KR100942964B1 - Process for preparing porous tablet composition for oral care - Google Patents

Abstract

The present invention relates to a method for preparing a porous tablet oral hygiene composition, wherein the binder solution is added to the porous plastic granule material, the gelling agent, and the water penetration expander in an amount of 5 to 70% by weight in the preparation of the wet granules, and then granulated to provide a specific surface area. To prepare porous plastic granules having 25 to 1000 m 2 / g; According to the method for producing a porous tablet-type oral hygiene composition comprising mixing the oral hygiene active ingredient into the porous plastic granules and tableting at a pressure of 500 kg / cm 2 or less to produce a tablet having a strength of 0.5 to 15 kg, In the present invention, a porous tablet oral hygiene composition can be obtained by simultaneously dissolving and gelling with water, saliva, or chewing to brush or gargle.

Porous, tablet, oral care compositions, dissolving, gelling, specific surface area.

Description

Production method of porous tablet oral hygiene composition {PROCESS FOR PREPARING POROUS TABLET COMPOSITION FOR ORAL CARE}

The present invention relates to a method for producing a porous tablet-type oral hygiene composition, specifically, a porous that can be dissolved or gelled by simultaneous dissolution and gelation by water or saliva in the oral cavity, or by chewing through the mouth. A method for producing a tablet oral hygiene composition of the present invention.

Common types of oral hygiene can be classified into toothpaste, dentifrice, film and spray. The purpose of the use of these oral products includes aesthetics such as whitening of the mouth, prevention of tartar deposition, suppression of bad breath, and treatment and prevention of tooth decay and gum disease.

Meanwhile, the pharmaceutical industry is making fast dissolving tablets so that tablets such as medicines and health supplements can be easily taken. Toshihiro Shimizu et al . Chem . Pharm. Bull. 51 (10) (2003), pointing out that fast dissolving tablets offer great benefits for those who have difficulty swallowing tablet drugs, tablet manufacturing, lyophilization, spray-drying, Disintegrant addition, sublimation, and sugar-induced diluents are used.

For the preparation of fast dissolving tablets, techniques such as lyophilization, molding, and compression processes can be used.

First, lyophilization is a process of drying a solvent, such as a frozen drug solution or a frozen drug suspension containing an excipient. Tablets obtained by lyophilization are generally very light and readily dissolve because they have many voids and plastic structures. However, lyophilization has the disadvantage that the process is relatively expensive, and that the final dosage form is very fragile, easy and of low strength, making blister packaging impossible.

In the molding process, the material dissolved in water or ethanol is compressed into tablets in a wet state below the general tableting pressure and dried to obtain fast-soluble tablets. The main component of the molded tablet is generally water soluble. Molded tablets have many voids, which facilitate water penetration and promote dissolution. On the other hand, as disclosed in U.S. Patent No. 5,082,677 to Van Scoik et al., The molded tablet has a disadvantage in that the strength is so weak that problems occur in the distribution process. In addition, there is a problem that a more complex process than the conventional compression process.

Obtaining fast dissolving tablets using conventional tableting compressors is a very attractive method in terms of manufacturing cost and technology transfer. In the conventional compression process, fast-soluble tablets could not be obtained because the voids in the tablets were not an important factor but the purpose was to increase the tablet strength by compressing at high pressure. The processes performed to obtain many voids include granulation, the use of certain soluble materials, and methods of making a complete tablet and post-treatment, each of which is briefly described below.

First, in the granulation method, wet granules by fluidized bed described in US Pat. No. 6,249,938 to Bonadeo et al., Dry granules described in US Pat. No. 5,939,091 to Eoga et al., Spray drying described in US Pat. No. 6,207,199 to Allen et al. And the scintillation method described in US Pat. No. 6,048,541 to Fuisz et al. Are used to prepare fast dissolving tablets.

In certain diluent methods, it is important to select calcium insoluble salts, specific disintegration combinations, and specific sugar composition diluents. In US Pat. No. 6,596,311 to Dobetti et al., An insoluble inorganic composition is used as a major component of fast dissolving tablets. As a method by adjustment of a sugar or a sugar derivative, Chang, R.-K. Et al., " Pharmaceutical Development & Technology, 24 : 52-58, 2000" reported the use of sugars or sugar derivatives in the formulation of almost all fast-soluble tablets. Next, almost all fast-dissolving tablets in the method of using disintegrants use effervescent conjugate / bases or some combination of non-foamable disintegrants. Such non-foamable disintegrants include carboxymethyl cellulose, cross-polyvinylpyrrolidone, starch, modified starch, carboxymethylated starch, microcrystalline cellulose and the like.

Compression and post-treatment is a method of making weak tablets through various post-treatment processes such as sublimation, sintering, and humidity treatment after the tablets are manufactured at low pressure. In US Pat. No. 6,316,026 to Roser et al., Fast-soluble tablets are prepared using volatiles. Humidity control processes are used to increase the strength of tablets by converting some of the sugars from the amorphous state into the crystalline state to control the humidity during the drying and granulation process to form crystals. Lagoviyer et al., US Pat. No. 6,465,010 discloses a method of increasing the strength of a tablet while raising the temperature to high temperature and then cooling to room temperature.

Little research has been conducted on applying the above-described manufacturing technique of fast dissolving tablets to oral hygiene. In the conventional oral hygiene, there is an example of manufacturing a fast dissolving tablet using a foaming and disintegrating agent using a foamed tablet, but in this case, there was a problem that the conjugated acid used for foaming adversely affects the sensitivity of consumers. In terms of usability, improvements are urgently needed. Specifically, Douglas C.S. US Patent Publications 2004/0101494 A1 and 2004/0101493 A1, et al., Relate to chewable solid unit dosage forms and methods of delivering the active agent into the occlusal surface of a tooth, including tooth and interdental and molar teeth, which may occur during chewing. Remains on the occlusal surface of the drug delivery. However, this formulation can not only provide a good feeling to consumers because it can give a sense of foreign body after use, but also does not exhibit gel properties like toothpaste within seconds because the tablet is not fast-soluble. There is a demand for improvement of ease of use.

SUMMARY OF THE INVENTION An object of the present invention is to provide a method for preparing a porous tablet oral hygiene composition which can be dissolved or geled quickly by dissolution in the oral cavity or by simultaneous dissolution and gelation by water or saliva in the oral cavity or through chewing. It is.

Method for producing a porous tablet oral hygiene composition according to the present invention for achieving the above object,

The binder solution was added to the porous plastic granule material, the gelling agent and the water penetration expander in an amount of 5 to 70% by weight in the preparation of the wet granules and granulated to prepare the porous plastic granules having a specific surface area of 25 to 1000 m 2 / g;

Mixing oral hygiene active ingredients to the porous plastic granules and tableting at a pressure of 500 kg / cm 2 or less to prepare a tablet having a strength of 0.5 to 15 kg.

In the present invention, in contrast to the conventional wet granulation process when manufacturing the porous plastic granules, the injection time or the amount of input is adjusted so that excessive wetting does not occur when the porous plastic granule material, the gelling agent, and the water penetrating expansion agent are added to the binder solution and mixed. In this way, it is possible to prepare a porous tablet which can dissolve rapidly in the oral cavity, or dissolve and gelate simultaneously with water or saliva in the oral cavity or through chewing to brush or gargle.

In order to speed up the dissolution of the tablets that dissolve in the oral cavity, it is essential to facilitate rapid delivery of water or saliva to the core of the tablets. It is therefore very important to maintain pores in the granules through which water can penetrate.

In the case of conventional dry granulation, it is possible to secure the voids to some extent by using a solid binder, but when used in the oral cavity, the blowing of powder may be a problem. On the other hand, in the case of wet granulation, the raw material powder is thoroughly wetted and kneaded, and then passed through a net to prepare pellet granules, so that the drying time is long and the pores in the obtained granules are long. There is a problem in that the dissolution rate is very slow because it hardly exists.

In the present invention, the granules are prepared by partial wetting in the granulation step, and the tablets are prepared by low pressure tableting. In other words, half wetting provides a certain level of tableting ability and provides more than a certain level of binding force to the compressed tablet, while also shortening the granulation time and decreasing a specific surface area in the granulation process, thereby infiltrating moisture. Only some of the possible porosities can be reduced or maintained, leading to rapid dissolution and / or gelation.

Hereinafter will be described in detail a method for producing a porous tablet oral hygiene composition according to the present invention.

Porous tablet oral hygiene composition prepared according to the method of the present invention has all the functions of the existing oral hygiene cleaning, caries prevention, gum disease prevention, dissolution and / or gelation by water or saliva or by chewing It is a product for oral hygiene. Tablet toothpaste is typical, and in the form of tablets by mouth chewing, dissolved or gelled by water or saliva on the toothbrush or in the mouth, it is refreshing the mouth simply by rinsing with water as well as brushing And can alleviate and prevent oral diseases.

The properties required for tablets to be dissolved and / or gelated in the oral cavity should be of high porosity for ease of penetration of water, within a few seconds the water should penetrate into the center of the tablet and have a strength above the proper to facilitate handling. Such fast dissolving tablets are prepared from high porosity plastic granule materials, water / saliva penetration enhancers, binders, gelling agents, anti-adhesion agents, moisturizers, abrasives, foaming agents, flavors, sweeteners, medicaments, and the like.

In general, fast-dissolving tablets used in pharmaceuticals are not intended for dissolution and gelation, as in toothpaste, because they are invented to speed up the absorption of the drug in the oral cavity. According to the method of the present invention, the tablet composition is prepared to have a gel texture similar to a general toothpaste.

Dissolution and gelation are both competitive processes that require water or saliva. Since some of the water or saliva used must be dissolved and the rest must be gelled, it is technically difficult to simultaneously dissolve and gel.

In the present invention, in order to obtain rapid dissolution and / or gelling properties, the preparation of porous plastic granules through partial wetting in the granulation process, the induction of rapid gelation using a high hydrophilic polymer, the use of water penetration extenders and binders A low pressure tablet high strength tablet was prepared via the solution.

The manufacture of porous plastic granules uses materials that can dissolve quickly or come into contact with water or saliva, or test materials that can be dispersed. At this time, the test materials used should be selected as drugs or foods that can be used harmlessly to the human body. When tableting porous plastic granules using a tableting machine, plastic deformation of the porous plastic granules occurs due to contact between the particles by tableting pressure, but the voids are maintained after deformation, thereby obtaining a tablet including pores.

In the present invention, when the polymer is used as the porous plastic material, the polymer should be free from interference with water due to water film formation due to an increase in viscosity that may occur on the surface of the tablet during dissolution in water. A method of making this type of tablet is to use a proportion of water / saliva penetration enhancer. It is the water penetration extender that serves to prevent the viscous water ingress from the tablet's surface. Generally, the water / saliva penetration extender and the porous plastic granules are different materials, but the plastic granules and the water / saliva penetration extender may be used in common.

The use of porous plastic granules and water / saliva penetration extenders may lead to plastic deformation and bonding to tablets, but it is very important to use binders to induce association between raw materials. The binder maintains the function of the pores of the porous plastic granules and the water / saliva penetration enhancer and serves to impart tabletting properties. In the absence of a binder, when the two materials are separated and tableted by tableting, the strength of tablets is low and fracture occurs. Typical binders are in the liquid or ointment semi-solid state, and it is very important that the binders retain the original properties of these two raw materials. The first way to achieve this property is to use high concentration binders that have little reactivity with water, and to give short mixing times at relatively low binder concentrations, which makes porous plastic granule materials and water / saliva penetration extenders inherent in nature. You can also prevent the loss.

The process up to the production and extrusion of the porous plastic granules can change the physical properties by varying the input position of each component, and can also be changed depending on the desired physical properties.

First, in the method for producing the fast dissolving tablet type dissolving and / or gelling oral hygiene composition according to the present invention, each raw material will be described in detail.

Porous plastic granule material

Porous plastic materials should have a porosity of 0.14 or more and a density of 0.86 or less, and maintain the original shape when plasticizing with a tablet press pressure of 1.27 cm diameter at a pressure of 500 kg / cm2 or less. . In general, tableting at a pressure of 675 kg / cm 2 or more does not maintain the properties of the fast dissolving tablet due to breakage of voids.

If the porosity of the porous plastic granule material is less than 0.14, water permeability and porosity are very low, so it cannot play a role as the porous plastic granule material.If the density is higher than 0.86, phase separation by gravity occurs after mixing the granular material. As a result, it is not suitable as a porous plastic granule material.

The porous plastic material is preferably soluble in water. The porous plastic material having high water solubility is preferably included in the range of 1 to 98% by weight based on the total weight of the tablet, more preferably 20 to 95% by weight. If the content of the porous plastic material is less than 1% by weight, the strength of the tablet may tend to be too weak because of insufficient contact. On the other hand, if the content is greater than 98% by weight, it is not preferable because there is no room for water penetration expander, binder, agonist and other additives.

Such a porous plastic material can be easily manufactured by purchasing a commercial item or using spray drying, a fluidized bed method, or the like. Soluble porous plastic materials include, for example, fructose, lactitol, lactitol, maltitol, maltose, mannitol, sorbitol, sugar, erythritol Maltodextrin, dextrin, ethylcellulose, polymethylmethacrylate, and pregelatinized starch (e.g., LYCATAB by Roquette American Inc.) as well as saccharides such as xylitol. Same organic polymers. Among the above-mentioned substances, the saccharide having the fastest dissolution rate is sorbitol, and erythritol has been found to be ideal for penetration of water / saliva, although its solubility is not high.

Other materials that may have a suitable porous plastic structure include gum arabic, xanthan gum and its derivatives, guar gum and its derivatives, seafood gum, carrageenan, dextran, gelatin, alginate, pectin, starch and starch derivatives (e.g. Hydroxypropyl starch or hydroxyethyl starch), cellulose esters (eg carboxymethyl cellulose or cellulose ether hydroxyethyl-methyl cellulose), homo or copolymers of unsaturated acids (eg acrylic acid or salts thereof), Homo or copolymers of unsaturated amides (e.g. acrylamides), homo or copolymers of acrylimines, vinyl polymers (e.g. polyvinyl alcohols), homo or copolymers of vinyl esters (e.g. Lollidon, vinyl oxazolidone, vinyl methyl oxazolidone, vinyl amine and vinyl pyridine), alkyl glycols and polyalkylenes Side (e.g. polyethylene oxide), oxyethylene alkyl esters, dexrate, dextrin, dextrose, microcrystalline cellulose, silicidated microcrystalline cellulose, powdered cellulose, cellulose acetate, calcium sulfate, calcium carbonate, calcium diphosphate, triphosphate Calcium, carboxymethyl cellulose calcium salt, silica, etc. are mentioned. Inorganic materials such as calcium carbonate and silica are fast in water absorption but weak in mutual bonding.

Water / saliva penetration extender

In tablet oral hygiene compositions according to the invention, water / saliva penetration enhancers are used to quickly disintegrate tablets. Here, the method of evaluating the water / saliva penetration extender is to put 200 mg of the raw material into a 1.27 cm diameter mold and tablet it with a force of 135 kg and then drop a few drops of water. At this time, when water remains in the form of water droplets, it cannot be used as a water / saliva penetration extender, and if water is spread or absorbed on the surface of the tablet within 60 seconds, it can be used as a water / saliva penetration extender.

Water / saliva penetration extenders should be very soluble in water and, if not soluble in water, should be able to absorb water quickly and disperse easily. In general, water / saliva penetration enhancers are hydrocarbons that are very soluble in water used as excipients. In the present invention, all kinds of hydrocarbons can be used, but organic acids are formed as by-products through the metabolism of Streptococcus mutans, and components that can eventually cause tooth decay are generally not used in small doses for oral hygiene-related prescriptions. Such hydrocarbons include, for example, dextrates, dextrins, dextrose, fructose, lactitol, lactose, maltitol, mannitol, sorbitol, sugar, erythritol, and xylitol. Materials that do not dissolve well in water but have good water dispersion and water delivery capabilities include: microcrystalline cellulose, silicidated microcrystalline cellulose, powdered cellulose, cellulose acetate, calcium sulfate, calcium carbonate, silica, calcium diphosphate, Calcium triphosphate, carboxymethyl cellulose calcium salt, and crosslinked polyvinyl pyrrolidone. Combinations of various hydrocarbons and polymers are possible. Preferred raw materials as water / saliva penetration enhancers are pore-rich materials that can be directly tableted. In addition, inorganic materials such as calcium carbonate, silica, calcium phosphate, and the like, which can deliver water, and crosslinked polyvinyl pyrrolidone, microcrystalline cellulose, cellulose, erythritol, and the like, are also excellent water / saliva penetration enhancers.

In the tablet compositions prepared according to the present invention, since the action of the water penetration dilator is also performed in the oral cavity together with mechanical tablet crushing operations such as chewing, water is compared with tablets which are dissolved and / or gelled only by water or saliva. Even low content of penetration extenders can result in no difference in time of dissolution and gelation. Water penetration extenders may be used in the range of 1 to 98% by weight of the total weight of the tablet, with 20 to 80% by weight being preferred. If the water penetration enhancer is less than 1% by weight, water cannot penetrate into the center of the tablet, and if it is more than 98% by weight, there is no room for the addition of components other than the water penetration extender, and the amount of saliva in the oral cavity for quick dissolution This is undesirable because it requires a lot of saliva or water.

In oral care compositions prepared in accordance with the present invention, where mastication is required for dissolution and / or gelation, by using a small amount of non-aqueous water penetration extender and increasing the amount of water soluble water penetration extender, This may lead to an increase in consumer preferences and usability. The water-insoluble water penetration extenders of the above-mentioned water penetration extenders may preferably be used in the range of 0.01 to 7% by weight.

On the other hand, if it is not necessary to chew for dissolution and / or gelation, it is necessary to use a relatively large amount of water-insoluble water penetration extender.

Binder

The binder is widely used in the conventional tablet compression process, and in the present invention, it is possible to prevent the separation between components by enhancing the binding force between all raw materials including high porosity plastic granules and water / saliva penetration enhancer, and the strength is low even in low pressure tableting. It is used for the purpose of obtaining a high porosity, fast dissolving / gelling tablet. The content of binder may be 1 to 90% by weight of the total weight of the tablet.

The binder may be liquid or semi-solid, depending on the difference in the granulation process. The most important requirement of the binder is to minimize pore damage of the porous plastic material obtained above and to be able to create new pores in the granulation process. This is possible by using a high concentration of binder saturated above water solubility to lower the activity of water and by uniformly dispersing the low concentration binder solution for a short time. To determine the damage to porosity and solubility, 1 ml of binder solution is added to 0.5 g of porous plastic material, and within 10 seconds, the binder solution is added to the present invention if the porous material does not completely dissolve and retains pores. Can be used.

The binder crystallized after wet granulation drying should preferably dissolve quickly in contact with water. In wet granulation, the type and amount of binder may vary depending on the desired physical properties, such as high plastic properties and good binding properties. Pharmaceutically acceptable organic solvents, such as ethyl alcohol, may also be used as solvents for the binder solution which less damage the pore structure. Binders include the hydrocarbons mentioned in the water penetration extenders and include acacia gum, alginic acid, carbopol, carboxymethyl cellulose, cellulose, dextrin, ethyl cellulose, gelatin, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxy Polymers such as propylmethyl cellulose, methyl cellulose, polydextrose, polyethylene oxide, polyvinylpyrrolidone and sodium alginate are also included.

Gelling agent

As the gelling agent, natural polymers such as water-soluble polymers or gums that can be easily swollen by water / saliva or the like can be used. In fast-dissolving and / or gelling tablet-type oral hygiene compositions, the gelling agent, along with the rapid dissolution of the tablet, has a major impact on the most important gel tissue in the physical properties of the tablet and is the most important factor in the usability of the final product. The requirement to be equipped as a gelling agent is to receive water / saliva and have the gel tissue in a few tens of seconds. To check this, you can use the following method: make 200 mg of gelling tablets, drop 1 ml of water and 10 seconds. If a gel-like property is observed within the surface, it can be used as a gelling agent. Another important element of the gelling agent is that when it gels by reacting with water or saliva, it should not form a hydration film on the surface of the tablets and impede the penetration of water or saliva.

In order to gel at a high rate, the gelling agent must be hydrophilic and gelation can be achieved by absorbing a small amount of water. Wet granulation should take place within 5 minutes so that the gelling agent does not clog pores of the porous plastic granules during the half wetting process. Gelling agents include acacia gum, agag gum, gellan gum, guar gum, pectin, gelatin, alginic acid, sodium alginate, carboxymethyl cellulose, polyvinylmaleic anhydride maleic acid copolymer, carbopol, polyethylene glycol, polyvinylpyrrolidone, Polyethylene oxide, xanthan gum, carrageenan, super porous hydrogel, and the like may be used, and one or two or more of these polymer mixtures may be used. Among these, xanthan gum (CP Kelco, USA), Carbopol (Noveon, USA), and carboxymethyl cellulose (Hercules, USA) are readily available as commercially available products.

The gelling agent is preferably used in the range of 0.1 to 10.0% by weight of the total weight of the tablet. If the gelling agent content is less than 0.1% by weight, it does not have a viscosity and cannot maintain the form of the tablet after dissolution. When using more than 10.0% by weight, water does not reach the center of the tablet and gelation occurs only on the surface. This is undesirable because of the problem that the binder sticks to the teeth.

Tooth attachment inhibitor

In the tablet oral hygiene composition prepared according to the present invention, when chewing is required for simultaneous dissolution and / or gelation, it may be a problem that the product remains between the teeth and degrades the consumer's feeling of use and quality of use after use. In order to compensate for this, the anti-adhesion agent is added to minimize the phenomenon of adhesion to the tooth during chewing.

Components used as anti-adhesion agents include surfactants such as glyceryl monooleate, glyceryl monostearate, and the like, which can be used so as not to adhere to hydrophilic tooth surfaces.

Anti-sticking agents can be used in the range of 0.01 to 10% by weight of the total weight of the tablet. If less than 0.01% by weight it is difficult to prevent the property attached to the teeth, when used more than 10% by weight will have a negative role in taste and feel.

Moisturizer

In the present invention, since the porous plastic granules are used in the preparation of the tablet-type oral hygiene composition, it may have a powdery feeling caused by an abrasive or the like after drying. In order to solve this problem, it is possible to use a component that can maintain the moisture content of the granules, that is, a moisturizer. Raw materials which can be used as humectants include glycerin, polyethylene glycol, propylene glycol, sorbitol solution and the like.

Moisturizing agents may use 0.01 to 20% by weight of the total weight of the tablet. If less than 0.01% by weight it is difficult to prevent the property attached to the teeth, when used more than 20% by weight can cause overwetting of the porous plastic granules.

Lubricant

The role of the lubricating agent in the manufacture of tablets is to prevent foreign matter from sticking to the punch of the tableting machine during the tableting process, and sodium lauryl sulfate, magnesium stearate, stearic acid, and the like may be used. Glidants are generally used in the range of 0.1 to 5% by weight of the total weight of the tablet.

Foaming Agent / Surfactant

In oral hygiene, foaming agents and surfactants not only cleanse teeth, but also generate bubbles, which is one of the most important attributes in oral hygiene. Generally foaming agents include anionic surfactants, cationic surfactants, nonionic surfactants, amphoteric surfactants, zwitterionic surfactants. Foaming agents can usually be used as a single substance, or a combination of foaming agents can be made by mixing two or more kinds. Foaming agents in the compositions prepared according to the invention can be used in the range of about 0.001 to 20% by weight of the total weight of the stagnation, preferably in the range of 0.1 to 5% by weight.

As the foaming agent optionally used in the present invention in a safe and effective amount, anionic surfactants are most representative of sodium lauryl sulfate and sodium coconut monoglyceride sulfonate. Other suitable anionic surfactants include sarcosinates, such as sodium lauroyl sarcosinate, taurate, sodium lauryl sulfoacetate, sodium lauroyl isethionate, sodium laureth carboxylate and sodium dodecyl benzenesulfonate There is. In addition, cochamidopropyl betaine, poloxamer, sorbitan monooleate, PEG-40 sorbitan isostearate, or mixtures thereof may also be used.

abrasive

Abrasives play the most important role in cleaning, such as plaque removal and food removal by oral care products. The abrasive must not damage the enamel of the tooth and must be compatible with the other ingredients of the composition. In the present invention, the abrasive is used by adjusting the content by selecting a substance that does not cause excessive grinding of dentin and a syringe. Currently abrasives suitable for oral hygiene preparations include silica, calcium pyrophosphate, aluminum hydroxide, tricalcium phosphate, calcium diphosphate dihydrate and anhydrides, including calcium and precipitates, calcium carbonate and the like. In addition, natural fibrous abrasives such as cellulose and derivatives thereof, and natural material ground powders such as egg shells and clam shell ground powders may also be used as abrasives. Abrasives in the compositions prepared according to the invention can be used in the range of about 5 to 70% by weight of the total weight of the tablet, with 15 to 50% by weight being preferred.

Flavor  And Sweetener

In the present invention, a flavoring agent and a sweetening agent may be added to the consumer's preference when preparing the tablet oral hygiene composition. As a flavoring agent, mint, such as peppermint and spearmint, wintergreen, anise, menthol, thymol, methyl salicylate, eucalyptol, eugenol, polypropylene glycol, melon, strawberry, orange, vanillin, and the like may be used. Generally flavoring agents can be used in the range of 0.001 to 10% by weight of the total weight of the tablet.

In addition, in the present invention, a sweetener may be used to overcome the basic taste of granules and the like in the tablet manufacturing process. As the sweetener, one or two or more kinds of saccharin, sucralose, sugar, xylitol, sorbitol, lactose, mannitol, maltitol, erythritol, aspartame, taurine, saccharin salt and D-tryptophan may be used. Among saccharin salts, saccharin sodium is the most widely used. The amount of sweetener is generally used in the range of 0.001 to 20% by weight of the total weight of the tablet.

Medicinal agents

As a medicament, depending on the purpose of using the oral hygiene, it is possible to use ingredients that are effective in preventing tooth decay, preventing gum disease, preventing tartar deposition, and whitening.

Drugs used to prevent tooth decay include compounds recognized as safe by the US Food and Drug Administration, including fluoride ions. Examples of the compound that can be used as a source of fluorine ions include sodium fluoride, sodium monofluorophosphate, tin fluoride, and amine fluoride. The amount of fluorine may vary depending on the country, but it is common to use one kind or a mixture of two or more of these sources, preferably to have a fluorine ion concentration in the range of 850 to 1500 ppm.

Remineralizing agents can also act as a caries preventer. Remineralization plays a role in regenerating and restoring hydroxyapatite, a major component of teeth. The main component of hydroxyapatite consists of divalent calcium cations and phosphate anions. Therefore, it can be a remineralizing agent if it contains at least one of calcium divalent ions or phosphate anions so as to simultaneously supply calcium ions and phosphate ions or to shift chemical equilibrium in the oral cavity toward the formation of hydroxyapatite. Substances that provide calcium and phosphorus include hydroxyapatite, dicalcium phosphate, calcium chloride, casein phosphate, calcium glycophosphate, sodium monophosphate, dibasic sodium phosphate, sodium triphosphate, potassium monophosphate, This includes potassium diphosphate, potassium triphosphate, and the like. In general, the remineralizing agent is preferably used in the range of 0.001 to 20% by weight of the entire composition. If it is less than 0.001% by weight, the remineralization effect is lowered. If it is more than 20% by weight, the tablet loses its original properties.

One purpose of using oral hygiene products is to prevent gum disease as well as to alleviate gum disease that is progressing through antiseptic or anti-inflammatory action against harmful microorganisms that survive in the oral cavity. For this purpose, thymol, cyclohexidine, cetylpyridinium chloride, triclosan, xantholizol, etc., which are known as antimicrobial agents, may be used, and vitamins and enzymes may also be used for anti-inflammatory action.

In addition to gum disease, hydrogen peroxide, carbamide peroxide, calcium peroxide, etc., which may have a whitening effect, may be used, and sodium pyrophosphate, acid pyrophosphate, potassium pyrophosphate, and sodium metaphosphate may also be used to suppress tartar deposition. . Generally, these agents are generally used in the range of 0.001 to 10% by weight of the entire composition.

A method for producing a porous tablet oral hygiene composition using the above components will be described in detail below.

(1) Preparation of Porous Plastic Granules

The porous plastic granule material, the gelling agent, and the water penetration extender are mixed in a dry state, and then a binder solution is added to the mixed raw materials and combined to prepare the porous plastic granules. The binder solution is prepared by dissolving the binder in ethanol or purified water, and a binder solution prepared to associate the porous plastic granule material, the gelling agent, the water penetration expander, and the like is introduced. When the binder solution is added, the amount of binder solution used and the granulation time are adjusted to minimize damage to the pores present in the raw material itself and to be assembled to create new pores through association. The dosage of the binder solution is 5 to 70% by weight of the amount to completely wet the granules, preferably 20 to 60% by weight. The degree of porosity can be adjusted by controlling the amount of binder added and the assembly time during the preparation of the porous plastic granules. The prepared porous plastic granules are dried after passing through a 20 mesh sieve, and the drying time is shortened by 10 to 70% compared to granules that are completely wet. The prepared granules include all granules prepared using a fluidized bed granulator or a high speed mixer. The specific surface area of the granules produced is in the range from 25 to 1000 m 2 / g, preferably in the range from 50 to 500 m 2 / g.

(2) tableting

An additive such as a lubricant is added to the prepared granules, mixed using a powder mixer, and then compressed using a tablet press at a pressure of 500 kg / cm 2 or less to prepare tablets having a strength of 0.5 to 15 kg. The tablets produced are kept in the range 25 to 1000 m 2 / g, preferably 50 to 500 m 2 / g, where the specific surface area is equal to the specific surface area of the granules.

When granules are prepared by the method of partial wetting with a binder solution according to the present invention, the specific surface area of the granules is in the range of 25 to 1,000 m 2 / g, which can save drying time of the granules, and the dissolution rate is within 1 minute. The tablets produced have a strength of about 1 to 15 kg, and when masticating, dissolution / gelation takes place within 1 minute, so that they can be dissolved or gelled simultaneously with water, saliva, or chewing in the oral cavity to brush teeth or A porous tablet oral hygiene composition capable of gargleing can be obtained.

Hereinafter, the present invention will be described in more detail with reference to preferred embodiments of the present invention. However, these examples are only illustrative to aid the understanding of the present invention, and the scope of the present invention is not limited thereto.

Porous rapid dissolution and / or gelled tablet oral hygiene was prepared according to the following process.

Example  1-3 and Comparative example  1, 2

Porous rapid dissolution and / or gelled tablet oral hygiene was prepared according to the following process.

First, Table 1 below shows the composition of raw materials used to prepare porous plastic granules.

Ingredient Content (% by weight) in porous plastic granules Sorbitol 51.88 Erythritol 5.00 Xylitol 10.00 Sodium Lauryl Sulfate 3.00 Cabopol 2.50 Precipitated silica 20.00 Sodium bicarbonate 1.00 Xanthan Gum 1.00 Crystalline cellulose 5.00 Sodium fluoride 0.22 Saccharin Sodium 0.40 gun 100.00

With respect to 100 g of the porous plastic granules mixed in the composition of Table 1, the binder solution was added and granulated as shown in Table 2 below. Comparative example 1 is a case where it is completely wet with an aqueous solution, and comparative example 2 is a case where it is completely wet with an alcohol solution. In Comparative Examples 1 and 2, when 100% was completely wetted with water and ethanol, Examples 1, 2, and 3 were partially wetted with 20%, 67%, and 50%, respectively.

Binder solution Example Comparative example One 2 3 One 2 2% Hydroxypropyl Cellulose Solution 10 g 25 g 50 g 5% hydroxypropylmethyl cellulose ethanol solution 80 g 120 g

After granulation, the resultant was dried using a fluidized bed dryer or a flatbed dryer to obtain a water content of 2 to 10%. For the uniformity of the experiment, the drying time according to the Examples and Comparative Examples was measured at the time when the moisture content is 5%. In addition, the dried granules were dried under vacuum for 24 hours, and then the specific surface area of the granules was measured using BET.

The dried porous plastic granules were compressed using a tableting machine. At the time of tableting, the lubricant was added at a rate of 1.5% for smooth tableting.

Hardness was measured for the tablets of the Examples and Comparative Examples obtained through tableting, and the specific surface area of the powder was measured after grinding.

effect Test Example

The following tests were carried out on the granules and tablets prepared in Examples and Comparative Examples.

(1) measurement of specific surface area of granules

The specific surface area is the BET ratio measured by nitrogen adsorption according to ASTM D 3663-78 described using the Brunuer-Emmett-Teller method described in The Journal of American Society 60 , 309 (1938). Means surface area.

3 g of the granules prepared in Examples and Comparative Examples were taken and vacuum dried for at least 24 hours, and then the specific surface area of the granules was measured using a BET measuring device. Table 3 below shows the BET surface area for the granules prepared in Examples and Comparative Examples.

Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Specific surface area (㎡ / g) 183 152 205 5 20

As shown in Table 3 above, the granules obtained according to the half wetting process according to the present invention have a specific surface area measured by BET in the range of 25 to 1,000 m 2 / g, and are obtained by conventional wet granulation. It can be seen that the specific surface area is remarkably large compared to 0.01 to 25 m 2 / g, so that the intra-granular porosity is high.

(2) measurement of dissolution rate of granules

0.5 g of granule samples are placed in a glass plate and 10 ml of water is added to measure the time until the granules are not felt when touched by hand. Table 4 shows the dissolution rates of the granules prepared in Examples and Comparative Examples.

Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Dissolution rate 17 seconds 30 seconds 35 seconds 300 seconds 180 seconds

As shown in Table 4 above, the granules obtained by the half wetting process according to the present invention have a dissolution rate of several seconds to one minute, which is very rapid compared to one to thirty minutes of granules obtained according to a conventional method. It was confirmed to dissolve.

(3) Drying time measurement of granules

Take 1 g of granules and measure the time when the moisture content is less than 5% when the plate is dried at 50 ° C. Table 5 shows the drying times of the granules prepared in Examples and Comparative Examples.

Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Drying time 15 minutes 10 minutes 25 minutes 65 minutes 30 minutes

As shown in Table 5, it was confirmed that the drying rate of the granules obtained by partial wetting according to the present invention can be reduced by more than 50% when the same solvent is used as compared to the case of complete wetting within tens of minutes.

(4) tablet strength measurement

The intensity of 10 tablets was measured using a texture analyzer (TA XT Plus, TA Instrument) and the average value was determined as the strength of the tablet. The measured value is the read value which is not converted. Table 6 shows the strengths of the tablets prepared in Examples and Comparative Examples.

Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Strength (kg) 7.5 ± 0.5 9.1 ± 0.4 7.5 ± 0.3 18.9 ± 0.9 13 ± 0.7

As shown in Table 6 above, the strength measured using the Texture Analyzer of the tablet prepared according to the present invention is 0.5-15 kg, which is similar to that of 1-50 kg of tablets obtained through conventional wet granulation and tableting. It was confirmed.

(5) Measurement of dissolution time of tablets

One tablet of tablets was added to 200 ml of distilled water, followed by visual observation while stirring at a stirring speed of 200 rpm, and the time until no longer in the form of tablets was measured. In addition, the time of dissolution and gelation when chewing was evaluated emotionally. Table 7 shows the dissolution time of the tablets prepared in Examples and Comparative Examples.

Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Dissolution time (distilled water) 15 minutes 9 minutes 25 minutes 100 minutes 90 minutes Dissolution / Gelation Time (Original) 15 seconds 20 seconds 25 sec 4 minutes 6 minutes

As described above, the strength of the tablets prepared according to the present invention is similar to those obtained through conventional wet granulation and tableting, but the tablets prepared according to the method of the present invention in the dissolution time of the tablets are several seconds to several minutes. It can be seen that very short compared to several minutes to several hours, which is the dissolution time of a general tablet. In the case of gelable tablets, gelation occurred within seconds to several minutes at the time of chewing and within minutes to several tens of minutes at non-creation.

(6) Measurement of specific surface area of tablets

1 g of the tablet was ground in a mortar and then vacuum dried for 24 hours to measure the specific surface area remaining in the tablet using the specific surface area measurement method of the granules. Table 8 below shows the BET surface area of the tablets prepared in Examples and Comparative Examples.

Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Specific surface area (㎡ / g) 136 96 159 5 15

As shown in Table 8 above, the specific surface area of the tablet prepared according to the method of the present invention was measured, and the specific surface area was decreased due to plastic deformation, but the specific surface area was still maintained in the range of 25 to 1,000 m 2 / g. We confirmed that it became.

As described above, when the granules are prepared by the method of partial wetting by the binder solution according to the present invention, the specific surface area of the granules is in the range of 25 to 1,000 m 2 / g, thereby saving drying time of the granules, The dissolution rate can be within 1 minute, and the tablets produced have strengths on the order of 1 to 15 kg and upon chewing, dissolution / gelation takes place within 1 minute. This can be compared with the specific surface area of the oral hygiene tablets, characterized in that the dissolution rate is within several tens of minutes of 0.01 to 25 m 2 / g.

Claims (11)

Binder solution was added to the porous plastic granule material, the gelling agent, and the water penetration expander to prepare 5 to 70% partial wet and adjust granule preparation time to produce porous plastic granules having a specific surface area of 25 to 1000 m 2 / g; A method for producing a porous tablet oral hygiene composition comprising mixing the oral hygiene active ingredient into the porous plastic granules and tableting at a pressure of 500 kg / cm 2 or less to produce tablets having a strength of 0.5 to 15 kg. 2. The method of claim 1, wherein the binder solution is added to wet 20 to 60% partially. The method for producing a porous tablet oral hygiene composition according to claim 1, wherein the porous plastic granules have a specific surface area of 50 to 500 m 2 / g. The method of claim 1, wherein the porous plastic granule material is fructose, lactitol, lactitol, maltitol, maltose, mannitol, mannitol, sorbitol, sugar, erythritol erythritol, xylitol, maltodextrin, dextrin, ethylcellulose, polymethylmethacrylate, pregelatinized starch, gum arabic, xanthan gum and derivatives thereof, guar gum and derivatives thereof, seafood gum , Carrageenan, dextran, gelatin, alginate, pectin, starch and starch derivatives, cellulose esters, homo or copolymers of unsaturated acids, homo or copolymers of unsaturated amides, homo or copolymers of acrylimines, vinyl polymers, vinyl esters Homo or copolymers of alkyl glycols and polyalkylene oxides, oxyethylene alkyl esters, dexates, dextrins, dextrose, microcrystalline cellulose, yarns Preparation of porous tablet-type oral hygiene composition, characterized in that the lysified microcrystalline cellulose, powdered cellulose, cellulose acetate, calcium sulfate, calcium carbonate, calcium diphosphate, calcium triphosphate, carboxymethyl cellulose calcium salt, silica, or mixtures thereof Way. The method of claim 1, wherein the water penetration enhancer is dexrate, dextrin, dextrose, fructose, lactitol, lactose, maltitol, mannitol, sorbitol, sugar, erythritol, xylitol, microcrystalline cellulose, silicified microcrystalline cellulose, Powdered cellulose, cellulose acetate, calcium sulfate, calcium carbonate, silica, calcium phosphate, calcium triphosphate, carboxymethyl cellulose calcium salt, crosslinked polyvinyl pyrrolidone, or a mixture thereof. Manufacturing method. The gelling agent of claim 1, wherein the gelling agent is acacia gum, agar gum, gellan gum, guar gum, pectin, gelatin, alginic acid, sodium alginate, carboxymethyl cellulose, polyvinylmaleic anhydride maleic acid copolymer, carbopol, polyethylene glycol, Polyvinylpyrrolidone, polyethylene oxide, xanthan gum, carrageenan, super porous hydrogel, or a mixture thereof. The method of claim 1, wherein the binder is dexrate, dextrin, dextrose, fructose, lactitol, lactose, maltitol, mannitol, sorbitol, sugar, erythritol, xylitol, acacia gum, alginic acid, carbopol, carboxy Methyl cellulose, cellulose, dextrin, ethyl cellulose, gelatin, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, methyl cellulose, polydextrose, polyethylene oxide, polyvinylpyrrolidone, sodium alginate, or mixtures thereof Method for producing a porous tablet oral hygiene composition, characterized in that. The method of claim 1, wherein the lubricant is added to the porous plastic granules together with the oral hygiene active ingredient. The method of claim 8, wherein the lubricant is sodium lauryl sulfate, magnesium stearate, stearic acid, or a mixture thereof. delete delete