JP2011246428A - Orally disintegrating medicine and production method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an orally disintegrating medicine, having a suitable function for handling of tablets and keeping the function while being stored.SOLUTION: The orally disintegrating medicine is produced by mixing sugar or sugar alcohol with a disintegrator and wet granulating by using an aqueous solution of a powdered and reduced maltose starch syrup.

Description

  The present invention is a pharmaceutical that rapidly disintegrates in the oral cavity, has an appropriate function in handling, and can maintain the function even during storage, and a method for producing the same About.

  In recent years, orally disintegrating tablets have been developed for the elderly and children who have weak swallowing power, and who are busy and do not have water. The importance of is increasing.

  However, since it is designed to be disintegrated with a small amount of saliva, when it is packaged in a single dose (packaging), it has only a hardness that would break in the packaging machine, and then packaged It is also known that some tablets absorb moisture and cause cracks and cracks during storage until the product is taken.

  It is also true that many attempts have been made to improve such a situation. For example, “(a) a main component selected from water-soluble saccharides, sugar alcohols or mixtures thereof, and (b) water-insoluble low A step of preparing a mixed powder with a hygroscopic polymer pharmaceutical additive and (c) an aqueous dispersion of a water-insoluble hydrophilic pharmaceutical additive; respectively; (d) medicinal effect to at least one of the prepared mixed powder and aqueous dispersion A step of adding ingredients; a step of granulating the mixed powder using the aqueous dispersion; and a step of mixing and compression-molding the resulting granule with at least a lubricant, and thereby to the atmosphere without packaging Method for obtaining an orally disintegrating tablet whose hardness reduction when exposed is within an acceptable range "(Patent Document 1) and" the following components (A), (B) and (C): (A) " Hydroxypropyl starch 40 ~ 0 wt%, have been reported (B) obtained by spray drying D- mannitol 15 to 50% by weight, (C) orally fast disintegrating formulations containing a physiologically active substance. "(Patent Document 2).

JP 2006-199632 A JP-A-2005-306770

  The present invention is a pharmaceutical that rapidly disintegrates in the oral cavity, has an appropriate function for handling, and provides an orally disintegrating tablet that can maintain its function even during storage. is there.

Furthermore, it is establishing the manufacturing method of the above-mentioned orally disintegrating tablet using the manufacturing method generally performed without using a difficult technique and a special apparatus.

  According to the present invention, as a result of diligent research to solve the above problems, a granulated product obtained by wet granulating a mixture of sugar or sugar alcohol and a disintegrant using an aqueous solution of powdered reduced maltose water candy is used. Thus, it was found that by producing a tablet, a tablet having an appropriate hardness and good disintegration property in the oral cavity can be produced. Furthermore, it was found that when this tablet was stored at a high humidity of 75% relative humidity, it did not generate any cracks or cracks during handling, and an appropriate hardness could be maintained.

  The present invention also provides an orally disintegrating tablet characterized by using a granulated product obtained by wet granulating a mixture of sugar or sugar alcohol and a disintegrant using an aqueous solution of powdered reduced maltose water candy. A manufacturing method is provided.

  The active ingredient used for this invention may use what is used as a pharmaceutical, The content is 90 mass% or less normally, Preferably it is 50%, More preferably, it is 25% or less.

  The particle size of the granule containing the active ingredient is usually 300 μm or less, preferably 250 μm or less, more preferably 200 μm or less.

  Any sugar or sugar alcohol may be used in the present invention, and examples thereof include lactose, D-mannitol, sucrose, sorbitol, xylitol, and erythritol.

  The average particle size of the sugar or sugar alcohol is usually 100 μm or less, preferably 70 μm or less, more preferably 50 μm or less.

  The orally disintegrating tablet of the present invention may contain various additives generally used for tablet production.

  The granule containing the active ingredient of the present invention is prepared by a process such as granulation in a fluidized bed granulator, stirring granulator, extrusion granulator, dry granulator, coating in a coating machine, or the like. is there.

  The mixing step of the present invention can be performed using, for example, a fluidized bed granulator, a stirring granulator, a diffusion mixer, or the like.

  The tableting process of the present invention can be performed using, for example, a single-shot tableting machine or a rotary tableting machine.

  The orally disintegrating tablet obtained in the present invention disintegrates in the oral cavity within 30 seconds, and the hardness is usually 40N, preferably 50N, more preferably about 70N.

  Furthermore, when the orally disintegrating tablet obtained in the present invention is stored under a high humidity of 75% relative humidity, the hardness is reduced, but it is maintained at about 30 N which does not cause a problem in handling.

  Therefore, the orally disintegrating tablet obtained by the present invention can be comfortably taken by patients with weak swallowing force such as elderly people and children, and even patients who are busy and do not have water, and are packaged in medical institutions. It can also be used comfortably when the patient stores and uses the packaged product thereafter.

  The orally disintegrating tablet of the present invention disintegrates rapidly in the oral cavity within 30 seconds, has an appropriate hardness for handling the tablet, and can maintain an appropriate hardness during storage. it can.

  In addition, the production of the orally disintegrating tablet of the present invention can be performed using a fluidized bed granulator or a stirring granulator, a drying by a dryer, or a mixer without using difficult techniques or special equipment. It can carry out using the method generally performed like mixing and tableting with a rotary type tableting machine.

  About an orally disintegrating tablet, it disintegrates rapidly in the oral cavity within 30 seconds, has an appropriate hardness for handling the tablet, and can maintain an appropriate hardness during storage. A tablet and its manufacturing method were realized.

  A fluidized bed granulator was charged with 4 g of mosapride citrate, 128 g of D-mannitol and 4.5 g of crospovidone and mixed for 1 minute. Next, a solution obtained by dissolving 6.8 g of powdered reduced maltose water candy in 60.2 g of water was sprayed and dried. After granulating the obtained granulated product, 4.5 g of a spray-dried suspension of synthetic aluminum silicate / hydroxypropyl starch / crystalline cellulose and 2.2 g of magnesium stearate were mixed. A tablet having a diameter of 8 mm and a mass of 200 mg was obtained using a single-type tableting machine.

  In a fluidized bed granulator, 130.3 g of D-mannitol and 4.5 g of crospovidone were added and mixed for 1 minute. Next, a solution obtained by dissolving 4.5 g of powdered reduced maltose water candy in 40.5 g of water was sprayed and dried. After sizing the resulting granulated product, mosapride citrate hydrate, 4.5 g of spray-dried suspension of synthetic aluminum silicate / hydroxypropyl starch / crystalline cellulose and 2.2 g of magnesium stearate are mixed did. A tablet having a diameter of 8 mm and a mass of 200 mg was obtained using a single-type tableting machine.

  Lactose hydrate 400 g is put into a rolling fluidized bed coating machine, 100 g of hypromellose is dissolved in 384 g of water and 896 g of absolute ethanol, and a liquid in which 211.6 g of mosapride citrate hydrate is suspended is sprayed and dried. Granule 1 was obtained.

200 g of Granule 1 was put into a rolling fluidized bed coating machine, and a solution obtained by dissolving 3.33 g of aminoalkyl methacrylate copolymer RS and 0.67 g of triethyl citrate in 316 g of absolute ethanol was sprayed and dried to obtain Granule 2.

  In a fluidized bed granulator, 21.5 g of granule 2, 117.3 g of D-mannitol and 1.5 g of crospovidone were added and mixed for 1 minute. Next, a solution obtained by dissolving 3 g of powdered reduced maltose water candy in 40 g of water was sprayed and dried. After granulating the obtained granulated product, 4.5 g of a spray-dried suspension of synthetic aluminum silicate / hydroxypropyl starch / crystalline cellulose and 2.2 g of magnesium stearate were mixed. A tablet having a diameter of 8 mm and a mass of 200 mg was obtained using a single-type tableting machine.

  In a fluidized bed granulator, 156.4 g of D-mannitol and 2 g of crospovidone were added and mixed for 1 minute. Next, a solution obtained by dissolving 4 g of powdered reduced maltose water candy in 40 g of water was sprayed and dried. After sizing the obtained granulated product, 28.6 g of granule 2 of Example 3, 6 g of a spray-dried suspension of synthetic aluminum silicate / hydroxypropyl starch / crystalline cellulose, and magnesium stearate (Taihei Chemical) 3 g) was mixed. A tablet having a diameter of 8 mm and a mass of 200 mg was obtained using a single-type tableting machine.

Comparative Example 1

  In the method of Example 1, no crospovidone was added.

Comparative Example 2

  In the method of Example 1, powdered reduced maltose water candy was not added.

Comparative Example 3

  The powder used in Example 1 was directly mixed, and a tablet having a diameter of 8 mm and a mass of 200 mg was obtained using a single-type tableting machine.

Test example 1

Evaluation of Oral Disintegration A tablet was placed in the oral cavity of three healthy adult men, and the time until complete disintegration with saliva alone was evaluated. The oral disintegration time was rated as o for 30 seconds or less and x for 30 seconds or more.

Test example 2

Measurement of hardness reduction Tablets were placed as they were in a thermo-hygrostat with a temperature of 30 ° C. and a relative humidity of 75%, and the hardness decrease over time was evaluated. The hardness meter used was a Kiya-type digital hardness meter, and was evaluated with 10 tablets.

  Table 1 shows the evaluation results of Test Examples 1 and 2 of Examples 1 to 6 and Comparative Examples 1 to 3.

  From the results shown in Table 1, in Examples 1 to 4, the oral disintegration was good and the hardness was less reduced. On the other hand, Comparative Example 1 was not good in oral disintegration. In Comparative Example 2, the hardness did not appear from the time of manufacture, and the hardness decreased significantly. In Comparative Example 3, the disintegration property in the oral cavity was not good and the hardness was remarkably reduced. The effectiveness of the present invention was confirmed.

Claims (3)

  It is produced by wet granulation using an aqueous solution of powdered reduced maltose water candy mixed with sugar or sugar alcohol, and the active ingredient or granules containing the active ingredient are directly mixed with the granulated product. Or an orally disintegrating tablet produced by adding when granulating.   The orally disintegrating tablet according to claim 1, comprising 5 to 90% by weight of sugar or sugar alcohol.   The orally disintegrating tablet according to claim 1, wherein the amount of disintegrant added during wet granulation is 10% by weight or less.