Effervescent composition and preparation method thereof

Abstract

The present disclosure relates to effervescent compositions and methods of making and using the same. In some embodiments, the disclosed effervescent compositions are formed from an input blend comprising an acid and a base by granulating the input blend in a twin-screw processor. The particles formed from the input blend may be formed by an in-situ granulating agent, which may be a portion of the acid that is melted during granulation. In some embodiments, the effervescent composition may be prepared using a twin-screw processor comprising a feed zone for receiving an input blend comprising an acid and a base; a granulation initiation zone for melting only a portion of the acid to be used as an in-situ granulating agent; a granulation finishing zone for granulating the input blend; and an outlet for discharging the particles.

Description

[0001] field

[0002] The present disclosure relates to effervescent compositions and methods of making and using the same.

[0003] background

[0004] When added to water, the effervescent composition that produces effervescence can be used for pharmaceutical, food, veterinary, nutrition, gardening, household, cooking, pest control, agriculture, cosmetics, weed control, industry, cleaning, candy and seasoning application. Effervescent composition, particularly in pharmaceutical application, is interesting dosage form, and it provides some unique advantages, for example, gives active pharmaceutical ingredient (API) in solution form and masks the taste of API. The patient that benefits by using effervescent tablet has elderly population, pediatric population and has a large amount of adult population of gag reflex and / or dysphagia. In addition, since API is used as solution, the problem relevant with dissolution, that is, the degree of absorption rate and bioavailability is minimized and fast action can be achieved.

[0005] The manufacture of effervescent compositions is complicated, because effervescent compositions are easy to become reactive in the presence of moisture, and careful environmental control is required. The reaction is autocatalytic and difficult to control. In addition, effervescent compositions require fast disintegration time, which depends on the porosity of the composition. For example, effervescent tablets require fast disintegration time generally less than 60 seconds. At the same time, effervescent compositions also need to be suitable for packaging and transportation. For example, effervescent tablets need to have enough hardness so that they can be suitable for packaging and transportation. Finally, effervescent compositions should emit enough carbon dioxide in water to work. Various methods have been developed for the preparation of effervescent compositions, such as wet granulation, dry granulation, direct compression and hot melt processing. However, the effervescent compositions obtained by these conventional techniques have one or more disadvantages, such as low carbon dioxide (CO2) content, low porosity and long disintegration time, such as when using external adhesives, particles are not free to flow, or are difficult to compress and form tablets, mechanical strength is low, manufacturing difficulties, etc.

[0006] Therefore, an effervescent composition needs to have high carbon dioxide retention, high porosity and high mechanical strength and does not require the addition of granulating agents and / or binders. A method for making such an effervescent composition is also needed, which is fast and easy to control. Such a method should be sustainable.

[0007] Overview

[0008] The present disclosure relates to a granular composition comprising an anhydrous acid component and an anhydrous base component, the anhydrous acid component comprising a combination of a portion of the acid that has been melted and a portion of the acid that has not been melted; the anhydrous base component comprising a carbonate functional group, wherein the base component is capable of reacting with the acid component to form carbon dioxide; wherein the anhydrous acid component and the anhydrous base component are present in a weight ratio of 1:9 to 9:1, and the composition does not include a definite added granulating agent.

[0009] The present disclosure also relates to a porous effervescent composition formed from an input blend comprising an acid and a base by granulating the input blend in a twin-screw processor, the porous effervescent composition comprising granules formed by an in-situ granulating agent, wherein the in-situ granulating agent is a portion of the acid that is the portion of the acid that melts during the granulation process.

[0010] The present disclosure also relates to an oral solid dosage form, such as an effervescent tablet or powder for oral administration, or a combination thereof, comprising a porous effervescent composition formed from an input blend comprising an acid and a base by granulating the input blend in a twin-screw processor, the porous effervescent composition comprising granules formed by an in situ granulating agent, wherein the in situ granulating agent is a portion of the acid that is the portion of the acid that is melted during the granulation process; and one or more optional processing excipients.

[0011] The present disclosure also relates to a twin-screw processor for preparing porous effervescent particles, the processor comprising a feed zone for receiving an input blend including an acid and a base; a granulation initiation zone for melting only a portion of the acid to be used as an in-situ granulating agent; a granulation finishing zone for granulating the input blend; and an outlet for discharging the granules.

[0012] The present disclosure also relates to a method for preparing porous effervescent particles, the method comprising feeding an input blend including an acid and a base into a twin-screw processor; melting only a portion of the acid to serve as an in-situ granulating agent; granulating the input blend to form particles; and optionally collecting the particles from the twin-screw processor.

[0013] The present disclosure is also directed to porous effervescent particles comprising an acid and a base, wherein the porosity of the particles is at least 50% greater than the porosity of an input blend used to prepare the particles, and the particles retain at least 90% of the carbon dioxide of the input blend. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 The screw configuration of a co-rotating twin-screw extruder according to an embodiment of the present disclosure is shown.

[0015] Figure 2 A processor for making porous effervescent particles according to an embodiment of the present disclosure is shown.

[0016] Detailed description

[0017] I. Explanation of terms

[0018] The following explanations of terms are provided to better describe the present disclosure and guide those of ordinary skill in the art to implement the present disclosure. As used herein, "including" means "including but not limited to", and the singular form "a" or "an" or "the" includes plural references unless the context clearly dictates otherwise. The term "or" refers to a single element of the alternative element or a combination of two or more elements, unless the context clearly indicates otherwise.

[0019] The devices, compositions, and methods as described herein should not be construed as limiting in any way. Rather, the present disclosure is directed to all novel and non-obvious features and aspects of the various disclosed embodiments, both individually and in various combinations and sub-combinations with one another. The devices, compositions, and methods described are not limited to any specific aspect or feature or combination thereof, nor do the devices, compositions, and methods require the presence of any one or more specific advantages or problems solved. Any theory of operation is for ease of explanation, but the disclosed devices, compositions, and methods are not limited to such theory of operation.

[0020] Although the operations of some methods in the disclosed methods are described in a specific sequential order for convenience of presentation, it should be understood that this description includes rearrangement unless the specific language set forth below requires a specific order. For example, the operations described in sequence can be rearranged or performed simultaneously in some cases. In addition, for simplicity, the accompanying drawings may not show that the disclosed devices, compositions and methods in various ways can be used in combination with other devices, compositions and methods. In addition, the description sometimes uses terms such as "produce" and "provide" to describe the disclosed methods. These terms are high-level abstractions of the actual operations performed. The actual operations corresponding to these terms will vary depending on the specific implementation, and can be easily discerned by a person of ordinary skill in the art.

[0021] In some embodiments, values, processes, or devices are referred to as "lowest," "optimal," "minimum," etc. It should be understood that such descriptions are intended to indicate that a choice can be made among a number of functional alternatives for use, and that such a choice is not necessarily better, lesser, or preferred over other choices.

[0022] The embodiments are described with reference to directions indicated as "above," "below," "upper," "lower," etc. These terms are used for convenience of description but do not imply any particular spatial orientation.

[0023] Unless otherwise stated, all technical and scientific terms used herein have the same meanings as those of ordinary skill in the art to which the present disclosure pertains. Unless otherwise stated, all numerals representing the amounts of components, molecular weights, percentages, temperatures, times, etc. used in the specification or claims are understood to be modified by the term "about". Therefore, unless otherwise stated, implied or explicitly, the numerical parameters are approximate values, which may depend on the desired properties and / or detection limits required under standard test conditions / methods. When directly and explicitly distinguishing an embodiment from the prior art discussed, the embodiment numerals are not approximate, unless the word "about" is cited. In addition, not all alternatives described herein are equivalent.

[0024] II. Overview

[0025] The present disclosure relates to porous effervescent compositions, more specifically, to particles. The composition has one or more key attributes, such as free-flowing ability, compressibility, porosity, significant amount of retained carbon dioxide and mechanical strength. The effervescent composition in particle form can be used as is, can be mixed with other excipients before use, or is suitable for, for example, forming an effervescent tablet with required mechanical strength, effectiveness and rapid disintegration time. In some embodiments, the porosity of the porous effervescent composition in particle form of the present disclosure is at least 50% greater than the porosity of the input blend, and retains all or substantially all carbon dioxide (CO2) content of the input blend. In this article, the porosity of the effervescent composition relative to the input blend is referred to as relative porosity. Relative porosity can be measured as relative volume porosity (relative bulk porosity) or relative tap porosity (relative tap porosity). The term "all or substantially all of the CO2 content of the input blend" refers to at least 90% of the CO2 content of the input blend, and is also expressed as the composition, particularly the percentage of the relative retained CO2 content of the particle.

[0026] The effervescent effect in the effervescent composition is obtained due to the presence of acid and alkaline substances, such as carbonates or bicarbonates, which react rapidly in the presence of water and release CO2 to provide a carbonated or frothy liquid beverage. Due to the release of CO2, dissolution of the API in water and taste masking of the API are achieved.

[0027] Manufacturing a satisfactory effervescent composition requires a balance between the porosity of the composition, the amount of carbon dioxide retained in the composition, and the mechanical strength of the composition.

[0028] A conventional technique for producing effervescent compositions is wet granulation. Wet granulation requires the addition or generation of a granulating agent (except the in situ granulating agent disclosed herein). The granulating agent determined to be added can be water, steam or a solvent such as alcohol, propylene glycol or glycerol or a binder such as polyvinyl pyrrolidone used as a wetting agent. A type of wet granulation preferably used to prepare an effervescent formulation is TOPO vacuum granulation, in which a small amount of water is added during the process. Additional water is produced during the chain reaction initiated by the reaction of citric acid with bicarbonate or carbonate. In order to control and manage this chain reaction, water is removed during the granulation process by repeatedly applying a vacuum for a period of time. The porosity of this composition is the result of the carbon dioxide produced during the reaction. The control of this process is very critical. The porosity and carbon dioxide content of the composition can vary according to the degree of reaction.

[0029] Fluidized bed spray granulators can also be used for wet granulation, where granulation and drying occur simultaneously. Although low moisture content is achieved throughout the process, large amounts of granulation fluid are required, making the process longer and expensive to operate, with the potential risk of losing effervescent quality.

[0030] Wet granulation can also be carried out by melting method. In this method, alkali is mixed with acid (it is hydrated acid at least in part). The mixture is heated until crystal water is released. The released crystal water is then used as a granulating agent. Although this method avoids using external water as a granulating agent, this method can also cause a chain reaction that is difficult to terminate, resulting in the need for additional moisture to be removed. The porosity of the composition is once again the result of the carbon dioxide produced in the reaction. The effervescent composition produced by this method has variable and lower CO2 content in some cases. In addition, the tablets prepared by these compositions do not have enough mechanical strength for product processing and packaging operations.

[0031] Wet granulation can also be performed by performing two separate granulation steps for the acid and base components followed by a dry blending step. A difficulty with this conventional technique is obtaining tablet uniformity as it is difficult to uniformly blend the materials into a homogeneous composition.

[0032] Another disadvantage of these conventional wet granulation techniques is that the use of solvents such as alcohols for wet granulation requires complicated equipment, such as fireproof type of the above equipment and higher safety requirements for handling the granulation fluid.

[0033] Another conventional method for forming an effervescent composition is dry granulation. This method generally involves pressing or roller compaction without the need for any liquid or binder. However, the composition obtained by this method has a low porosity. Direct compression technology has also been used to prepare an effervescent composition with a low porosity, resulting in a longer disintegration time and lower mechanical strength.

[0034] Hot melt processing has also been used to prepare effervescent compositions and is widely related to the melting of adhesives. One such method is disclosed in U.S. Patents 6,071,539, 6,488,961 and 6,649,186 to Robinson, which discuss hot melt extrusion involving molten adhesives. Although the use of adhesives may avoid the disadvantages of using water or solvents, there are restrictions on the types of adhesives that can be used, and the resulting composition has low porosity and CO2 content. U.S. Patent 6,426,111 describes another hot melt method, in which acid is melted and mixed with alkali and other ingredients. The method ensures that the alkali and other ingredients are completely captured by the molten acid, thereby forming a protective layer. The toffee mass formed by the method can be directly extruded to form a desired shape. The method is limited to the excipients required for imparting porosity to the composition so formed. The method also requires all acids present in the melted composition to achieve the results disclosed therein. In addition, it does not provide an effervescent tablet with improved properties and performance exhibited by the composition of the present disclosure. The inventors repeated the method disclosed in U.S. Patent 6,426,111 and determined that it is the same. As disclosed in the patent, the required amount of anhydrous citric acid was placed in a stainless steel container and placed on a hot plate maintained at 125° C. However, even after the anhydrous citric acid was exposed to 125° C., there was no sign of melting after 45 minutes. Therefore, the temperature was raised to 145-50° C. The effervescent composition formed according to the method disclosed in the patent had a relative percentage of retained CO2 content of about 71.55% and a relative specific bulk porosity of only 14.10%.

[0035] In contrast to these conventional methods, the present disclosure relates to a porous effervescent composition formed from an input blend including an acid and a base by granulating the input blend in a twin-screw processor, the composition including particles formed from an in-situ granulating agent, wherein the in-situ granulating agent is a portion of the acid that is melted during the granulation process. The in-situ granulating agent of the present disclosure is different from a granulating agent that is added, which is a granulating agent in addition to (other than) the acid component that reacts with the base to provide effervescence.

[0036] The contribution of the present disclosure over the conventional methods described above is that the resulting porous effervescent composition has a porosity that is at least 50% greater than the porosity of the input blend.

[0037] The contribution of the present disclosure over the above conventional methods is that the obtained porous effervescent composition has a retained carbon dioxide content of at least 90% of the input blend.

[0038] Melting of only a portion of the acid results in the formation of solid bridges with molecules of other particles. This results in the bonding of particles in close proximity to form deformable, irregularly shaped, porous particles with improved compressibility. Melting of only a portion of the acid can provide particles suitable for tableting. As described in the method of U.S. Patent No. 6,426,111, complete melting of the acid results in excessive granulation, thus resulting in poor quality effervescent tablets with low foaming efficiency.

[0039] During granulation, little or no reaction occurs between acid and base, and the loss of carbon dioxide in the granulation process is negligible or non-loss. In some embodiments, the particles retain all or substantially all of the CO2 content of the input blend. This also results in improved effervescence when exposed to water. In some embodiments, the effervescent tablet prepared by the particles of the present disclosure has a disintegration time of less than 60 seconds.

[0040] Furthermore, the granules formed according to the present invention exhibit improved mechanical strength due to the close proximity of the acid and base molecules. For example, tablets formed from the granules exhibit improved hardness and disintegration time when exposed to water.

[0041] Thus, the porous effervescent composition formed using the in-situ granulation agent has a porosity at least 50% greater than the porosity of the input blend or retains at least 90% of the carbon dioxide content of the input blend, thereby avoiding the problems associated with conventional methods (e.g., using a defined added granulation agent, such as water or a binder, or completely melting the acid component). It further eliminates the need for additional steps, such as drying and other processing steps that provide ease of manufacture.

[0042] III. Compositions and methods of making and using the same

[0043] Embodiments of porous effervescent compositions are disclosed herein, which exhibit improved properties and contribute to the use of compositions in various fields. In some embodiments, the porous effervescent compositions can be formed using an input blend comprising an acid and a base. In some embodiments, the porosity of the porous effervescent composition is at least 50% greater than the porosity of the input blend. In some embodiments, the porous effervescent composition maintains a carbon dioxide content of at least 90% of the input blend. It has been observed that the increase in the porosity of the particles can be achieved without compromising other properties of the particles.

[0044] According to an exemplary embodiment, the composition contains no or no defined added granulating agent. The composition is understood to contain no defined added components (other than acid or base) that deleteriously affect the function of the acid and base components and / or defined added granulating agents (e.g., water, binders, or any conventional granulating agents described above).

[0045] According to one embodiment, the acid can be any organic acid in the form of free acid, anhydride and acid salt. Specifically, the acid can be selected from citric acid and other acids, such as tartaric acid, maleic acid, fumaric acid, malic acid, adipic acid, succinic acid, lactic acid, glycolic acid, alpha hydroxy acid, ascorbic acid, amino acids and their alkaline hydrochlorates. A mixture of one or more acids can also be used. According to one embodiment, the acid is an API. Examples of such acids include aspirin, N-acetylcysteine, ibandronic acid, ibuprofen, ketoprofen, mefenamic acid, ascorbic acid and other acidic amino acids.

[0046] According to one embodiment, the base is a carbon dioxide precursor and can be selected from a carbonate-containing compound, such as a carbonate; a sesquicarbonate; a bicarbonate of potassium, lithium, sodium, calcium, ammonium; an L-lysine carbonate; an arginine carbonate; a glycine sodium carbonate; or an amino acid sodium carbonate. A mixture of one or more bases can also be used. For example, in some embodiments, the base is a mixture of sodium carbonate and sodium bicarbonate.

[0047] In some embodiments, the composition consists essentially of an acid and a base. The acid and base are present in an amount sufficient to cause effervescence when water is added. The amount of acid and base in the composition can vary depending on the acid and base used. In some embodiments, the amount of acid in the composition can be 10% w / w to 90% w / w, such as 20% w / w to 70% w / w or 40-50% w / w. In an exemplary embodiment, the amount of acid in the composition can be selected from 40% w / w to 50% w / w. The amount of base in the composition can be 10% w / w to 90% w / w, such as 20% w / w to 70% w / w or 45% to 55% w / w. In an exemplary embodiment, the amount of base in the composition can be selected from 45% w / w to 55% w / w. In some embodiments, the molar ratio of acid and base can vary depending on the desired pH maintenance of the solution during effervescence. In an exemplary embodiment, the molar ratio of acid and base can be selected from 3:1 to 1:5. In an exemplary embodiment, the weight ratio of the acid to the base may be selected from 1:9 to 9:1.

[0048] In one embodiment, the components of the input blend are anhydrous. According to an exemplary embodiment, an anhydrous form of the acid is used to ensure that no crystal water is released when the acid is heated in the granulation starting zone of the twin screw processor. According to an exemplary embodiment, an anhydrous form of the base is used. In another embodiment, an anhydrous form of the acid and an anhydrous form of the base can be used. According to another embodiment, the moisture content of the input blend is less than 0.5%. One or more components of the input blend can be subjected to a moisture removal step before entering the processor. In some embodiments, it is beneficial to keep the moisture content of the acid and the base less than 0.25% w / w. The moisture of the acid and the base can be removed by any drying method known to those of ordinary skill in the art. For example, moisture can be removed by tray drying the components at 45 to 60° C. These components can then be sieved to obtain fine particles for homogeneous processing. In some embodiments, each component is sieved by ASTM#40 and / or #60 mesh sieves to obtain particles with a size less than 420 microns and 250 microns, respectively.

[0049] In some embodiments, the input blend may further comprise one or more active ingredients selected from pharmaceutical, food, veterinary, nutraceutical, horticultural, household, culinary, pesticidal, agricultural, cosmetic, herbicide, industrial, detergent, confectionery, and flavoring agents.

[0050] The medicament includes any API covering a complete range of therapeutic indications, such as anti-infectives, antibacterial agents, antihistamines and decongestants, anti-inflammatory agents, antiparasitic agents, antivirals, antifungals, amoebicidal or trichomonocidal agents, analgesics, antiarthritics, antiasthmatics, anticoagulants, anticonvulsants, antidepressants, antidiabetics, antitumor agents, antipsychotics, antihypertensives, expectorants, electrolytes, laxatives, botanicals, muscle relaxants, diuretics, etc. The amount of the API can vary depending on the desired application and can be, for example, a unit dose based on clinically determined efficacy. For example, based on the selected API, the amount of the API can be from 0.01 mg to about 1000 mg.

[0051] In some embodiments, one or more APIs are added during formation of the effervescent composition. In an alternative embodiment, the API is added after the effervescent composition is formed.

[0052] The input blend may further comprise one or more processing excipients selected from soluble and insoluble lubricants, flavoring substances, colorants, or combinations thereof.

[0053] Soluble lubricants may include, but are not limited to, polyethylene glycols (PEGs), such as PEG 4000, PEG 6000, and PEG 8000, polyoxyethylene stearates, and sodium or magnesium lauryl sulfate, sodium benzoate, L-leucine, and the like, and combinations thereof. Insoluble lubricants may include, but are not limited to, magnesium stearate, stearic acid, palmitoyl stearin, and the like, and combinations thereof. The amount of lubricant depends on the desired lubricating effect and is well known to those of ordinary skill in the art.

[0054] Flavoring substances may include, but are not limited to, synthetic flavoring oils and flavoring aromatics and / or natural oils, extracts from plants, leaves, flowers, fruits, etc., and combinations thereof. These may include cinnamon oil, wintergreen oil, peppermint oil, clove oil, bay oil, anise oil, eucalyptus, thyme oil, cedar leaf oil, nutmeg oil, sage oil, bitter almond oil, cassia oil, etc. Also useful as spices are vanilla, citrus oils, including lemon, orange, grape, lime and grapefruit, and fruit essences, including apple pear, peach, strawberry, raspberry, cherry, plum, pineapple, apricot, etc. It has been found that particularly useful spices include commercially available orange, grape, cherry and bubble gum spices and mixtures thereof. The amount of flavoring agent may depend on many factors, including the desired sensory effect.

[0055] Useful colorants may include, but are not limited to, food, drug and cosmetic (FD&C) colors such as dyes, pigments, lakes, natural colorants and derived colorants and natural colorants. Useful lakes include dyes adsorbed on aluminum hydroxide and other suitable carriers. Examples of suitable colors include FD&C Red No. 3, FD&C Red No. 40, FD&C Blue No. 1, FD&C Blue No. 2, FD&C Yellow No. 5, FD&C Yellow No. 6, FD&C Green No. 3 and combinations thereof. The amount of colorant depends on the desired aesthetic appearance and is well known to those skilled in the art.

[0056] The present disclosure also relates to oral solid dosage forms comprising the above-mentioned porous effervescent composition. Examples of oral solid dosage forms include, but are not limited to, effervescent tablets, powders, or combinations thereof for oral administration. The term effervescent tablet also includes variants thereof, such as orally disintegrating tablets and rapidly disintegrating tablets that utilize effervescence to achieve the desired result.

[0057] The oral solid dosage form comprises a porous effervescent composition formed from an input blend comprising an acid and a base by granulating the input blend in a twin screw processor, the composition comprising granules formed from an in situ granulating agent, wherein the in situ granulating agent is a portion of the acid that has melted during granulation; and optionally, a processing excipient.

[0058] Processing excipients may be selected from non-effervescent disintegrants, soluble and insoluble lubricants, flavoring substances, colorants or combinations thereof.

[0059] Non-limiting examples of non-effervescent disintegrants include microcrystalline cellulose, cross-linked polyvinylpyrrolidone, starch, modified starch, clays such as bentonite, gums such as pectin, tragacanth, alginates, sodium starch glycolate and cross-linked sodium carboxymethylcellulose. The amount of the non-effervescent disintegrant can be up to about 20% by weight of the oral solid dosage form, preferably about 2 to 10% by weight.

[0060] According to one embodiment, the tablet has a disintegration time of 20 to 90 seconds in water at room temperature, about 25°C ± 5°C. According to an exemplary embodiment, the tablet has a disintegration time of 30 to 60 seconds in water at room temperature, about 25°C ± 5°C. According to one embodiment, the tablet has a hardness of at least 3Kp (kilo pounds). According to an exemplary embodiment, the tablet has a hardness of 3 to 20Kp.

[0061] Any conventional compression technique known to those skilled in the art can be used to form the oral solid dosage forms of the present disclosure.

[0062] The present disclosure also relates to a twin-screw processor for preparing porous effervescent particles. The processor includes a feed zone for receiving an input blend comprising an acid and a base, a granulation initiation zone for melting only a portion of the acid to be used as an in-situ granulation agent; a granulation finishing zone for granulating the input blend; and an outlet for discharging the granules.

[0063] Figure 2 A processor (200) for preparing an effervescent composition according to an embodiment of the present disclosure is shown. The processor (200) includes a feed zone (202) for receiving an input blend comprising an acid and a base, a granulation initiation zone (204) for melting only a portion of the acid to be used as an in-situ granulation agent; a granulation finishing zone (206) for granulating the input blend, and an outlet (208) for discharging granules.

[0064] The granulation start zone of the processor is provided with a heating element to heat the processor barrel to a temperature sufficient to cause only a portion of the acid to melt. In some embodiments, the granulation start zone is maintained at a temperature of 10 to 40°C below the melting temperature of the acid. In an exemplary embodiment, the granulation start zone is maintained at a temperature of about 20°C below the melting temperature of the acid. According to one embodiment, the melting of only a portion of the acid is ensured by a low residence time in the granulation start zone. According to one embodiment, the residence time in the processor is less than 10 seconds. According to a specific embodiment, the residence time in a processor with an L / D of 60 is 8 to 10 seconds. According to a specific embodiment, the residence time in the granulation start zone is 3 to 5 seconds. In some embodiments, the granulation start zone consists only of conveying elements. In some embodiments, the granulation start zone consists essentially of conveying elements. Conveying elements are elements used to convey material downstream in the processor without applying any significant shear to the material. Conveying elements help prevent material stagnation and provide low residence time.

[0065] In some embodiments, the granulation finishing zone is maintained at about 25 to 35° C. In some embodiments, the granulation finishing zone of the processor is also provided with a conveying element. According to one embodiment, the granulation finishing zone of the processor consists only of the conveying element. In some embodiments, the granulation finishing zone consists essentially of the conveying element.

[0066] In some embodiments, the processor may further include a transition zone between the granulation start zone and the granulation finish zone. The transition zone may also include a heating element. The temperature of the transition zone is less than the temperature of the granulation start zone. In some embodiments, the transition zone is maintained at a temperature lower than the temperature of the granulation start zone and higher than the temperature of the granulation finish zone. In an exemplary embodiment, the transition zone is maintained at 50 to 70°C. According to one embodiment, the transition zone of the processor consists of a conveying element or a conveying and kneading mixing element. The kneading element is an element for introducing shear energy into the material, thereby facilitating mixing. Increasing the angle of the kneading element results in a decrease in the conveying capacity of the element. In an exemplary embodiment, a forward conveying angle of 45° is used.

[0067] In some embodiments, the twin screw processor is a co-rotating twin screw processor. According to one embodiment, the co-rotating twin screw processor is a co-rotating twin screw extruder. The screw configuration of an exemplary co-rotating twin screw extruder is shown in Figure 1 middle.

[0068] The present disclosure also relates to methods of preparing porous effervescent compositions. In some embodiments, the method is used to prepare a porous effervescent composition having a porosity at least 50% greater than the porosity of the blend and maintaining at least 90% of the CO2 content of the input blend.

[0069] In some embodiments, the method includes feeding an input blend comprising an acid and a base into a twin screw processor, melting only a portion of the acid to serve as an in-situ granulating agent, granulating the input blend to form granules, and collecting the granules from the twin screw processor.

[0070] In some embodiments, the melting of only a portion of the acid can be achieved by maintaining the granulation starting zone at a temperature 10 to 40° C. lower than the melting temperature of the acid. In some embodiments, the melting of only a portion of the acid can be achieved by maintaining a low residence time in the processor, such as in the granulation starting zone of the processor. In some embodiments, the melting of only a portion of the acid can be achieved by reducing the length of the granulation starting zone. In some embodiments, a lower L / D ratio can be used to achieve the melting of only a portion of the acid. In some embodiments, the L / D ratio is 60. The melting of only a portion of the acid can also be achieved by preventing the material from stagnating in the granulation starting zone. In some embodiments, the melting of only a portion of the acid is achieved only by using a conveying element only in the granulation starting zone. In some embodiments, the melting of only a portion of the acid is achieved by using a conveying element only in the granulation starting zone. A combination of embodiments can also be used to achieve the desired melting of only a portion of the acid. The melting of only a portion of the acid also minimizes any potential reaction between the acid and the base, providing a large amount (90-100%) of carbon dioxide retained in the effervescent granules.

[0071] According to one embodiment, the melting of part of the acid comprises surface melting of the acid.Surface melting is defined as the melting of that part of the acid which is in physical contact with the inner surface of the granulation initiation zone.

[0072] The torque observed in the processor can be used to estimate the portion of acid that is melted, and used to calculate the power (P) and specific energy input (SEI). SEI is a measure of the energy input by the twin screw processor used to produce the particles, and can be in the form of thermal energy, mechanical energy, etc. and combinations thereof. According to an embodiment, SEI can be a combination of thermal energy and mechanical energy. It is,

[0073] SEI=SEI 机械 +SEI 热

[0074] According to another embodiment, the SEI may be substantially mechanical energy. According to one embodiment, the SEI of the processor is less than the energy required to completely melt the acid (Em). According to an exemplary embodiment, the SEI of the processor may be approximately 50% of Em. An estimate of the percentage of acid melt may be obtained using equation (1):

[0075] Melting percentage = SEI / Em×100.......(1)

[0076] The energy required to completely melt the acid (Em) can be obtained from the differential scanning calorimetry (DSC) thermograms of the input blend and its components.

[0077] According to embodiments where the SEI is substantially mechanical energy, the power (P) and specific energy input (SEIMATIC) may be calculated using equations (2) and (3):

[0078] P=2πNτ / 60,000......(2)

[0079] Where P = power (kW)

[0080] N = screw speed (rpm)

[0081] τ=Torque (Nm)

[0082] SEI 机械 = Power (kW) / Throughput or feed rate (kg / h)......(3)

[0083] Among them, SEI 机械 is the mechanical specific energy input of the twin screw processor (kWh / kg).

[0084] The input blend is processed and conveyed from the granulation starting area through the granulation finishing area toward the outlet of the processor. Processing and conveying allow a part of the melted acid to solidify, thereby realizing granulation in the processor. In certain embodiments, only conveying elements or basic conveying elements are used in the granulation finishing area of ​​the processor. The granulation step helps to form discrete free-flowing particles with high porosity and compressibility. In some embodiments, the method using a twin screw processor to form a porous effervescent composition can be an intermittent process. In some embodiments, the method using a twin screw processor to form an effervescent composition can be a continuous process. The term "intermittent process" refers to a process in which all materials are added before the start of processing and are discharged at the end of processing. The term "continuous process" refers to a process in which materials are added and discharged simultaneously during processing.

[0085] According to one embodiment, the input blend fed into the processor has a moisture content of less than 0.5%.

[0086] IV. Overview of Several Embodiments

[0087] Compositions, methods and processor embodiments disclosed herein provide for the production of effervescent compositions having key attributes (e.g., higher porosity and higher carbon dioxide content) compared to conventional similar effervescent compositions. These porous effervescent compositions can be further processed using processing excipients to form, for example, effervescent tablets that exhibit improved mechanical strength and also show a fast disintegration time of typically less than 60 seconds.

[0088] The disclosed method embodiments do not require any additives, such as water, solvents, or defined added binders. The method and processor embodiments disclosed herein also provide a cost-effective continuous system. The method embodiments disclosed herein are scalable and suitable for rapid production of large quantities of effervescent compositions.

[0089] It is believed that the melting of only a portion of the acid helps to achieve effervescent particles with a relative porosity of at least 50% and a retained carbon dioxide content of at least 90% of the input blend. In some embodiments, the composition has a normal particle size distribution, wherein at least 90% of the particles are no more than 1000 microns. This particle size distribution contributes to the free-flowing properties of the particles. Melting only a portion of the acid is also believed to help increase the relative porosity of the particles. The high porosity of the particles contributes to the rapid disintegration of the tablet. The melting of only a portion of the acid is also believed to help form irregular particles, thereby increasing its compressibility, thereby making the particles suitable for tableting, resulting in tablets having sufficient hardness for product handling and packaging activities. The tablets obtained from the granules of the present disclosure have a disintegration time of less than 60 seconds and a hardness of at least 3kp.

[0090] V. EXAMPLES

[0091] Porous effervescent compositions formed using embodiments of the claimed methods are described herein, particularly examples of moisture content, retained CO2 content, disintegration time, porosity, bulk density and tap density, and other properties of the particles. Some examples highlight the benefits of using the presently disclosed compositions and methods compared to conventional methods.

[0092] Exemplary methods for measuring these properties are described below.

[0093] Determination of moisture content: The input blend and pellets were analyzed by infrared moisture balance analyzer at 75°C for 5 minutes. The weight loss was recorded as the percentage (%) moisture content relative to its initial weight.

[0094] Determination of retained CO2 content: 5.0 g of the input blend and 5.0 g of the pellets were added to two separate 100 ml 10% v / v sulfuric acid solutions. The weight loss of the input blend and pellets due to the release of CO2 due to the reaction between the sulfuric acid and the bicarbonate or carbonate present in the blend or pellets was recorded as the observed weight of carbon dioxide. The difference between the weight of the input blend and the pellets after the reaction and the difference between the initial weight of the input blend and the pellets were calculated to measure the CO2 content (g) retained in the blend or pellets. The percentage (%) of the relative retained CO2 content in the pellets was then calculated using the following formula:

[0095] Relative retained CO2 content (%) = (weight of CO2 observed in particles (g) x 100) / weight of CO2 observed in input blend.

[0096] Determination of disintegration time of effervescent tablets: The disintegration time was calculated as the average time required for each of three effervescent tablets (number of units tested (n) = 3) to disintegrate in 200 ml of purified water at room temperature, about 25°C ± 5°C, and form a clear solution.

[0097] Determination of hardness and thickness of effervescent tablets: Hardness was calculated as the average hardness measured for each of five effervescent tablets (number of units tested (n) = 5) using an Inweka TBH125 hardness tester (Germany). Thickness was calculated as the average thickness measured for each of five effervescent tablets (number of units tested (n) = 5) using a vernier caliper.

[0098] Measurement of volume and tap density: Add known amounts (m) of input blend and granules into two separate dry, graduated 100 ml cylinders. Level the contents of the two cylinders without compaction; and read the unsettled apparent volume (V0) to the nearest graduated unit.

[0099] Calculate bulk density (g / ml) using the following formula:

[0100] Bulk density = mass (m) / bulk volume (V0)

[0101] To calculate the tap density, the contents of the two cylinders are mechanically tapped to a maximum of 1250 strokes and the apparent tap volume (V t ). The tap density is calculated using the following formula:

[0102] Tap density = mass (m) / tap volume (V t )

[0103] Porosity Measurement: Porosity is measured based on the percentage of relative volume porosity and the percentage of relative tap porosity.

[0104] The percentage of relative volume porosity is calculated by considering the 1g specific (Sp) product using the following formula:

[0105] % Relative volume porosity = ((volume specific area of ​​1g particles - volume specific area of ​​1g input blend) × 100) / volume specific area of ​​1g input blend

[0106] Wherein, the volume specific product of 1g of particles = 1 / particle packing density; and

[0107] Volumetric product of 1g input blend = 1 / bulk density of input blend

[0108] The relative tapped porosity percentage was calculated considering 1 g specific volume using the following formula:

[0109] % Relative pore volume porosity = ((tapped volume of 1g particles - tapped volume of 1g input blend) × 100) / tapped volume of 1g input blend

[0110] Among them, the tap volume of 1g of particles = 1 / tap density of particles

[0111] Tap volume of 1g input blend = 1 / tap density of input blend

[0112] Measurement of Compressibility: Compressibility is measured according to the Hausner ratio and the compressibility index as provided in Hausner, HH, Int. J. Powd. Metall, Vol 3, pg 7, 1967 and Carr, RL, Chem. Eng., Vol 72, Issue 1, pg 163 and Issue 2, pg 69, 1965, respectively. Both of these references are incorporated herein by reference.

[0113] Example 1: Preparation of the porous effervescent composition of the present disclosure:

[0114] Four experiments were conducted to form exemplary particles with different acids. The ingredients used to form the exemplary particles are listed below.

[0115] Table 1: Ingredients used to prepare exemplary effervescent granules

[0116]

[0117] To form the pellets, the ingredients of the input blend were tray dried at 45°C to reduce their moisture content to less than 0.5% w / w, followed by sieving each ingredient individually through an ASTM #60 mesh sieve. The sieved ingredients were mixed in a conical mixer to form the input blend. The input blend was immediately processed in a co-rotating twin-screw extruder. The machine specifications and process parameters are described in Table 2 below:

[0118] Table 2: Machine specifications and process parameters

[0119]

[0120]

[0121]

[0122]

[0123] *Residence Time (RT) is defined as the duration of time a material is consumed within a processor. RT can be affected by feed rate, screw speed, free volume of the processor, and density of the material.

[0124] List of component abbreviations

[0125]

[0126] While the above parameters were kept constant for the four experiments, the feed rate and barrel temperature profile were varied as described below.

[0127] Feed rates: The feed rates for citric acid were maintained at 186 g / min; for malic acid at 205 g / min; for adipic acid at 225 g / min and for tartaric acid at 215 g / min.

[0128] Drum temperature profiles for exemplary particles formed using different acids: Please refer to Table 3 provided below.

[0129] Table 3. Barrel temperature curve

[0130]

[0131] The granules obtained from the outlet of the co-rotating twin-screw extruder were dried on a tray at 45°C until the loss on drying was less than 0.5% w / w; and stored in moisture-proof packaging. The granules were then evaluated to determine their properties. The properties of the granules obtained in the four experiments are summarized in Table 4 below.

[0132] Table 4: Properties of effervescent granules

[0133]

[0134]

[0135] **Note: Due to random errors in the measurement, the values ​​of the retained CO2 content may vary from +5% to over 100%.

[0136] As an example, the calculation of the % relative retained CO2 content of an exemplary particle 1 comprising citric acid is as follows:

[0137] % Relative CO2 content retained = (weight of CO2 observed in particles (g) x 100) / weight of CO2 observed in input blend (g)

[0138] When placed in the above equation, the values ​​in Table 4 produce the following values:

[0139] % Relative retained CO2 content = (1.36 × 100) / 1.43 = 95.10

[0140] As an example, the calculation of the % relative specific bulk porosity for an exemplary particle 1 comprising citric acid is as follows:

[0141] The bulk volume of 1g of particles = 1 / the bulk density of particles

[0142] Bulk volume of 1g input blend = 1 / bulk density of input blend

[0143] % Relative bulk porosity = ((bulk area of ​​1g particle - bulk area of ​​1g input blend) × 100) / bulk area of ​​1g input blend

[0144] When placed in the above equation, the values ​​in Table 4 produce the following values:

[0145] The bulk volume of 1g of particles = 1 / 0.389 = 2.570

[0146] Bulk volume of 1g input blend = 1 / 0.680 = 1.470

[0147] % Relative volume porosity = (2.57-1.47×100) / 1.47 = 74.81

[0148] As an example, the calculation of the % relative specific pore size porosity for an exemplary particle 1 comprising citric acid is as follows:

[0149] The tap volume of 1g of particles = 1 / tap density of particles

[0150] Tap volume of 1g input blend = 1 / tap density of input blend

[0151] % Relative pore volume porosity = ((tap volume of 1 g of particles - tap volume of 1 g of input blend) × 100) / tap volume of 1 g of input blend

[0152] When placed in the above equation, the values ​​in Table 4 produce the following values:

[0153] The compacted volume of 1g of particles = 1 / 0.555 = 1.801

[0154] The tap volume of 1g input blend = 1 / 1.137 = 0.879

[0155] % Relative pore volume porosity = (1.801-0.879×100) / 0.879 = 10.86

[0156] Observations: The % relative retained CO2 content was found to be greater than 90% and the relative specific area porosity as well as the relative specific pore size porosity of the particles were found to be greater than 50%.

[0157] Example 2: Preparation of an exemplary effervescent tablet

[0158] The exemplary granules 1-4 obtained in the four experiments described in Example 1 were kept at 45°C until the loss on drying was 0.5% w / w. The dried granules were passed through an ASTM #20 screen. The granules from the above steps were compressed into tablets weighing 2.5 grams using a single bench top Inweka tablet press (Ahmedabad, India) with a 20 mm round flat bevel tool. The tablets were then evaluated to determine their properties. The properties of the tablets obtained in the four experiments are summarized in Table 5 below.

[0159] Table 5: Properties of tablets obtained using exemplary effervescent granules

[0160]

[0161] Observations: The tablets were observed to have a hardness of at least 3 Kp and a disintegration time of 20 to 90 seconds.

[0162] Example 3: Preparation of effervescent tablets with API

[0163] Three experiments were conducted to form effervescent tablets containing the APIs - aspirin, N-acetyl-L-cysteine ​​(NAC) and cefixime. The ingredients used to form the effervescent tablets are provided below.

[0164] Table 6: Ingredients used to prepare effervescent tablets containing API

[0165]

[0166]

[0167] In order to form effervescent tablets 1, 2 and 3 with the composition described in Table 6 above, the exemplary granules 1 prepared according to Example 1 were passed through an ASTM#30 mesh sieve. API was sieved separately through an ASTM#30 mesh sieve. The exemplary granules 1 thus obtained and API were manually mixed. Other ingredients (sucralose and strawberry flavor) were passed through an ASTM#60 mesh sieve and then mixed with the mixture obtained above. The final mixture was lubricated with sodium benzoate that had passed through an ASTM#60 mesh sieve. The lubricated mixture was pressed into tablets using a single workbench top Inweka tablet press (Ahmedabad, India) with a 20mm round flat bevel tool.

[0168] The effervescent tablets thus obtained were then evaluated to determine their properties. The properties of the tablets obtained in the three experiments are summarized in Table 7 below.

[0169] Table 7: Properties of effervescent tablets

[0170] nature Aspirin tablets NAC Tablets Cefixime Tablets Thickness (mm) (n=5) 9.80 6.20 4.93 Hardness (Kp) (n=5) 7.0 6.1 5.7 Disintegration time (seconds) (n=3) 36 26 25

[0171] Observations: Tablets were observed to have a hardness of at least 5 Kp and a disintegration time as low as 25 seconds.

[0172] Example 4: Preparation of effervescent granules by using a meltable binder as a definite added granulating agent

[0173] In one example, tablets were prepared using a defined added binder method for forming granules. The ingredients used to form tablets in this example are provided below.

[0174] Table 8: Ingredients for preparing granules using a process involving the use of defined added binders

[0175]

[0176]

[0177] Each ingredient was tray dried at 45°C to reduce the moisture content to less than 0.5% w / w and sieved individually through an ASTM #60 mesh screen. The assigned ingredients were mixed manually and immediately processed using a co-rotating twin-screw extruder according to the following processing conditions. The machine specifications and process parameters are described in Table 9 below:

[0178] Table 9: Machine specifications and processing conditions

[0179] 1 machine Omega 20 2 Cylinder diameter 20mm 3 Each tube length 120mm 4 Total number of cylinders 10nos. 5 Total length of tube 1200mm 6 Machine aspect ratio L / D 60 7 Screw speed 600rpm 8 Screw structure Please see Figure 1 9 Feed rate 10Hz(215g / min) 10 Barrel temperature curve As shown in Table 10

[0180] The process is carried out in a twin screw extruder having a novel screw configuration and elements used in the disclosed process.

[0181] Table 10: Barrel temperature curve

[0182]

[0183] The granules thus obtained were tray dried at 45°C until the moisture content was less than 0.5% w / w and stored in moisture proof packaging. The granules were then evaluated to determine their properties. The properties of the granules are summarized in Table 11 below.

[0184] Table 11: Particle properties

[0185] parameter Particles <![CDATA[Relative CO2 content retained by the particles (%)]]> 84.74 Bulk volume (g / cc3) 0.463 Relative % Bulk Porosity 15

[0186] Observation: The CO2 content efficiency of the granules prepared using the above method was found to be much lower than that obtained using the teachings of the present disclosure. The lower CO2 content may be attributed to the loss of CO2 due to the reaction between the acid and the base. It is conceivable that if any additional elements such as kneading elements are added in the initial zone of granulation, satisfactory granules will not be produced.

[0187] In view of the many possible embodiments to which the principles of the present disclosure may be applied, it should be recognized that the illustrated embodiments are merely preferred examples of the present disclosure and should not be taken as limiting the scope of the disclosed subject matter. Rather, the scope of the present disclosure is defined by the appended claims.

[0188] Specific implementations are described below

[0189] A granular composition comprising an anhydrous acid component and an anhydrous base component, the anhydrous acid component comprising a combination of a portion of melted acid and a portion of unmelted acid; the anhydrous base component comprising carbonate functional groups, wherein the base component is capable of reacting with the acid component to form carbon dioxide; and wherein the anhydrous acid component and the anhydrous base component are present in a weight ratio of 1:9 to 9:1, and the composition does not contain a defined added granulating agent.

[0190] The composition, wherein the composition further comprises an active agent selected from the group consisting of an anti-infective agent, an antibacterial agent, an antihistamine, a decongestant, an anti-inflammatory agent, an antiparasitic agent, an antiviral agent, an antifungal agent, an amoebicide, a trichomonocide, analgesics, antiarthritic agents, antiasthmatic agents, anticoagulants, anticonvulsants, antidepressants, antidiabetic agents, antitumor agents, antipsychotic agents, antihypertensive agents, expectorants, electrolytes, laxatives, botanicals, muscle relaxants, diuretics, or a combination thereof.

[0191] The composition, wherein the composition further comprises aspirin, N-acetyl-L-cysteine, cefixime or a combination thereof.

[0192] A porous effervescent composition is formed from an input blend comprising an acid and a base, the porous effervescent composition being formed by granulating the input blend in a twin screw processor, the porous effervescent composition comprising granules formed by an in situ granulating agent, wherein the in situ granulating agent is a portion of the acid, the portion of the acid being the portion of the acid that melts during the granulation process.

[0193] Such a composition wherein the porosity of the porous effervescent composition is at least 50% greater than the porosity of the input blend.

[0194] Such a composition wherein the porous effervescent composition maintains a carbon dioxide content of at least 90% of the input blend.

[0195] Such a composition, wherein the composition does not contain or has no defined added granulating agent.

[0196] Such a composition wherein one or both of the acid and base of the input blend are anhydrous.

[0197] A composition wherein the moisture content of the input mixture is less than 0.5% w / w of the composition.

[0198] Such a composition, wherein the acid is selected from citric acid, tartaric acid, adipic acid, malic acid or a combination thereof.

[0199] Such a composition, wherein the input blend further comprises one or more ingredients selected from the group consisting of pharmaceutical, food, veterinary, nutraceutical, horticultural, household, culinary, pesticidal, agricultural, cosmetic, herbicide, industrial, cleaning, confectionery and flavoring agents, or combinations thereof.

[0200] Such a composition, wherein the input blend further comprises one or more processing excipients selected from the group consisting of soluble and insoluble lubricants, flavoring substances, colorants, or combinations thereof.

[0201] An oral solid dosage form comprising a porous effervescent composition formed from an input blend comprising an acid and a base by granulating the input blend in a twin screw processor and one or more optional processing excipients, the porous effervescent composition comprising granules formed by an in situ granulating agent, the in situ granulating agent being a portion of the acid which is the portion of the acid that melts during the granulation process.

[0202] Such a dosage form wherein one or both of the acid and base of the input blend are anhydrous.

[0203] Such a dosage form wherein the porosity of the porous effervescent composition is at least 50% greater than the porosity of the input blend.

[0204] Such a dosage form wherein the porous effervescent composition has a retained carbon dioxide content percentage of at least 90% of the input blend.

[0205] Such a dosage form, wherein the acid is selected from citric acid, tartaric acid, adipic acid, malic acid or a combination thereof.

[0206] Such dosage forms may further comprise one or more ingredients selected from the group consisting of pharmaceutical, food, veterinary, nutritional, horticultural, household, culinary, insecticide, agricultural, cosmetic, herbicide, industrial, cleaning, confectionery and flavoring agents, or combinations thereof.

[0207] Such a dosage form, wherein the processing excipients are selected from: non-effervescent disintegrants, soluble and insoluble lubricants, flavoring substances, colorants, or combinations thereof.

[0208] Such a dosage form, wherein the oral solid dosage form is selected from effervescent tablets, powders or a combination thereof for oral administration.

[0209] Such a dosage form, wherein the effervescent tablet is a fast disintegrating tablet or an orally disintegrating tablet.

[0210] Such a dosage form, wherein the effervescent tablet has a disintegration time in water of about 20 to 90 seconds at room temperature of about 25°C ± 5°C.

[0211] Such a dosage form, wherein the effervescent tablet has a hardness of at least 3Kp.

[0212] A method for preparing porous effervescent particles, the method comprising feeding an input blend comprising an acid and a base into a twin-screw processor; melting only a portion of the acid to be used as an in-situ granulating agent; granulating the input blend to form granules; and optionally collecting the granules from the twin-screw processor, granulating the input blend to form granules.

[0213] A process in which only a portion of the acid melting is effected in the granulation start zone of the twin-screw processor without any material stagnation, the granulation start zone consisting essentially of conveying elements.

[0214] Such a process, wherein melting of only a portion of the acid is achieved by maintaining a low residence time within the twin screw processor.

[0215] Such a process, in which melting of only a portion of the acid is achieved by maintaining a low residence time in the granulation initiation zone of the twin screw processor.

[0216] Such a process wherein the granulation initiation zone is maintained at a temperature sufficient to cause melting of only a portion of the acid.

[0217] A process wherein the specific input energy of the twin screw processor is less than the energy required to completely melt the acid.

[0218] Such a process wherein the twin screw processor is a co-rotating twin screw extruder.

[0219] A process wherein the porosity of the particles collected from the twin screw processor is at least 50% greater than the porosity of the input blend.

[0220] A process wherein the pellets collected from the twin screw processor have a retained carbon dioxide content of at least 90% of the input blend.

[0221] Such a process, wherein the process is a continuous process or a batch process.

[0222] A twin-screw processor for preparing porous effervescent particles, the twin-screw processor comprising a feed zone for receiving an input blend comprising an acid and a base; a granulation initiation zone for melting a portion of the acid to be used as an in-situ granulating agent; a granulation finishing zone for granulating the input mixture; and an outlet for discharging the particles.

[0223] This processor, in which the granulation starting zone is essentially composed of conveying elements.

[0224] The processor wherein the granulation initiation zone includes a heating element to maintain the granulation initiation zone at a temperature sufficient to melt only a portion of the acid.

[0225] This processor, in which the granulation finishing zone is essentially composed of conveying elements.

[0226] This processor, wherein the granulation finishing zone is maintained at a lower temperature than the granulation starting zone.

[0227] The processor further comprises a transition zone between the granulation starting zone and the granulation finishing zone, wherein the transition zone is maintained at a temperature lower than the temperature of the granulation starting zone and higher than the temperature of the granulation finishing zone.

[0228] Such a processor, wherein the twin screw processor is a co-rotating twin screw extruder.

[0229] A porous effervescent granule comprising an acid and a base, wherein the porosity of the porous effervescent granule is at least 50% greater than the porosity of an input blend used to prepare the granule, and the granule retains at least 90% of the carbon dioxide of the input blend.

[0230] A composition comprising a carbonate-containing base; and a combination of a molten acid and an unmolten acid, the combination being configured to increase the porosity of the composition by at least 50%.

[0231] A composition comprising a carbonate-containing base; and a combination of molten acid and unmolten acid, the combination being configured to retain at least 90% of the carbon dioxide.

[0232] A porous effervescent composition formed from an input blend comprising an acid and a base by granulating the input blend in a twin-screw processor, the porous effervescent composition comprising granules formed by an in-situ granulating agent, wherein the in-situ granulating agent is a portion of the acid that is melted during the granulation process, and wherein the specific input energy of the twin-screw processor does not exceed 50% of the energy required to completely melt the acid.

Claims

1. A method for preparing porous effervescent particles, the method comprising: feeding an input blend including an anhydrous acid and an anhydrous base into a feed zone of a twin-screw processor, the anhydrous acid being capable of reacting with the anhydrous base to generate carbon dioxide and produce effervescence; causing only a portion of the anhydrous acid to melt in a granulation initiation zone in a twin-screw processor to obtain molten anhydrous acid and unmelted anhydrous acid, wherein the molten anhydrous acid serves as an in-situ granulating agent; The melting of only a portion of the anhydrous acid is achieved by maintaining a residence time of 3 to 5 seconds in the granulation starting zone of the twin-screw processor and by maintaining the granulation starting zone at a temperature of 10 to 40° C. below the melting temperature of the anhydrous acid. Among them, the molten anhydrous acid and the unmolten anhydrous acid are the same anhydrous acid; And, wherein the anhydrous acid is selected from citric acid, tartaric acid, malic acid and adipic acid; granulating the input blend in a granulation finishing zone in a twin-screw processor to form granules, wherein the granulation finishing zone is maintained at a lower temperature than the granulation initiation zone; and collecting pellets from a twin-screw processor; Furthermore, the method does not require the affirmative addition of granulating agents and / or binders; The porous effervescent particles have a porosity at least 50% greater than the porosity of the input blend used to prepare the particles, and the particles retain at least 90% of the carbon dioxide of the input blend.

2. The method of claim 1, wherein: The melting of only a portion of the anhydrous acid is effected without any material stagnation in the granulation start zone of the twin-screw processor, which essentially consists of conveying elements.

3. The method of claim 1, wherein: The residence time of the input blend in the twin screw processor was 8 to 10 seconds.

4. The method of claim 1, wherein: The twin-screw processor is a co-rotating twin-screw extruder.

5. The method of claim 1, wherein: The infusion blend includes an active agent selected from the group consisting of anti-infectives, antibacterials, antihistamines, decongestants, anti-inflammatory agents, antiparasitics, antivirals, antifungals, amoebicides, trichomonocides, analgesics, antiarthritics, antiasthmatics, anticoagulants, anticonvulsants, antidepressants, antidiabetics, antineoplastic agents, antipsychotics, antihypertensives, expectorants, electrolytes, laxatives, botanicals, muscle relaxants, and diuretics.

6. The method of claim 1, wherein: The anhydrous base is selected from the following group: carbonate; sesquicarbonate; bicarbonate of potassium, lithium, sodium, calcium, ammonium; L-lysine carbonate; arginine carbonate; glycine sodium carbonate; or amino acid sodium carbonate; or a combination thereof.

7. The method of claim 1, wherein: The anhydrous acid component and the anhydrous base are present in a weight ratio of 1:9 to 9:

1.

8. The method of claim 1, wherein: The input blend includes one or more ingredients selected from the group consisting of pharmaceutical, food, veterinary, nutraceutical, horticultural, household, culinary, pesticidal, agricultural, cosmetic, herbicidal, industrial, cleaning, confectionery, and flavoring agents, or combinations thereof.

9. The method of claim 1, wherein: The input blend comprises one or more processing excipients selected from the group consisting of soluble and insoluble lubricants, flavoring substances, colorants, or combinations thereof.

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