JP3004758B2 - Processed starch with excellent binding and disintegration properties - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a modified starch having excellent binding and disintegration properties and a pharmaceutical composition containing the modified starch.

[0002]

2. Description of the Related Art Starches have been widely used as pharmaceutical additives having binding, disintegrating, and bulking effects, because of their ease of availability and the sense of security provided by natural products that have been used for a long time. Was. Starches are classified into three types: raw starch, physically modified processed starch, and chemically modified modified starch. Among these, processed starch exhibits various physicochemical properties by changing the degree of gelatinization, is inexpensive, and chemically chemically the same as raw starch, so it does not react with drugs. It is widely used because there is almost no. Suspending raw starch in water, heating it to boiling to form starch paste, and using it as a binder for wet granulation can be said to be the oldest processed starch use. Modified starch has been proposed.

[0003] The processed starch described in JP-B-46-21471 has a raw starch content of about 20 to 50% by weight, and is compacted at a temperature of 20 to 50 ° C by a differential roll mill and dried. It is obtained by pulverization, shows solubility in cold water in the range of about 4 to 40% by weight, the swelling power of the dry substance is about 2.5 to 12, and the free density is about 0.5. ０．７0.7 g / ml and the water content is about 9-16% of the total weight.

The modified starch described in Japanese Patent Publication No. 59-47600 is prepared by converting raw starch into a slurry, and heating the raw starch at a temperature of 50 ° C. or more and a temperature not exceeding about 10 ° C. above the gelatinization start temperature. The starch is obtained by swelling without destroying the outer shell thin film structure and then drying, having a bulk density of 0.25 g / cc or more, a cold water soluble content of less than 10% by weight, and a swelling volume of About 3 to 15 ml / g,
Water retention capacity is about 2 or more.

[0005] The modified starch described in JP-A-58-32828 is obtained by gelatinizing, cooling, and then drying raw starch, and has a swelling degree of 3.0 to 6.0. . The processed starch described in Japanese Patent Application Laid-Open No. 60-230319 is derived from a cold water-soluble granular starch obtained by treating starch with an acid, an alkali and / or an α-amylase enzyme at a temperature below the gelatinization temperature. Things.

[0006] Starch 1500 (manufactured by Nippon Colorcon Co., Ltd.) and PCS (manufactured by Asahi Kasei Kogyo Co., Ltd.) are commercially available.
And partially pregelatinized starch.

[0007]

[Problems to be solved by the invention]
The processed starch described in Japanese Patent No. 21471 has excellent binding properties when formed into tablets by the direct compression method, but has a poor ability to disintegrate tablets in water. In addition, Japanese Patent Publication No. 59-4
The modified starch described in JP-A-7600 and JP-A-58-32828 has excellent disintegratability when incorporated into tablets, granules and capsules, but binds when used in the direct compression method. Because of poor properties, it can not be blended in large quantities,
In addition, it was necessary to use another binder in combination. Further, the processed starch described in JP-A-60-2333019 is effective as a binder for tablets used in a direct compression method or a dry granulation compression method, but is manufactured under the disintegration property of tablets, especially at high molding pressure. There is a drawback that the disintegration of the tablet is impaired when tableted. As for commercially available products, Starch 1500
Shows a binding property when used in the direct compression method, but has a drawback that the disintegration time of the tablet is delayed. PCS also
When incorporated into tablets and granules, it exhibited the best disintegration properties as a modified starch, but had little function as a binder for direct compression.

[0008] As described above, in conventional processed starch,
When used in the direct tableting method or the dry granulation method, none of them satisfy the functions of binding and disintegration at the same time, and a modified starch having both functions has been desired.

[0009]

Means for Solving the Problems and Action As a result of intensive studies, the present inventor has found that a raw starch obtained by heat-treating raw starch in the presence of moisture has a water content of 8 to 15% and a cold water soluble component. It has been found that a modified starch having a ratio of less than 10% and a swelling volume of 5 to 15 ml / g has both binding and disintegrating functions when used in a direct compression method or a dry granulation compression method. Reached.

That is, the present invention provides a method for preparing raw starch in the presence of moisture.
Processed starch obtained by heat treatment, having a water content of 8 to 15%, a soluble component of cold water of less than 10%, a swelling volume of 5 to 15 ml / g, and substantially destroying starch particles.
The starch particle morphology is maintained without being
More particles exhibiting foldability than particles exhibiting birefringence
The present invention relates to a modified starch excellent in binding property and disintegration, and a pharmaceutical composition containing the modified starch. The modified starch of the present invention has a specified water content, cold water soluble content, swelling volume, and excellent binding properties, so that powders or granules are compressed into tablets using a direct compression method or a dry granule compression method. In this case, a tablet having high hardness can be obtained. Also,
When granules are formed using the dry granulation method, granules with low powdering and high strength can be obtained. At the same time, the disintegration is also excellent, so that when the preparation containing the modified starch is administered into the body, the modified starch absorbs water and swells, so that the preparation shows rapid disintegration and the drug is rapidly dissolved. I do. In addition, compared to other binders such as microcrystalline cellulose and lactose, it has good disintegration properties as well as high drug stability, and it has both binding and disintegration functions, so quality design can be simplified. Has the advantage of being easier.

Hereinafter, the present invention will be described in detail. The processed starch referred to in the present invention is obtained by subjecting raw starch to heat treatment in the presence of moisture, and has a water content of 8 to 1%.
5%, preferably 10-15%, cold water soluble less than 10%, preferably less than 5%, swelling volume 5-15 ml /
g, preferably 5 to 11 ml / g. Also preferably, the bulk density is from 0.35 to 0.65
g / ml, particularly preferably 0.4 to 0.6 g / ml, 1
00 mesh (aperture 150 μm) fraction is 50% or less,
It is particularly preferably at most 30%.

The term "modified starch" as used herein refers to one obtained by heating and drying in the presence of moisture, and does not include chemically modified starch. When the modified starch of the present invention is put into water and observed with a microscope, most of the particles are swollen, but the particle morphology of the starch is maintained, and the individual particles are identifiable. Non-birefringent starch, in which the individual particles are destroyed so as to be indistinguishable, increases the amount of soluble components in cold water, which is undesirable as described later.
When observed with a polarizing microscope, more particles exhibit non-birefringence than particles exhibit birefringence.

When the water content of the modified starch is 8% or less, the plasticity of the starch is reduced, and the elastic recovery after compression is increased. 15 moisture content
%, The plasticity of the starch increases, but it is not preferable because the moisture contained in the particles oozes out on the particle surface due to the compression, or conversely, the binding property decreases. Preferably it is 10 to 15%. Processed starch having a cold water soluble content of 10% or more has many components that absorb and dissolve in water, and when used in tablets, dissolves in disintegrating liquid and becomes sticky, slowing the penetration of the liquid into the inside of the tablet. Therefore, the disintegration is undesirably delayed. Preferably it is less than 7%. 5 ml swelling volume
If it is less than / g, the swelling due to water absorption is small, so that a sufficient force to disintegrate the tablet cannot be given. Swelling volume is 15m
In order to produce a processed starch of 1 / g or more, it is necessary to increase the degree of gelatinization, and at the same time, the amount of soluble components in cold water increases, so the upper limit is 15 ml / g. Preferably 5 to 11
ml / g.

The bulk density of the processed starch is 0.35 ml /
If it is less than g, the powder will be light and the fluidity as a powder will be poor. In addition, there is a disadvantage that the tablet after compression becomes thick. If the bulk density is 0.65 g / ml or more, the deformability at the time of compression becomes small, and the bonding property becomes small, which is not preferable. Particularly preferably, it is 0.40 to 0.60 g / ml. If the particle size of the modified starch is as large as 50% or more, the dispersion of the modified starch content among the preparations is large, and the dispersion of tablet hardness and disintegration time is large. In addition, since the tablet shows block-type disintegration, the dissolution of the drug is delayed, which is not preferable. Particularly preferably, 30%
It is as follows.

The method for producing the modified starch of the present invention will be described. This production method is a method comprising subjecting raw starch to heat treatment in the presence of moisture to swell the starch particles without destroying the particle morphology, followed by drying and, if necessary, grinding. The moisture content of the raw starch at the time of heating may be about 50% or more based on the dry weight of the raw starch. However, the temperature required for gelatinization of the raw starch is such that the moisture content is such that the starch is wet. The smaller the amount, the higher the temperature. Therefore, it is preferable to perform heat treatment in a state of having a water content of 100% or more and in a paste or slurry state, because it is advantageous in terms of energy cost. Heating in this state is preferable because all particles can be uniformly heated. In addition, it is difficult to specify the heating temperature because the gelatinization start temperature varies depending on the type of starch, the particle size, the place of production, the purification conditions, the water content of raw starch, and the like. It is preferable to treat at a temperature not higher than 10 ° C. which is higher than the gelatinization start temperature peculiar to. Incidentally, according to the "Starch Science Handbook" (supervised by Jiro Fukukoku, Asakura Shoten, 1977, p. 36), the main gelatinization start temperature of starch by the photopaste method is corn;
8 ° C., potato; 61.0 ° C., tapioca; 65.4 ° C., sweet potato; 65.8 ° C.

Next, the heating method is as follows.
After making a water suspension containing water, a method of raising the temperature by passing warm water through the jacket in a jacketed stirring tank, or a method of directly adding hot water while stirring the starch suspension and raising the temperature, or instead of warm water There are a method of blowing steam and a method of heating a starch suspension through a plate heat exchanger. The starch content may be further increased, and the mixture may be heated at a high temperature in a closed state. The heating time can be freely selected from several tens of seconds to about one hour, but if the paste or slurry is heated for a long time at a temperature approximately 10 ° C higher than the gelatinization start temperature, gelatinization will progress too much and the starch particle form Is destroyed, and the amount of soluble components in cold water increases, which is not preferable. After the completion of the predetermined heating, it is preferable to add a step of cooling the mixture to a temperature lower than the gelatinization start temperature because the quality is constant. Before, during, or after heating, the soluble starch, dextrin, and pregelatinized starch may be added so that the amount of cold water-soluble components in the starch does not exceed 10%. Also,
During or after heating, the cold water soluble content of starch is 10%
Stirring, grinding, etc. may be added to such an extent that does not exceed. Next, as for the drying method, a spray drier or a flash drier which can instantaneously dry a paste or slurry is optimal. If the solid content concentration is high, it may be dried by the above method after adding water,
It is also possible to dry as it is at a temperature lower than the gelatinization start temperature.

Raw starch which is a raw material of the processed starch of the present invention will be described. Examples of the raw starch include ground starch such as corn, wheat and rice, and underground stem starch such as potato, tapioca and sweet potato, and any of them can be used. Further, a mixture of two or more raw starches may be used. Since the degree of gelatinization of the rhizome starch varies greatly depending on the temperature, it can be used if the degree of gelatinization is controlled by strictly controlling the conditions, for example, by cooling immediately after reaching a predetermined temperature. Otherwise, the production is easy if, for example, a method using plate heat exchange is used.

Next, a pharmaceutical composition using the modified starch of the present invention will be described. The pharmaceutical composition of the present invention is a tablet, a granule or a capsule filled with granules. Tablets, granules, and capsules that are superior in both tablet (granule) hardness and disintegration time (and, consequently, drug dissolution rate) as compared with the case of using conventional processed starch. In addition, in the case of a drug with poor stability when crystalline cellulose or lactose is blended, the use of a modified starch results in a formulation with good stability. In addition, it should be considered that the formulation herein includes foods in the form of tablets, granules, and capsules such as tablets and functional foods produced by the following method. The added amount of the processed starch is affected by the amount of the drug and the size of the preparation, but is about 2 to 70% to satisfy both functions of binding and disintegration. Preferably, it is about 5 to 50%. As other additives, commonly used additives such as crystalline cellulose, lactose and corn starch can be blended.

Next, a method for producing the pharmaceutical composition will be described. First, for tablets, mixing a powder consisting of one or more drugs, modified starch and, if necessary, other additives,
A direct compression method, which is compression as it is, or a dry granule compression method in which the powder is compressed into a plate or tablet and then crushed to prepare granules and further compress the granules. Granules are prepared by a method in which granules are prepared by the above method and, if necessary, sieved. Capsules are made by filling the granules into capsules. In addition, tablets and granules are free to be film-coated or sugar-coated.

[0020]

The present invention will be described below with reference to examples. In addition, the physical property evaluation method of a processed starch and a tablet is as follows. Processed starch / moisture content (%) 10 g of sample was dried at 105 ° C. for 6 hours, and the weight loss was
Divide by and ask.

Cold water soluble matter (%) 3 g of a sample (in terms of dry matter) is added to 297 ml of pure water at 25 ° C., and the mixture is stirred at 1500 rpm for 2 minutes using an ace homogenizer (manufactured by Nippon Seiki Co., Ltd.). Next, the obtained suspension is filtered using filter paper. Take 30 ml of the filtrate,
Dry to constant weight at 05 ° C. Dry matter weight 100
The value obtained by multiplying by 0 and dividing by the weight of the sample used is defined as a soluble component in cold water.

Swelling volume (ml / g) 5 g of a sample is added and dispersed in about 80 g of pure water at 25 ° C.
The dispersion is placed in a 100 ml graduated cylinder with a stopper, and pure water is added to make 100 ml. After sealing and allowing to stand for 24 hours, the swollen sample volume is divided by 5 to obtain the swollen volume. -Bulk density (g / ml) Measure the volume of the sample when 30 g of the sample is poured little by little into a 100 ml measuring cylinder. 30 g is divided by the sample volume to obtain the bulk density.

100-mesh fraction (%) A 100-mesh fraction (100%) was measured using a low tapping type sieve manufactured by Yanagimoto Seisakusho Co., Ltd.
A mesh sieve (150 μm opening) is attached, and the sample is 30 g
Is the residue on the sieve after sieving for 30 minutes. Tablet hardness (kg) Expressed as the force at the time of breaking when a force is applied in the radial direction of the tablet using a Schroinger hardness tester manufactured by Freund Corporation. The number of repetitions is 20, and the average value is taken.

Disintegration time (minutes) The disintegration test was performed using a disintegration tester NT-2HS manufactured by Toyama Sangyo Co., Ltd. using pure water as a disintegration liquid. The number of repetitions is 6, and the average value is taken. No disks were used.

[0025]

Example 1 Corn starch (manufactured by Nisse Chemical Co., Ltd.) 1k
g was dispersed in 7 kg of hot water at 60 ° C., and the slurry was heated at a rate of 1 ° C./min while stirring, heated to 68 ° C., and 2 kg of water at about 20 ° C. was added thereto. Stopped. Next, using a small spray dryer (manufactured by Okawara Kakoki Co., Ltd.), the slurry was sprayed under the conditions of an inlet temperature of about 160 ° C. and a slurry supply speed of 7 kg / hr to obtain a processed starch (A). . Table 1 shows the physical properties of the modified starch (A).

[0026]

Example 2 A modified starch (B) was obtained in the same manner as in Example 1, except that the inlet temperature of the spray dryer was about 130 ° C. Table 1 shows the physical properties of the processed starch (B).

[0027]

[Comparative Example 1] This was carried out by a method according to Japanese Patent Publication No. 59-47600. Cornstark (manufactured by Nisseki Chemical Co., Ltd.) 1k
g was dispersed in 7 kg of warm water at 60 ° C., and the slurry was heated at a rate of 1 ° C./min while stirring, heated to 65 ° C., and then heated for 20 minutes. Then, the inlet temperature was set to about 180
The same operation as in the example was conducted except that the temperature was changed to ° C.
I got Table 1 shows the physical properties of the processed starch (C).

[0028]

Comparative Example 2 A modified starch (D) was obtained in the same manner as in Example 1 except that the inlet temperature of the spray dryer was about 115 ° C. Table 1 shows the physical properties of the processed starch (D).

[0029]

Example 3 The modified starch (C) was left in an atmosphere of 25 ° C. and 75% RH for 12 hours and 24 hours, respectively, to obtain modified starches (E) and (F). Table 1 shows the physical properties of the processed starches (E) and (F).

[0030]

Comparative Example 3 The modified starch (C) was left under the conditions of Example 3 for 72 hours to obtain a modified starch (G). Table 1 shows the physical properties of the processed starch (G).

[0031]

Example 4 A modified starch (H) was obtained in the same manner as in Example 1 except that the temperature was raised to 65 ° C and the inlet temperature of the spray dryer was set to about 150 ° C. Processed starch (H)
Table 1 shows the physical properties of the compound.

[0032]

Example 5 A modified starch (I) was obtained in the same manner as in Example 4, except that the temperature was raised to 72 ° C. Table 1 shows the physical properties of the processed starch (I).

[0033]

Comparative Example 4 A modified starch (J) was obtained in the same manner as in Example 4 except that the temperature was raised to 63 ° C. Table 1 shows the physical properties of the processed starch (J).

[0034]

Comparative Example 5 A modified starch (K) was obtained in the same manner as in Example 4 except that the temperature was raised to 80 ° C. and the temperature was maintained for 1 hour. Table 1 shows the physical properties of the processed starch (K).

[0035]

Example 6 Phenacetin (fine powder, manufactured by Yamamoto Chemical Co., Ltd.)
200 parts, crystal cellulose (Abicel PH-101, manufactured by Asahi Kasei Corporation), lactose (DMV, 10 parts)
(0 mesh) and 295 parts of magnesium stearate (manufactured by Taihei Chemical Co., Ltd.) were mixed with 100 parts of the processed starch (A) and mixed as usual, followed by a rotary tableting machine (Kikusui Seisakusho Co., Ltd.). 8) tablet diameter using Collect 12)
φ, tablets having an average tablet weight of 200 mg were obtained. Table 2 shows the physical properties of the tablets.

[0036]

Example 7 The same operation as in Example 6 was carried out except that the modified starch (B) was used. Table 2 shows the physical properties of the tablets.

[0037]

Example 8 The same operation as in Example 6 was carried out except that the modified starch (E) was used. Table 2 shows the physical properties of the tablets.

[0038]

Example 9 The same operation as in Example 6 was carried out except that the modified starch (F) was used. Table 2 shows the physical properties of the tablets.

[0039]

Example 10 Example 6 except that modified starch (H) was used.
The same operation was performed. Table 2 shows the physical properties of the tablets.

[0040]

Example 11 Example 6 except that modified starch (I) was used.
The same operation was performed. Table 2 shows the physical properties of the tablets.

[0041]

Comparative Example 6 The same operation as in Example 6 was carried out except that the modified starch (C) was used. Table 2 shows the physical properties of the tablets.

[0042]

Comparative Example 7 The same operation as in Example 6 was carried out except that the modified starch (D) was used. Table 2 shows the physical properties of the tablets.

[0043]

Comparative Example 8 The same operation as in Example 6 was carried out except that the modified starch (G) was used. Table 2 shows the physical properties of the tablets.

[0044]

Comparative Example 9 The same operation as in Example 6 was carried out except that the modified starch (J) was used. Table 2 shows the physical properties of the tablets.

[0045]

Comparative Example 10 Example 6 except that modified starch (K) was used.
The same operation was performed. Table 2 shows the physical properties of the tablets.

[0046]

Comparative Example 11 Instead of modified starch, corn starch (C
S, manufactured by Nisset Chemical Co., Ltd.) in the same manner as in Example 6. Table 1 shows the physical properties of CS, and Table 2 shows the results of tableting.

[0047]

Example 12 1.5 kg of a constarch was dispersed in 4 kg of hot water at 60 ° C, and the temperature was raised to 67 ° C. Next, transfer this to a tray and use a hot-air dryer at 40 ° C to reduce the water content to about 12%.
After drying until the mixture became ground, it was pulverized with a bantam mill (manufactured by Hosokawa Micron Corporation) to obtain a processed starch (L). Table 3 shows the physical properties of the processed starch (L).

[0048]

[Comparative Example 12] Except for drying to about 7% moisture,
The same operation as in Example 12 was performed to obtain a processed starch (M). Table 3 shows the physical properties of the modified starch (M).

[0049]

Example 13 Same as Example 4 except that before spray drying, treatment was performed at 500 rpm for 5 minutes using a batch type attritor 10S (using Mitsui Miike Kakoki Co., Ltd., 3 mmφ alumina ball). To obtain a processed starch (N). Table 3 shows the physical properties of the processed starch (N).

[0050]

Example 14 A modified starch (O) was obtained in the same manner as in Example 13, except that the treatment was carried out with a batch attritor 10S for 20 minutes. Table 3 shows the physical properties of the processed starch (O).

[0051]

Comparative Example 13 A modified starch (P) was obtained in the same manner as in Example 13 except that the batch type attritor 10S was used for 40 minutes. Table 3 shows the physical properties of the processed starch (P).

[0052]

Comparative Example 14 A modified starch (Q) was prepared in the same manner as in Comparative Example 1 except that before spray drying, the mixture was treated at 500 rpm for 2 minutes using a batch type attritor 10S (using 3 mmφ alumina balls). ) Got. Processed starch (Q)
The physical properties of are shown in Table 3.

[0053]

Example 15 A modified starch (R) was obtained in the same manner as in Example 2 except that the potato starch (manufactured by Nisseki Chemical Co., Ltd.) was used and the temperature reached was 62 ° C. Table 3 shows the physical properties of the modified starch (R).

[0054]

Example 16 The procedure of Example 2 was repeated, except that dextrin (Paindex-100, manufactured by Matsutani Chemical Co., Ltd.) was added at 3% to the solid content of the corn starch before spray drying. Then, a modified starch (S) was obtained. Table 3 shows the physical properties of the processed starch (S).

[0055]

Comparative Example 15 Technology 3 of Japanese Patent Publication No. 46-21472
Performed according to the method described in That is, after water was added to corn starch to make the water content 25%, a roll mill (manufactured by Noritake Company, NR-42A) was ground three times and dried with a hot air dryer at 60 ° C. until the water content became 8%. Next, after pulverizing with a bantam mill, the mixture was humidified to a water content of 12% to obtain a modified starch (T). Table 3 shows the physical properties of the processed starch (T).

[0056]

Comparative Example 16 Example 2 of JP-A-60-2333019
Performed according to the method described in That is, 1 kg of corn starch is dispersed in 1.5 kg of water, and 2.5 g of calcium chloride is added. The pH is adjusted to 6.0-6.5 by adding dilute sodium hydroxide solution. After adding 250 ml of a 4% α-amylase (manufactured by Kanto Chemical Co., Ltd.) solution, the temperature is raised to 55 ° C., and the reaction is carried out for 4 hours. Then adjust the pH to 2-3 with dilute hydrochloric acid.
After maintaining for 15 minutes, dilute sodium hydroxide is added again to adjust the pH to about 6. After the residue is filtered and washed, it is dried with a hot air drier, pulverized with a bantam mill, and processed starch (U)
I got Table 3 shows the physical properties of the processed starch (U).

[0057]

Comparative Example 17 A commercially available starch 1500 (manufactured by Nippon Colorcon Co., Ltd.) is used as processed starch (V). Table 3 shows the physical properties of the processed starch (V).

[0058]

Comparative Example 18 A commercially available product PCS (manufactured by Asahi Kasei Kogyo Co., Ltd.) is used as a processed starch (W). Table 3 shows the physical properties of the processed starch (W).

[0059]

Example 17 495 g of L-ascorbic acid (manufactured by Takeda Pharmaceutical Co., Ltd.) and 500 parts of modified starch (L) were mixed, and then 5 parts of magnesium stearate were mixed. , Tablets were obtained. Table 4 shows the physical properties of the tablets.

[0060]

Example 18 Example 1 except that modified starch (N) was used.
The same operation as in 7 was performed. Table 4 shows the physical properties of the tablets.

[0061]

Example 19 Example 1 except that modified starch (O) was used.
The same operation as in 7 was performed. Table 4 shows the physical properties of the tablets.

[0062]

Example 20 Example 1 except that modified starch (R) was used.
The same operation as in 7 was performed. Table 4 shows the physical properties of the tablets.

[0063]

Example 21 Example 1 except that modified starch (S) was used.
The same operation as in 7 was performed. Table 4 shows the physical properties of the tablets.

[0064]

Comparative Example 19 Example 1 except that the modified starch (M) was used.
The same operation as in 7 was performed. Table 4 shows the physical properties of the tablets.

[0065]

Comparative Example 20 Example 1 except that modified starch (P) was used.
The same operation as in 7 was performed. Table 4 shows the physical properties of the tablets.

[0066]

Comparative Example 21 Example 1 except that modified starch (Q) was used.
The same operation as in 7 was performed. Table 4 shows the physical properties of the tablets.

[0067]

Comparative Example 22 Example 1 except that the modified starch (T) was used.
The same operation as in 7 was performed. Table 4 shows the physical properties of the tablets.

[0068]

Comparative Example 23 Example 1 except that modified starch (U) was used.
The same operation as in 7 was performed. Table 4 shows the physical properties of the tablets.

[0069]

Comparative Example 24 Example 1 except that modified starch (V) was used.
The same operation as in 7 was performed. Table 4 shows the physical properties of the tablets.

[0070]

Comparative Example 25 Example 1 except that modified starch (W) was used.
The same operation as in 7 was performed. Table 4 shows the physical properties of the tablets.

[0071]

Example 22 400 g of processed starch (B), 400 g of aspirin (manufactured by Hoei Pharmaceutical Co., Ltd.) and 190 g of lactose 200 mesh (manufactured by DMV) are mixed, and 10 g of magnesium stearate is further added and mixed. Next, the mixed powder was compressed on a plate with a pressure of 2 tons using a roller compactor mini (manufactured by Freund Corporation) and then crushed. Next, the pulverized product was sieved, passed through 12 mesh (aperture 1410 μm), and granules remaining in an 80 mesh (aperture 180 μm) were tableted in the same manner as in Example 6 using a rotary tableting machine. , Tablets were obtained. Table 5 shows the physical properties of the tablets.

[0072]

Example 23 Example 2 except that modified starch (N) was used.
The operation was the same as in 2. Table 5 shows the physical properties of the tablets.

[0073]

Comparative Example 26 Example 2 except that modified starch (C) was used.
The operation was the same as in 2. Table 5 shows the physical properties of the tablets.

[0074]

Comparative Example 27 Example 2 except that the modified starch (T) was used.
The operation was the same as in 2. Table 5 shows the physical properties of the tablets.

[0075]

Comparative Example 28 Example 2 except that modified starch (U) was used.
The operation was the same as in 2. Table 5 shows the physical properties of the tablets.

[0076]

[Table 1]

[0077]

[Table 2]

[0078]

[Table 3]

[0079]

[Table 4]

[0080]

[Table 5]

[0081]

According to the present invention, when a processed starch having both the binding property and the disintegration function at the same time and having the specified physical properties is used, and the product is formulated by direct compression or dry granulation, the binding property is excellent. Alternatively, a preparation having high granule strength can be obtained. At the same time, since the preparation is excellent in disintegration, the preparation shows rapid disintegration after administration, and the dissolution rate of the drug is increased. As described above, since the processed starch has both functions of binding and disintegration, the quality can be easily designed by simplifying the formulation and having high stability to drugs.

Claims (2)

(57) [Claims] 1. A modified starch obtained by subjecting raw starch to heat treatment in the presence of water, wherein the starch has a water content of 8 to 15%.
%, Soluble in cold water is less than 10%, swelling volume is 5 to 15 ml
/ G without substantially destroying the starch particles
Non-birefringent particles that maintain starch particle morphology
Are present more than particles exhibiting birefringence.
Binding, processed starch having excellent disintegration property that. 2. A pharmaceutical composition comprising the modified starch according to claim 1.