TW201532634A - Solid preparation - Google Patents

Abstract

A solid preparation containing mannitol, sucrose, and starch; the mannitol content being at least 10 mass parts in relation to 1 mass part of sucrose and the starch content being preferably at least 0.01 mass parts in relation to 1 mass part of sucrose; the solid preparation preferably further containing a drug such as acetaminophen, scopolamine or a salt thereof, chlorpheniramine or a salt thereof, carbinoxamine or a salt thereof, a belladonna total alkaloid, loratadine, fexofenadine or a salt thereof, mequitazine, loxoprofen or a salt thereof, meclizine or a salt thereof, ibuprofen, caffeine, ascorbic acid, or pseudoephedrine or a salt thereof; and the solid preparation being an orally disintegrating tablet or a chewable tablet exhibiting a speedy disintegrating performance in the oral cavity while having a high hardness and excellent dosability. This orally disintegrating tablet or chewable tablet can be manufactured without using special equipment, manufacturing methods, or excipients.

Description

Solid preparation

The present invention relates to a solid preparation which can be rapidly disintegrated in the oral cavity or simply chewed with a tooth, and an intraoral disintegrating tablet or a chewable tablet containing an appropriate hardness and having an excellent administration property, without drinking water A preparation that can be taken.

An orally disintegrating tablet is defined as a tablet having an appropriate disintegration after being rapidly dissolved or collapsed in the oral cavity, and a chewable tablet is defined as a tablet after chewing (Non-Patent Document 1) . Since both are preparations that can be taken without drinking water, there is no need to choose to take them, and there is an advantage that they can be taken without water to drink.

The previous orally disintegrating ingots are known to be formed by freeze-drying using a substance such as gelatin in a container, and by wet-type tablets or granules by wet-type ingots, but such ingots are known. From time to time, the agent occurs when the tablet is broken and defective, and it is difficult to assert that it has sufficient hardness, and the manufacturing method is rather cumbersome. Therefore, in the manufacture of an orally disintegrating ingot or a chewable ingot, the time of disintegration in the oral cavity and the hardness of the tablet are allowed to stand, and it takes a lot of effort. another In addition, in order to disintegrate in the mouth, it is also necessary to consider taking it.

To date, various reviews have been conducted to obtain an orally disintegrating ingot having rapid disintegration and high hardness. For example, an orally disintegrating tablet containing a starch powder and a gelatinized starch, a water-soluble excipient of mannitol, and sodium fumarate and a medicinal ingredient has been reported (Patent Document 1); An orally soluble type compression-molded article comprising a moldable low-sugar and a high-formity saccharide, and having rapid disintegration and solubility in the oral cavity (Patent Document 2); containing at least one selected from the group consisting of mannitol and disintegrating A method for producing an orally disintegrating ingot of a drug, a cellulose, a slip agent, a starch, and a lactose (Patent Document 3).

However, in Patent Document 1, when starch powder and gelatinized starch are used, problems such as adhesion to a manufacturing apparatus are liable to occur, and handling in manufacturing is extremely difficult. Further, according to the method of Patent Document 2, in order to produce an orally disintegrating ingot, the step of humidifying and drying after tableting at a low pressure is a necessary condition, and the number of manufacturing steps is increased, and the operation is complicated. Although Patent Document 3 is based on mannitol, it is actually an orally disintegrating tablet containing a rapid disintegrating agent such as crospovidone or croscarmellose, but a large amount of rapidly disintegrating agent is blended. There is a concern that the hardness is lowered due to moisture absorption and the appearance is changed.

Prior technical document Patent document

Patent Document 1: Patent No. 4435424

Patent Document 2: Patent No. 3122141

Patent Document 3: JP-A-2000-273039

Non-patent document

Non-Patent Document 1: Sixteenth Revision Japanese Pharmacopoeia Interpretation Shares Limited Hikawakawa Bookstore Pages A-33-34

The object of the present invention is to provide a solid preparation which can be rapidly disintegrated in the oral cavity or which can be chewed by a tooth, and which comprises an orally disintegrating ingot or a chewable tablet having an appropriate hardness and having excellent ingestibility, and can be taken without drinking water. .

In order to achieve the above object, the present inventors have found that a solid preparation containing mannitol, sucrose, and starch and having a mannitol content of 10 parts by mass or more based on 1 part by mass of sucrose is obtained in the oral cavity. The present invention has been completed by an in-oral disintegrating tablet or a chewable tablet which has rapid disintegration properties while having appropriate hardness and excellent ingestability.

That is, the present invention is:

(1) A preparation which can be administered without drinking water, and which is characterized in that it contains mannitol, sucrose, and starch, and the content of mannitol is 10 parts by mass or more based on 1 part by mass of sucrose.

(2) The preparation according to (1) which is an orally disintegrating ingot or a chewable ingot.

(3) The preparation according to (1) or (2), wherein the content of the starch is 0.01 parts by mass or more based on 1 part by mass of the sucrose.

(4) The preparation according to any one of (1) to (3), which further comprises a medicine Things.

(5) The preparation according to any one of (1) to (4) wherein the drug is selected from the group consisting of ethamamine, guanamine or a salt thereof, chlorpheniramine or a salt thereof, and carbenoxamine (Carbinoxamine) Or its salt, belladonna total alkaloid, Loratadine, fexofenadine or its salt, allergy Mequitazine, Loxoprofen or its salt, sensitive One or two or more kinds of meclizine or a salt thereof, Ibuprofen, caffeine, ascorbic acid, pseudoephedrine or a salt thereof.

According to the present invention, it is possible to manufacture an orally disintegrating ingot or a chewable ingot which disintegrates in the oral cavity and which has a desired appropriate hardness and which has excellent ingestibility without using a special apparatus, a manufacturing method, and an excipient.

Hereinafter, a preparation containing an orally disintegrating ingot and a chewable ingot, which can be taken without drinking water, according to the present invention will be described in detail.

The orally disintegrating tablet of the present invention refers to a tablet which has an extremely fast disintegration time in the oral cavity under normal chewing conditions. Further, the chewable tablet of the present invention means a tablet which is taken after chewing. Since it is not necessary to drink water when taking an orally disintegrating tablet or chewing an ingot, it is suitable for a dosage form in which, for example, a general period of inconvenience of a tablet is inconvenient and a symptom suddenly occurs.

The preparation containing the orally disintegrating ingot and the chewable tablet, which can be taken without drinking water, according to the present invention, contains 10 parts by mass or more of the mannose based on 1 part by mass of the sucrose. When it is less than 10 parts by mass, it is difficult to obtain the disintegration time in the oral cavity and the hardness and the take-up property of the tablet. In addition, the preparation containing the orally disintegrating ingot and the chewable tablet in the case of the present invention which does not require drinking water, preferably contains mannitol in an amount of 950 parts by mass or less based on 1 part by mass of sucrose. It is more preferably 100 parts by mass or less, and most preferably 50 parts by mass or less. Further, in the case of an orally disintegrating ingot and a chewable tablet, the amount of mannitol contained in the preparation which can be taken without drinking water according to the present invention has an upper limit value from the viewpoints of the physical properties of the tablet and the compression formability. Good quality 95% by mass.

The starch in the present invention may, for example, be corn starch, potato starch, rice starch, wheat starch, sweet potato starch, mung bean starch, tapioca starch or the like, and is preferably corn starch or potato starch. Further, when the preparation contains powdered sugar, the corn starch contained in the powdered sugar is contained in the starch of the present invention. The preparation containing the orally disintegrating ingot and the chewable tablet and which can be taken without drinking water according to the present invention preferably contains 0.01 to 20.0 parts by mass based on 1 part by mass of the sucrose. From the viewpoint of the effects of the present invention, it is more preferably 0.01 parts by mass to 15.0 parts by mass. Further, the content of the starch contained in the preparation of the present invention is preferably 70% by mass from the viewpoint of the physical properties of the tablet and the compression moldability.

The sucrose contained in the powdered sugar is contained in the sucrose contained in the powdered sugar, and the sucrose contained in the powdered sugar is contained in the sucrose contained in the powdered sugar, and the sucrose contained in the powdered sugar is contained in the preparation of the present invention. In the amount. This hair The sucrose content of the phlegm is generally 0.01 to 30% by mass, preferably 0.1 to 30% by mass, more preferably 0.1 to 20% by mass, more preferably 1.0 to 20% by mass, more preferably 2.0 to 20% by mass relative to the total mass of the preparation. 10% by mass.

Further, the in-oral disintegrating tablet and the chewable tablet may be blended with the drug of the present invention which can be taken without drinking water. The medicine which can be incorporated into a preparation for ingesting an orally disintegrating ingot and a chewing ingot according to the present invention and which can be taken without drinking water can be either solid or crystalline, and can be selected from the group consisting of antipyretic analgesic and anti-inflammatory drugs. , nourishing strong health care drugs, hypnotic sedatives, antispasmodic drugs, gastrointestinal drugs, antacids, antitussive expectorants, antiemetics, respiratory agents, bronchodilators, allergic drugs, antihistamines, central nervous system drugs, vitamins One or more components, such as a drug, a dental oral drug, and a sedative. For example, ethamamine, guanamine or a salt thereof, chlorfenibamine or a salt thereof, carbinozamine or a salt thereof, strontium, leratadine, lysine or a salt thereof, allergic melamine ingot, ring Oxyprofen or a salt thereof, sensible or its salt, pufufen, caffeine, ascorbic acid, pseudoephedrine or a salt thereof. The content of the drug is generally 0.01 to 90% by mass, preferably 0.01 to 80% by mass, more preferably 0.1 to 80% by mass, more preferably 0.1 to 70% by mass, more preferably 0.5 to 70% by mass, based on the total mass of the preparation. 50% by mass.

The preparation for ingesting the orally disintegrating ingot and the chewing ingot according to the present invention, which can be taken without drinking water, may also contain various types of in-oral disintegrating tablets and chewing ingots, without affecting the effects of the present invention. additive. Examples of such additives include excipients, disintegrators, binders, sour agents, foaming agents, sweeteners, perfumes, slip agents, colorants, and the like. Include mouth The intracavitary disintegrating tablet and the chewable tablet are not particularly limited in size and shape, and may be prepared as a divided ingot having a cutting line.

There is no particular limitation on the preparation of a preparation which can be taken without the use of water in the present invention, which comprises an orally disintegrating ingot and a chewable ingot, and the manufacturing method previously employed can be used. For example, the following methods can be mentioned.

Mix mannitol, sucrose, and starch, and mix the additives as needed. The method of producing the granules is not particularly limited, and it can be produced by any of wet granulation and dry granulation. Drying can be suitably carried out after the granulation process or granulation production. Examples of the wet granulation method include a fluidized bed granulation method, a stirring granulation method, a granulation granulation method, a rotary granulation method, and a melt solvent method, and the dry granulation method may be a crude granulation method or a dry granulation method. The granulator method is preferably produced by a fluidized bed granulation method or a stirring granulation method. In the obtained granules, a post-addition component can be appropriately added, and general compression molding such as tableting can be carried out to obtain a preparation which can be taken without drinking water according to the present invention including an orally disintegrating ingot and a chewable ingot. Further, in the case of production by the wet granulation method, the granulating solvent is preferably an aqueous solution containing at least one of water or mannitol, low-substituted hydroxypropylcellulose, and light anhydrous citric acid, particularly for use. In the case of a granulating solvent containing mannitol, it is more preferable to further improve the hardness and the take-up property of the tablet of the present invention.

Alternatively, it can be produced by a direct tableting method without a granulation step. As the tableting device, a device generally used for forming a tablet can be used. For example, a single-type tableting machine, a rotary tableting machine, or the like can be used.

In this way, the obtained orally disintegrating ingot or chewing ingot is shown in The disintegration property in the oral cavity is preferably within 60 seconds, preferably within 30 seconds, according to the disintegration test of the Japanese Pharmacopoeia or the intraoral disintegration test by the human body. Further, it has an appropriate strength in the preparation step and further in the case where no damage occurs during the circulation, and the tablet strength is converted into a preparation having a good tensile property in a tensile strength of 0.7 MPa or more.

[Examples]

Hereinafter, the present invention will be described in more detail by way of examples and comparative examples, but the invention is not limited to the examples and the like. Further, in the powders of the comparative examples and the examples, powdered sugar (containing 98.3% sucrose, 1.7% corn starch) manufactured by Decang Company was used.

(Comparative Example 1)

In the powder which was weighed and mixed according to the components shown in the mixed powder of Table 1, an aqueous solution in which the components of the granulating solvent shown in Table 1 were dissolved and dispersed was added, and the mixture was mixed in a mortar and sufficiently dried. Thereafter, it was sieved through a No. 22 hole sieve to prepare a granulated product. The obtained granules were added to the components added in the subsequent period as shown in Table 1, and then weighed and mixed, and then the table-type simple tablet molding machine (trade name: HANDTAB; Shiqiao Seiki) was used to set the tensile strength of the obtained tablet. For a tableting pressure of 0.7 MPa or more (6 to 15 kN), a tablet having a tablet diameter of 8 mm is obtained.

(Comparative Examples 2 to 3, Examples 1 to 6, 8)

According to the formulation shown in Table 1, the same tablet as in Comparative Example 1 was produced.

(Example 7)

The powder which was weighed and mixed with the mixed powder of Table 1 and the component added later, and sieved with a No. 22 hole sieve was produced into a tablet in the same manner as in Comparative Example 1.

(Experimental example) <Evaluation method 1>

With respect to the orally disintegrating ingots of Examples 1 to 15 and the respective comparative examples, the hardness and disintegration time of the tablet were measured by the following respective test methods, and the following evaluation criteria were applied to the take-up property (roughness and powdery feeling). Evaluate and add points.

(1) Hardness test

The measurement was performed using a Schleuniger tablet hardness meter (manufactured by Schleuniger). The hardness of each tablet was measured three times. Further, the obtained result was calculated using the following [number 1], and the tensile strength was calculated, and the average value was obtained.

[Number 1] Tensile strength (MPa) = 2F / π Dt

F: tablet hardness (N)

D: tablet diameter (mm)

t: tablet thickness (mm)

(2) Disintegration test

The measurement was carried out in accordance with the disintegration test method described in the Sixteenth Revision of the Japanese Pharmacopoeia. The disintegration time of each tablet was measured three times, and the average value was obtained.

(3) Taking test 1: rough feeling

Three healthy adult testers were used to evaluate the roughness in the oral cavity without chewing, and the roughness was evaluated by the following evaluation criteria, and the average value was obtained.

Rough sense evaluation criteria

Very rough: 4 points

Slightly rough: 3 points

Almost no rough feeling: 2 points

No roughness: 1 point

(4) Taking test 2: Powder feeling

Three healthy adult testers were used to evaluate the powdery feeling in the oral cavity without chewing, and the average of the powder was evaluated by the following evaluation criteria, and the average value was obtained.

Evaluation criteria for powdery feeling

Very powdery: 4 points

Slightly powdery: 3 points

Almost no feeling of powder: 2 points

No feeling of powder at all: 1 point

(result)

The disintegration time, the tensile strength, and the take-up property of each tablet are shown in Table 1.

As shown in Tables 1 and 3, Examples 1 to 8 containing mannitol, sucrose, and starch and having a mannitol content of 1 part by mass of sucrose mixed with 10 parts by mass or more showed collapse. The solution has an excellent disintegration rate of less than 30 seconds, and shows good values in both the tensile strength and the administration items. On the other hand, in Comparative Example 1 in which the sucrose was not blended in the formulation, even if it was produced at a high tableting pressure, a tablet having a hardness of 0.7 MPa or more could not be produced, and it was not satisfactory in terms of the take-up property. Further, in Comparative Example 2 in which the corn starch was not blended in the formulation, the disintegration time and the take-up property were unsatisfactory results with respect to 1 part by mass of sucrose and mannitol-based 10 parts by mass or less of Comparative Example 3. .

(Example 9)

Using acetaminophen as a drug, the components of the granulated granules shown in Table 4 were weighed and mixed, and a granulated product was produced using a fluidized bed granulator (trade name: FLO-1; manufactured by FREUND). After weighing and mixing the obtained granules and the components added later, the small-sized rotary tablet machine (trade name: VELA 5; Kikusui Seisakusho Co., Ltd.) was used, and the tensile strength of the obtained tablet was set to 0.7 MPa. The above tableting pressure (600~1500kgf) obtains a tablet with a tablet diameter of 8~10mm.

(Embodiment 10)

A lozenge was produced in the same manner as in Example 9 using a guanamine hydrobromide water mixture and a chlorfenapyr maleate as a drug.

(Example 11)

A tablet was produced in the same manner as in Example 9 using hydrazine and chlorfenibamine maleate as a drug.

(Embodiment 12)

A lozenge was produced in the same manner as in Example 9 using Luretta as a drug.

(Example 13)

A tablet was produced in the same manner as in Example 9 using hydrazine and carbinomin maleate as a drug.

(Example 14)

A tablet was produced in the same manner as in Example 9 using a guanamine hydrobromide water and a chlorhexidine hydrochloride as a drug.

(Example 15)

A lozenge was produced in the same manner as in Example 9 using a drug of sodium oxaprofen dihydrate as a drug.

(result)

As shown in Table 4, in Examples 9 to 15 of the solid preparation in which the drug was blended, the results of satisfying the standard value were also obtained in all the items of disintegration time, tensile strength, and administration.

(Embodiment 16)

Using cumene as a drug, the components of the granulated granules shown in Table 5 were weighed and mixed, and a granulated product was produced using a fluidized bed granulator (trade name: FLO-1; manufactured by FREUND). According to the weighing and mixing shown in Table 5 After the granules and the components are added in the later stage, the tablet-type simple tablet molding machine (trade name: HANDTAB; Shiqiao Seiki) is used, and the tensile strength of the obtained tablet is set to a tableting pressure of 6 MPa or more (6 to 15 kN). A lozenge having a lozenge mass of 125 mg and a lozenge diameter of 8 mm was obtained.

(Example 17)

A tablet was produced in the same manner as in Example 16 using caffeine as a drug.

(Embodiment 18)

A tablet was produced in the same manner as in Example 16 using ascorbic acid as a drug.

(Embodiment 19)

A lozenge having a tablet mass of 150 mg was produced in the same manner as in Example 16 using lyophilized hydrochloride as a drug.

(Embodiment 20)

A lozenge was produced in the same manner as in Example 16 using an allergic melon tablet as a drug.

(Example 21)

A tablet was produced in the same manner as in Example 16 using pseudoephedrine hydrochloride as a drug.

<Evaluation method 2>

With respect to the orally disintegrating ingots of Examples 16 to 21, the disintegration time and the taking property (roughness, powdery feeling) were measured by the following respective test methods, and evaluated according to the following evaluation criteria, and the points were counted.

(1) Hardness test

This was carried out in the same manner as in Evaluation Method 1.

(2) Disintegration test (intraoral disintegration test)

Two healthy adult testers were used to test the time during which the tablet completely disintegrated in the oral cavity without chewing in the oral cavity, and the average value was obtained.

(3) Taking test 1: rough feeling

Two healthy adult testers were used in the same manner as in Evaluation Method 1.

(4) Taking test 2: Powder feeling

Two healthy adult testers were used in the same manner as in Evaluation Method 1.

(result)

The disintegration time, the tablet hardness and the take-up property of the tablets obtained in Examples 16 to 21 are shown in Table 5.

Among the solid preparations (Examples 16 to 21) in which the drugs shown in Table 5 were blended, the results of satisfying the standard values were also obtained in all the items of disintegration time, tensile strength, and administration.

[Industrial Applicability]

According to the present invention, it is possible to provide an orally disintegrating ingot or a chewing ingot which can be rapidly disintegrated or dissolved in the oral cavity, has an appropriate hardness which is expected, and has excellent taking properties, without using special equipment, a manufacturing method, and an excipient. .

Claims (5)

A preparation which can be administered without drinking water, and which is characterized in that it contains mannitol, sucrose, and starch, and the content of mannitol is 10 parts by mass or more based on 1 part by mass of sucrose. The preparation of claim 1, which is an orally disintegrating ingot or a chewable ingot. The preparation of claim 1 or 2, wherein the content of the starch is 0.01 parts by mass or more based on 1 part by mass of the sucrose. The preparation according to any one of claims 1 to 3, which further comprises a drug. The preparation according to any one of claims 1 to 4, wherein the drug is selected from the group consisting of ethamamine, guanamine or a salt thereof, chlorpheniramine or a salt thereof, Carbinoxamine or a salt thereof, Bella (belladonna total alkaloid), Loratadine, fexofenadine or its salt, allergy Mequitazine, Loxoprofen or its salt, meclizine Or one or more of a group of salts thereof, Ibuprofen, caffeine, ascorbic acid, pseudoephedrine or a salt thereof.