JP2008037853A - Rapidly disintegrating solid drug preparation containing isomaltose - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a formulation design capable of maintaining tablet hardness with no practical problem together with rapid disintegration of tablets even if made into a tablet at a low compression, and allowing smooth mass production by a high productive tabletting apparatus such as a rotary tabletting machine due to a high content of Isomalt in tablets. <P>SOLUTION: The tablets with a hardness of 40 N or over and rapid disintegration within 20 seconds can be provided by compression molding a mixture containing Isomalt as a main ingredient in the tablets and further added with an active ingredient and a disintegrator at an appropriate ratio by a rotary tabletting machine. For example, a formulation of 88 wt.% of Isomal, 2 wt.% of croscarmellose sodium and 10 wt.% of crystalline cellulose gives tablet with a disintegration time of 20 seconds or less and a hardness of 40 N or over. Furthermore, a smooth production of tablets can be carried out by a rotary tableting machine even if the ratio of an essential lubricant is 0.125 wt.% in dry tableting process such as magnesium stearate. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

The present invention relates to a method for producing a solid pharmaceutical preparation characterized by containing isomalt.

In recent years, the demand for rapidly disintegrating tablets as a pharmaceutical dosage form to be taken by patients has increased rapidly, and excipients that are a part of pharmaceutical raw materials are also required to have higher functions in accordance with the demand. Particularly in the case of elderly people and patients who have difficulty swallowing, tablets that rapidly disintegrate in the body are required. Further, it is desired to produce tablets having the above-described characteristics using a general production facility without requiring a special mechanical device. Specific excipient functions required by the current market are to obtain tablets with fast disintegration time, tablet hardness that can be used for packaging and transport, and excellent taste, texture, and appearance. .

Among the solid pharmaceutical preparations, especially in the production of fast disintegrating tablets that require quick disintegration, it is sufficient hardness that does not cause problems in handling the tablets, but it exhibits quick disintegration in water. As physical properties, conflicting properties are required. Various methods and products have been developed to solve this problem, but these tend to depend on the original technology of each pharmaceutical manufacturer. Yes.

In the present invention, by preparing a tablet containing isomalt (trade name: galen IQ, manufactured by Palatinit), which is a novel sugar-based excipient, sufficient tablet hardness is maintained while maintaining high disintegration. In addition, the present invention provides a method capable of producing a fast disintegrating tablet excellent in productivity even in general production facilities. In other words, by replacing with lactose or corn starch that has been conventionally used as an excipient for tablets, it is possible to prepare tablets with high functionality and high added value.

Examples of sugar alcohols having a similar function other than isomalt include D-mannitol, sorbitol, erythritol, etc. Isomalt is characterized by high hardness and rapid disintegration characteristics, especially in tableting under low pressure. It is. Therefore, in the case of a prescription in which tablet hardness tends to decrease or when there is a problem in disintegration, significant improvement can be expected by replacing the excipient with isomalt.

Isomalt is optimal when tableting is required at a low tableting pressure, for example when there is a concern about the inactivation of active ingredients in the tablet due to the tableting pressure, and the load on the tableting device itself due to the high pressure is high. Since it can avoid, it is preferable on production.

A tablet that contains isomalt as a main ingredient in a tablet and that contains an active ingredient and a disintegrant at an appropriate ratio is compressed by a rotary tableting machine to provide a fast disintegrating tablet that has no practical problems. it can.

For example, with a formulation in which isomalt is 88% by weight, croscarmellose sodium is 2% by weight, and crystalline cellulose is 10% by weight, a disintegration time of 20 seconds or less and a hardness of 40 N or more can be obtained. In addition, even if the lubricant, which is indispensable in the dry tableting process, for example, the proportion of magnesium stearate is 0.125% by weight (outer percentage), smooth production can be performed in the rotary tableting machine.

According to the present invention described in claims 1 to 3, by containing isomalt in a high content, even if tableting is performed at a low pressure (for example, 400 kgf / 杵, 8 mm tablet), tablet hardness that causes no practical problems is maintained. In the formulation containing croscarmellose sodium and crystalline cellulose, a formulation capable of continuously and stably producing tablets even with a smaller amount of magnesium stearate than usual, for example, 0.125% by weight can be provided. As a result, a tablet having a disintegration time of 20 seconds or less and a tablet hardness of 40 N or more could be obtained. Thus, a highly functional pharmaceutical solid preparation can be provided in preparations such as intraoral rapidly disintegrating tablets containing isomalt and granules containing isomalt.

The tablet produced according to the present invention disintegrates rapidly and can have sufficient hardness, but the content of isomalt is preferably 50 to 95%, more preferably 70 to 95% in the tablet. .

As content of an active ingredient, 0.1 to 50% is preferable in a tablet, More preferably, it is 1 to 30%.

As content of a disintegrating agent, 1-10% in a tablet is preferable, More preferably, it is 2-5%.

The present invention will be specifically described with reference to examples. The ingredients used to make the tablets for Example 1 are shown in Table 1.

In Example 1-1, in addition to isomalt for direct hitting (trade name: galen IQ721, manufactured by Palatinit), croscarmellose sodium (trade name: croscalmerdon, manufactured by Mingtai Chemical Co., Ltd.), crystalline cellulose, (Product name: Seldon, manufactured by Mingtai Chemical Co., Ltd.) was added to make a prescription of fast disintegrating tablets.

In Example 1-2, disintegrant crospovidone (trade name: Polyplastidone INF-10, ISP Japan) was added to isomalt for direct compression to prepare a fast disintegrating tablet. All formulations of Example 1 were tableted with 0.5% by weight of magnesium stearate (Mallinckrodt) added as a lubricant.

Furthermore, in order to produce a rapidly disintegrating tablet that disintegrates rapidly, the formulation of Example 2 was examined, and the components are shown in Table 2. In Example 2, the amount of lubricant that delays disintegration was decreased, and 0.125% by weight of lubricant corresponding to one-fourth of the concentration normally used was added to make tablets.

A high-speed rotary tableting machine (Clean Press Correct HUK-12AW, manufactured by Kikusui Seisakusho) was used as a tableting machine for tableting. The shape of the tablet was an R tablet having a diameter of 8 mm, and the average weight was 180 mg. The raw material supply method was an open feed shoe, and the tableting speed was 20 rpm. The tableting pressure was 300 kgf / 杵, 400 kgf / 杵, and 500 kgf / 杵.

The following test was done about the tablet obtained in the Example.

In the tablet hardness test, 10 tablets out of tablets after tableting were randomly sampled, and the average of the hardness was calculated using a tablet hardness meter (PC-30, manufactured by Okada Seiko Co., Ltd.). did.

In the disintegration test, measurement was performed using a tablet disintegration tester (NH-1HM type, manufactured by Toyama Sangyo Co., Ltd.) based on the 14th revision of the Japanese Pharmacopoeia. In the test, the disintegration time of each of 6 test tablets was measured, and the average time was defined as the disintegration time.

In the tablet friability test, based on the Japanese Pharmacopoeia 14th revision reference information, the tablet friability test was performed using a tablet friability tester (TFT-120, manufactured by Toyama Sangyo Co., Ltd.). The reduction rate of the tablet weight after the test was defined as the tablet friability (%) based on the weight charged into the testing machine.

For the tablet weight deviation test, 10 tablets out of tablets after tableting were randomly sampled to determine the weight deviation. The CV value (%) was calculated and the filling variation of the tableting machine into the die was examined.

The results of the tablet hardness test are shown in Table 3. In Example 1 and Example 2-1, when tableting is performed at 400 kgf / 杵, the average tablet hardness exceeds 60 N, and generally, problems such as cracking do not occur when taking out the tablet from the PTP sheet. It was possible to secure a tablet hardness of 50 N or more. In Example 2-2, tablets were not formed on the high-pressure side, making tableting difficult.

The results of the tablet disintegration test are shown in Table 4. The disintegration time was measured as an average of 17.5 seconds when tableting was performed at 300 kgf / 杵 in Example 2-1, and sufficiently quick disintegration was obtained. Even when the tableting pressure of Example 2-1 was 400 kgf / 杵, the disintegration time was approximately 30 seconds. It can be said that fast disintegration is achieved for these two conditions.

Table 5 shows the results of the tablet friability test. In the formulation using Example 1, the best results were seen. Stable results were obtained with a friability of 0.1% or less. If the friability does not exceed 0.5%, it is unlikely to be a problem in production. The formulations of Example 1 and Example 2-1 were confirmed to have sufficient properties with respect to tablet friability.

The results of the tablet weight deviation test are shown in Table 6. In Examples 1 and 2-1, good results were seen. A good result with a weight deviation of about 1.0% CV was stably obtained. In Example 2, a slightly higher result was obtained than in Example 1, but it is unlikely that this level would be a problem in production. It was confirmed that the characteristics relating to the weight deviation of the tablet can be sufficiently retained.

Orally disintegrating tablets

Preparations for use (dry syrup preparations, etc.)

Tablets that require low-pressure tableting when manufacturing tablets

Claims (3)

Isomalt, which is a mixed composition of 6-O-α-D-Glucopyranosyl-D-sorbitol (1,6-GPS) and 1-O-α-D-Glucopyranosyl-D-mannitol dihydrate (1,1-GPM) A method for producing a tablet having a high content, which can obtain a high tablet hardness even when tableted at a low pressure, and also has a rapid disintegration property. Isomalt, which is a mixed composition of 6-O-α-D-Glucopyranosyl-D-sorbitol (1,6-GPS) and 1-O-α-D-Glucopyranosyl-D-mannitol dihydrate (1,1-GPM) Containing a high content, and further containing an appropriate amount of additives such as active ingredients, disintegrants, crystalline cellulose, etc., enables stable and stable tableting production even with a small amount of lubricant, for example, 0.125% by weight. This is a technique for producing tablets that are capable of high tablet hardness and that have rapid disintegration. Isomalt, which is a mixed composition of 6-O-α-D-Glucopyranosyl-D-sorbitol (1,6-GPS) and 1-O-α-D-Glucopyranosyl-D-mannitol dihydrate (1,1-GPM) Contains a pharmaceutical solid preparation. For example, tablets, granules, fine granules, capsules, and dry syrup preparations used by dissolving at the time of use.