JP2000086506A - Production of granule containing teprenone - Google Patents

Abstract

PROBLEM TO BE SOLVED: To efficiently obtain the subject granules by allowing granules to adsorb teprenone, wherein the granules are obtained by dissolving lactose, mannitol, silicon dioxide and a water-soluble binder in water and subsequently spray- drying the solution. SOLUTION: The granules containing teprenone are preferably obtained by dissolving (A) 500-1,000 pts.wt. of lactose, (B) 700-1,500 pts.wt. of mannitol, (C) 100-500 pts.wt. of silicon dioxide and (D) 50-150 pts.wt. of a water-soluble binder (for example, hydroxypropylcellulose) in 2,000 pts.wt. of water, spray- drying the obtained solution in 100-300 deg.C hot air to prepare granules, and subsequently allowing the granules to adsorb (E) the teprenone (chemical name: 6,10,14,18-tetramethyl-5,9,13,17-nonadecatetraene-2-one). The component E is preferably adsorbed in an amount of 100 pts.wt. to 700-1,500 pts.wt. of the granules obtained by the above spray drying treatment.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing teprenone-containing granules.

[0002]

Background of the Invention and Prior Art Teprenone is widely used as a therapeutic agent for gastritis and gastric ulcer. Since teprenone is an oily substance that is liquid at normal temperature, it is made into fine granules or capsules by adsorbing teprenone on a powder having an oil-absorbing ability during formulation. To make it into fine granules,
Lactose, excipients such as starch are mixed by a tumbling granulator or a fluidized bed granulator, and granulation is performed while gradually adding an aqueous solution in which a binder such as polyvinylpyrrolidone is dissolved. Is gradually added for adsorption.

[0003]

The method used in the prior art has the advantage that granulation of excipients and adsorption of teprenone can be performed continuously by the same preparation machine, but the size of the preparation machine is limited. However, there is a problem in terms of cost reduction due to the limited amount of production per operation. As a result of intensive studies on a manufacturing method for reducing the cost while maintaining the same quality as that of the current teprenone-containing fine granule, the present inventors have found that the problems can be solved by the following method, and have invented the present invention.

[0004]

DISCLOSURE OF THE INVENTION The present invention comprises a method of adsorbing teprenone to granules obtained by dissolving lactose, mannitol, silicon dioxide and a water-soluble binder in water and then spray-drying the resulting mixture. This is a method for producing granules. Teprenone in the present invention is a chemical name of 6,10,14,18-tetramethyl-5,9,13,17-nonadecatetraen-2-one, and usually, cis trans at the 5-position is 3: 2. In the present invention, there are eight types of geometric isomers of teprenone, and isomers are not particularly limited in the present invention. Since Teprenone is unstable to oxidation, it is preferable to add an antioxidant such as Vitamin E.

[0005] Lactose and mannitol in the present invention are general-purpose excipients listed in the Japanese Pharmacopoeia, and are readily available commercially. Silicon dioxide is listed in the Japanese Pharmacopoeia as light anhydrous silicic acid, and can be easily obtained under the trade name “thyricia” or the like. The binder plays a role of “paste” when granulating excipients and the like. In the present invention, a water-soluble binder is preferable, and specifically, hydroxypropyl cellulose, polyvinylpyrrolidone, hydroxy Propylmethylcellulose and the like can be mentioned.

In the present invention, the concentration of each component in the spray-dried liquid is 500 to 100 parts by weight of lactose per 2,000 parts by weight of water.
0 parts by weight, 700-1500 parts by weight of mannitol, 100-500 parts by weight of silicon dioxide, and 50-
It is 150 parts by weight. A solution containing each component can be easily obtained by weighing out a desired amount and then dissolving and suspending in water.

The spray drying method in the present invention is not particularly limited, and any of a disk method, a nozzle method and the like can be used. The temperature of the hot air introduced into the spray dryer is not particularly limited, but is usually about 100 ° C to about 300 ° C. The temperature is
It can be appropriately selected to obtain the spray amount of the solution and the desired loss on drying of the spray-dried granules. The outlet temperature of hot air from the spray dryer (exhaust air temperature) is usually about 100C to about 150C.
Spray dryers are more advantageous for cost reductions,
Further, it is more advantageous to use an apparatus that can continuously spray-dry. In order to adsorb teprenone to the granules obtained by spray drying, a commonly used apparatus such as a fluidized bed apparatus is used. The ratio of teprenone to spray-dried granules is 1
The spray-dried granules are 700 to 1500 parts by weight based on 00 parts by weight.

[0008] In the present invention, granules mean particles larger than a powder having good flowability, and the particle size thereof is not particularly limited. For example, granules in the Japanese Pharmacopoeia serve as a standard of the granules of the present invention. In the present invention, so-called fine granules are also included in the granules.

The method for producing teprenone-containing granules in the present invention will be described with reference to examples. 100 g of hydroxypropylcellulose as a water-soluble binder, 250 g of Sylysia (trade name) as a silicic acid hydrate, D-mannitol 11
After dissolving and suspending 20 g and lactose 100 g in 2200 g of water, it is spray-dried at an exhaust air temperature of 120 to 150 ° C. to obtain granules. Next, the obtained granules are transferred to a fluidized bed dryer, and teprenone is sprayed to obtain teprenone-containing granules.

[0010]

The granules containing teprenone according to the present invention can be produced at lower cost than the granules prepared by the conventional method. This is because the method according to the present invention has a small number of steps, a large scale, and a continuous production of spray-dried granules. For example, in the granules according to the conventional method, in order to obtain granules before adsorption of teprenone, mixing, primary granulation, secondary granulation,
Although seven steps of drying, sizing, crushing, and sizing were necessary, in the present invention, three steps of dissolution / suspension, spray drying, and sieving were sufficient, and the production scale was 1 in the conventional method. Although the weight was about 150 kg per treatment, the spray-dried granules according to the present invention can be produced in an amount of 2000 kg or more at one time, and continuous production is possible depending on the device. In the present invention, since the step of obtaining the spray-dried granules and the step of adsorbing teprenone are not continuous, and a separate manufacturing machine must be used, no such manufacturing method has been attempted in the past.
The present inventors have intensively studied a more efficient manufacturing method, and the discontinuous manufacturing method that has not been attempted conventionally is superior to the conventional method in addition to man-hours, costs, and the like, In addition, they found that the quality was the same, and completed the present invention.

[0011]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the present invention is limited thereto.

Example 1 100 kg of hydroxypropylcellulose, 250 kg of anhydrous silicic acid anhydride (trade name: Sylysia), 1125 kg of D-mannitol and 712 kg of lactose were mixed with 2187 k of water.
g, and were spray-dried using a spray dryer 3SD machine (nozzle type). During spray drying, the solution continued to be stirred, the spray speed was 400 kg / h, and the exhaust air temperature was about 120 ° C. The obtained dried powder is sieved into a 30 mesh to 100 mesh product by a vibration sieve,
90 kg thereof was put into a fluidized bed dryer, and 10 kg of teprenone containing 0.2% of vitamin E was adsorbed while flowing to obtain teprenone-containing granules according to the present invention.

Claims (3)

[Claims] [1] A granule obtained by dissolving lactose, mannitol, silicon dioxide and a water-soluble binder in water and then spray-drying,
A method for producing teprenone-containing granules, wherein teprenone is adsorbed. 2. Lactose 500 to 1 with respect to 2000 parts by weight of water.
000 parts by weight, 700-1500 parts by weight of mannitol,
100 to 500 parts by weight of silicon dioxide and water-soluble binder 5
2. The method for producing teprenone-containing granules according to claim 1, wherein 0 to 150 parts by weight are dissolved. 3. Granules 700 to 150 obtained by spray drying.
2. A method for adsorbing 100 parts by weight of teprenone to 0 parts by weight.
Or the method for producing teprenone-containing granules according to 2.