WO2019059652A1 - Taste-masked and orally administered pharmaceutical preparation and preparation method therefor - Google Patents

Abstract

The present invention relates to a taste-masked and orally administered pharmaceutical preparation and a preparation method therefor, and the pharmaceutical preparation can be in the form of a liquid or an orally disintegrating film and has a remarkably excellent effect of taste-masking a raw drug. In addition, a liquid preparation method enables existing liquid preparation equipment and processes to be used as is, and enables a one-stop solution, by which taste-masking (lipid coating) of a drug raw material can be achieved during the liquid preparation processes, to be provided. Furthermore, an orally disintegrating film preparation method, which is a one-stop solution method allowing lipids for masking the taste of a raw drug to be formed simultaneously with the preparation of the film, enables taste-masked and orally disintegrating film to be prepared without additional processes.

Description

Taste-masked pharmaceutical preparations for oral administration and methods for their preparation

The present invention relates to a pharmaceutical preparation for orally administrable taste and a preparation method thereof, wherein the form of the pharmaceutical preparation may be a liquid preparation or a mouth disintegration film.

Of the formulations with a drug delivery system, the orally administered drug may be in the form of a solid, such as a capsule, a caplet, or a tablet, a liquid form such as a solution, a syrup, an emulsion or a suspension, or a liquid form such as a tablet, a chewable tablet, And various oral dissolution preparations.

In such oral dosage form, taste is an important indicator and it is very important in the pharmaceutical industry to mask the unpleasant taste when taking it. Many pharmaceutical companies have tried various efforts to develop bitter taste-masked formulations while sufficiently exhibiting the drug's efficacy. They have tried to coat raw drug particles, form molecular complexes between drugs and other substances, Or the like as a taste masking agent or by minimizing dissolution by acupuncture or the like.

Therefore, various studies have been made on the liquid preparations among the above-mentioned oral preparations. In particular, the liquid preparations can be swallowed easily, unlike the other dosage preparations, and thus can be used for infants, And furthermore, when it is necessary to administer a large amount of drug, the liquid form is advantageous over the chewable dosage form.

However, a general problem associated with a liquid preparation is that it shields the unpleasant taste such as bitter taste, argin taste, rough taste, pungent taste of the raw drug when the pharmacologically active agent is administered in a liquid dosage form, There has existed a method of attempting shielding using various sweeteners or fragrances or a separate process such as coating a raw material to form a shielding film against a raw material of a drug.

However, these studies also have the disadvantage that they are limited to the use of sweeteners in the case of stimulant drugs and can only be applied to specific drugs. Further, there is also a disadvantage that the coating process is also inferior in productivity due to the fear of damage to the coating film and the complexity of the process.

Korean Patent Laid-Open Publication No. 2010-0135316 discloses a conventional technique for shielding the taste of a liquid agent, in which, in order to shield the bitter taste of a raw material drug, the taste of the raw drug is added by a method of adding a sweetener, However, this method has a limitation in shielding with a sweetener or a fragrance in the case of a drug having a severe irritation to an arine taste drug or oral mucosa, and a flavoring system for a drug is often applied to other drugs It can not be applied to the case.

US Patent Application Publication 2008/0044454 discloses a method of coating a raw material drug with an active material using various coating techniques and putting it into a film forming agent so as to shield the bitter taste, Since the manufacturing process is complicated and the liquid agent is manufactured after coating the active material, there is a high possibility that the drug is released into the solution through the coating film through the heating, mixing and dissolving processes during the liquid agent manufacturing process, There is a disadvantage that it may be deteriorated.

In addition, Orodispersible Tablet (ODT), which developed a solid oral disintegration form, is one of the new drug delivery systems. However, it has been pointed out that all the drugs are not disintegrated in a short period of time, and even when water needs to be taken again, it is pointed out that there is a problem in the oral cavity disassembly. Also, since the thickness is too thick and the tablet hardness is weak, There is a disadvantage that it is easily broken.

To solve these problems, the newly proposed formulation is a mouth rinse film preparation. The oral disintegration film is a drug-loaded formulation in thin film formulations, and the oral disintegrating film formulation provides several advantages over conventional solid dosage forms, liquids, and oral disintegrating tablets. That is, since the oral disintegrating film preparation can be taken without water, it is very useful not only for the elderly who have difficulties in taking tablets or capsules but also for children, persons with disabilities, patients lying in bed, busy modern people, It is estimated that disintegration is more advanced than any existing formulations. Particularly, when the drug is absorbed into the buccal mucosa, the first pass of the liver can be avoided. Therefore, the buccal disintegration film has an advantage that it can be applied to drugs that are highly metabolized in the liver among the drugs absorbed from the digestive tract. Therefore, many efforts have been made to manufacture oral disintegrating film formulations of various techniques for the physical properties of the film and compliance with the patient's taking.

Among them, various studies have been conducted to shield the unpleasant taste such as bitter taste, arine taste, rough taste, and pungent taste of the raw material drug when taking the oral disintegration film.

In order to shield the taste of the oral disintegration film, various sweeteners and fragrances have been used for the purpose of shielding the taste of the raw drug. However, a method of shielding the taste by using the sweetener or the fragrance, There is a limit to shielding the taste of drug which is highly stimulated to mucous membrane.

As a conventional technique for preventing the taste of the oral disintegrating film, WO 2001/70194 discloses a method for producing a readily consumable oral consumable film by adsorbing an active ingredient to an ion exchange resin as a taste-masking agent This method has disadvantages in that the ion exchange resin is contained in the water-soluble polymer and scratches are generated during the film forming, resulting in poor merchantability and inferior productivity due to complicated operations.

US Patent Application 2008/0044454 discloses a method for coating a raw drug with an active substance using various coating techniques and then injecting it into a film forming agent to mask bitter taste, Coating process, so that the manufacturing process is complicated and the film is produced after the coating of the active material, so that the coating layer is damaged in the film production process and the taste shielding function may be deteriorated.

Accordingly, the inventors of the present invention have been studying a method of shielding the taste of a liquid drug, and as a new pharmaceutical formulation for oral administration, a shielding film for a drug substance is formed during the liquid preparation process, The inventors of the present invention have completed the present invention by disclosing a method of shielding the taste of a raw material drug by forming a shielding film in a raw material material during the film manufacturing process without further processing Respectively.

It is an object of the present invention to provide a pharmaceutical preparation for orally administrable taste and a method for producing the same.

In order to achieve the above object,

According to the present invention,

Lipids; And

And a raw material drug distributed in the above-mentioned lipids.

More particularly,

Lipids; And

Wherein the drug is a taste masked liquid containing the drug substance distributed in the lipid classes.

Further, according to the present invention,

Adding lipids to a water-soluble solution and heating at a temperature above the melting point of the lipids to form an emulsion (step 1);

Adding a raw drug to the emulsion of step 1 (step 2); And

Cooling the emulsion added with the raw drug (step 3); The present invention also provides a method of producing the taste masked liquid agent.

Further, according to the present invention,

Lipids; And

Wherein the flavor-blocking agent is a flavor-masked oral disintegration film containing a drug substance dispersed in the lipids.

Further, according to the present invention,

Adding lipids to a water-soluble solution and heating at a temperature above the melting point of the lipids to form an emulsion (step 1); And

And adding a raw drug to the emulsion of step 1 (step 2). The present invention also provides a method for producing the taste-masked oral disintegration film.

The pharmaceutical preparation for oral administration of the present invention has a remarkable advantage in that the drug is distributed in the inner phase of the emulsion (lipid phase) so that the unpleasant taste of the drug is shielded through the liquid agent in which the matrix of the lipid and the drug is suspended And oral disintegration film type pharmaceutical preparations for oral administration are advantageous in that the raw material drugs are distributed in the lipids and thus the taste blocking effect of the raw drug is remarkably excellent. In addition, the manufacturing method of the liquid agent has an advantage that it can apply the equipment and the process for manufacturing the existing liquid agent as it is, and the taste shielding (lipid coating) for the drug raw material is one-stop solution solution can be provided. In addition, a method for producing an oral disintegration film is a one-stop solution method in which lipids that block the taste of a raw material drug are formed at the same time as a film is produced, There is an advantage that a film can be produced.

1 shows an optical microscope photograph of Example A-1.

2 shows an optical microscope photograph of Comparative Example A-1.

3 is a photograph of the surface of the oral disintegration film produced according to Example B-12 of the present invention, observed using a scanning electron microscope (SEM)

4 is a photograph of the surface of the oral disintegration film produced according to Example B-13 of the present invention, observed using a scanning electron microscope (SEM)

5 is a photograph of the surface of the oral disintegration film produced according to Comparative Example B-3 of the present invention, using a scanning electron microscope (SEM).

According to the present invention,

Lipids; And

And a raw material drug distributed in the above-mentioned lipids.

Hereinafter, the pharmaceutical preparation for oral administration in which the taste is masked will be described in detail.

In the present invention, the pharmaceutical preparations for oral administration in which the taste is masked may be more specifically described. The pharmaceutical preparations for oral administration may be in the form of a liquid or a mouth disintegration film.

The present invention

Lipids; And

A raw drug distributed in the lipid species; Wherein the taste masking agent is a taste masking agent.

The liquid agent of the present invention is a liquid agent in which the taste of a raw material drug is shielded to improve the feeling of use and satisfaction and convenience of taking in patients (particularly, children).

Hereinafter, the taste-masked liquid agent of the present invention will be described in detail.

The liquid agent according to the present invention includes lipids.

The lipids are used for shielding the taste of the raw drug. By distributing the raw drug to the lipids, the taste of the raw drug can be physically shielded when taken.

The above-mentioned lipids can be formed simultaneously with the production of a liquid preparation.

For example, the lipid, which is a component of the above-mentioned lipids, is placed in a solution containing a water-soluble solvent and heated to 70 ° C to form an emulsion. After the drug substance is distributed in the lipid phase of the emulsion, The raw drug can be distributed in lipids to form a suspension liquid.

For this purpose, it is preferable that the above-mentioned lipids are produced by using lipids having a melting point of 40 ° C or higher and lower than 100 ° C.

If the melting point of the above-mentioned lipids is less than 40 ° C, the lipids may be liquefied during storage at room temperature after the production of the liquid agent, resulting in a problem of deteriorating the physical stability of the liquid agent, ° C., the water is vaporized because the melting point of the above-mentioned lipids is higher than the boiling point of water, so that the weight ratio of the solution and the lipids is varied, which may make it difficult to control the manufacturing conditions of the liquid agent.

For example, the lipids may be used as GELUCIRE 44/14 having a melting point of 44 ° C.

In addition, it is preferable that lipids having a hydrophilic-lipophilic balance (HLB) of 0 to 16 are used.

The value of hydrophilic lipophilic balance (HLB) is a value indicating the degree of affinity with respect to water and oil. Of the values of 0 to 20, values closer to 0 indicate good lipophilicity, and values closer to 20 indicate hydrophilicity. When the hydrophilic / lipophilic balance (HLB) of the flow exceeds 16, it is difficult to stably form a matrix with the drug because it is easily dissolved in water, thereby causing a problem of deteriorating the taste shielding effect.

Thus, the lipid may be prepared from at least one lipid selected from the group consisting of fatty acid glycerides, PEG fatty acid esters, and sugar surfactants.

Preferably, the fatty acid may be a fatty acid having 10 to 30 carbon atoms, and more preferably a fatty acid having 12 to 22 carbon atoms.

The fatty acid glyceride may be mono-, di-, triglyceride, or a combination thereof, and the PEG fatty acid ester may be mono-, diester or a mixture thereof.

Specific examples of fatty acid glycerides or PEG fatty acid esters of said lipids, glycerol mono as stearate (Glycerol monostearate), glycerol di-behenate (Glycerol dibehenate), glyceryl behenate (Glyceryl behenate) Comp erythritol (Compritol) ^® 888 ATO , C8-18 glycerides (C8-18glycerides) as a gel Lucy LES (Gelucire) ^® 43/01, lauroyl polyoxyl -32 glycerides as (lauroyl polyoxyl-32 glycerides) gel Lucy LES (Gelucire) ^® 44/14 la, in one polyoxyalkylene -32- glycerides with stearic (stearoyl polyoxyl-32 glycerides) as a gel Lucy LES (Gelucire) ^® 50/13, lauroyl polyoxyl-6 glycerides (lauroyl polyoxyl-6 glycerides) Bra LABRAFIL M2130 CS, and Glyceryl Palmitostearate PRECIROL ATO 5, which are commercially available from Mitsubishi Chemical Corporation.

The saccharide surfactant may be selected from the group consisting of sucrose monostearate, sucrose distearate, sucrose mono-distearate, sucrose monopalmitate, But are not limited to, Sucrose dipalmitate, Sucrose monolaurate, Sucrose dilaurate, Sucrose monooleate, Sucrose dioleate, It is also possible to use one or more of sucrose monocaprate, sucrose dicaprate, sucrose monocaprylate, sucrose dicaprylate, sucrose monomyristate, Sucrose dimyristate, Sucrose monolinolenate and Sucrose monolinolenate, dilinolenate, and the like.

The above-mentioned lipid classes may be sucrose esters of the following Table 1, but are not limited thereto.

	Type	HLB	Content of major fatty acids (% by weight)	Ester composition (% by weight)		shape
				Monoester	Di (di), tri (tri), polyester
Sucrose Stearate	D-1803F	3	About 70	About 20	About 80	P
"	D-1805	5	70	30	70	P
"	D-1807	7	70	40	60	P
"	D-1809	9	70	50	50	P
"	D-1811	11	70	55	45	P
"	D-1811F	11	70	55	45	P
"	D-1815	15	70	70	360	P
"	D-1816	16	70	75	25	P
Sucrose palmitate	D-1615	15	80	70	30	P
"	D-1616	16	80	80	20	P
Sucrose laurate	D-1216	16	95	80	20	P

(P: paste)

On the other hand, the liquid preparation of the present invention may be a form in which a raw material drug is mixed with a lipid.

At this time, the raw drug may be uniformly mixed with lipids to form a matrix, but since the portion of the raw drug exposed to the outside is remarkably small, the dissolution rate in the mouth is temporarily reduced by the lipids, The taste shielding effect is remarkably excellent.

In addition, the raw drug suspended in the liquid preparation of the present invention may be in the form of being formed in the lipids. At this time, the raw drug is shielded from the outside by lipids, and the taste of the drug can be completely blocked by the lipids, thereby remarkably excelling in the taste shielding effect of the drug.

The liquid agent according to the present invention includes a raw drug distributed in the above-mentioned lipids.

At this time, the drug substance may be a diabetic drug having an unpleasant taste; An insomnia remedy; Genitourinary therapy; Obesity remedy; Enzymes; Peptic ulcer solvent; Jinhae expectorant; A therapeutic agent for skin diseases; Antistatic agent; Antidepressants; Antihistamines; Antipyretic analgesics; Hormone preparations; Therapeutic agents for circulation; Therapeutic agent for digestive tract disorders; Psychotropic solvent; Erectile dysfunction treatment; A therapeutic agent for osteoporosis; Arthritis remedy; Antiepileptics; Muscle relaxants; Brain function improvers; A therapeutic agent for schizophrenia; Immunosuppressants; Antiviral agents, anti-malarial therapeutic agents, anti-tuberculosis agents, antibiotics; Anticancer agents; Anticancer adjuvants; Vaccines; Mouthwash; Anemia treatment agent; Constipation remedy; vitamin; Nutrients; Lactic acid bacteria preparation; Comprehensive cold medicine; And a health functional food.

The raw drug may also be selected from the group consisting of dexibuprofen, ibuprofen, naproxen, flurbiprofen, phosphodiesterase-5 inhibitor, but are not limited to, trimebutine, nicotine, varenicline, oseltamivir, prednisolone, donepezil, desmopressin, meclizine, entecavir, but are not limited to, entecavir, lamivudine, abacavir, atazanavir, zidovudine, cobicistat, stavudine, didanosine, dolutegravir, (eg, dolutegravir), darunavir, efavirenz, etravirine, elvitegravir, emtricitabine, fosamprenavir, indinavir indinavir, lopinavir, nevirapine, The present invention relates to a pharmaceutical composition comprising raltegravir, ritonavir, rilpivirine, tenofovir, tipranavir, saquinavir and pharmaceutically acceptable salts thereof. Lt; / RTI > drug.

On the other hand, the liquid agent of the present invention may contain additives.

This is for further improving the taste shielding effect of the liquid agent, and may include various flavors or aromas while shielding the taste of the raw drug through the additive.

At this time, the additive may be at least one selected from the group consisting of sweeteners, flavors, stabilizers, and pH adjusters. In this way, it can contain various flavors or aromas while at the same time shielding the taste.

The sweetener to be used as the additive may be selected from the group consisting of sugar, glucose, maltose, oligosaccharide, galactose, starch, sorbitol, maltitol, phosgene, xylitol, erythritol, hydrogenated starch, mannitol, trehalose, aspartame, acesulfamate, sucralose, A sweetener which is at least one selected from the group consisting of saccharin salt, neo-time, thaumatin, tothomic mixture, cyclamate salt, tothmine, nahan and extract, licorice extract, stevioside, May be used, but the sweetening agent is not limited thereto.

In addition, the above-mentioned flavor used as the additive may include strawberry flavor essence, lemon flavor essence, banana flavor essence, strawberry incense cotton, lemon incense cotton, grape incense cotton, banana incense cotton or orange incense cotton, peppermint, cinnamon, menthol, Mint, peach flavor, cherry flavor, vanillin flavor, and raspberry flavor, but the flavor is not limited thereto.

The pH adjusting agent used as the additive may be selected from the group consisting of citric acid, tartaric acid, ascorbic acid, fumaric acid, malic acid, adipic acid, Succinic acid, sodium dihydrogen phosphate, monosodium phosphate, disodium dihydrogen pyrophosphate, acid citrate salts, amino acid hydrochlorides, Sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, sodium sesquicarbonate, sodium glycine, sodium bicarbonate, sodium carboxymethylcellulose, carbonate, l-lysine carbonate, arginine carbonate, amorphous calcium carbonate, calcium carbonate, calcium carbonate, and the like. However, the pH adjusting agent is not limited thereto.

Further, according to the present invention,

Adding lipids to a water-soluble solution and heating at a temperature above the melting point of the lipids to form an emulsion (step 1);

Adding a raw drug to the emulsion of step 1 (step 2); And

Cooling the emulsion added with the raw drug (step 3); The present invention also provides a method of producing the taste masked liquid agent.

The method for producing a liquid agent according to the present invention is a one-stop solution method in which a shielding film can be formed on a raw material drug during the production of a liquid agent, There is an advantage that this shielded liquid agent can be manufactured.

In this way, it is possible to produce a liquid drug effectively shielded from unpleasant taste such as bitter taste, arginine taste, rough taste, bitter taste and the like of the raw material drug, thereby making it possible to more easily take the raw drug.

Hereinafter, the method for producing a liquid-taste masking liquid of the present invention will be described in detail for each step.

In the method for producing a liquid agent according to the present invention, step 1 is a step of adding lipids to an aqueous solution and heating at a temperature above the melting point of the lipids to form an emulsion.

At this time, the water-soluble solution may be purified water as a solvent, but not limited thereto, and other conventional water-soluble solvents may be used.

The step 1 may further include adding an additive to the solution.

At this time, the additive may be at least one selected from the group consisting of sweeteners, flavors, stabilizers, and pH adjusters.

Among the additives, the sweetener is included to add flavor to the taste of the liquid or to further enhance the taste shielding effect.

The sweetener may be selected from, for example, sugars, glucose, maltose, oligosaccharides, galactose, starch, sorbitol, maltitol, phytonutrients, xylitol, erythritol, hydrogenated starch syrup, mannitol, trehalose, aspartame, acesulfamoyl, At least one member selected from the group consisting of salt, neo-time, thaumatin, tothomic mixture, cyclamate salt, tothmine, nahan and extract, licorice extract, stevioside, enzyme-treated stevioside, neohesperidin and monelin But is not limited thereto.

At this time, the sweetener is preferably contained in an amount of 0.1 to 40% based on the total weight of the solution.

In addition, the flavoring agent is included to add a flavor suitable for the liquid agent or to further enhance the taste shielding effect.

The flavors include, for example, strawberry incense, lemon incense essence, banana incense essence, strawberry incense cotton, lemon incense cotton, grape incense cotton, banana incense cotton or orange incense cotton, peppermint, cinnamon, menthol, At least one selected from the group consisting of peach flavor, cherry flavor, vanillin flavor and raspberry flavor may be used, but the flavor is not limited thereto.

At this time, the flavoring agent is preferably contained in an amount of 0.01 to 10% based on the total weight of the solution.

The pH adjusting agent used as the additive may be selected from the group consisting of citric acid, tartaric acid, ascorbic acid, fumaric acid, malic acid, adipic acid, Succinic acid, sodium dihydrogenphosphate, monosodium phospate, disodium dihydrogen pyrophosphate, acid citrate salts, amino acid hydrochlorides, Sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, sodium sesquicarbonate, sodium glycine, sodium bicarbonate, sodium carboxymethylcellulose, carbonate, l-lysine carbonate, arginine carbonate, amorphous calcium carbonate, calcium carbonate (cal cadmium carbonate, and cadmium carbonate. However, the pH adjusting agent is not limited thereto.

On the other hand, in step 1, lipids are added to the aqueous solution, and the emulsion is formed by heating the lipids above the melting point of the lipids.

At this time, it is preferable that the lipids have a melting point of 40 ° C or higher and lower than 100 ° C.

This is to dissolve the lipids in the solution to form an emulsion so that the drug substance is distributed in the lipid phase of the emulsion.

If the melting point of the above-mentioned lipids is less than 40 ° C, the lipids may be liquefied during storage at room temperature after the production of the liquid agent, resulting in a problem of deteriorating the physical stability of the liquid agent, ° C., the water is vaporized because the melting point of the above-mentioned lipids is higher than the boiling point of water, so that the weight ratio of the solution and the lipids is varied, which may make it difficult to control the manufacturing conditions of the liquid agent.

For example, the lipids may be used as GELUCIRE 44/14 having a melting point of 44 ° C.

Thus, the lipid may be prepared from at least one lipid selected from the group consisting of fatty acid glycerides, PEG fatty acid esters, and sugar surfactants.

Preferably, the fatty acid may be a fatty acid having 10 to 30 carbon atoms, and more preferably a fatty acid having 12 to 22 carbon atoms.

The fatty acid glyceride may be mono-, di-, triglyceride, or a combination thereof, and the PEG fatty acid ester may be mono-, diester or a mixture thereof.

Specific examples of fatty acid glycerides or PEG fatty acid esters of said lipids, glycerol mono as stearate (Glycerol monostearate), glycerol di-behenate (Glycerol dibehenate), glyceryl behenate (Glyceryl behenate) Comp erythritol (Compritol) ^® 888 ATO , C8-18 glycerides (C8-18glycerides) as a gel Lucy LES (Gelucire) ^® 43/01, lauroyl polyoxyl -32 glycerides as (lauroyl polyoxyl-32 glycerides) gel Lucy LES (Gelucire) ^® 44/14 la, in one polyoxyalkylene -32- glycerides with stearic (stearoyl polyoxyl-32 glycerides) as a gel Lucy LES (Gelucire) ^® 50/13, lauroyl polyoxyl-6 glycerides (lauroyl polyoxyl-6 glycerides) Bra LABRAFIL M2130 CS, and Glyceryl Palmitostearate PRECIROL ATO 5, which are commercially available from Mitsubishi Chemical Corporation.

The saccharide surfactant may be selected from the group consisting of sucrose monostearate, sucrose distearate, sucrose mono-distearate, sucrose monopalmitate, But are not limited to, Sucrose dipalmitate, Sucrose monolaurate, Sucrose dilaurate, Sucrose monooleate, Sucrose dioleate, It is also possible to use one or more of sucrose monocaprate, sucrose dicaprate, sucrose monocaprylate, sucrose dicaprylate, sucrose monomyristate, Sucrose dimyristate, Sucrose monolinolenate and Sucrose monolinolenate, dilinolenate, and the like.

In the step 1, the lipids are preferably contained in an amount of 1 to 40% by weight based on the total weight of the aqueous solution.

If the weight of the lipid is less than 1% by weight based on the total weight of the aqueous solution, it is difficult to distribute the raw drug on the lipid, The shielding effect may be deteriorated. If the weight of the lipids exceeds 40% by weight based on the total weight of the aqueous solution, the dissolution rate may be excessively delayed.

In the method for producing a liquid agent according to the present invention, the step 2 is a step of injecting a raw material drug into the emulsion of the step 1 so that the raw material drug is distributed in the phase of the lipids.

At this time, in step 2, it is preferable that the drug substance is distributed in the phase of lipids of the emulsion.

 This is to prevent the drug substance from interfering with the outside by lipids, and the taste of the drug can be completely blocked by the lipids, thereby effectively shielding the taste of the drug.

At this time, the drug substance may be a diabetic drug having an unpleasant taste; An insomnia remedy; Genitourinary therapy; Obesity remedy; Enzymes; Peptic ulcer solvent; Jinhae expectorant; A therapeutic agent for skin diseases; Antistatic agent; Antidepressants; Antihistamines; Antipyretic analgesics; Hormone preparations; Therapeutic agents for circulation; Therapeutic agent for digestive tract disorders; Psychotropic solvent; Erectile dysfunction treatment; A therapeutic agent for osteoporosis; Arthritis remedy; Antiepileptics; Muscle relaxants; Brain function improvers; A therapeutic agent for schizophrenia; Immunosuppressants; Antiviral agents, anti-malarial therapeutic agents, anti-tuberculosis agents, antibiotics; Anticancer agents; Anticancer adjuvants; Vaccines; Mouthwash; Anemia treatment agent; Constipation remedy; vitamin; Nutrients; Lactic acid bacteria preparation; Comprehensive cold medicine; And a health functional food.

The raw drug may also be selected from the group consisting of dexibuprofen, ibuprofen, naproxen, flurbiprofen, phosphodiesterase-5 inhibitor, but are not limited to, trimebutine, nicotine, varenicline, oseltamivir, prednisolone, donepezil, desmopressin, meclizine, entecavir, but are not limited to, entecavir, lamivudine, abacavir, atazanavir, zidovudine, cobicistat, stavudine, didanosine, dolutegravir, (eg, dolutegravir), darunavir, efavirenz, etravirine, elvitegravir, emtricitabine, fosamprenavir, indinavir indinavir, lopinavir, nevirapine, A group consisting of raltegravir, ritonavir, rilpivirine, tenofovir, tipranavir, saquinavir and pharmaceutically acceptable salts thereof. ≪ / RTI >

In the method for producing a liquid agent according to the present invention, the step 3 is a step for cooling the emulsion added with the raw drug after the step 2.

At this time, in step 3, it is preferable that the temperature of the emulsion to which the raw drug is added is lowered while stirring to cool it to room temperature.

This is to prevent the drug substance from being externally blocked by lipids, and the taste of the drug can be completely blocked by the lipids, thereby effectively shielding the taste of the drug. Through the above steps, Can be prepared.

The above-mentioned manufacturing method is advantageous in that a taste-masked liquid agent can be produced without a further process by a one-stop solution method in which lipids surrounding the raw material are formed simultaneously with the formation of a liquid agent.

According to the present invention,

Lipids; And

Wherein the flavor-blocking agent is a flavor-masked oral disintegration film containing a drug substance dispersed in the lipids.

The oral disintegration film of the present invention is a mouth disintegration film in which the taste of a raw material drug is shielded and convenience of taking is improved.

Hereinafter, the taste-masked oral disintegration film of the present invention will be described in detail.

The oral disintegration film according to the present invention comprises lipids.

The lipids are used for shielding the taste of the raw drug. By distributing the raw drug to the lipids, the taste of the raw drug can be physically shielded when taken.

The lipids can be formed at the same time as the preparation of the oral disintegration film.

For example, the lipid, which is a component of the above-mentioned lipids, is placed in a solution containing a water-soluble solvent and heated to 70 ° C to form an emulsion. After the drug substance is distributed in the lipid phase of the emulsion, And then dried to form lipids and lipid disintegration film containing the drug substance distributed therein.

For this purpose, it is preferable that the above-mentioned lipids are produced by using lipids having a melting point of 40 ° C or higher and lower than 100 ° C.

If the melting point of the lipids is less than 40 ° C, the lipids may be liquefied during storage at room temperature after the preparation of the oral disintegration film, resulting in separation of the oil phase from the film or softening of the film. When the melting point is 100 ° C or higher, the melting point of the above-mentioned lipids is higher than the boiling point of water, so that water is vaporized and the weight ratio of the solution and the lipids is varied, so that it is difficult to control the production conditions of the film.

For example, the lipids may be used as GELUCIRE 44/14 having a melting point of 44 ° C.

In addition, it is preferable that lipids having a hydrophilic-lipophilic balance (HLB) of 0 to 16 are used.

The value of hydrophilic lipophilic balance (HLB) is a value indicating the degree of affinity with respect to water and oil. Of the values of 0 to 20, values closer to 0 indicate good lipophilicity, and values closer to 20 indicate hydrophilicity. When the hydrophilic / lipophilic balance (HLB) of the flow exceeds 16, it easily dissolves in water and the lipid flow easily dissolves in the mouth, so that the taste shielding effect may be deteriorated.

Thus, the lipids may be selected from the group consisting of Glycerol monostearate, Glycerol dibehenate, Glyceryl behenate, COMPRITOL 888, Gelucire 43/01, GELUCIRE 44/14, GELUCIRE 44/14, GELUCIRE 50/13, LABRAFRL M2130 CS, glyceryl palmitostearate (PRECIROL ATO 5), beads wax Beeswax, carnauba wax, and sugar-based surfactants.

The saccharide surfactant may be selected from the group consisting of sucrose monostearate, sucrose distearate, sucrose mono-distearate, sucrose monopalmitate, Sucrose dipalmitate, Sucrose monolaurate, Sucrose diraurate, Sucrose monooleate, Sucrose dioleate, Sucrose dipalmitate, Sucrose monocaprate, Sucrose dicaprate, Sucrose monocaprylate, Sucrose dicaprylate, Sucrose monomyristate, Sucrose monocarboxylate, , Sucrose dimyristate, sucrose monolinolenate, and sucrose di Tease carbonate may be at least one selected from the group consisting of (Sucrose dilinolenate).

* The above-mentioned lipids may be sucrose esters of the following Table 2, but are not limited thereto.

	Type	HLB	Content of major fatty acids (% by weight)	Ester composition (% by weight)		shape
				Monoester	Di (di), tri (tri), polyester
Sucrose Stearate	D-1803F	3	About 70	About 20	About 80	P
"	D-1805	5	70	30	70	P
"	D-1807	7	70	40	60	P
"	D-1809	9	70	50	50	P
"	D-1811	11	70	55	45	P
"	D-1811F	11	70	55	45	P
"	D-1815	15	70	70	360	P
"	D-1816	16	70	75	25	P
Sucrose palmitate	D-1615	15	80	70	30	P
"	D-1616	16	80	80	20	P
Sucrose laurate (sucrose)	D-1216	16	95	80	20	P

(P: paste)

Meanwhile, the oral disintegration film of the present invention may be a form in which the raw material drug is mixed with lipid streams.

At this time, the raw drug may be uniformly mixed with lipids to form a matrix, but since the portion of the raw drug exposed to the outside is remarkably small, the dissolution rate in the mouth is temporarily reduced by the lipids, The taste shielding effect is remarkably excellent.

In addition, the oral disintegration film of the present invention may be in the form of a raw material drug formed in lipids. At this time, the raw drug is shielded from the outside by lipids, and the taste of the drug can be completely blocked by the lipids, thereby remarkably excelling in the taste shielding effect of the drug.

The oral disintegration film according to the present invention includes a raw drug distributed in the above lipid classes.

At this time, the drug substance may be a diabetic drug having an unpleasant taste; An insomnia remedy; Genitourinary therapy; Obesity remedy; Enzymes; Peptic ulcer solvent; Jinhae expectorant; A therapeutic agent for skin diseases; Antistatic agent; Antidepressants; Antihistamines; Antipyretic analgesics; Hormone preparations; Therapeutic agents for circulation; Therapeutic agent for digestive tract disorders; Psychotropic solvent; Erectile dysfunction treatment; A therapeutic agent for osteoporosis; Arthritis remedy; Antiepileptics; Muscle relaxants; Brain function improvers; A therapeutic agent for schizophrenia; Immunosuppressants; Antiviral agents, anti-malarial therapeutic agents, anti-tuberculosis agents, antibiotics; Anticancer agents; Anticancer adjuvants; Vaccines; Mouthwash; Anemia treatment agent; Constipation remedy; vitamin; Nutrients; Lactic acid bacteria preparation; Comprehensive cold medicine; And a health functional food.

The raw drug may also be selected from the group consisting of dexibuprofen, ibuprofen, naproxen, flurbiprofen, phosphodiesterase-5 inhibitor, but are not limited to, trimebutine, nicotine, varenicline, oseltamivir, prednisolone, donepezil, desmopressin, meclizine, entecavir, but are not limited to, entecavir, lamivudine, abacavir, atazanavir, zidovudine, cobicistat, stavudine, didanosine, dolutegravir, (eg, dolutegravir), darunavir, efavirenz, etravirine, elvitegravir, emtricitabine, fosamprenavir, indinavir indinavir, lopinavir, The pharmaceutical composition of the present invention is a pharmaceutical composition comprising at least one compound selected from the group consisting of nevirapine, raltegravir, ritonavir, rilpivirine, tenofovir, tipranavir, saquinavir, Or a salt thereof, or a salt thereof.

Meanwhile, the oral disintegration film of the present invention may contain additives.

This is to further improve the taste-shielding effect of the oral disintegration film. The additive may shield the taste of the raw material drug, may include various flavors or fragrances, and may facilitate the production of the film .

At this time, the additive may be at least one selected from the group consisting of a polymer, a plasticizer, a sweetener, a flavor, a stabilizer, and a pH adjuster. In this way, it may contain various flavors or aromas while at the same time shielding the taste, and may also assist in the production of the film.

The polymer used as the additive is a film-forming agent for forming a film, and examples thereof include pullulan, gelatin, pectin, low viscosity pectin, hydroxypropylmethylcellulose, low viscosity hydroxypropylmethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose Cellulose, carboxymethylcellulose, polyvinyl alcohol, polyacrylic acid, methyl methacrylate copolymer, carboxyvinyl polymer, polyethylene glycol, alginic acid, low viscosity alginic acid, sodium alginate, carrageenan, modified starch, casein, The water-soluble polymer may be at least one water-soluble polymer selected from the group consisting of water, a water-soluble polymer, a water-soluble polymer, a separation product, jane, levan, elscan, gluten, acacia gum, carrageenan, gum arabic, guar gum, locust bean gum, xanthan gum, However, is not limited thereto.

The plasticizer used as the additive may be selected from the group consisting of glycerin fatty acid ester, sucrose fatty acid ester, lecithin, enzyme-treated lecithin, polysorbate, sorbitan fatty acid ester, sorbitol, maltitol, xylitol, glycerin, polyethylene glycol, propylene glycol, , Starch syrup, glycerin, triacetin, glycerol oleate, triethyl citrate, and a medium chain fatty acid. However, the plasticizers are not limited thereto.

The sweetener used as the additive may be selected from sugar, glucose, maltose, oligosaccharide, galactose, starch, sorbitol, maltitol, phosgene, xylitol, erythritol, hydrogenated starch, mannitol, trehalose, aspartame, acesulfamate, sucralo One selected from the group consisting of oats, saccharin salts, neo time, thaumatin, tothmine mixture, cyclamate salt, tothmine, nahan and extract, licorice extract, stevioside, enzyme-treated steviosides, neohesperidin and monelin Of the sweetener may be used, but the sweetener is not limited thereto.

In addition, the above-mentioned flavor used as the additive may include strawberry flavor essence, lemon flavor essence, banana flavor essence, strawberry incense cotton, lemon incense cotton, grape incense cotton, banana incense cotton or orange incense cotton, peppermint, cinnamon, menthol, Mint, peach flavor, cherry flavor, vanillin flavor, and raspberry flavor may be used, but the flavor is not limited to this.

The pH adjusting agent used as the additive may be selected from the group consisting of citric acid, tartaric acid, ascorbic acid, fumaric acid, malic acid, adipic acid, Succinic acid, sodium dihydrogenphosphate, monosodium phospate, disodium dihydrogen pyrophospate, acid citrate salts, amino acid hydrochlorides, Sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, sodium sesquicarbonate, sodium glycine, sodium bicarbonate, sodium carboxymethylcellulose, carbonate, l-lysine carbonate, arginine carbonate, amorphous calcium carbonate, calcium carbonate (calc ium carbonate, and the like. However, the flavor is not limited to this.

Further,

Adding lipids to a water-soluble solution and heating at a temperature above the melting point of the lipids to form an emulsion (step 1); And

And adding a raw drug to the emulsion of step 1 (step 2). The present invention also provides a method for producing a taste-masked oral disintegration film.

The method for producing an oral disintegration film according to the present invention is a one-stop solution method for forming a shielding film on a raw material drug during the process of manufacturing an oral disintegration film, There is an advantage that the oral disintegration film having a taste can be easily manufactured without the use of the above-mentioned method.

In this way, an oral disintegration film effectively shielding the unpleasant taste such as bitter taste, arginine taste, rough taste, bitter taste, etc. of the raw material drug can be produced, and thereby the raw drug can be more easily taken.

Hereinafter, the method for producing the mouth-shrink film having the taste of the present invention will be described in detail for each step.

In the method for producing an oral disintegration film according to the present invention, step 1 is a step of adding lipids to an aqueous solution and heating the lipid to a temperature above the melting point of the lipids to form an emulsion.

At this time, the water-soluble solution may be purified water as a solvent, but not limited thereto, and other conventional water-soluble solvents may be used.

The step 1 may further include adding an additive to the solution.

At this time, the additive is poly, and at least one selected from the group consisting of plasticizers, sweeteners, flavors, stabilizers, and pH adjusters may be used.

Among these additives, the polymer may be a water-soluble polymer used as a conventional film-forming agent.

The polymer may be selected from, for example, pullulan, gelatin, pectin, low viscosity pectin, hydroxypropylmethylcellulose, low viscosity hydroxypropylmethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, polyvinylalcohol, But are not limited to, polyacrylic acid, methyl methacrylate copolymer, carboxyvinyl polymer, polyethylene glycol, alginic acid, low viscosity alginic acid, sodium alginate, carrageenan, modified starch, casein, whey protein isolate, soy protein isolate, But is not limited to, at least one selected from the group consisting of gluten, acacia gum, carrageenan, gum arabic, guar gum, locust bean gum, xanthan gum, gellan gum and agar.

At this time, the polymer is preferably contained in an amount of 30 to 85% based on the total weight of the solution.

Further, the plasticizer among the additives is included to control the flexibility of the film.

Such plasticizers include, for example, glycerin fatty acid esters, sucrose fatty acid esters, lecithin, enzyme-treated lecithin, polysorbate, sorbitan fatty acid ester, sorbitol, maltitol, xylitol, glycerin, polyethylene glycol, propylene glycol, At least one selected from the group consisting of glycerin, triacetin, glycerol oleate, sucrose fatty acid ester and medium chain fatty acid may be used, but the plasticizer is not limited thereto.

In this case, the plasticizer is preferably contained in an amount of 0.1 to 30% based on the total weight of the solution.

In addition, the sweetener among the additives is included in order to add a flavor suited to the taste of the oral disintegration film or to further enhance the taste shielding effect.

The sweetener may be selected from, for example, sugars, glucose, maltose, oligosaccharides, galactose, starch, sorbitol, maltitol, phytonutrients, xylitol, erythritol, hydrogenated starch syrup, mannitol, trehalose, aspartame, acesulfamoyl, At least one member selected from the group consisting of salt, neo-time, thaumatin, tothomic mixture, cyclamate salt, tothmine, nahan and extract, licorice extract, stevioside, enzyme-treated stevioside, neohesperidin and monelin But is not limited thereto.

At this time, the sweetener is preferably contained in an amount of 0.1 to 40% based on the total weight of the solution.

In addition, the flavors among the above additives are included to add a flavor appropriate to the mouth disintegration film or to further enhance the taste shielding effect.

The flavors include, for example, strawberry incense, lemon incense essence, banana incense essence, strawberry incense cotton, lemon incense cotton, grape incense cotton, banana incense cotton or orange incense cotton, peppermint, cinnamon, menthol, At least one selected from the group consisting of peach flavor, cherry flavor, vanillin flavor and raspberry flavor may be used, but the flavor is not limited to this.

At this time, the flavoring agent is preferably contained in an amount of 0.01 to 10% based on the total weight of the solution.

The pH adjusting agent used as the additive may be selected from the group consisting of citric acid, tartaric acid, ascorbic acid, fumaric acid, malic acid, adipic acid, Succinic acid, sodium dihydrogenphosphate, monosodium phospate, disodium dihydrogen pyrophospate, acid citrate salts, amino acid hydrochlorides, Sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, sodium sesquicarbonate, sodium glycine, sodium bicarbonate, sodium carboxymethylcellulose, carbonate, l-lysine carbonate, arginene carbonate, amorphous calcium carbonate, calcium carbonate (calc ium carbonate, and the like. However, the flavor is not limited to this.

On the other hand, in step 1, lipids are added to the aqueous solution, and the emulsion is formed by heating the lipids above the melting point of the lipids.

At this time, it is preferable that the lipids have a melting point of 40 ° C or higher and lower than 100 ° C.

This is to dissolve the lipids in the solution to form an emulsion so that the drug substance is distributed in the lipid phase of the emulsion.

If the melting point of the lipids is less than 40 ° C, the lipids may be liquefied during storage at room temperature after the preparation of the oral disintegration film, resulting in separation of the oil phase from the film or softening of the film. When the melting point is 100 ° C or higher, the melting point of the above-mentioned lipids is higher than the boiling point of water, so that water is vaporized and the weight ratio of the solution and the lipids is varied, so that it is difficult to control the production conditions of the film.

For example, the lipids may be used as GELUCIRE 44/14 having a melting point of 44 ° C.

The lipids are selected from the group consisting of Glycerol monostearate, Glycerol dibehenate, Glyceryl behenate, COMPRITOL 888, Gelucire 43/01, GELUCIRE ) 44/14, GELUCIRE 44/14, GELUCIRE 50/13, LABRAFRL M2130 CS, glyceryl palmitostearate (PRECIROL ATO 5), beeswax (Beeswax ), Carnauba wax, and sugar-based surfactants.

The saccharide surfactant may be selected from the group consisting of sucrose monostearate, sucrose distearate, sucrose mono-distearate, sucrose monopalmitate, Sucrose dipalmitate, Sucrose monolaurate, Sucrose diraurate, Sucrose monooleate, Sucrose dioleate, Sucrose dipalmitate, Sucrose monocaprate, Sucrose dicaprate, Sucrose monocaprylate, Sucrose dicaprylate, Sucrose monomyristate, Sucrose monocarboxylate, , Sucrose dimyristate, sucrose monolinolenate, and sucrose di Tease carbonate may be at least one selected from the group consisting of (Sucrose dilinolenate).

In the step 1, the lipids are preferably contained in an amount of 1 to 40% by weight based on the total weight of the aqueous solution.

If the weight of the lipid is less than 1% by weight based on the total weight of the aqueous solution, it is difficult to distribute the raw drug on the lipid, There is a problem that the shielding effect is lowered. If the weight of the lipids exceeds 40 wt% of the total weight of the aqueous solution, it is difficult to form the film, May occur.

In the method of manufacturing the oral disintegration film according to the present invention, the step 2 is a step of injecting the raw drug into the emulsion of the step 1 so that the raw drug is distributed in the lipid phase.

At this time, in step 2, it is preferable that the drug substance is distributed in the phase of lipids of the emulsion.

 This is to prevent the drug substance from interfering with the outside by lipids, and the taste of the drug can be completely blocked by the lipids, thereby effectively shielding the taste of the drug.

At this time, the drug substance may be a diabetic drug having an unpleasant taste; An insomnia remedy; Genitourinary therapy; Obesity remedy; Enzymes; Peptic ulcer solvent; Jinhae expectorant; A therapeutic agent for skin diseases; Antistatic agent; Antidepressants; Antihistamines; Antipyretic analgesics; Hormone preparations; Therapeutic agents for circulation; Therapeutic agent for digestive tract disorders; Psychotropic solvent; Erectile dysfunction treatment; A therapeutic agent for osteoporosis; Arthritis remedy; Antiepileptics; Muscle relaxants; Brain function improvers; A therapeutic agent for schizophrenia; Immunosuppressants; Antiviral agents, anti-malarial therapeutic agents, anti-tuberculosis agents, antibiotics; Anticancer agents; Anticancer adjuvants; Vaccines; Mouthwash; Anemia treatment agent; Constipation remedy; vitamin; Nutrients; Lactic acid bacteria preparation; Comprehensive cold medicine; And a health functional food.

The raw drug may also be selected from the group consisting of dexibuprofen, ibuprofen, naproxen, flurbiprofen, phosphodiesterase-5 inhibitor, but are not limited to, trimebutine, nicotine, varenicline, oseltamivir, prednisolone, donepezil, desmopressin, meclizine, entecavir, but are not limited to, entecavir, lamivudine, abacavir, atazanavir, zidovudine, cobicistat, stavudine, didanosine, dolutegravir, (eg, dolutegravir), darunavir, efavirenz, etravirine, elvitegravir, emtricitabine, fosamprenavir, indinavir indinavir, lopinavir, The pharmaceutical composition of the present invention is a pharmaceutical composition comprising at least one compound selected from the group consisting of nevirapine, raltegravir, ritonavir, rilpivirine, tenofovir, tipranavir, saquinavir, Or a salt thereof, or a salt thereof.

The method for producing the oral disintegration film of the present invention preferably further comprises cooling and drying the emulsion after the emulsion is heated after step 2.

This is for forming a film form, through which the oral disintegration film can be produced.

The preparation method is a one-stop solution method in which a lipid surrounding the raw material is formed simultaneously with the formation of an oral disintegration film, and a mouth-shrinking film having a taste can be produced without further processing There are advantages.

Hereinafter, the present invention will be described in detail with reference to Examples and Experimental Examples.

However, the following Examples and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following Examples.

≪ Example A-1 > Preparation of a taste-masked liquid agent

i) Step 1: Preparation of thickener

Xanthan Gum is swollen in water, carboxymethyl cellulose (CMC) is swollen in water to another beaker, and the temperature of the two solutions is then brought to 60 ° C.

ii) Step 2: Preparation of syrup

Glycerin is dissolved in water at 60 ° C to prepare a solution, and white sugar and sorbitol are dissolved in the solution, and the thickener of step 1 is added thereto.

iii) Step 3: Encapsulation of lipid and drug

After the lipid is heated to 80 DEG C and melted, the molten lipid is rapidly stirred, the drug is added, and stirring is continued until the drug is sufficiently dissolved. 15 ml of water is added little by little to make an emulsion, and the temperature is lowered to 60 ° C with rapid stirring.

iv) Step 4: Preparation of drug syrup

The emulsion produced in step 3 is rapidly stirred, the syrup prepared in step 2 is added, and then stirred rapidly. Cool the preparation to 30 ° C and add other excipients.

≪ Examples A-2 to A-10 > Preparation of taste-masked liquid agent

A liquid agent was prepared in the same manner as in Example A-1, except that each component in Example A-1 was changed as shown in the following Tables 3 and 4.

≪ Comparative Example A-1 >

The components in Example A-1 were varied as shown in the following Table 3, and in the emulsion preparation of Step 3 in Example A-1, the lipid was heated to 80 DEG C to melt, and the molten lipid A solution was prepared by performing the same procedure as in Example A-1, except that the process of rapidly stirring and loading the drug was omitted.

function	Component (g / 100 mL)	Comparative Example A-1	Example A-1HLB 2	Example A-2HLB2	Example A-3 HLB 7	Example A-4HLB 9	Example A-5 HLB 14	Example A-6 HLB 1	Example A-7 HLB 5
Increasing agent / Sweetener	White sugar	40	40	40	40	40	40	40	40
	Sorbitol	27.5	27.5	27.5	27.5	27.5	27.5	27.5	27.5
Sweetener	Sucral Rose	0.1			0.1	0.1	0.1		0.1
"	Enzyme treatment Stevia		0.1	0.1				0.1
Acidic	Malic acid	0.2	0.2	0.2	0.2	0.2	0.2	0.2	0.2
Incrementer	Xanthan gum	0.4	0.4	0.4	0.4	0.4	0.4	0.4	0.4
"	CMC	0.6	0.6	0.6					0.6
"	Carrageenan				0.6	0.6	0.6	0.6
Plasticizer	glycerin	One	One	One	One	One	One	One	One
pH adjusting agent	Citric acid	0.4	0.4	0.4			0.4		0.4
"	Sodium hydrogencarbonate				0.4	0.4		0.4
Flavor	Grape incense	One	One	One	One	One	One	One	One
drug	Ibuprofen	1.2	1.2	1.2	1.2	1.2	1.2	1.2	1.2
Lipid (HLB 2)	Precirol ATO 5		1.8		1.05	0.75			1.35
(HLB 2)	Compritol 888 ATO			1.8
(HLB 14)	Gelucire 44/14				0.75	1.05	1.8		0.45
(HLB 1)	Gelucire 43 / 01pellets							1.8
	Purified water	Suitable amount	Suitable amount	Suitable amount	Suitable amount	Suitable amount	Suitable amount	Suitable amount	Suitable amount
	Total (mL)	100.00	100.00	100.00	100.00	100.00	100.00	100.00	100.00

function	Component (g / 100 mL)	Example A-8	Example A-9	Example A-10
Increasing agent / Sweetener	White sugar	40	40	40
	Sorbitol	27.5	27.5	27.5
Sweetener	Sucral Rose		0.1	0.1
	Enzyme treatment Stevia	0.1
Acidic	Malic acid	0.2	0.2	0.2
Incrementer	Xanthan gum	0.4	0.4	0.4
"	CMC	0.6	0.6
"	Carrageenan			0.6
Plasticizer	glycerin	One	One	One
pH adjusting agent	Citric acid	0.4	0.4	0.4
Flavor	Grape incense	One
"	Strawberry incense		0.5	One
"	Chrysanthemum		0.5
drug	Ibuprofen	1.2	1.2	1.2
Lipid	Beeswax	1.8
"	Carnauba wax		1.8
"	Castor wax			1.8
	Purified water	Suitable amount	Suitable amount	Suitable amount
	Total (mL)	100.00	100.00	100.00

<Experimental Example A-1>

The following experiment was conducted to confirm the taste shielding effect of the liquid preparation of the present invention.

In order to confirm the taste shielding effect of the ibuprofen drug, for the liquid preparation prepared in Examples A-1 and A-2 and Comparative Example A-1, six subjects drank 10 mL of the liquid agent and recorded the degree of the arine taste Respectively. At this time, for accurate evaluation of the taste, the subjects rinsed the mouth with distilled water before taking the liquid. The liquid formulations prepared in Examples A-1, A-2 and Comparative Example A-1 were evaluated and are shown in Table 5 below.

At this time, the degree of arine taste was expressed as follows.

+: Very tasty

++: slightly tasty

+++: very slightly aring flavor

++++: tasteless or shielded flavor

	Example A-1	Example A-2	Comparative Example A-1
flavor	++++	++++	++

As shown in the results of Table 5, in the case of the liquid preparation of the present invention, there was no taste or shielding taste for ibuprofen, whereas in the case of the liquid preparation prepared in Comparative Example A-1, Able to know.

Thus, it can be seen that the taste masking effect of the liquid agent of the present invention is remarkably excellent.

&Lt; Example A-11 > Preparation of taste-masked liquid agent

i) Step 1: Preparation of thickener

Xanthan Gum is swollen in water, carboxymethyl cellulose (CMC) is swollen in water to another beaker, and the temperature of both solutions is then brought to 60 ° C.

ii) Step 2: Preparation of syrup

Glycerin is dissolved in water at 60 ° C to prepare a solution, and white sugar and sorbitol are dissolved in the solution, and the thickener of step 1 is added thereto.

iii) Step 3: Encapsulation of lipid and drug

* After heating the lipid to 80 ° C and melting it, stir the molten lipid rapidly, add the drug, and continue stirring until the drug is sufficiently dissolved. 15 ml of water is added little by little to make an emulsion, and the temperature is lowered to 60 ° C with rapid stirring.

iv) Step 4: Preparation of drug syrup

The emulsion produced in step 3 is rapidly stirred, the syrup prepared in step 2 is added, and then stirred rapidly. Cool the preparation to 30 ° C and add other excipients.

&Lt; Examples A-12 to A-20 > Preparation of a taste-masked liquid agent

A liquid agent was prepared in the same manner as in Example A-11, except that the respective components in Example A-11 were changed as shown in the following Tables 6 and 7.

<Comparative Example A-2> Preparation of liquid agent

The components in Example A-11 were changed as shown in the following Table 6, and the process of melting and heating the lipids by heating to 80 DEG C in the tanning process of Step 3 in Example A-11, A liquid agent was prepared by performing the same procedure as in Example A-11, except that the process of rapidly stirring and loading the drug was omitted.

function	Component (g / 100 mL)	Comparative Example A-2	Example A-11 HLB 2	Example A-12 HLB 2	Example A-13 HLB 7	Example A-14 HLB 9	Example A-15 HLB 14	Example A-16 HLB 1	Example A-17 HLB 5
Increasing agent / Sweetener	White sugar	40	40	40	40	40	40	40	40
	Sorbitol	27.5	27.5	27.5	27.5	27.5	27.5	27.5	27.5
Sweetener	Sucral Rose	0.1			0.1	0.1	0.1		0.1
"	Enzyme treatment Stevia		0.1	0.1				0.1
Acidic	Malic acid	0.2	0.2	0.2	0.2	0.2	0.2	0.2	0.2
Incrementer	Xanthan gum	0.4	0.4	0.4	0.4	0.4	0.4	0.4	0.4
"	CMC	0.6	0.6	0.6					0.6
"	Carrageenan				0.6	0.6	0.6	0.6
Plasticizer	glycerin	One	One	One	One	One	One	One	One
pH adjusting agent	Citric acid	0.4	0.4				0.4	0.4	0.4
"	Sodium hydrogencarbonate			0.4	0.4	0.4
Flavor	Grape incense	One	One	One	One	One	One	One	One
drug	Dexibupropene	1.2	1.2	1.2	1.2	1.2	1.2	1.2	1.2
Lipid (HLB 2)	Precirol ATO 5		1.8		1.05	0.75			1.35
(HLB 2)	Compritol 888 ATO			1.8
(HLB 14)	Gelucire 44/14				0.75	1.05	1.8		0.45
(HLB 1)	Gelucire 43 / 01pellets							1.8
	Purified water	Suitable amount	Suitable amount	Suitable amount	Suitable amount	Suitable amount	Suitable amount	Suitable amount	Suitable amount
	Total (mL)	100.00	100.00	100.00	100.00	100.00	100.00	100.00	100.00

function	Component (g / 100 mL)	Example A-18	Examples A-19	Example A-20
Increasing agent / Sweetener	White sugar	40	40	40
"	Sorbitol	27.5	27.5	27.5
Sweetener	Sucral Rose		0.1	0.1
"	Enzyme treatment Stevia	0.1
Acidic	Malic acid	0.2	0.2	0.2
Incrementer	Xanthan gum	0.4	0.4	0.4
"	CMC	0.6	0.6
"	Carrageenan			0.6
Plasticizer	glycerin	One	One	One
pH adjusting agent	Citric acid	0.4	0.4	0.4
Flavor	Grape incense		One
"	Strawberry incense	One
"	Chrysanthemum			One
drug	Dexibupropene	1.2	1.2	1.2
Lipid	Beeswax	1.8
"	Carnauba wax		1.8
"	Castor wax			1.8
	Purified water	Suitable amount	Suitable amount	Suitable amount
	Total (mL)	100.00	100.00	100.00

<Experimental Example A-2>

The following experiment was conducted to confirm the taste shielding effect of the liquid preparation of the present invention.

In order to confirm the taste shielding effect of the dexibuprofen medicines, for the liquid preparations prepared in Examples A-11 and A-13 and Comparative Example A-2, six subjects drank 10 mL of the liquid agent, Were recorded and evaluated. At this time, for accurate evaluation of the taste, the subjects rinsed the mouth with distilled water before taking the liquid. The evaluation results of the liquid formulations prepared in Examples A-11, A-13 and Comparative Example A-2 are shown in Table 8 below.

At this time, the degree of arine taste was expressed as follows.

+: Very tasty

++: slightly tasty

+++: very slightly aring flavor

++++: tasteless or shielded flavor

	Example A-11	Example A-13	Comparative Example A-2
flavor	++++	++++	+

As shown in the results of the above Table 8, in the case of the liquid preparation of the present invention, there was no taste or shielding taste for dexibupropene, whereas for the liquid preparation prepared in Comparative Example A-2, As shown in FIG.

Thus, it can be seen that the taste masking effect of the liquid agent of the present invention is remarkably excellent.

&Lt; Example A-21 > Preparation of a taste-masked liquid agent

i) Step 1: Preparation of thickener

Xanthan Gum is swollen in water, carboxymethyl cellulose (CMC) is swollen in water to another beaker, and the temperature of both solutions is then brought to 60 ° C.

ii) Step 2: Preparation of syrup

Glycerin is dissolved in water at 60 ° C to prepare a solution, and white sugar and sorbitol are dissolved in the solution, and the thickener of step 1 is added thereto.

iii) Step 3: Encapsulation of lipid and drug

* After heating the lipid to 80 ° C and melting it, stir the molten lipid rapidly, add the drug, and continue stirring until the drug is sufficiently dissolved. 15 ml of water is added little by little to make an emulsion, and the temperature is lowered to 60 ° C with rapid stirring.

iv) Step 4: Preparation of drug syrup

The emulsion produced in step 3 is rapidly stirred, the syrup prepared in step 2 is added, and then stirred rapidly. Cool the preparation to 30 ° C and add other excipients.

&Lt; Examples A-22 to A-30 > Preparation of a taste-masked liquid agent

A liquid agent was prepared in the same manner as in Example A-21, except that each component in Example A-21 was changed as shown in Tables 9 and 10 below.

<Comparative Example A-3> Preparation of liquid agent

The components in Example A-21 were varied as shown in Table 9 below, and in the emulsion preparation process of Step A-21 of Example A-21, the process of melting and heating the lipid to 80 DEG C and the process of melting the molten lipid A liquid agent was prepared in the same manner as in Example A-21, except that the process of rapidly stirring and loading the drug was omitted.

function	Component (g / 100 mL)	Comparative Example A-3	Example A-21 HLB 2	Example A-22 HLB 2	Example A-23 HLB 7	Example A-24HLB 9	Example A-25 HLB 14	Example A-26 HLB 1	Example A-27 HLB 5
Increasing agent / Sweetener	White sugar	40	40	40	40	40	40	40	40
"	Sorbitol	27.5	27.5	27.5	27.5	27.5	27.5	27.5	27.5
Sweetener	Sucral Rose	0.1			0.1	0.1	0.1		0.1
"	Enzyme treatment Stevia		0.1	0.1				0.1
Acidic	Malic acid	0.2	0.2	0.2	0.2	0.2	0.2	0.2	0.2
Incrementer	Xanthan gum	0.4	0.4	0.4	0.4	0.4	0.4	0.4	0.4
"	CMC	0.6	0.6	0.6					0.6
"	Carrageenan				0.6	0.6	0.6	0.6
Plasticizer	glycerin	One	One	One	One	One	One	One	One
pH adjusting agent	Citric acid	0.4	0.4			0.4	0.4		0.4
"	Sodium hydrogencarbonate			0.4	0.4			0.4
Flavor	Grape incense	One	One	One	One	One	One	One	One
drug	Oseltamivir	0.6	0.6	0.6	0.6	0.6	0.6	0.6	0.6
Lipid (HLB 2)	Precirol ATO 5		0.9		0.525	0.375			0.675
(HLB 2)	Compritol 888 ATO			0.9
(HLB 14)	Gelucire 44/14				0.375	0.525	0.9		0.225
(HLB 1)	Gelucire 43 / 01pellets							0.9
	Purified water	Suitable amount	Suitable amount	Suitable amount	Suitable amount	Suitable amount	Suitable amount	Suitable amount	Suitable amount
	Total (mL)	100.00	100.00	100.00	100.00	100.00	100.00	100.00	100.00

function	Component (g / 100 mL)	Example A-28	Example A-29	Example A-30
Increasing agent / Sweetener	White sugar	40	40	40
"	Sorbitol	27.5	27.5	27.5
Sweetener	Sucral Rose		0.1	0.1
"	Enzyme treatment Stevia	0.1
Acidic	Malic acid	0.2	0.2	0.2
Incrementer	Xanthan gum	0.4	0.4	0.4
"	CMC	0.6	0.6
"	Carrageenan			0.6
Plasticizer	glycerin	One	One	One
pH adjusting agent	Citric acid	0.4	0.4	0.4
Flavor	Grape incense	One
"	Strawberry incense		0.5	One
"	Chrysanthemum		0.5
drug	Oseltamivir	0.6	0.6	0.6
Lipid	Beeswax	0.9
"	Carnauba wax		0.9
"	Castor wax			0.9
	Purified water	Suitable amount	Suitable amount	Suitable amount
	Total (mL)	100.00	100.00	100.00

<Experimental Example A-3>

The following experiment was conducted to confirm the taste shielding effect of the liquid preparation of the present invention.

To confirm the taste shielding effect of the oseltamivir drug, the liquid preparations prepared in Examples A-21, A-26 and Comparative Example A-3 were administered to 6 subjects in an amount of 5 mL of the solution, And recorded. At this time, for accurate evaluation of the taste, the subjects rinsed the mouth with distilled water before taking the liquid. The evaluation results of the liquid agents prepared in Examples A-21, A-26 and A-3 are shown in Table 11 below.

The degree of bitter taste was expressed as follows.

+: Very bitter taste

++: slightly bitter taste

+++: very bitter taste

++++: tasteless or shielded flavor

	Example A-21	Example A-26	Comparative Example A-3
flavor	+++	+++	+

As shown in the results of Table 11, in the case of the liquid preparation of the present invention, a slightly bitter taste appeared for oseltamivir, whereas for the liquid preparation prepared in Comparative Example A-3, a very bitter taste Able to know.

Thus, it can be seen that the taste masking effect of the liquid agent of the present invention is remarkably excellent.

&Lt; Example A-31 > Preparation of Taste-Shielding Liquid Agent

i) Step 1: Preparation of thickener

Xanthan Gum is swollen in water, carboxymethyl cellulose (CMC) is swollen in water to another beaker, and the temperature of both solutions is then brought to 60 ° C.

ii) Step 2: Preparation of syrup

Glycerin is dissolved in water at 60 ° C to prepare a solution, and white sugar and sorbitol are dissolved in the solution, and the thickener of step 1 is added thereto.

iii) Step 3: Encapsulation of lipid and drug

After the lipid is heated to 80 DEG C and melted, the molten lipid is rapidly stirred, the drug is added, and stirring is continued until the drug is sufficiently dissolved. 15 ml of water is added little by little to make an emulsion, and the temperature is lowered to 60 ° C with rapid stirring.

iv) Step 4: Preparation of drug syrup

The emulsion produced in step 3 is rapidly stirred, the syrup prepared in step 2 is added, and then stirred rapidly. Cool the preparation to 30 ° C and add other excipients.

&Lt; Examples A-32 to A-40 > Preparation of a taste-masked liquid agent

A liquid agent was prepared in the same manner as in Example A-31, except that the respective components in the above Example A-31 were changed as shown in the following Tables 12 and 13.

<Comparative Example A-4> Preparation of liquid agent

[0215] The procedure of Example A-31 was repeated except that the components in Example A-31 were changed as shown in Table 12 below and the lipid was heated to 80 [deg. A liquid agent was prepared in the same manner as in Example A-31 except that the process of rapidly stirring and loading the drug was omitted.

function	Component (g / 100 mL)	Comparative Example A-4	Example A-31 HLB 2	Example A-32 HLB 2	Example A-33 HLB 7	Example A-34 HLB 9	Example A-35 HLB 14	Example A-36 HLB 1	Example A-37 HLB 5
Increasing agent / Sweetener	White sugar	40	40	40	40	40	40	40	40
"	Sorbitol	27.5	27.5	27.5	27.5	27.5	27.5	27.5	27.5
Sweetener	Sucral Rose	0.1			0.1	0.1	0.1		0.1
"	Enzyme treatment Stevia		0.1	0.1				0.1
Acidic	Malic acid	0.2	0.2	0.2	0.2	0.2	0.2	0.2	0.2
Incrementer	Xanthan gum	0.4	0.4	0.4	0.4	0.4	0.4	0.4	0.4
"	CMC	0.6	0.6	0.6					0.6
"	Carrageenan				0.6	0.6	0.6	0.6
Plasticizer	glycerin	One	One	One	One	One	One	One	One
pH adjusting agent	Citric acid	0.4	0.4			0.4	0.4		0.4
"	Sodium hydrogencarbonate			0.4	0.4			0.4
Flavor	Grape incense	One	One	One	One	One	One	One	One
drug	Trimebutine	0.48	0.48	0.48	0.48	0.48	0.48	0.48	0.48
Lipid (HLB 2)	Precirol ATO 5		0.72		0.42	0.30			0.54
(HLB 2)	Compritol 888 ATO			0.72
(HLB 14)	Gelucire 44/14				0.30	0.42	0.72		0.18
(HLB 1)	Gelucire 43 / 01pellets							0.72
	Purified water	Suitable amount	Suitable amount	Suitable amount	Suitable amount	Suitable amount	Suitable amount	Suitable amount	Suitable amount
	Total (mL)	100.00	100.00	100.00	100.00	100.00	100.00	100.00	100.00

function	Component (g / 100 mL)	Example A-38	Example A-39	Example A-40
Increasing agent / Sweetener	White sugar	40	40	40
"	Sorbitol	27.5	27.5	27.5
Sweetener	Sucral Rose		0.1	0.1
"	Enzyme treatment Stevia	0.1
Acidic	Malic acid	0.2	0.2	0.2
Incrementer	Xanthan gum	0.4	0.4	0.4
"	CMC	0.6	0.6
"	Carrageenan			0.6
Plasticizer	glycerin	One	One	One
pH adjusting agent	Citric acid	0.4	0.4	0.4
Flavor	Grape incense	One
"	Strawberry incense			One
"	Chrysanthemum		One
drug	Oseltamivir	0.48	0.48	0.48
Lipid	Beeswax	0.72
"	Carnauba wax		0.72
"	Castor wax			0.72
	Purified water	Suitable amount	Suitable amount	Suitable amount
	Total (mL)	100.00	100.00	100.00

<Experimental Example A-4>

The following experiment was conducted to confirm the taste shielding effect of the liquid preparation of the present invention.

In order to confirm the taste shielding effect of the trimesbutin drug, for the liquid preparation prepared according to Examples A-31, A-32 and Comparative Example A-4, six subjects drank 5 mL of the liquid agent, And recorded. At this time, for accurate evaluation of the taste, the subjects rinsed the mouth with distilled water before taking the liquid. The evaluation results of the liquid preparations prepared in Examples A-31, A-32 and Comparative Example A-4 are shown in Table 14 below.

At this time, the degree of arine taste was expressed as follows.

+: Very tasty

++: slightly tasty

+++: very slightly aring flavor

++++: tasteless or shielded flavor

	Example A-31	Example A-32	Comparative Example A-4
flavor	++++	++++	+

As shown in the results of Table 14, in the case of the liquid preparation of the present invention, a flavorless or shielded taste appeared for trimethoin, whereas for the liquid preparation prepared in Comparative Example A-4, Can be seen.

Thus, it can be seen that the taste masking effect of the liquid agent of the present invention is remarkably excellent.

<Experimental Example A-5>

In order to observe that the drug was transferred to the lipid in the preparation of the liquid preparation in the present invention, the liquid preparations of Example 1 and Comparative Example 1 were stained using the liposoluble means III dye, and the particles were observed under an optical microscope, (Example A-1) and Fig. 2 (Comparative Example A-1).

The observation of the optical microscope showed that the drug crystals were observed in the absence of lipids, but the drug crystals were found in the lipids (red color (dark color)) when lipids were present.

Accordingly, it can be seen that the liquid agent of the present invention minimizes direct contact of the drug with the oral cavity or the digestive system upon administration and that the drug is present in the lipid matrix, thereby effectively shielding bitter taste and arginine taste.

Hereinafter, the present invention will be described in detail with reference to Examples and Experimental Examples relating to oral disintegration films.

However, the following Examples and Experimental Examples of the oral disintegration film are merely illustrative of the present invention, and the content of the present invention is not limited by the following Examples.

	Example B-1 (% by weight)	Example B-2 (% by weight)	Comparative Example B-1 (% by weight)
Pullulan	49.27	49.27	64.00
Carrageenan	1.24	5.24	1.30
Triethanol citrate	4.13	4.13	4.30
Sodium hydrogencarbonate	18.24	18.24	19.00
Peppermint incense	1.90	1.90	2.00
nicotine	5.00	5.00	5.00
Aspartame	4.22	4.22	4.40
Precirol ato 5	3.36	-	-
Compritol 888 ato	3.36	-	-
Gelucire 44/14	9.28	-	-
Sucrose stearate (D-1809)	-	12	-
Sum	100	100	100

	Example B-3 (% by weight)	Example B-4 (% by weight)	Comparative Example B-2 (% by weight)
Pullulan	74.16	74.16	82.40
Carrageenan	9.80	1.80	2.00
Triethanol citrate	3.60	3.60	4.00
Citric acid	1.80	1.80	2.00
Peppermint incense	2.25	2.25	2.50
Barrenicin tartrate	0.40	0.40	0.40
saccharin	6.03	6.03	6.70
Sucrose stearate (D-1807)	1.96	9.96	-
Sum	100	100	100

	Example B-5 (% by weight)	Example B-6 (% by weight)	Example B-7 (% by weight)	Example B-8 (% by weight)
Pullulan	36.83	26.83	36.83	36.80
Carrageenan	1.30	1.30	2.30	1.30
Triethanol citrate	1.30	1.30	1.30	1.30
Citric acid	1.00	1.34	1.34	1.00
Orange incense	2.00	2.40	2.40	2.00
Dexibupropene	36.83	36.83	-	-
Ibuprofen	-	-	36.92	36.60
Acesulfame K	4.00	4.00	4.00	4.00
Gelucire 43/01 pellets	16.74	-	-	-
Precirol ato 5	-	26.00	-	15.64
Geleol pellets	-	-	15.00	-
Gelucire 44/14	-	-	-	1.36
Sum	100	100	100	100

	Example B-9 (% by weight)	Example B-10 (% by weight)	Example B-11 (% by weight)	Comparative Example B-4 (% by weight)
Pullulan	45.43	25.43	42.55	25.43
Carrageenan	2.50	2.50	3.72	2.50
Triethanol citrate	2.00	2.00	2.30	2.00
Sodium hydrogencarbonate	-	-	2.66	-
Citric acid	2.00	2.00	-	2.00
Strawberry incense	2.00	2.00	4.50	2.00
Trimebutine	26.07	26.07	-	26.07
Oseltamivir	-	-	26.07	-
Aspartame	-	-	-	-
Stevioside	4.00	4.00	-	4.00
Sucralose	-	-	4.50	-
Gelucire 50/13 pellets	16.00	-	-	-
Gelucire 44/14	-	36.00	-	-
Oleic acid	-	-	-	36.00
Sucrose stearate (D-1805)	-	-	13.70	-
Sum	100	100	100	100

	Comparative Example B-3 (% by weight)	Example B-12 (% by weight)	Example B-13 (% by weight)
Pullulan	47.96	44.66	29.66
Carrageenan	1.30	1.30	1.30
Triethanol citrate	13.0	1.30	1.30
Citric acid	1.34	1.34	1.34
Orange incense	2.40	2.40	2.40
Dexibupropene	30.00	30.00	30.00
Acesulfame K	4.00	4.00	4.00
Precirol ato 5	-	15.00	30.00
Sum	100	100	100

&Lt; Example B-1 >

Step 1: Pullulan and other excipients in the weight% of the above table were added to purified water and stirred to form an aqueous solution. Lipids were added to the aqueous solution in the kind and weight% of the lipid disclosed in Example B-1 of Table 15. [ Concretely, 3.36% by weight of Precirol ato 5, 3.36% by weight of Compritol 888 ato and 9.28% by weight of Gelucire 44/14 were added and heated to 95 ° C to form an emulsion.

Step 2: 5% by weight of nicotine as a raw drug was added to the emulsion and mixed with the emulsion so that nicotine was distributed in the lipid phase.

Step 3: The emulsion was placed on top, cooled and dried to prepare a taste-masked oral disintegration film having the composition of the above table.

&Lt; Example B-2 >

In Example B-1, the lipids added in Step 1 were performed in the same manner as in Example B-1 except that 12% by weight of sucrose stearate ((D-1809) was used, To prepare a flavor-masked oral disintegration film.

&Lt; Example B-3 >

Except that in step 1 of Example B-1 the lipids were changed to 1.96% by weight of sucrose stearate ((D-1807) and in step 2 the raw drug was changed to 4% by weight of barrenicin tartaric acid Was performed in the same manner as in Example B-1 to prepare a taste-masked oral disintegration film having the above-mentioned composition.

&Lt; Example B-4 >

Except that in Step 1 of Example B-1 the lipids were changed to 9.96 wt% sucrose stearate ((D-1807) and the raw drug was changed to 4 wt% barrenicin tartaric acid in step 2 Was performed in the same manner as in Example B-1 to prepare a taste-masked oral disintegration film having the above-mentioned composition.

&Lt; Example B-5 >

In Example B-1, the lipids were run with 16.74% by weight of Gelucire 43/01 pellets in Step 1, and in Example B-1 except that the raw drug was changed to 36.83% of dexibupropene in Step 2. [ 1 to prepare a taste-masked oral disintegration film having the composition of the above table.

&Lt; Example B-6 >

Example B-1 was prepared in the same manner as in Example B-1 except that in Step 1, the lipids were run with 26.00 wt% of Precirol ato 5, and the raw drug was changed to 36.83% of dexibupropene in Step 2. The same procedure was followed to prepare a taste-masked oral disintegration film having the composition of the above table.

&Lt; Example B-7 >

In Example B-1, in the same manner as in Example B-1 except that in Step 1, the lipids were run with 15.00 wt% of Geleol pellets and the raw drug was changed to 36.83% of bipopen in Step 2 To prepare a taste-masked oral disintegration film having the composition of the above table.

&Lt; Example B-8 >

In Example B-1, except that in step 1 the lipids were 15.64 wt% Precirol ato 5 and 1.36 wt% Gelucire 44/14 and in step 2 the raw drug was changed to 36.60% ibuprofen A taste-masked oral disintegration film having the composition of the above table was prepared in the same manner as in Example B-1.

&Lt; Example B-9 >

Example B-1 was prepared in the same manner as in Example B-1 except that in Step 1, the lipids were changed to 16.0 wt% of Gelucire 50/13 pellets, and the raw drug was changed to 26.07% To prepare a flavor-masked oral disintegration film having the composition of the above table.

&Lt; Example B-10 >

Example B-1 was prepared in the same manner as in Example B-1, except that in Step 1, the lipids were changed to 36.00 wt% of Gelucire 44/14 and the raw drug was changed to 26.07% The same procedure was followed to prepare a taste-masked oral disintegration film having the composition of the above table.

&Lt; Example B-11 >

Example B-1 was prepared in the same manner as in Example B-1 except that in Step 1, the lipids were changed to 13.70 wt% of sucrose stearate (D-1805), and the raw drug in Step 2 was changed to 26.07% of oseltamivir. -1 to prepare a taste-masked oral disintegrating film having the composition of the above table.

&Lt; Example B-12 >

Example B-1 was prepared in the same manner as in Example B-1 except that in Step 1, the lipids were changed to 15% by weight of Precirol ato 5, and the raw drug was changed to 30.00% of dexibupropene in Step 2. The same procedure was followed to prepare a taste-masked oral disintegration film having the composition of the above table.

&Lt; Example B-13 >

Example B-1 was prepared in the same manner as in Example B-1, except that in Step 1, the lipids were changed to 30% by weight of Precirol ato 5, and the raw drug was changed to 30.00% of dexibupropene in Step 2. The same procedure was followed to prepare a taste-masked oral disintegration film having the composition of the above table.

&Lt; Comparative Example B-1 &

Step 1: Pullulan and other excipients were added to purified water and stirred to prepare a water-soluble solution. Then, 5 wt% of nicotine was added to the aqueous solution as a raw material drug, uniformly mixed, and then degassed using a centrifuge.

Step 2: The solution of Step 1 was pre-heated, and then cooled and dried to prepare a mouth rinse film having the composition shown in the above table.

&Lt; Comparative Example B-2 >

In Comparative Example B-1, an oral debonding film having the composition of the above table was prepared by performing the same procedure as in Comparative Example B-1, except that the nicotine in Step 2 was changed to barrenicin tartaric acid.

&Lt; Comparative Example B-3 >

In Comparative Example B-1, an oral debonding film having the composition of the above table was prepared by performing the same procedure as in Comparative Example B-1, except that the nicotine in Step 2 was changed to dexibupropene.

&Lt; Comparative Example B-4 >

In Example B-10, a taste-masked oral disintegration film having the composition of the above table was prepared by performing the same procedure as in Example B-10 except that the lipids were changed to oleic acid in Step 1.

<Experimental Example 1>

In order to confirm the taste shielding effect of the oral disintegration film of the present invention, the following experiment was conducted.

To confirm the taste shielding effect of the nicotine drug, for the oral disintegration films produced by Examples B-1, B-2 and Comparative Example B-1, films were placed in the mouths of six subjects, Then, the disintegrated film was spit out and the degree of bitter taste was recorded and evaluated. At this time, for accurate evaluation of the taste, the subjects rinsed the mouth with distilled water before taking the film sample. The evaluation results of the oral disintegration films produced by Examples B-1, B-2 and Comparative Example B-1 are shown in Table 20 below.

At this time, the degree of bitter taste was expressed as follows.

+: Very bitter taste

++: slightly bitter taste

+++: very bitter bitter

++++: tasteless or shielded flavor

	Example B-1	Example B-2	Comparative Example B-1
flavor	+++	+++	+

As shown in the results of the above Table 20, in the case of the oral disintegration film of the present invention, a slight bitter taste appears to nicotine, whereas in the case of the oral disintegration film produced by Comparative Example B-1, The taste can be seen.

As a result, it can be seen that the taste-masking effect of the oral disintegration film of the present invention is remarkably excellent.

<Experimental Example 2>

 In order to confirm the taste shielding effect of the oral disintegration film of the present invention, the following experiment was conducted.

The oral disintegration films prepared in Examples B-3 and B-4 and Comparative Example B-2 were tested in the same manner as in Experimental Example 1, in order to confirm the taste shielding effect of the barrenicin tartaric acid drug . The evaluation results of the oral disintegration films produced by Examples B-3, B-4 and Comparative Example B-2 are shown in Table 21 below.

	Example B-3	Example B-4	Comparative Example B-2
flavor	+++	++++	+

As shown in the results of the above Table 21, in the case of the oral disintegration film of the present invention, the slightly bitter or bitter taste was completely shielded against the barrenicin tartaric acid drug, In the case of the disintegrable film, a very bitter taste appears.

As a result, it can be seen that the taste-masking effect of the oral disintegration film of the present invention is remarkably excellent.

<Experimental Example 3>

 In order to confirm the taste shielding effect of the oral disintegration film of the present invention, the following experiment was conducted.

To confirm the taste shielding effect of dexibupropene and acesulfame K, the oral disintegration films prepared in Examples B-12, B-13 and Comparative Example B-3 were evaluated in the same manner as in Experimental Example 1 By doing so. The evaluation results of the oral disintegration films prepared in Examples B-12, B-13 and Comparative Example B-3 are shown in Table 22 below.

	Example B-12	Example B-13	Comparative Example B-3
flavor	++	+++	+

As shown in the results of Table 22, it can be seen that the oral disintegration film of the present invention has a higher bitter taste shielding effect than the oral disintegration film produced by Comparative Example B-3.

<Experimental Example 4>

The following experiment was conducted to confirm the degree of exposure of the drug through the surface shape of the oral disintegration film of the present invention.

The oral disintegration films prepared by Example B-12, Example B-13, and Comparative Example B-3, which were prepared containing dexibupropene and acesulfame K drugs, were examined by scanning electron microscopy (SEM) The surface shape was confirmed, and the results are shown in Figs. 3 to 3, respectively.

(Comparative Example B-3), as shown in FIG. 5, when a large crystal drug was formed on the surface but the ratio of lipid and drug was 1: 2 (Example B-13). As shown in FIG. 3, small drug crystals can be seen between the agglomerates of lipids. When the ratio of lipids to drug is 1: 1 (Example B-14) As shown in Fig. 4, it is seen that almost no drug crystals are observed on the surface.

Thus, in the case of Examples B-13 and B-14 containing lipids, compared with that prepared by Comparative Example B-3 which does not contain lipids, The effect of the drug on the taste can be expected to be high.

<Experimental Example 5>

In order to confirm the durability of the oral disintegration film of the present invention, the following experiment was conducted.

(Example B-10) prepared by using Gelucire 44/14 having a melting point of 40 占 폚 as a lipid and the oral disintegration film prepared by using oleic acid having a melting point of 14 占 폚 as a lipid (Comparative Example B-4), a state change with time after the production was confirmed, which is shown in Table 23 below.

	1 hours	6 hours	12 hours	24 hours
Example B-10	No phase change	No change in status	No change in status	No change in status
Comparative Example B-4	No change in status	No change in status	The film is softened	Separation of oil phase from film

As shown in Table 23, in the case of the oral disintegration film produced by Example B-10, it was maintained for a long time without changing the state after production, whereas in the case of the oral disintegration film produced by Comparative Example B-4, It can be seen that the film is softened after 12 hours and the oil is separated.

As a result, it can be seen that the durability of the prepared oral disintegration film is remarkably lowered when the lipids having a temperature lower than 40 ° C are used.

The pharmaceutical preparations for oral administration in which the taste of the present invention is shielded and the preparation method thereof can be usefully used for drug formulation in the pharmaceutical industry.

Claims (25)

1. Lipids; And

   And a source drug distributed in the lipid species.
2. The method according to claim 1,

   The pharmaceutical preparation for oral administration may be,

   Lipids; And

   And a raw material drug distributed in the above-mentioned lipids. [Claim 5] &lt; 73 &gt;
3. 3. The method of claim 2,

   The lipid species

   Wherein the melting point is from 40 占 폚 to less than 100 占 폚.
4. 3. The method of claim 2,

   The lipid species

   Wherein the composition has a hydrophilic-lipophilic balance (HLB) of 0 to 16.
5. 3. The method of claim 2,

   The lipid species

   Wherein the flavor is at least one selected from the group consisting of fatty acid glycerides, PEG fatty acid esters, and sugar-based surfactants.
6. 6. The method of claim 5,

   Wherein the fatty acid is a fatty acid having 10 or more carbon atoms and 30 or less carbon atoms.
7. 6. The method of claim 5,

   Wherein the fatty acid glyceride is a mono-, di-, or triglyceride, or a mixture thereof, and the PEG fatty acid ester is a mono, diester, or mixture thereof.
8. 6. The method of claim 5,

   The saccharide-based surfactant

   But are not limited to, sucrose monostearate, sucrose distearate, sucrose mono-distearate, sucrose monopalmitate, sucrose dipalmitate, The composition of the present invention may be selected from the group consisting of sucrose dipalmitate, sucrose monolaurate, sucrose diraurate, sucrose monooleate, sucrose dioleate, sucrose monooleate, monocaprate, monocaprate, sucrose dicaprate, sucrose monocaprylate, sucrose dicaprylate, sucrose monomyristate, sucrose monomyristate, dimyristate, sucrose monolinolenate, and sucrose dilinolenate. 1 kinds of the pharmaceutical preparations for oral administration, taste masked, characterized in that at least selected from the group true luer.
9. 3. The method of claim 2,

   The liquid agent

   9. A pharmaceutical composition for oral administration, which is shielded from taste, comprising an additive.
10. 10. The method of claim 9,

    The additive

    Wherein the flavor is at least one selected from the group consisting of sweeteners, flavors, stabilizers, and pH adjusters.
11. Adding lipids to a water-soluble solution and heating at a temperature above the melting point of the lipids to form an emulsion (step 1);

    Adding a raw drug to the emulsion of step 1 (step 2); And

    Cooling the emulsion added with the raw drug (step 3); The method of producing a taste masked liquid agent according to claim 2,
12. 12. The method of claim 11,

    The lipids of step 1

    Wherein the solution is contained in an amount of 1 to 40 wt% based on the total weight of the solution.
13. 12. The method of claim 11,

    Wherein the step (2) distributes the raw drug to the inner surface of the emulsion.
14. 12. The method of claim 11,

    Wherein the step (3) is carried out while cooling the emulsion with the raw drug added thereto at a reduced temperature while stirring the emulsion.
15. The method according to claim 1,

    The pharmaceutical preparation for oral administration may be,

    Lipids; And

    Wherein the taste-masked oral disintegration film is a film containing a raw drug distributed in the lipid species.
16. 16. The method of claim 15,

    The lipid species

    Characterized in that the melting point is not lower than 40 ° C and lower than 100 ° C.
17. 16. The method of claim 15,

    The lipid species

    Wherein the composition has a hydrophilic-lipophilic balance (HLB) of 0 to 16.
18. 16. The method of claim 15,

    The lipid species

    Glycerol monostearate (Glycerol monostearate), glycerol di-behenate (Glycerol dibehenate), a glyceryl behenate (Glyceryl behenate) Comp erythritol (Compritol) ^® 888 ATO, a C8-18 glyceride (C8-18glycerides) gel Lucy les (Gelucire) ^® 43/01, lauroyl polyoxyl -32 glycerides (lauroyl polyoxyl-32 glycerides) as a gel Lucy LES (Gelucire) ^® 44/14, as one polyoxyethylene stearate -32- glycerides (stearoyl polyoxyl- 32 glycerides) as a gel Lucy LES (Gelucire) ^® 50/13, lauroyl polyoxyl-6 glycerides (lauroyl polyoxyl-6 glycerides) as LabrafilTM (LABRAFIL) M2130 CS, glyceryl palmitostearate stearate (glyceryl Wherein the palmitostearate is at least one selected from the group consisting of PRECIROL ATO 5, Beeswax carnauba wax, and sugar-based surfactants. Pharmaceutical formulation.
19. 19. The method of claim 18,

    The saccharide-based surfactant

    But are not limited to, sucrose monostearate, sucrose distearate, sucrose mono-distearate, sucrose monopalmitate, sucrose dipalmitate, The composition of the present invention may be selected from the group consisting of sucrose dipalmitate, sucrose monolaurate, sucrose diraurate, sucrose monooleate, sucrose dioleate, sucrose monooleate, monocaprate, monocaprate, sucrose dicaprate, sucrose monocaprylate, sucrose dicaprylate, sucrose monomyristate, sucrose monomyristate, dimyristate, sucrose monolinolenate, and sucrose dilinolenate. 1 kinds of the pharmaceutical preparations for oral administration, taste masked, characterized in that at least selected from the group true luer.
20. 16. The method of claim 15,

    The oral disintegration film

    9. A pharmaceutical composition for oral administration, which is shielded from taste, comprising an additive.
21. 21. The method of claim 20,

    The additive

    Wherein the flavor is at least one selected from the group consisting of a water-soluble polymer, a plasticizer, a sweetener, a flavor, a stabilizer, and a pH adjuster.
22. Adding lipids to a water-soluble solution and heating at a temperature above the melting point of the lipids to form an emulsion (step 1); And

    The method of claim 15, further comprising the step of adding a raw drug to the emulsion of step 1 (step 2).
23. 23. The method of claim 22,

    The lipids of step 1

    Wherein the solution is contained in an amount of 1 to 40% by weight based on the total weight of the solution.
24. 23. The method of claim 22,

    And the step (2) is such that the drug substance is distributed in the lipid phase of the emulsion.
25. 23. The method of claim 22,

    The above-

    Further comprising the step of cooling and drying the emulsion after the step 2, after the emulsion has been baked.

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