DISINTEGRATIVE PARTICLE COMPOSITION INCLUDING PULVERIZED LACTOSE OR GRANULATED LACTOSE

Abstract

The purpose of the present invention is to provide a new disintegrative particulate composition having an optimal balance between the tablet hardness and disintegrability that are mutually opposing properties, and disintegrating tablets for pharmaceuticals and various kinds of foods comprising said composition.

The present invention relates to a disintegrative particulate composition comprising milled lactose and/or granulated lactose as an excipient, and to a disintegrating tablet for pharmaceuticals or foods, comprising the disintegrative particulate composition, especially the tablet having tablet hardness of from 20 to 200 N, and disintegration time in water of from 1 to 60 sec.

Claims

1. A disintegrative particulate composition comprising milled lactose and/or granulated lactose as an excipient.

2. The disintegrative particulate composition according to claim 1, further comprising micro-fibrillated cellulose.

3. The disintegrative particulate composition according to claim 1, further comprising starch and processed starch as a disintegrator component.

4. The disintegrative particulate composition according to claim 3, wherein the starch is corn starch, potato starch, waxy corn starch, α-starch and/or partially α-starch.

5. The disintegrative particulate composition according to claim 4, wherein the starch is corn starch and/or partially α-starch.

6. A disintegrating tablet for pharmaceuticals or foods, comprising the disintegrative particulate composition according to claim 1.

7. The disintegrating tablet according to claim 6, which has tablet hardness of from 20 to 200 N, and disintegration time in water of from 1 to 60 sec.

8. The disintegrating tablet according to claim 7, which has tablet hardness of from 70 to 120 N, and disintegration time in water of from 15 to 30 sec.

9. The disintegrative particulate composition according to claim 2, further comprising starch and processed starch as a disintegrator component.

Description

EXAMPLE 1

Production of Disintegrative Particulate Composition 1

[0083] 270 g of milled lactose (GranuLac, MEGGLE Co., LTD), 80 g of corn starch (NIHON SHOKUHIN KAKO CO., LTD.) and 20 g of partially α-starch (PCS PC-10, Asahi Kasei Chemicals Corp.) were charged to the fluidized-bed granulator (FL-LABO, Freund Corporation), and 600 g of 5% suspension of wet material of micro-fibrillated cellulose (“CELISH FD-200L”, Daicel FineChem Ltd.) in water was sprayed onto the resulting mixture at a rate of 12 g/minute, so that the mixture was granulated to thereby obtain disintegrative particulate composition 1. The resulting disintegrative particulate composition 1 had the following values for physical properties: (1) an average particle size of 103 microns and (2) a water content of 3.1% by weight.

Production of Orally Disintegrating Tablet 1

[0084] 99.5 parts by weight of the resulting disintegrative particulate composition 1 was mixed with 0.5 parts by weight of magnesium stearate (Taihei Chemical Industrial Co. Ltd.). The mixture was then subjected to tableting at a tablet compression force of from 6 to 8 Kn with a simple tableting machine (HANDTAB-100, ICHIHASHI-SEIKI Co., Ltd.) to thereby obtain an angled-corner flat tablet having a diameter of 8.0 mm and a weight of 250 mg.

EXAMPLE 2

Production of Disintegrative Particulate Composition 2

[0085] 270 g of granulated lactose (FlowLac, MEGGLE Co., LTD), 80 g of corn starch (NIHON SHOKUHIN KAKO CO., LTD.) and 20 g of partially α-starch (PCS PC-10, Asahi Kasei Chemicals Corp.) were charged to the fluidized-bed granulator (FL-LABO, Freund Corporation), and 600 g of 5% suspension of wet material of micro-fibrillated cellulose (“CELISH FD-200L”, Daicel FineChem Ltd.) in water was sprayed onto the resulting mixture at a rate of 12 g/minute, so that the mixture was granulated to thereby obtain disintegrative particulate composition 2. The resulting disintegrative particulate composition 2 had the following values for physical properties: (1) an average particle size of 169 microns and (2) a water content of 2.3% by weight.

Production of Orally Disintegrating Tablet 2

[0086] The resulting disintegrative particulate composition 2 was subjected to tableting in the same manner as Example 1 to thereby obtain an angled-corner flat tablet having a diameter of 8.0 mm and a weight of 250 mg.

EXAMPLE 3

Production of Disintegrative Particulate Composition 3

[0087] 54 g of sieved lactose (SpheroLac, MEGGLE Co., LTD), 216 g of milled lactose (GranuLac, MEGGLE Co., LTD), 80 g of corn starch (NIHON SHOKUHIN KAKO CO., LTD.) and 20 g of partially α-starch (PCS PC-10, Asahi Kasei Chemicals Corp.) were charged to the fluidized-bed granulator (FL-LABO, Freund Corporation), and 600 g of 5% suspension of wet material of micro-fibrillated cellulose (“CELISH FD-200L”, Daicel FineChem Ltd.) in water was sprayed onto the resulting mixture at a rate of 12 g/minute, so that the mixture was granulated to thereby obtain disintegrative particulate composition 3. The resulting disintegrative particulate composition 3 had the following values for physical properties: (1) an average particle size of 136 microns and (2) a water content of 3.0% by weight.

Production of Orally Disintegrating Tablet 3

[0088] The resulting disintegrative particulate composition 3 was subjected to tableting in the same manner as Example 1 to thereby obtain an angled-corner flat tablet having a diameter of 8.0 mm and a weight of 250 mg.

EXAMPLE 4

Production of Disintegrative Particulate Composition 4

[0089] 135 g of sieved lactose (SpheroLac, MEGGLE Co., LTD), 135 g of milled lactose (GranuLac, MEGGLE Co., LTD), 80 g of corn starch (NIHON SHOKUHIN KAKO CO., LTD.) and 20 g of partially α-starch (PCS PC-10, Asahi Kasei Chemicals Corp.) were charged to the fluidized-bed granulator (FL-LABO, Freund Corporation), and 600 g of 5% suspension of wet material of micro-fibrillated cellulose (“CELISH FD-200L”, Daicel FineChem Ltd.) in water was sprayed onto the resulting mixture at a rate of 12 g/minute, so that the mixture was granulated to thereby obtain disintegrative particulate composition 4. The resulting disintegrative particulate composition 4 had the following values for physical properties: (1) an average particle size of 142 microns and (2) a water content of 3.2% by weight.

Production of Orally Disintegrating Tablet 4

[0090] The resulting disintegrative particulate composition 4 was subjected to tableting in the same manner as Example 1 except tableting at a tablet compression force of from 8 to 10 kN to thereby obtain an angled-corner flat tablet having a diameter of 8.0 mm and a weight of 250 mg.

COMPARATIVE EXAMPLE 1

[0091] 270 g of sieved lactose (SpheroLac, MEGGLE Co., LTD), 80 g of corn starch (NIHON SHOKUHIN KAKO CO., LTD.) and 20 g of partially α-starch (PCS PC-10, Asahi Kasei Chemicals Corp.) were charged to the fluidized-bed granulator (FL-LABO, Freund Corporation), and 600 g of 5% suspension of wet material of micro-fibrillated cellulose (“CELISH FD-200L”, Daicel FineChem Ltd.) in water was sprayed onto the resulting mixture at a rate of 12 g/minute, so that the mixture was granulated to thereby obtain disintegrative particulate composition. The resulting disintegrative particulate composition had the following values for physical properties: (1) an average particle size of 157 microns and (2) a water content of 2.7% by weight.

Production of Orally Disintegrating Tablet

[0092] 99.5 parts by weight of the resulting disintegrative particulate composition 1 was mixed with 0.5 parts by weight of magnesium stearate (Taihei Chemical Industrial Co. Ltd.). The mixture was then subjected to tableting at a tablet compression force of from 8 to 10 kN with a simple tableting machine (HANDTAB-100, ICHIHASHI-SEIKI Co., Ltd.) to thereby obtain an angled-corner flat tablet having a diameter of 8.0 mm and a weight of 250 mg.

Evaluation of the Test of Hardness and Disintegration Time

[0093] The above Examples and Comparative Example were measured with respect to their hardness and disintegration time in water based on the following conditions/methods. The test results of hardness and disintegration time are shown in Table 1.

TABLE-US-00001 TABLE 1 Orally Disintegrating Tablet Example 1 Example 2 Tablet Compression Force (kN) 6 8 6 8 Tablet Hardness (N) 74 100 61 84 Disintegration Time in Water (s) 21 24 15 18 Orally Disintegrating Tablet Example 3 Example 4 Tablet Compression Force (kN) 8 10 8 10 Tablet Hardness (N) 78 94 73 92 Disintegration Time in Water(s) 22 29 25 23 Comparative Orally Disintegrating Tablet Example 1 Tablet Compression Force (kN) 8 10 Tablet Hardness (N) 49 60 Disintegration Time in Water (s) 12 12

[0094] The results shown in Table 1 demonstrate that the orally-disintegrating tablets, which are produced by using the disintegrative particulate composition comprising the milled lactose and/or granulated lactose in place of or in addition to the conventionally-used sieved lactose, have an optimal balance between the tablet hardness and disintegrability, that is, a high tablet moldability and an excellent disintegrability, when compared with the orally-disintegrating tablets produced by using the disintegrative particulate composition comprising the sieved lactose only as lactose.

INDUSTRIAL APPLICABILITY

[0095] The present invention significantly contributes to research and development of disintegrating tablets having excellent tablet hardness and disintegrability.