Method for improving dissolvability of anticoagulant
A technology of additives and disintegrants, which is applied in the field of dissolution improvement of anticoagulants, and can solve problems such as solubility decline
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Examples
Embodiment 1
[0154] (granulation)
[0155] Under each condition described in Table 1, 1010 g of compound Ia, 2480 g of sieved mannitol (Mannit P, manufactured by TOWA-KASEI Co., Ltd.), 1050 g of pregelatinized starch (PCS PC-10, manufactured by Asahi Kasei Chemicals Corp.) and 267.5 g of crospovidone (Polyplasdone INF-10, manufactured by ISP) with 7 w / v% hydroxypropyl cellulose (HPC-L, manufactured by Nippon Soda Co., Ltd. ) of 2179 mL aqueous solution for fluidized bed granulation. In the fluidized bed granulation, a fluidized bed granulator (FLO-5, manufactured by Freund Corp.) was used
[0156] [Table 1]
[0157]
[0158] (dry).
[0159] Next, the granules thus granulated under the respective conditions were dried so that the water content of the granules after drying was 4.0% or more (A-1 and B-1 in Table 2), 2.0% or more and less than 4.0% (A in Table 2). -2 and B-2), or less than 2.0% (A-3 and B-3 in Table 2)
[0160] [Table 2]
[0161]
[0162] (compression).
[0163] 1...
Embodiment 2
[0175] The dissolution profile of Compound I from each tablet in pH 6.8 phosphate buffer was tested varying the maximum water content of the granules during granulation.
[0176] 7.274 kg of compound Ia, 17.85 kg of sieved mannitol (Mannit P, manufactured by TOWA-KASEI Co., Ltd.), 7.56 kg of pregelatinized starch (PCS PC-10, manufactured by Asahi Kasei Chemicals Corp.) and 1.926 kg Crospovidone (Polyplasdone INF-10, manufactured by ISP) was fluidized with 15.5 L of an aqueous solution containing 7 w / v% hydroxypropylcellulose (HPC-L, manufactured by Nippon Soda Co., Ltd.) Granulate. In fluidized bed granulation, FLO-30 or FLO-30SJ (manufactured by Freund Corp.) is used. The air inlet temperature, liquid spraying speed and spraying air pressure were set to 90 °C, 250 mL / min and 0.25 MPa, respectively. As a result, granules with a maximum water content of 9.6% of the granules during granulation were successfully prepared. Moreover, keeping the granule preparation ratio unchang...
Embodiment 3
[0179] 20.2 kg of compound Ia, 49.6 kg of sieved mannitol (PEARITOL 50C, manufactured by Roquette Corp.), 21 kg of pregelatinized starch (PCS PC-10, manufactured by Asahi Kasei Chemicals Corp.) and 5.35 kg of crospovidone (Polyplasdone INF-10, manufactured by ISP) Fluidized bed granulation was performed with 43.57 kg of an aqueous solution containing 7 w / w% hydroxypropylcellulose (HPC-L, manufactured by Nippon Soda Co., Ltd.). In fluidized bed granulation, WSG-120 (manufactured by Powrex Corp.) was used. The inlet temperature, liquid spraying speed, and air injection volume were set at 90 °C, 700 g / min, and 750 NL / min, respectively, so that the maximum water content (%) of the granules during granulation was below 10%.
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Abstract
Description
Claims
Application Information
- IPC
- A61K31/444; A61K9/16; A61K9/20; A61K9/32; A61K9/36; A61K47/10; A61K47/32; A61K47/36; A61K47/38; A61P7/02
- CPC
- A61K9/1652; A61K9/2077; A61K31/444; A61K9/1635; A61K9/1623; A61K9/1694; A61P7/02
- Inventors
- 釜田信; 关口学