tablets with symmetrical upper and lower surfaces. It is characterized by obtaining a formulation.

The aqueous composition can be frozen by conventional cooling processes. For example, the aqueous composition can be dispersed into a preform mold corresponding to the size and shape of the desired formulation and then frozen by cooling the mold on a freezer shelf or in a freezer. Alternatively, the mold containing the mixture can be passed through a cooling gas or vapor, such as a stream of liquefied nitrogen in the refrigeration tunnel. In a preferred method of refrigeration, the composition is passed through a refrigeration tunnel into which liquefied nitrogen is injected, the liquefied nitrogen evaporates and the resulting cooling gaseous nitrogen passes over the composition. Another method of freezing the aqueous composition in the mold is to enclose the mold in dry ice until the aqueous composition is frozen.

The best known method of removing the solvent from the freezing solution or dispersion is lyophilization, which includes solvent removal of the mixture by sublimation of the solvent under vacuum. If desired, the frozen composition can be stored in a cold reservoir before the sublimation process is performed. Sublimation can be carried out in a freeze dryer by keeping the refrigeration composition in the mold under reduced pressure and, if necessary, controlling the heat to aid sublimation. The pressure may be 4 mmHg (533 Pa) or less, for example 0.3 mmHg (40 Pa) or less, for example 0.1 to 0.2 mmHg (13.3 to 26.6 Pa) or even 0.05 mmHg (6.7 Pa) or less. The initial temperature in the lyophilizer may be as high as, for example, 60 ° C. and this temperature may decrease as the temperature of the freezing composition increases (eg up to 40 ° C.). Various methods and improvements are described in the references cited immediately preceding the specification. The freezing composition may also be removed from the mold prior to lyophilization.

Formulations can also be prepared by a solid-state dissolution method that removes a solid solvent from a frozen sample. In this conventional method, one or more matrix formers are dissolved or dispersed in the first solvent, frozen and then combined with the second solvent at or above the freezing point of the second solvent and at or below the freezing point of the first solvent. Contact. The first solvent in the solidified state may be substantially mixed with the second solvent, whereas the matrix former is substantially insoluble in the second solvent. The first solvent is thereby substantially removed from the coagulation matrix to yield a solid matrix that is substantially free of the first solvent. Typically, the first solvent is water and the second solvent is ethanol.

Both convex formulations obtainable by the process according to the invention can be prepared in various sizes. The volume of the mold is conveniently 300 to 2,000 mm ³ (0.3 to 2 ml) and the volume of the formulation is 350 to 2500 mm ³ (0.35 to 0.8 ml). Preferably, the volume of the mold is 350 to 800 mm ³ (0.35 to 0.8 ml) and the volume of the formulation is 450 to 1,000 mm ³ (0.45 to 1 ml). In other words, the volume of the overfilled or convex meniscus on the mold may be less than 30% of the volume of the mold itself. Generally speaking, the overfill will be from 20% to about 26% of the mold volume. In addition to the range of overfilling, the size of the convex meniscus is constrained by the contact angle between the aqueous composition and the material forming the frame of the mold and the surface tension of the aqueous composition. It is important to note that the greater the overfill, the greater the curvature of the uneven surface. This, in turn, maximizes both reduction in crushability and improvement in handling characteristics.

The maximum depth of the mold is conveniently 3.4 to 6 mm; The maximum thickness of the refrigeration composition in the mold is 5.0 to 8.5 mm. This maximum distance is measured along an axis perpendicular to the rim of the mold and is the distance through the top end of the top meniscus of the mold and the bottom end of the bottom of the mold. Lower values are generally not desirable because the formulations obtained are so thin that their strength is sometimes insufficient, whereas higher values for thickness, in particular, effectively remove all solvents from these freezing compositions when using lyophilization to remove solvent. It is sometimes undesirable because of the difficulty in removing it.

The frame defined surface area of the mold is typically from 100 to 500 mm ² and has a round shape. Round shape contributes to the mechanical strength of the formulation by reducing its crushability. This round shape may be circular, elliptical, oblong, oblong or polygonal, and the polygon preferably has a rounded corner if the inner angle is 90 °.

For example, the mold may be a depression in a metal plate (eg an aluminum plate). The plate may contain one or more depressions, each recessed in size and shape corresponding to the desired size of the molded article. However, the mold may also be a depression in the sheet of film material. The film material may contain one or more depressions. The film material may be similar to that used in conventional blister packaging materials used to package pharmaceutical tablets and similar therapeutic drug forms. For example, the film material may be made of a thermoplastic material with depressions formed by thermoforming. Preferred film materials are talc-filled polypropylene films or polyvinyl chloride films. Laminates of film materials such as polyvinyl chloride / polyvinylidene chloride, polyvinyl chloride / polytetrafluoroethylene or polyvinyl chloride / polyvinylidene chloride / polyethylene may also be used.

When lyophilization is used, it is desirable to freeze the matrix material solution in a coated or lined mold for easy release of the frozen material. Preferred molds are thermoformed cups made of talc-filled polypropylene sheets, optionally siliconized with a layer of baked silicone / simethicone baked on the surface in contact with the aqueous composition.

The profile and volume of the bottom of the mold can be measured as described below. The first mold with the desired round shape and the desired volume and flat bottom (parallel to the rim of the mold) is flooded to the desired range with the aqueous solution in which the final formulation is to be prepared. This is treated into a formulation by freezing and solvent removal. The volume of the meniscus can be measured by subtracting the mold volume from the volume added to the mold, or separately calculating the volume from many equations describing the meniscus top surface. One such approach involves subdividing the formulation along one or more planes of symmetry, measuring the cross section where the planes of symmetry intersect the top surface of the meniscus, and determining the equation describing the intersection. Since the ellipse can be safely estimated to describe these intersections properly, measurements of long and small diameters easily provide the necessary variables for each equation. The equations for the intersections of the top surfaces of the meniscus with various planes of symmetry (hence the cross section) can then be used to derive the equations describing the top surface of the meniscus, using known integration methods, The volume of the meniscus can be calculated. The information thus obtained can be used to calculate how to reshape the mold in order to obtain a biconvex symmetric formulation. For example, one can calculate how much the initial mold depth needs to be reduced so that the mold volume is reduced by the meniscus volume, and then add a mirror image of the upper meniscus to the bottom of the mold. This process ensures that the convex bottom has both the shape and volume of the meniscus at the top that will eventually be used. The data obtained by this calculation is then provided to the manufacturer of the mold so that the convex mold can be molded into metal.

Aqueous compositions may be in various forms such as solutions, suspensions, dispersions, emulsions, or foams. Those skilled in the art will recognize an acceptable method of making each of these. Preference is given to using water as the solvent in the composition which is frozen and solvent freed. Additional cosolvents (such as alcohols) may also be used if necessary to increase the solubility, dispersibility or hydration of either component of the composition.

The formulation comprises a porous network of the following matrix forming materials:

i) water-soluble, hydratable gels or foam-forming materials,

ii) a curing agent for gels or foam-forming materials, and optionally

iii) one or more amino acids.

Suitable water soluble, hydratable gels or foam-forming materials contain gelatin, gelatin A, gelatin B, fluid gelatin, modified fluid gelatin, gelatin derivatives, albumin, soybean protein, wheat and chafer seed proteins, potato proteins, papain matter; Phospholipids such as coacervate egg lecithin, or lecithin; Gums such as acacia, guar, agar, locust bean, xanthan and tragacanth gum; Alginate (polymannuronic acid), chitosan, carrageenan, dextran, dextrin, maltrine (maltodextrin), pectin (polygalacuronic acid), microcrystalline cellulose, corn syrup solids, konjac flour, rice flour, wheat Polysaccharides such as gluten; Synthetic polymers such as polyvinylpyrrolidone, sodium carboxymethylcellulose, sodium starch glycolate, hydroxyethylcellulose; And polypeptide / protein or poly-saccharide complexes such as gelatin-acacia complexes, alone or in combination, respectively.

Suitable curing agents include monosaccharides, linear and cyclic oligosaccharides and polysaccharides such as mannitol, xylitol, sorbitol, dextrose, fructose, sucrose, lactose, maltose, galactose, trehalose; Cyclic sugars such as cyclodextrins such as beta-cyclodextrin and 2-hydroxypropyl-beta-cyclodextrin; Dextran, including dextrins; And inorganic materials such as sodium phosphate, sodium chloride, magnesium aluminum silicate, magnesium trisilicate, natural clay, or combinations thereof. Preferred curing agents are mannitol.

Suitable amino acids have 2 to 12 carbon atoms, for example glycine, L-alanine, L-aspartic acid, L-glutamic acid, L-hydroxyproline, L-isoleucine, L-leucine, L-phenylalanine, or Combination. Glycine is the preferred amino acid. Formulations containing glycine as one of the matrix forming ingredients have several advantages: fast dissolution and disintegration in aqueous media, sweet taste and feel, nutritional value, low calorie content and non-causticity. Of particular importance is the fact that these formulations can be prepared with minimal cracking or remelting and that they are homogeneous porosity and suitable handling strength, i.e., resistant to disintegration or grinding under normal production and handling conditions. These latter properties contribute to the usefulness of the postfilling process whereby the active ingredient is filled onto a placebo or unfilled formulation.

Preferred matrix formers include pharmaceutical grade gelatin, pectin (not hydrolyzed, partially hydrolyzed or hydrolyzed), glycine and mannitol. Particularly preferred combinations of matrix formers include gelatin, glycine and mannitol.

All percentages and ratios mentioned in the following paragraphs are by weight.

The solution or dispersion of material for preparing the matrix may contain 0.1% to 15% by weight, in particular 1% to 5%, more specifically 1.2% to 3%, of the gel or foam forming material. It may additionally contain 0.5% to 10% amino acids, in particular 0.8% to 2.5% by weight, and 0.5% to 10%, in particular 1% to 4%, of a curing agent, the balance being the solvent and the second component mentioned hereafter.

The ratio between these materials can vary within a certain range. Specifically, the weight ratio of the total amount of amino acids to the weight of the water soluble, water hydratable gel or foam-forming material is 1: 1 to 1: 3. Preferred ratio is 1: 1.5 . The weight ratio of the amount of water-soluble, water-soluble gel or foam-forming material to the amount of curing agent is from 2: 1 to 1: 2. Preferred ratio is 1.5: 2.

Typically, the weight ratio of the total amount of nonsolvent component to the total amount of water in the aqueous composition is about 1: 9 to 1:33, especially about 1:13 to 1:30, for example about 1:20.

Fast dissolving solid formulations find many applications, particularly when it is necessary to administer, formulate or vice versa a predetermined amount of active ingredient. The active ingredient is in particular a human or veterinary drug substance.

The active ingredient used in the fast dissolving solid formulations may be in the form of a coating. For example, it may be present in particulate form and the particles of the active ingredient may be coated with a coating suitable to protect the process diluent, suspension or aqueous environment of oral or other mucosal cavities, or other environmental conditions that dissolve or degrade the active ingredient. have. These coating materials can be selected from natural or synthetic polymers that are hydrophilic or hydrophobic in nature, or other hydrophobic materials such as fatty acids, glycerides, triglycerides, and mixtures thereof. In this way, the taste of the active or bioactive agent can be blocked, while at the same time the solid formulation allows for rapid dissolution upon contact with the physiological diluent. Examples of bitter active ingredients that can be coated in accordance with the present invention include acetaminophene, ibuprofen, chlorpheniramine maleate, pseudo-ephedrine, dextrometophan, cisapride, domperidone, risperidone. Pharmaceutical applications include mucoadhesive or formulations designed to degrade the drug at a controlled rate; A dosage unit designed to distribute the drug to the eye, vagina, rectum and other body cavities; Solid dosage forms designed to replace liquid formulations; Dry therapeutic formulations for topical application after resolvation (water ride); Therapeutic unit or sheet formulation for topical application; Preparations of more palatable formulations of drugs that exhibit unpleasant sensory properties; Formulations for oral drug delivery to persons who are difficult to swallow tablets or capsules.

Ingredients such as nutrients, vitamins, other active ingredients, sweeteners, flavors, colorants, surfactants, preservatives, antioxidants, viscosity increasing agents, minerals, diagnostics, fertilizers and pesticides may also be incorporated into the formulations of this formulation. .

The solution or suspension for preparing the formulation may further contain the J ingredient mentioned previously. Xanthan gum or polyacrylic acid polymers and salts thereof (also referred to as carbomer or carboxyvinyl polymers such as Carbopol ™) may be added to increase the viscosity or to maintain the components of the mixture in suspension.

The present invention also provides both convex, rapid disintegrating solid formulations obtainable by any of the methods previously described.

The rate at which both convex tablets produced by the process of the present invention disintegrate is generally or at least mostly dependent on the choice of matrix former, its concentration and coagulation / solvent removal process conditions. Specifically, the formulations of the sizes mentioned in the examples described below dissolve rapidly within, for example, less than about 10 seconds and generally faster, for example less than about 5 seconds or even less, for example within 1 to 2 seconds. Will be distributed.

The formulations disperse rapidly in water, for example less than 10 seconds. The disintegration time of the formulation is described in the literature (British Pharmacopoeia, 1980, VolII, Appendix XII A), but the formulation is sufficiently rapid by water using a standard tablet disintegrating device in which a standard 2.00 mm wire mesh is replaced with a stainless steel 40 mesh screen. It is measured by checking whether it can collapse. The sample product is placed in a drying tube placed on the surface of the water. Run the apparatus and immerse the sample in water at 20 ° C. The sample is dispersed on the liquid surface and the solid residue passes through a 40 mesh screen within 10 seconds, preferably within 5 seconds and ideally within 1 to 2 seconds.

Claims (27)

A process for preparing a rapid disintegrating solid formulation comprising a porous network of matrix forming materials, Filling the mold with an amount of an aqueous composition comprising a matrix forming material such that convex meniscus is produced on top of the mold; Freezing the aqueous composition in the mold; Removing the solvent from the frozen composition by performing lyophilization or solid state dissolution on the frozen composition, thus obtaining a porous network of matrix forming material, The shape of the lower surface of the mold is a mirror image in the form of an upper frozen meniscus, the mirror-plane being parallel to the plane defined by the rim of the mold, and thus shaped as both convex tablets with symmetrical upper and lower surfaces. Method for producing a fast disintegrating solid dosage form, characterized in that to obtain a dosage form. The method of claim 1, wherein the mold volume is 300 to 2,000 mm ³ (0.3 to 2 ml) and the formulation volume is 350 to 2500 mm ³ (0.35 to 2.5 ml). The method of claim 2, wherein the mold volume is 350-800 mm ³ (0.35-0.8 ml) and the formulation volume is 450-1,000 mm ³ (0.45-1 ml). The method of claim 1, wherein the maximum depth of the mold is 3.4 to 6 mm; The maximum thickness of the refrigeration composition in the mold is 5.0 to 8.5 mm. The method according to claim 1, wherein the surface area of the mold is limited to 100 to 500 mm ² and is round. The method according to claim 5, wherein the rounded shape is circular, elliptical, oblong, oblong or polygonal and the polygon has rounded corners when the internal angle is ≤ 90 °. The method of claim 1 wherein the mold has depressions in the sheet or metal plate of film plastics material. 8. The method of claim 7, wherein the mold is a cup thermoformed with a polypropylene sheet and the sheet surface is siliconized or not siliconized. The method of claim 1 wherein the aqueous composition is in the form of a solution, suspension, dispersion, emulsion, or foam. The method of claim 9, wherein the matrix forming material comprises the following material: i) a water soluble, hydratable gel or foam-forming material, and ii) curing agents for gels or foam-forming materials. The method of claim 10, wherein the gel or foam-forming material, each alone or in combination, comprises gelatin, gelatin A, gelatin B, fluid gelatin, modified fluid gelatin, gelatin derivatives, albumin, soybean fiber protein, wheat and chaff seed protein, potato Protein-containing substances selected from proteins, papain; Coacervate egg lecithin, or phospholipid selected from lecithin; Gums selected from acacia, guar, agar, locust bean, xanthan and tragacanth gum; Alginate (polymannuronic acid), chitosan, carrageenan, dextran, dextrin, maltrine (maltodextrin), pectin (polygalacuronic acid), microcrystalline cellulose, corn syrup solids, konjac flour, rice flour, wheat Polysaccharides selected from gluten; Synthetic polymers selected from polyvinylpyrrolidone, sodium carboxymethylcellulose, sodium starch glycolate, hydroxyethylcellulose; And a polypeptide / protein or poly-saccharide complex selected from gelatin-acacia complexes. The method of claim 10, wherein the cured material is a monosaccharide, linear or cyclic oligosaccharide, polysaccharide, or inorganic material, or a combination thereof. The method of claim 12, wherein the cured material is mannitol, xylitol, sorbitol, dextrose, fructose, sucrose, lactose, maltose, galactose, trehalose; Inorganic substances selected from cyclic sugars, dextran, dextrin, sodium phosphate, sodium chloride, magnesium aluminum silicate, magnesium trisilicate, natural clay, or combinations thereof selected from beta-cyclodextrin or 2-hydroxypropyl-beta-cyclodextrin Phosphorus manufacturing method. The method of claim 10, wherein the matrix forming material comprises: i) 0.1% to 15% (w / w) of water soluble, water hydratable gel or foam-forming material; And ii) 0.5% to 10% (w / w) curing agent for gels or foam-forming materials. The method of claim 14, wherein the matrix forming material comprises: i) 1.2% to 3% (w / w) of water soluble, water hydratable gel or foam-forming material; And ii) 1% to 4% (w / w) curing agent for gels or foam-forming materials. The method of claim 1 wherein the aqueous composition is a human or veterinary drug substance as an active ingredient. 17. The preparation of claim 16 wherein the aqueous composition further contains a nutrient, vitamin, other active ingredient, sweetener, flavor, colorant, surfactant, preservative, antioxidant, viscosity increasing agent, mineral, diagnostic agent, fertilizer or pesticide. Way. The method of claim 16 wherein the drug is cisapride [(±) -cis-4-amino-5-chloro-N- [1- [3- (4-fluorophenoxy) propyl] -3-methoxy-4 -Piperidinyl] -2-methoxy-benzamide monohydrate]. The method of claim 1, wherein the matrix material can disintegrate at 20 ° C. within 10 seconds with water. A fast disintegrating solid dosage form obtainable by any one of the methods of preparation of claims 1-13, 14, 15, or 16-22. A film for use in any one of claims 1 to 13, 14, 15, or 16 to 19, comprising a plurality of molds arranged in a regular pattern. A sheet of plastic material or metal, the shape of the lower surface of each mold being a mirror image in the form of a constant convex meniscus at the top, the mirror-plane being parallel to the plane defined by the mold frame, and thus the sheet being symmetrical A sheet, characterized in that it is suitable for producing a shaped formulation as a biconvex tablet with a surface. The method of claim 10, wherein the matrix forming material further comprises iii) amino acids. The method of claim 22, wherein the amino acid is glycine, L-aspartic acid, L-glutamic acid, L-hydroxyproline, L-isoleucine, L-phenylalanine, or a combination thereof. The method of claim 14, wherein the matrix forming material further comprises iii) 0.5% to 10% (w / w) amino acids. The method of claim 15, wherein the matrix forming material further comprises iii) 0.8% to 2.5% (w / w) amino acids. 23. The method of claim 22, wherein the weight ratio of total amount of amino acids to weight of water soluble, water hydratable gel or foam-forming material is 1: 1 to 1: 3; The weight ratio of the amount of water-soluble, water-soluble gel or foam-forming material to the amount of curing agent is from 2: 1 to 1: 2; The weight ratio of the total amount of the nonsolvent component to the total amount of water in the aqueous composition is 1: 9 to 1:33. 27. The method of claim 25, wherein the weight ratio of the total amount of amino acids to the weight of the water-soluble, hydratable gel or foam-forming material is 1: 1.5; The weight ratio of the amount of water-soluble, water-soluble gel or foam-forming material to the amount of curing agent is 1.5: 2; The weight ratio of the total amount of the nonsolvent component to the total amount of water in the aqueous composition is 1:13 to 1:30.