JP780H - Processed starch - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention can be used by mixing it with pharmaceuticals, cosmetics, foods, etc.
A new starch that exhibits excellent performance as a disintegrating agent and water retention agent
Powder and its manufacturing method. The processed starch obtained according to the present invention is produced by chemical modification.
The proper water absorption and swelling ability only by physical treatment.
It was the one. The processed starch obtained by the present invention is used as tablets, granules and fine granules.
When applied to pharmaceutical preparations such as drugs, pills, capsules, etc.
Produces a fast disintegration effect and a substantial weight gain effect
It The processed starch of the present invention is especially used in tablets and granules in the above pharmaceutical preparation.
To improve the disintegration pattern of drugs and fine granules.
It also has the feature of improving the dissolution of these active ingredients (main drug)
Have A typical example of the above disintegrant is carboxymethylcetone.
Lulose calcium, low viscosity carboxymethyl cellulose
Sodium, low-substituted hydroxypropyl cellulose
And cross-linked sodium carboxymethyl cellulose etc.
Lurose derivatives; guar gum, sodium alginate, etc.
Plant gums; cross-linked polyvinylpyrrolidone; cations
Exchange resins; hydroxypropyl starch, carboxy
Examples include starch derivatives such as methyl starch.
Almost all of these are chemical products, such as cellulose and starch.
Those starting from natural products are also chemically modified products thereof.
Starch and cellulos that have not been modified by chemicals
So far, a form that exhibits excellent disintegration performance has been obtained
It is not. For example, cellulose itself has a molding function
As a binder in the fields of pharmaceuticals and foods,
It is used, but its collapse power is poor. Also, as an inexpensive disintegrant that has not been chemically modified
There is raw starch, but it has a poor swelling power, and it is
A large amount of addition is required to give quick disintegration.
Therefore, as is well known, the capping phenomenon
And the softening of the molded product over time.
It Heat treatment or acid treatment of raw starch and completely dissolve it in cold water
The pregelatinized starch that has been made available may also be used as a disintegrant.
However, if this is used, the collapsing liquid (through
In the process of permeation of water (usually water is used)
The powder dissolves in the disintegration liquid, significantly increasing its viscosity,
This makes it difficult for the liquid to permeate and imparts rapid disintegration.
Is difficult to do. In addition to this, starch, which is rich in natural resources, is used as a disintegrant.
There is an example used. According to Japanese Patent Publication No. 46-21471
Is composed of birefringent particles and non-birefringent particles.
Some form aggregates, in the range of about 4-40% by weight
It is soluble in cold water and its swelling power is about 2.5.
-12, the free density is about 0.5-0.7 g / ml,
The water content is about 9-16% of the total weight, and the particle size is
The size may be substantially 40 mesh or more, but the total weight
90% or more of powder is 80 mesh or less and about 1
0-70% solid powder is 270 mesh or more,
30 ~ 90% solid powder should be less than 270 mesh
Introducing starch that is used as a binder and disintegrant
There is. This starch has a water content of about 20-50% by weight.
Using raw material starch with differential roll mill and co-current roll mill
Compacted in the temperature range of 20 to 50 ° C and then dried.
It is obtained by drying and crushing. But this
The starch obtained by the method was once granulated by adding water.
So-called wet pressing, such as pressing the granulated product under pressure.
Almost all of the disintegration effects occur when moldings are made by the tablet method.
There was a drawback that it did not exhibit. Also in the publication
As described, for example tablets as medicinal moldings
Addition to the agent to fully exert its function as a binder
Means that this starch represents at least 50% of the total tablet weight.
Is present in an amount of
Be the only binder added to the formula for purpose, etc.
Must be within the constraints of
The function of the mixture-disintegrant is not exerted, and the formulation of the molded product is free
It also had the drawback that it could not be assembled. Moreover, Japanese Patent Publication No. 53-5725 discloses a binder and a disintegrant.
The manufacturing method of granules and tablets using α-type β-starch
Have been through. The starch introduced here is β type starch,
That is, the raw starch powder surface is coated with α type starch, or
High-pressure steam is sprayed while flowing in a fluidized bed.
Or the raw starch powder is suspended in water and the suspension is heated to the air temperature.
By spraying in an atmosphere of 200 to 400 ° C, the surface
Trying to obtain starch that is only α-converted and the inside is β-type
It was something. However, obtained in this way
Since the surface of the starch is α type, it has excellent binding properties.
However, the collapsing liquid passes through the α-formation part and reaches the β-type part
It may take some time before
When the disintegration liquid permeates, the α-ized part dissolves in the disintegration liquid and thickens.
Because it has an effect and thus impedes the penetration of the disintegration liquid
Or the collapse power was not enough. In addition, the surface is made alpha
The general characteristics of alpha starch starch are:
Book: Supervised by Jiro Nikuni, published by Asakura Shoten, (1972)
As described on P.35, for enzymes and chemicals
Therefore, it should be added to pharmaceuticals, foods, etc.
However, there is also the problem of narrowing the application range. Therefore, the object of the present invention is to have excellent disintegration performance,
Provide processed starch powder in chemically unmodified form
Is Rukoto. The processed starch of the present invention that achieves this object is a raw starch powder
A substantially non-birefringent structure that substantially preserves the shell thin film structure.
Powder, which is 60 Tyler mesh or
With a particle size distribution that has substantially no large fraction,
Bulk density of 0.25 g / cc or more, cold water soluble content of less than 10% by weight,
The swelling volume is about 3 to 15 ml / g and the water retention capacity is about 2 or more.
And are characterized by. The processed starch of the present invention is in the form of tablets, granules, fine granules and the like.
Extremely mixed as a disintegrant in pharmaceuticals, foods, seasonings, etc.
It can have an excellent collapse effect. Also food
(Eg powdered foods) and cosmetics (eg antiperspirant sticks,
For perfume powder, summer candy etc.)
Excellent as a water retention agent and anti-blocking agent
It is possible to exert an effect. The present invention will be specifically described below. The starch powder of the present invention comprises, first of all, a non-birefringent starch powder.
It All raw starch present in plant cells has a granular structure.
This is called Tono flour. This raw starch powder is water
When placed inside and observed with a polarizing microscope,
Although it shows a unique birefringence, the starch powder of the present invention is substantially
Non-birefringent, and thus amorphous with no crystallinity
It The raw starch powder is covered with a thin film shell.
It The starch powder of the present invention is birefringent,
The thin film structure of the shell is maintained and the thin film does not burst.
The starch particle morphology is maintained and individual particles can be identified
belongs to. The non-birefringent starch with the outer shell thin film destroyed is not
It reversibly swells (dissolves), resulting in an increase in the viscosity of the liquid
With increased reactivity to enzymes or chemicals
Become. In contrast, the starch powder of the present invention is a thin film portion of the outer shell.
As a result, the water-soluble component amylose is less likely to exude.
Therefore, there is little content soluble in cold water. Throw this in water again
When put in, the starch powder's starch powder is non-birefringent
Absorbs water, re-swells, and does not gelatinize
It can exhibit a disintegrating force. The processed starch powder of the present invention is less than 10% by weight, preferably
Shows cold water soluble content of less than 4% by weight (method for measuring cold water soluble content
Will be shown later). Adhesiveness when absorbing moisture above 10%
Becomes large and the collapsing power decreases. Most when less than 4%
A favorable disintegration force is obtained. Cold water soluble content of starch powder is about 0.
2 to 0.4% by weight. Therefore, the cold water soluble content is less than this.
It never becomes a value. The processed starch powder of the present invention is about 3 to 15 ml / g, preferably
Swelling of about 7 to 13 ml / g, particularly preferably about 8 to 11 ml / g
It has a volume (a definition and a measuring method will be described later). Raw buttocks
The swelling volume is about 1-2 ml / g. Swelling volume less than 3 ml / g
Cannot impart rapid disintegration to the added moldings.
Yes. The processed starch powder of the present invention has been chemically modified.
The upper limit of the swelling volume is
It is about 15 ml / g. Water retention capacity of processed starch powder of the present invention (Definition and measurement method will be described later
Yes) is about 2 or more and usually takes a value of 4 to 7. Raw starch
The water retention capacity of the grains is less than 2. Therefore, the processed starch powder of the present invention
Powder gives good water retention at the same time as disintegration to the added molded product.
You can The processed starch powder of the present invention is 48 Tyler mesh powder or more.
It should not contain coarse particles, preferably 60
Less Tyler mesh (hereinafter referred to as mesh)
95% by weight or more, most preferably 100% by weight
It must have a particle size distribution of Grain size
If the value is large, the disintegration time between additive moldings varies widely.
When added to cosmetics, etc.
Not good. The processed starch powder of the present invention is about 0.25 g / cc or more, preferably
It must have a bulk density of at least 0.3 g / cc. Raw Lord
The true density of the powder is about 1.6 g / cc. Bulk less than about 0.25g / cc
In terms of density, compression moldability becomes poor when dry molding,
The fluidity of the powder is also poor, which is not preferable. Next, a method for producing the processed starch powder of the present invention will be described. The method for producing processed starch powder of the present invention is a method of converting raw starch powder into water.
The outer shell film structure of raw starch particles by heating in the presence of
Swell without destroying the structure and then the outer shell thin film structure
It is a method characterized by drying without destroying
It The starting materials of the present invention include corn starch and wheat
Any above-ground starch such as flour and rice starch, that is, cereal starch
Can also be used, but the availability of raw materials, the production method of the present invention
Corn starch is particularly preferred for reasons such as ease of application.
Good Root starch such as potato starch (tapioca starch)
Or tuber starch has a large swelling power, but as a manufacturing condition
When it is necessary to select a particularly narrow range,
At that time, deterioration over time, especially the decrease in action effect due to moisture absorption
It is difficult to use because it is seen. 2 or more starting materials
Although it is free to combine the above starch, it is difficult.
Wear It is the swelling speed in water depending on the type of starch.
However, the different processed starches are different from each other.
There is no problem in mixing and using the powder. The particle size of the raw starch is based on the request from the particle size of the processed starch.
What can be obtained is desirable. Of course, screen the starch after processing
Good. In the underwater heating and drying of the production method of the present invention, raw materials
The outer shell thin film of starch powder is destroyed, resulting in irreversible swelling (dissolution).
Solution) and never form an aqueous solution into a paste
There must be. That is, do not allow the starch particles to gelatinize.
No The gelatinization temperature of starch starch particles is measured, the type of starch, and the grain
A little different depending on the diameter, production area, weather conditions at the time of growing and harvesting, etc.
It is said that tracking changes in the transparency of the suspension
Photopaste Graphie by Hirama Co., Ltd.
Table 1 shows an example of the values measured by the manufacturer. For example, raw starch in the presence of a slurry-like large excess of water
If you want to swell without heating and destroying,
The temperature is significantly higher than the gelatinization start temperature as shown in Table-1.
Heating should be avoided. In this case, the heating temperature range
The enclosure indicates the gelatinization start temperature, which is unique to each raw starch, by about 10 ° C.
It should be within the range of rotation. Also, for example, if the water content is
Add raw starch-water mixture in a low moisture range of about 30-70%.
When heated, the temperature is around the boiling point of water, specifically about 80
It is possible to heat in the range of ~ 140 ° C.
Uniform heating is difficult with the method, and non-birefringent particles and birefringent particles
It is easy for children to coexist. Therefore, if you want uniform heating,
At least a pasty or slurry-like flow state is exhibited.
It is preferable to perform low temperature heating in the presence of an excessive amount of water.
Of course, simply immersing the starch in water gives the effect of the present invention.
No fruit is obtained, and should be heated at a temperature of at least 50 ° C.
It is The heating time is almost free. Ah
The heating time is 1 to 2 when heating at a temperature
Freely choose from minutes to minutes to hours
It Of course it is possible to heat it for a longer time than that,
Prolonging the heating time has no benefit.
Yes. Considering energy efficiency, processing in a shorter time
Should be. However, the potatoes obtained by drying after heating for a short time
Torch is a birefringent grain that is rarely obscured when examined under a microscope.
Occasionally there is a very small proportion of children. It is an example
For example, about 10 or less per 100 heat-treated particles
It is the ratio of degrees. Why these imperfect particles appear
This is probably because the raw starch powder has a wide particle size distribution.
As can be seen, it is compared with the clear birefringence of the raw starch powder particles.
If so, its birefringence may be unclear or weak.
Because they can be distinguished. Unclear birefringence with such a small proportion
It is considered that cornstarch containing folded particles is also included in the present invention.
Should be obtained. Of course, the proportion of particles in such a transition state
Is preferably as small as possible. In the present invention, the heating method is arbitrary. Also,
At this time, the amount of water to coexist with starch is also free,
From a thin slurry, for example, with a water content of about 30%
The wet state can be freely selected, but preferably about 40% or less
The upper water content range is good. In addition, when heating,
You can mix, shake, and mix for the same purpose.
However, in the present invention, most particles are destroyed.
It's important to heat up and then dry,
Strong shearing force of differential roll mill or co-current roll mill
It is unsuitable to mix and knead using such equipment
Is. It should be noted that in order to facilitate the drying in the drying treatment step described later.
In the above heating step, the organic solvent is mixed with water.
You are free to leave it. One kind of this organic solvent
May exist in more than one kind, and is compatible or incompatible with water
Either may be acceptable. An organic solvent that is compatible with water
When mixed, the gelatinization temperature of starch powder is indicated by water alone.
It may be higher than this value, but in such a case
The outer thin film of starch particles is
Heat to a temperature at which starch particles become amorphous without breaking
You can do it. What should be noted in the drying process is the drying temperature and the drying speed.
The starch powder suspended in a slurry, for example,
Drying at a slower drying rate than the curing temperature
Therefore, the effect of the present invention cannot be obtained. Slurry-like excess water
If you want to dry the product in good condition,
Flash dryer, spray dryer, etc.
You should use the device of. Of course, the temperature below the gelatinization temperature
To dry slowly, decompress or vacuum dry, vacuum
Freeze drying, organic solvent replacement and other drying methods are free.
is there. The starch powder of the present invention was examined under the method described below.
Most of the particles have not been destroyed.
I have to. The particle damage scratches the original raw starch powder particles.
Heat treatment temperature and / or dryness in the presence of moisture.
It occurs when the drying temperature is too high. At too high a heating temperature
The destruction of starch particles caused by the treatment is
Since it cannot be restored in the subsequent drying process, it will be described later.
If starch powder obtained by the method is investigated, particle loss
The scratched state can be observed. Next, the application of the processed starch of the present invention will be described. The present invention
The processed starch powder satisfying the above requirements of has good swelling ability.
It can be used as a disintegrant for molded articles in all fields.
However, such as pharmaceutical tablets, granules, fine granules, etc.
Administered and requires rapid disintegration of moldings in body fluids
It is especially effective in the fields considered to be. The processed starch powder of the present invention
To add disintegrating property to powder by adding powder,
About 1 to 10% by weight may be added to the total weight of the product. Of course
However, the processed starch powder of the present invention has no medicinal effect by itself.
Therefore, do not add more than 10% by weight as an excipient-disintegrant.
Both are possible. The processed starch powder of the present invention is, for example, untreated raw starch corn.
Unlike starch, etc.
Crystal cell because it does not cause
Loose, lactose, dicalcium phosphate, glucose, etc.
With the formulation additives of 10
% Or more can be added if desired. This place
Of course, a better disintegration effect will result.
not. When the processed starch of the present invention is applied to tablets, crystalline cellulose
When combined with a broth, a more preferable formulation becomes possible.
That is, the processed starch of the present invention has an excellent water-absorption swelling power and crystalline segregation.
The excellent forming ability and water-conducting effect of Lulose are combined.
Of high hardness, less pulverization and short disintegration time
It becomes possible to manufacture. The pharmaceutical composition to which the processed starch powder of the present invention is added is
Granulated and / or molded by conventional methods to obtain fine granules, condyles
Can be granules, tablets, pills. Fill these moldings
Muco coating, sugar coating, wax coat
Ing is free. The pharmaceutical molded product obtained by using the processed starch powder of the present invention is
When it was put into the disintegration liquid, it melted from the surface
Shows a so-called "dissolution type collapse pattern" that collapses as if it were
However, it is characterized by a good dissolution rate of the main drug. This melting type
The disintegration pattern is based on the existing raw powder and alpha-formation powder.
It cannot be obtained at all in the system to which powder is added, and in these systems, the
Shows only tsukushi-like collapse. Therefore, raw starch, alpha starch
The containing system often resulted in low dissolution rates. Before
Therefore, in the pharmaceutical industry
The appearance of a disintegrating agent such as
I think it is also meaningful in the sense of responding. Moreover, the processed starch obtained by the present invention maintains the outer shell structure.
The amount of amylose exuded is small even when it comes into contact with water.
So, even when mixed with drugs, it is more stable than conventional α-starch
It also has the feature of being The processed starch powder of the present invention is a water-retaining agent for foods as described above.
Can be used as an agent and anti-blocking agent, as well as in cosmetics
It is applied to give excellent water absorption and usability. Powdered food
1 when used as an anti-blocking agent when added to
The effect is exhibited by adding more than%. Also serves as a bulking agent
When using it as a liquid medicine, the amount added can be adjusted freely.
Good. Further, the processed starch powder of the present invention has excellent disintegrating power,
Even if it absorbs water, it will not become sticky. In addition, these powders
Alternatively, when added to granular or tablet foods, cold water
While improving the dispersibility, even if it is added directly to hot water,
Of foods with excellent disintegration and dispersibility to prevent
Can be manufactured. Of course, if added to boiling water, the paste will
It becomes a thickening agent. Dispersion of the above cold water or hot water
In case of waiting, 2% by weight or more, preferably about 5% by weight
It is necessary to add. On the other hand, antiperspirant status, perfume powder, summer
Trying to utilize its water retention by applying it to foundation
If it is, about 1 wt% or more, preferably about 3 wt% or less
It is better to add above. Suitable for the processed starch powder of the present invention.
It also has good moldability and is suitable for use in molded products.
It Next, the definitions of the terms used in the present invention and the measurement methods are summarized.
Show. Precisely weigh 3 g of cold water soluble sample (anhydrous equivalent) and add 297 ml of pure water at 25 ° C.
In addition, high speed stirring is performed at 1500 rpm for 2 minutes. The resulting suspension
Into 6 rounds and transfer to a round-bottom centrifuge tube, 2000 rpm for 15 minutes
Centrifuge for 10 minutes. Take 30 ml of this supernatant and weigh it with a wide mouth.
Transfer into a weighing pan, dry and evaporate on a steam bath, then
Dry at 110 ° C. to constant weight. Dry matter weight in the dish
Is multiplied by 1000 and divided by the dry weight of the first sample.
It is the amount of powdered powder dissolved in cold water, and is indicated by the average value of n = 3 to 6.
You Collect 5g of swelling volume sample into a 100ml graduated cylinder with a stopper, 25 ℃
After adding about 80 ml of pure water to shake gently to defoam,
To 100 ml with pure water. Seal tightly, leave it for 24 hours, and absorb water
Read the volume of the wet sample and divide it by 5 to give the swollen volume.
To do. Water retention capacity A sample was prepared according to the measurement method of swelling volume, and the obtained dispersion
Transfer the solution to a centrifuge tube and centrifuge at 4500 rpm for 30 minutes.
It Discard the supernatant and weigh the wet deposit (W _g ), Next
Weigh the deposit with an _og ), Water retention capacity is calculated by the following formula
Put out. Observation of particle destruction (damage):
(P.289) 0.5 g of the sample is placed in a 10 ml centrifuge tube and safrani
About 2 ml of 1% aqueous solution of O (made by Tokyo Kasei Kogyo Co., Ltd.)
Well, stir well with a glass rod and let stand for 15 minutes to dye.
It Then add distilled water and repeat the centrifugation 3-5 times,
Wash off excess dye. A sample that has been thoroughly washed like this
Picked up on a slide, Nippon-Sky-Blue (manufactured by Yamato Processing Co., Ltd.)
1% aqueous solution is added and mixed evenly, and a cover glass is hung.
And speculate. Safranine O and N
ippon-Sky-Blue color index number (CIN
o.) are 50240 and 24400, respectively. The starch powder referred to in the present invention is a pink dyeing like that of raw starch.
Not a color but a deep blue dyeing caused by completely gelatinized starch.
It is not colored but shows purplish-purple or bluish-purple. Of course
, The surface of α-type β-starch, that is, α-type part
Dyeing in which the color is blue and β-type starch has two phases, pink and pink
It is composed of birefringent particles and non-birefringent particles.
Some parts of the starch are pink, some are
It's blue, and some parts have both colors.
It does not show any stained state. Almost all particles are in the outer layer
It shows a uniform red-purple or blue-purple color from the inside to the inner layer, and
The outer shell of the powder particles is elongated but remains in the form of a thin film.
Observed a different structure from that of the gently gelatinized mud
To be done. Incidentally, for example, surface α type internal β other than the processed starch of the present invention
Composed of type starch, birefringent particles and non-birefringent particles
When dyeing such starch and performing a microscopic examination, safranin O is used to
During the dye washing process after dyeing to a color, the water-soluble α-modified starch
Or amylose that has been damaged and exposed can be
As a result, the number of particles washed away with the resulting deep blue dyeing
Note that the rate may decrease and the rate may be observed.
I need to put it. Also, the color of the test object may change slightly depending on
Be careful as it may be changed. As natural as possible
You should use light. Next, examples will be shown. Example 1 Concentration of 5, 10, 15% by weight of solid content of Pharmacopoeia cornstarch
Dispersed in water at a degree
Warm to 5 ° C. for 20 minutes. Then has a two-fluid nozzle
Inlet temperature of about 180 using a laboratory scale spray dryer
℃, outlet temperature of about 90 ℃ in an atmosphere of 5l / hr slurry supply
Spray at the feed rate and sample A-1, A-2, A respectively
-3 was obtained. The physical properties of each sample are shown in Table 2. Example 2 Pharmacopoeia cornstarch in water at a solids concentration of 30% by weight
Disperse and warm this at 67 ° C. for 30 minutes. Next
Transfer this to a tray and place it in a hot air dryer adjusted to 40 ℃.
After drying to a water content of about 4%, use a hammer mill
Passed twice, the first pass was sample B-1, twice
The portion passing through the eyes was designated as sample B-2. Physical properties of each sample
Is shown in Table-2. Example 3 Pharmacopoeia cornstarch in water at a solids concentration of 30% by weight
Disperse and warm this at 67 ° C. for about 30 minutes. this
Pour into approximately 3 times the volume of methyl alcohol, and then separate again
Put into excess methyl alcohol to dehydrate,
Air dry, cut coarse particles with a 60 mesh sieve and sample.
I got Le C. The physical properties are shown in Table 2. Comparative Example 1 Pharmacopoeia cornstarch in water at a solid concentration of 10% by weight
Disperse and vigorously stir it at 76 ° C for 60 minutes.
Warmed for a while. Then put this in an equal volume of cold water to cool.
The residue was lyophilized after passing. Han the dried product
It was crushed with a mar mill to obtain a sample D. Example 4 Water was added to pharmacopoeia cornstarch to give a water content of 30% (fixed
Adjust the concentration to 70%), and in a closed container at 105 ℃ for 30 minutes.
Heated for a while. Open after cooling, dry with hot air adjusted to 60 ℃
It was dried in a dryer until the water content was about 4%. Dried food
Pass through a speed mill (Fuji Paudal Co., Ltd.), then
Coarse particles are cut with a 60 mesh sieve to obtain sample E.
It was Physical properties of the sample are shown in Table-2. Comparative Example 2 Water was added to Pharmacopoeia cornstarch to obtain a water content of 24 to 25%.
And pressed with a pellet mill (manufactured by Fuji Paudal Co., Ltd.)
Then, after drying to a water content of about 7%, hammer mill
Grind with, and make a powder that can pass through 100 mesh.
The powder thus obtained is added to the water in a ribbon blender.
The water content is adjusted to 12% and the compacted starch powder and sa
Sample F was obtained (see Example 1 of Japanese Patent Publication No. 46-21471).
See). The physical properties are shown in Table-2. Comparative Example 3 Pharmacopoeia cornstarch was fluidized bed granulator (manufactured by Okawara) as usual.
Unistar, manufactured by Seisakusho Co., Ltd., cornstarch
Granulate the surface α-type β-type starch powder with the glue liquid as the binding liquid,
Sample G was obtained. The ratio of sprayed alpha starch is about 1
It was 4%. The physical properties are shown in Table 2. Comparative Example 4 3% by weight of pharmacopoeial cornstarch was slurried at 90 ° C.
Completely gelatinize by heating to spray dried by the method of Example 1.
Coarse particles were removed by a 60 mesh sieve to obtain sample H.
The physical properties are shown in Table 2. Example 5 Pharmacopoeial phenacetin powder 200 parts, pharmacological cellulose 400 parts,
345 parts of crystalline lactose, 5 parts of magnesium stearate
Parts, total 950 parts, 50 parts of each sample shown in Table-2
In addition, a rotary type tablet press (Kikusui Manufacturing)
Tablet (manufactured), RT-S22, pestle 8mmφ, 12R)
It was The tablet weight should be 250 ± 10mg on average for 20 tablets.
Adjusted to. The tablet evaluation results are shown in Table-3 and Table-4.
The tablet evaluation method is as follows. Tablet weight variation 20 tablets were precisely weighed and the coefficient of variation (n = 20) was calculated.
Ask. 20 tablets of hardness each with a Kiya type hardness tester (unit: kg)
It is subjected to a destructive test and the average value is calculated. Disintegration degree Measured according to the 9th revision of the Japanese Pharmacopoeia. However, day
Remove the disc and do. Average of n = 6. Disintegration pattern Observe using the following two methods. (1) Static method Pour the disintegrating liquid into a dish and submerge one tablet in the center. Stillness
Let it sit for 15 minutes. Shows "dissolution type disintegration"
The tablet is broken into fine powder so that it dissolves from the surface.
When I add a slight vibration to the sheare, a coarse block
Shows no lamellae. (2) When performing a disintegration test in the rocking method disintegration tester, "dissolution type disintegration"
Tablets exhibiting "sex" disintegrate as if melting from the surface,
Does not produce small blocky pieces during disintegration. Dissolution rate According to the rotating basket method of US Pat. No. 3,622,677
I did it. Adjust the eluent (0.1N HCl) to 37 ± 1 ℃
Pass 2 ml of test solution through a membrane filter at regular intervals
Sample and dilute it 50 times, then use a UV meter to
Measure the absorbance at 5 nm and obtain the elution amount by the calibration curve method.
It The dissolution rate was measured 5 times with the same tablet system,
Calculate the average value of. The tablets in Table-3 were stored at 40 ° C and 75% RH for 2 weeks.
When subjected to an abuse test, each sample of F, G, H, CS
Had a lower tablet hardness and a significantly longer disintegration time.
The systems of Samples A to E show little or no change.
It turned out to be a little. Example 6 Pharmacopoeial phenacetin powder 400 parts, pharmacological cellulose 200 parts,
Pharmacopoeia Lactose 320 parts, hydroxypropyl cellulose
(Nippon Soda Co., Ltd. SL) 20 parts, each sun shown in Table-2
Granulate by mixing 50 parts of pull powder and adding water as usual.
After drying, the granules are sized after dryness and steered according to pharmacopoeia for 990 parts of dried granules
Add 10 parts of magnesium phosphate and mix. Then carried out
Compress according to the method of Example 5 and evaluate the tablets. Evaluation result
It shows in Table-5. Example 7 200 parts of pharmacopoeial acetaminophen powder, crystalline lactose 445-49 of pharmacopoeia
5 parts, pharmacological cellulose 300 parts, pharmacological stearate mug
5 parts of Nesium, each of A-1, D, F, CS of Table-2
Pull and pharmacopoeial carboxymethyl cellulose calcium
Add 0, 10 and 80 parts respectively and mix as usual
Tablets were directly compressed by the method of Example 5. The evaluation results of the obtained tablets
It shows in Table-6. Example 8 Pharmacopeial Lactose 480 parts, Pharmacopoeial Corn Starch 100 parts, Pharmacopoeial Crystal Separation
Luloose 395 parts, Pharmacopoeial magnesium stearate 5 parts,
Mix well with 20 parts of hydroxypropyl cellulose and mix well.
Add water according to the method, granulate, dry, and pass through a 24 mesh screen.
Then, coarse particles were removed to obtain granules. For 1000 parts of the granule
Then add 60 parts of disintegrant and compression mold according to Example 5.
did. The types of disintegrants are A-2, F, G, H in Table-2 and
It was CS. Table 7 shows the physical property evaluation results of the obtained Brasevo tablets.
Shown in. Example 9 A formulation shown in Table-8 was prepared and powdered in 250 ml of boiling water.
15 g of the body mixture were added directly with stirring. After that
Boil on a low heat for about 2 minutes with stirring, and then put it through a cloth
Moved into the ball. Formula 1 can be used as Makoto even if added directly to boiling water.
A viscous dispersion formed without any formation. Formulation 2 forms large lumps and disperses even with stirring
Shinakatsu Example 10 To 200 g of raw miso (solid content 50%), C
1g, 2g, 5g of each sample is added and kneaded,
It was freeze-dried and then pulverized to prepare a dry powder miso. Each sample
Take 5g of each and throw in 200cc of boiling water at 90-95 ℃
When added, about 2% by weight or more of the processed starch of the present invention is added.
The prepared system exhibited a rapid dispersion state, but about 1% by weight was added.
A part of the added system was left alone. Example 11 Raw miso was freeze-dried and then pulverized to prepare a dry powder miso.
It was 95 parts of the dried powder miso, A-1 sample of Table 2 above
5 parts of the above and added by a static pressure press
Was prepared (5 g / piece). Add this molded miso to 200cc of water
When charged and stirred, it was completely dispersed and dissolved in about 1 minute. On the other hand, in the system in which the processed starch (A-1) is not added,
It took about 3 minutes to completely disperse and dissolve it. Example 12 An antiperspirant powder having the formulation shown in Table 9 was prepared. Dedicated to each sample
As a result of use evaluation by 5 female panelists, Table-10
I got the result. Example 13 Nonfat dry milk 10%, powdered oil / fat 3%, sugar 5%, dexton
Spray drying a slurry consisting of 5% residual water and water content
2% powder was obtained. To this powder, add 2% of the processed starch of A-3 in Table-2
Mixed. Mixed powder for 2 months at 20 ℃ and 70% RH
After leaving it for a while, the dispersibility in cold water was examined.
I got the result. In addition, the processed starch-added product causes blocking even after absorbing moisture.
However, the additive-free product caused blocking. Example 14 For samples A-1, B-2, F, G, H and CS of Table-2
Then, the color difference was measured by dyeing according to the following procedure. First, add 1g of starch sample to a 50ml centrifuge tube, and add
Add 6 ml of 1% aqueous solution of nin O / ethanol (70/100).
Well, stir well with a glass rod and let stand for 15 minutes for dyeing. Add pure water, repeat centrifugation and decantation 5 times
And wash away excess dye. Next, add 1% aqueous solution of Nippon-Sky-Blue until it becomes uniform.
Well, mix. Next, Toyo Paper Co., Ltd. general qualitative filter paper N
Using o.1 (6μ), overwash with pure water while sucking
It The washing is repeated until the liquid becomes transparent. Then profit
Transfer the wetted material to an appropriate holder and float it on the surface.
Suga Test Machine Co., Ltd. CD after absorbing water with filter paper
JIS Z8730 by ES CH-GV4 type direct reading color difference computer
In accordance with, measure the Lab color difference. The measurement results are as follows. In samples G and H, the soluble components in cold water gradually expanded during dye washing.
The viscosity increases, probably because it dissolves and dissolves, and it is impossible to pass it.
I couldn't measure. On the other hand, the processed starch of the present invention is
Was quite smooth. It is clear that the measurement results in Table-12 are expressed in Lab color coordinates.
However, the sample of F is more raw material than the samples of A-1 and B-1.
Take color coordinates close to that of the corn starch CS sample. This
This is because the damaged starch or solubles in cold water contained safranin O.
At the same time when the dye was removed by decantation
Therefore, the blue dyed area is reduced and the hue is close to CS.
It is an ivy. Color difference measurement was not possible, but the colors G and H contain water
It was deep blue in the form of a viscous paste. Comparative Example 5 30 g of cornstarch was dispersed in 470 ml of water and the temperature was 1.5 ° C / min.
Heat up to 88 ° C at the heating rate of
And leave it in a refrigerator at 5 ℃ for 20 hours to age the starch.
It was Next, this is dried with hot air at 80 ° C. and then crushed,
A processed corn starch was obtained. The swelling volume of this sample was as large as about 9.2 ml / g, but
When the outer shell thin film structure of raw starch powder was not observed, and
Tablet hardness when applied to a wet press formulation by the method of Example 8.
And the degree of collapse were outside the acceptable range. Comparative Example 6 Potato starch with a water content of 19% by weight was placed in a closed system.
The sample was heat-treated at 120 ° C. for 120 minutes and opened to obtain a sample (1). Sample I contains mostly coarse particles of 60 mesh or more.
Since it was crushed, it is crushed and then passed through a 60 mesh sieve.
The physical properties of the components were evaluated. Bulk density is 0.49 g / cc, cold water soluble content 9.
3%, swelling volume 5.6 ml / g, water retention capacity 28, birefringence
About 30% of the particles were observed. When applied to a wet formulation according to Example 8, the hardness of tablets
The degree of disintegration was about 4 to 5 kg, but the disintegration degree was within an acceptable range.
It was out of the box. Example 15 In an aqueous medium having an ethanol concentration of 50, 65 or 80% by weight
Then, cornstarch is dispersed at a concentration of 10% by weight and stirred.
Autoclave with machine, 90 ℃, 115 ℃, 140 respectively
It heat-processed at 20 degreeC for about 20 minutes. After opening, it is filtered and air dried as it is, and finally the liquid content is 4
It was dried and pulverized so as to be not more than%. Got three
The characteristics of the samples, J, K and L are shown in Table-13.
Samples obtained by heating in a single system, A-1, A-2, A-
3, the same characteristics as B-1, B-2, C and the like were shown. In addition, a wet formulation was prepared according to the procedure of Example 8, and a representative
Table 14 shows the results of tableting evaluation of Sample K as a sample.
Got the result. Products obtained by treating with alcohol / water system have the effect of the present invention.
It is clear to bring. Comparative Example 7 Potato starch was treated and tested according to the procedure of Example 3.
The fee (M) was obtained. However, the heating temperature is the temperature (6
1.5 ° C). Sample M has a bulk density of 0.48 g / cc, a cold water soluble content of 13.4%, and a swelling capacity.
It has a product of about 16 ml / g and a water retention capacity of about 5.2.
It was not recognized. When this product is formulated according to the method of Example 5, tablet hardness
Shows a sufficient value, but the disintegration time is long (molding pressure 1000
kg / cm ² : 15 minutes or more), and its collapse pattern is poor
Atsuta The elution of the main drug from the tablets was 9.2 after 10 minutes.
% After 30 minutes and 56.2% after 60 minutes. Example 16 The disintegration property and dissolution rate of the granules obtained in Example 6 were evaluated. result
Is shown in Table-15. Example 17 Above-ground starch such as cornstarch, rice starch and rhizome starch
8% by weight of three starches of a potato starch
Disperse these slurries in water at a solids concentration of
Humidification was carried out for 30 seconds under the temperature conditions shown in the table. Then two fluid nod
Using a laboratory-scale spray dryer with
Slurry of 5 l / hr in an atmosphere of about 180 ℃ and outlet temperature of about 90 ℃
The sample was obtained by spraying at a Lee feeding rate. Each service
The physical properties of the sample are shown below. As shown in the table above, the gelatinization start temperature of yourself is 10 ℃ or higher.
Sample No. 4 and No. 7 heated at the rotating temperature are slurries.
Li spray dispersion Viscosity is extremely high.
The product particle size (60 mesh fraction) is as high as 10% or more
And a bulky powder was obtained. In addition, these samples have an upper limit of swelling volume of 15 ml / g.
And the dyeing test result gives a deep blue color and particle damage
It became clear that it was doing. Next, the method of Example 6 was performed on the above seven types of samples.
Was prepared according to the following formula and the physical properties of the obtained tablets were evaluated.
The evaluation results are shown in Table-18. As shown in the table above, it is much higher than the gelatinization start temperature of oneself.
Samples No.4 and No.7 heated at the temperature are disintegrated tablets
Significantly prolongs the time and elutes the medicinal component from the tablet
The rate was also low. In return, heat near the gelatinization start temperature of your own.
Or above the gelatinization start temperature by at least 10 ° C
Samples heated under non-rotating temperature conditions
Disintegration pattern with short disintegration time and good dissolution rate
It was also excellent.

Claims (1)

Claims: What is claimed is: 1. A substantially non-birefringent starch powder which substantially preserves the outer shell thin film structure of raw starch, the powder being 60 Tyler mesh or more. The particle size distribution is substantially free of large fractions, the bulk density is 0.25 g / cc or more, the cold water soluble content is less than 10% by weight, the swelling volume is about 3 to 15 ml / g, and the water retention capacity is about 2. The processed starch characterized by the above. 2. The processed starch according to claim 1, wherein the starch species is a cereal starch such as corn starch, rice starch, wheat starch and the like. 3. An outer shell thin film of raw starch granules by heating the raw starch granules in the presence of water at a temperature of at least 50 ° C. and below a temperature above the gelatinization start temperature specific to the raw starch granules by about 10 ° C. A method for producing a processed starch, which comprises swelling without destroying a structure and then drying without destroying the outer shell thin film structure. 4. The method according to claim 3, wherein the raw starch grains are cereal starch. 5. The method according to claim 4, wherein the cereal starch particles are corn starch. 6. A substantially non-birefringent starch powder which substantially preserves the outer thin film structure of raw starch granules and has a particle size distribution substantially free of fractions of 60 Tyler mesh or larger. A processed starch having a bulk density of 0.25 g / cc or more, a cold water-soluble content of less than 10% by weight, a swelling volume of about 3 to 15 ml / g, and a water retention capacity of about 2 or more. A method of using a modified starch, which is used as a disintegrating agent for cosmetics or a water retention agent.