JP2006022060A - Aqueous dispersion for antacid/laxative and tablet therefor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain an aqueous dispersion that is administered by tube feeding and contains magnesium oxide particles and a tablet therefor. <P>SOLUTION: The aqueous dispersion for antacid/laxative comprises 1-30 wt.% of magnesium oxide particles having 0.5-10μm average secondary particle diameter and is administered by tube feeding. The tablet comprises magnesium oxide particles for preparing the dispersion. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to an aqueous dispersion containing magnesium oxide particles, and relates to an antacid / relaxed aqueous dispersion for administration by a tube feeding tube and a method for administering the aqueous dispersion. The present invention further relates to a tablet containing magnesium oxide particles for preparing the aqueous dispersion.

  When a drug is administered to a patient with dysphagia, tube administration may be selected if severe. If the drug used at the time of tube administration is a tablet, it must be pulverized. In addition, there were many problems such as complicated dispensing operations and health hazards to dispensers. Thus, a method has been proposed in which the tablets are disintegrated and suspended in water without being pulverized, and the dispersion is administered through a tube feeding tube. Magnesium oxide has been provided mainly as fine granules as an antacid or laxative, but it has been pointed out to occlude tube feeding tubes. In order to prevent obstruction of the tube feeding tube, pre-preparation is carried out by crushing fine granules in a mortar, but magnesium oxide is difficult to make into a fine powder and the drug sticks to the mortar. It was a burden.

  An aqueous dispersion containing magnesium oxide particles that can be administered without obstruction by a tube feeding tube and a tablet containing magnesium oxide particles therefor are provided. In particular, this tablet has the advantage that an aqueous dispersion can be prepared by adding a necessary amount in water at the time of administration, and can be administered as a tube.

  The first object of the present invention is to use a tube feeding tube that can be used as a tablet capable of simpler counting dispensing than metered dispensing such as fine granules and powder, and is disintegrated and suspended in water. It is to provide a magnesium oxide tablet and an aqueous dispersion that can be administered by tube.

  A second object of the present invention is a magnesium oxide particle dispersion suspended in water, and the dispersion flows smoothly through the tube feeding tube without causing blockage in the tube feeding tube. An object of the present invention is to provide a magnesium oxide particle dispersion that can be used.

  The third object of the present invention is to provide a magnesium oxide tablet for administration by a tube feeding tube, which can easily and quickly prepare an aqueous dispersion from a tablet at the time of administration.

  According to the study of the present inventor, an aqueous dispersion formed from fine magnesium oxide having an average secondary particle diameter in a specific range can be smoothly administered by a tube feeding tube without causing occlusion, and the specific range. Found that tablets containing a certain amount of fine magnesium oxide, a specific binder and a disintegrant in a certain proportion disintegrate rapidly in water, and that the resulting aqueous dispersion can be administered without obstruction by a tube feeding tube. The invention has been reached.

Thus, according to the present invention, there are provided the following antacid / relaxed aqueous dispersions (a) to (c), a method of administration through a tube feeding tube, and a tablet for preparing the aqueous dispersion.
(B) A tube feeding tube comprising an aqueous dispersion containing 1 to 30% by weight of magnesium oxide particles having an average secondary particle diameter of 0.5 to 10 μm measured by a laser diffraction scattering method. An antacid / relaxed aqueous dispersion for administration.
(B) administering an aqueous dispersion containing 1 to 30% by weight of magnesium oxide particles having an average secondary particle diameter of 0.5 to 10 μm measured by a laser diffraction scattering method to a human through a tube feeding tube; A method for administering an aqueous antacid / relaxing aqueous dispersion.
(C) An antacid / relaxation tablet containing magnesium oxide particles for administration through a tube feeding tube as an aqueous dispersion dispersed in water, the tablet being a requirement of the following (i) to (iii) A tablet characterized by satisfying
(I) Magnesium oxide particles have an average secondary particle diameter of 0.5 to 10 μm measured by a laser diffraction scattering method.
(Ii) The tablet has a content of magnesium oxide particles of 88 to 97% by weight.
(Iii) Disintegration time in water is 10 seconds or less.

  Hereinafter, the present invention will be described in more detail.

  In the present invention, the antacid / relaxed aqueous dispersion for administration through a tube feeding tube contains 1 to 30% by weight, preferably 5 to 30% by weight, more preferably 10 to 25% by weight of magnesium oxide particles in water. Contains at a concentration of The magnesium oxide particles in the aqueous dispersion have an average secondary particle diameter measured by a laser diffraction scattering method of 0.5 to 10 μm, preferably 1 to 7 μm.

  Since the aqueous dispersion in the present invention has small average secondary particles of magnesium oxide particles and is excellent in dispersibility, it smoothly flows down in the tube feeding tube and does not clog. Here, the tube is usually used as a tube feeding tube, the inner diameter is in the range of 1.0 to 6.0 mm, and the inner diameter is generally 2.7 to 4.0 mm for adults. Has been used. The most commonly used one has an inner diameter of about 2.7 mm. The aqueous dispersion of the present invention is supplied to the patient's body (esophagus or stomach) using such a tube feeding tube, but does not cause obstruction in the tube, and is necessary due to a small amount of water. An amount of magnesium oxide particles can be administered. That is, when administering magnesium oxide particles (MgO) for antacid / relaxation by a tube feeding tube, 20 mL of water is used. Therefore, when MgO 2 g is administered at a time, the MgO concentration is 10 w / v%. When 3 to 4 g of MgO is administered, the MgO concentration is 15 to 20 w / v%. Further, when MgO 6 g is administered, the MgO concentration is 30 w / v%. Even such various MgO concentrations can be administered without obstructing smoothly by using a tube having an inner diameter of about 2.7 mm. On the other hand, when a tube having an inner diameter of 4.0 mm is used, even if the MgO concentration is 40 w / v%, no blockage occurs.

  In carrying out tube administration, when dispensing an aqueous dispersion, a certain amount of magnesium oxide particles can be weighed and added to water (eg, 20 mL). This method has to go through the steps of preparation (micronization) of magnesium oxide particles, measurement, addition to water and dispersion, and an excessive burden has been placed on the pharmacist in the actual medical field.

According to the inventor's research, a method has been found that can easily and quickly dispense a dispersion that can be administered by tube in the form of a tablet without handling magnesium oxide as a powder at the stage of dispensing. That is, according to the present invention, a magnesium oxide particle-containing tablet that satisfies the following requirements (i) to (iii) is provided for preparation of an aqueous dispersion for tube administration.
(I) Magnesium oxide particles have an average secondary particle diameter of 0.5 to 10 μm measured by a laser diffraction scattering method.
(Ii) The tablet has a content of magnesium oxide particles of 88 to 97% by weight.
(Iii) Disintegration time in water is 10 seconds or less.

  Tablets satisfying the requirements (i) to (iii) can be rapidly disintegrated in water to prepare an aqueous dispersion of magnesium oxide particles, and can be administered as it is by tube. When this tablet is used, the content of magnesium oxide particles in one tablet is predetermined, so the aqueous dispersion is prepared by a simple method of adding the required amount to water based on the number of tablets. Can do.

  That is, the use of tablets does not require complicated operations such as preparation, storage, measurement, and aqueous dispersion of magnesium oxide particles (fine powder).

  Next, the magnesium oxide particle-containing tablet used in the aqueous dispersion will be specifically described.

As the tablet, magnesium oxide particles having an average secondary particle diameter of 0.5 to 10 μm, preferably 1 to 7 μm, measured by a laser diffraction scattering method are used.
The tablet can be obtained by using magnesium oxide particles having this particle size and combining a specific binder and a disintegrant described later, and the obtained tablet has a short disintegration time in water of 10 Less than a second. It is desirable that the magnesium oxide particles in the tablet have a high content ratio of 88% to 97% by weight, preferably 89% to 96% by weight, particularly preferably 90% to 95% by weight.

  Magnesium oxide particles used for tableting may be powdery or granular, but the granular is superior in the anti-abrasion effect of the tableting machine, and a tablet with a higher content can be obtained. it can.

  Magnesium oxide particles are usually obtained by firing magnesium hydroxide particles. Magnesium oxide particles obtained by firing magnesium hydroxide having an average secondary particle diameter of 1 to 10 μm by a laser diffraction scattering method at 700 to 1,000 ° C. When it is made into a tablet, it is not hard like the conventional magnesium oxide particle, and there exists an advantage which does not wear a tablet press.

  The binder used in the tablets is crystalline cellulose, or starch (eg corn starch) and the disintegrant is croscarmellose sodium, carmellose calcium, sodium carboxystarch, low substituted hydroxypropylcellulose or polyvinylpyrrolidone. Two or more of these disintegrants may be combined. As the disintegrant, croscarmellose sodium, carmellose calcium or carboxystarch sodium is preferable. In particular, croscarmellose sodium or carboxystarch sodium disintegrates in an extremely small amount as compared with conventional disintegrants, so the amount of the disintegrant is reduced. In addition, it is possible to obtain a tablet having very little change with time and excellent stability. The most preferred disintegrant is croscarmellose sodium.

  The binder is added in an amount of 1 to 10% by weight, preferably 1 to 8% by weight, and the disintegrant is added in an amount of 1 to 3.5% by weight, preferably 1 to 3% by weight.

  Since the compounding quantity of the disintegrant in a tablet can be decreased, the content rate of a magnesium oxide particle can be made high as a result. As described above, the disintegrant has very little change with time, and a tablet having excellent stability is provided without deterioration of disintegration for a long time after tableting. That is, even when the tablet is held for 6 months under the conditions of a temperature of 40 ° C. and a relative humidity (RH) of 75%, the disintegration time of the tablet in water maintains a characteristic of 10 seconds or less.

  Magnesium oxide particles alone can be formed into tablets at low pressure by using a powder blended with the above additives (binder and disintegrant) into a powder that must be compressed at high pressure during dry granulation. Become. Granules molded at high pressure are hard, and when tableting with them, clogging and tableting spots are generated and capping and mechanical parts are severely worn. Magnesium oxide particles, binders and disintegrants as shown below In combination, it can be formed into a tablet at a low pressure, and the blackening of the tablet and the occurrence of tableting spots do not occur.

  The size and shape of the tablet are not particularly different from normal oral tablets. The diameter is 5 to 12 mm, preferably 6 to 10 mm, particularly preferably 6 to 9 mm. The thickness is suitably 2 to 6 mm, preferably 2 to 5 mm, particularly preferably 2.5 to 4.5 mm. Furthermore, the weight per tablet is 100 to 1,000 mg, preferably 150 to 800 mg, and most preferably 200 to 600 mg.

  The above-mentioned tablet containing magnesium oxide particles has a very short disintegration time in water, and usually disintegrates in water in 10 seconds or less, and in 9 seconds or less under suitable conditions.

  Therefore, when administered by tube, an aqueous dispersion can be prepared by adding the required number of tablets to an appropriate amount of water or warm water (for example, 20 mL) at the time of administration. The obtained aqueous dispersion is smoothly administered to the patient through a tube feeding tube.

  Next, the tube feeding tube and its usage for antacid / relaxation will be briefly described.

  The thickness of the tube feeding tube is generally 1.0 to 6.0 mm, but an adult tube having a thickness of about 2.7 to 4.0 mm is often used. If the tube with a large diameter is placed for a long period of time, ulcers will occur in the mucous membrane of the nasal cavity, pharynx, esophagus, stomach, etc. where the tube hits. There is a risk of causing pneumonia. The use of a thin tube significantly reduces patient discomfort and improves safety. Therefore, a tube having an inner diameter of about 2.7 mm is more preferable.

  The usage of the aqueous dispersion containing magnesium oxide particles as an antacid or laxative is, for example, 2 g as MgO per day, taken three times before or after a meal, or once before going to bed. When taking 2 g once before going to bed, the MgO concentration becomes 10 w / v% when suspended in 20 mL of water. In addition, for severe constipation, a large dose of 3 to 4 g is also performed. At this time, when suspended in 20 mL of water, the MgO concentration is 15 to 20 w / v%. When using a tube feeding tube having an inner diameter of 2.7 mm, the tablet can be administered at least 6 g at a time when suspended in 20 mL of water, and the MgO concentration of magnesium oxide is 30 w / v%. Become. When a tube feeding tube having an inner diameter of 4.0 mm is used, if suspended in 20 mL of water, 8 g can be administered at least once, and the MgO concentration of magnesium oxide is 40 w / v%.

  In performing tube administration, it is preferable to disintegrate in water in a short time. The tablets that disintegrate with a little water have a disintegration time of 10 seconds or less when tested by the JP General Test Method Disintegration Test. In the tube administration method, the disintegration time is not specified, but a shorter one is desirable.

  Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples.

Example 1
(1) Formulation Example 1
Magnesium oxide particles 330mg (88%)
Crystalline cellulose 23mg (6.1%)
Corn starch 7mg (1.9%)
Croscarmellose sodium 11 mg (2.9%)
Calcium stearate 4mg (1.1%)
375mg
(2) Tablet production method 39.6 kg of magnesium oxide particles with an average secondary particle size of 6.50 μm, 2.76 kg of crystalline cellulose, 0.84 kg of corn starch, 1.32 kg of croscarmellose sodium in a container type mixer After mixing, the molded product granulated at a roll pressure of 5 MPa with a roll mold dry granulator was granulated with an oscillator grinder. 40.81 kg of this granule and 0.44 kg of calcium stearate are mixed in a container type mixer to form a granule for tableting, and a tableting pressure of 9 kN is used in a rotary type tableting machine equipped with 36 9R diameter, 13R punches. To obtain magnesium oxide tablets weighing 375 mg and having a thickness of 4.8 mm per tablet.

Example 2
(1) Formulation example 2
Magnesium oxide particles 255mg (89.5%)
Crystalline cellulose 15mg (5.3%)
Corn starch 5mg (1.8%)
Croscarmellose sodium 7mg (2.5%)
Calcium stearate 3mg (1.1%)
285mg
(2) Manufacturing method of tablets 38.25 kg of magnesium oxide particles having an average secondary particle size of 6.50 μm, 2.25 kg of crystalline cellulose, 0.75 kg of corn starch, and 1.05 kg of croscarmellose sodium are used in a container type mixer. After mixing, the molded product granulated at a roll pressure of 5 MPa with a roll mold dry granulator was made into granules with an oscillator grinder. 40.89 kg of this granule and 0.435 kg of calcium stearate are mixed in a container type mixer to form a granule for tableting. A rotary type tableting machine equipped with 36 8R diameter, 12R punches is used to produce a tableting pressure of 7 Tableting was performed at 0.5 kN to obtain magnesium oxide tablets having a weight of 285 mg and a thickness of 4.5 mm per tablet.

Comparative Example 1
(1) Formulation Example 3
Magnesium oxide particles 330mg (88%)
Crystalline cellulose 23mg (6.1%)
Corn starch 7mg (1.9%)
Croscarmellose sodium 11 mg (2.9%)
Calcium stearate 4mg (1.1%)
375mg
(2) Tablet production method 33.0 kg of magnesium oxide particles with an average secondary particle size of 170 μm, 2.3 kg of crystalline cellulose, 0.7 kg of corn starch, 1.1 kg of croscarmellose sodium were mixed in a container-type mixer. Thereafter, 0.4 kg of calcium stearate was further added and mixed with the same machine to obtain granules for tableting. This was tableted with a tableting pressure of 9 kN using a rotary tableting machine equipped with 36 9R diameter and 36 13R punches to obtain magnesium oxide tablets having a weight of 375 mg and a thickness of 4.2 mm per tablet.

Comparative Example 2
In one tablet, a commercially available pharmaceutical pharmaceutical magnesium oxide tablet A tablet containing 330 mg of magnesium oxide was used. This tablet was produced mainly using the magnesium oxide particles of Comparative Example 1.
Comparative Example 3
Among the 3 tablets, commercially available Oxide Magnesium Oxide Tablet B containing 1 g of magnesium oxide was used. This tablet was produced mainly using the magnesium oxide particles of Comparative Example 1.

Comparative Example 4
Among the 3 tablets, commercially available Oxide Magnesium Oxide Tablet C containing 1 g of magnesium oxide was used. This tablet was manufactured using the magnesium oxide particles of Comparative Example 1.

Comparative Example 5
Commercially available magnesium oxide fine granules were used for ethical drugs. The particle size distribution of the fine particles was tested by the following measuring method, and the average particle size was determined to be 246.26 μm.
Equipment: Endecots made octagonal sieve (between meshes): 500, 355, 180, 150, 106 μm
Test conditions: vibration intensity 5, sieve time 5 minutes, connection 10 seconds, stop 2 seconds, fly aviator 5 minutes About 30 mL of the sample and placed in the upper sieve of the container overlaid with the receiver, after the upper lid Set the device. After testing under the above conditions, weigh each sieve and receiver residue to the nearest 0.01 g. The particles are accumulated from particles having a large particle size distribution, and the particle size of the particles having an accumulated value of 50% by weight is defined as the average particle size.

Test method Test method 1-Disintegration suspension test In the case of tablets, take out the piston part of the dispenser, put 6 tablets into the dispenser as they are, return the piston, suck up 20 mL of hot water of 55 ° C into the dispenser, and cover the tube tip And let stand for 5 minutes. After 5 minutes, roll the dispenser 90 degrees 15 reciprocally by hand and observe the state of disintegration and suspension. If it does not disintegrate after 5 minutes, leave it for another 5 minutes and then do the same.
In the case of powder, 2.0 g of powder is placed in a beaker containing 20 mL of hot water at 55 ° C. and left to stand for 10 minutes, and then stirred with a spatula to draw a circle 20 times to the right, 20 times to the left, 20 times to the right Observe the suspension.
The results are shown in Table 1.

Test Method 2-Passability Test The obtained suspension is sucked into a dispenser, and injected at a rate of about 2 to 3 mL / second from the injection end of a tube feeding tube having an inner diameter of 2.7 mm, and the passage is observed. The results are shown in Table 1.

Test Method 3-Disintegration Test The disintegration time was measured by the Japanese Pharmacopoeia General Test Method Disintegration Test Method. The results are shown in Table 2.
As shown in Tables 1 and 2, as in Comparative Examples 1 to 5, tube administration using a tube feeding tube having an inner diameter of 2.7 mm is difficult with tablets mainly using fine granules. As the reason, it can be considered that the particle diameter of magnesium oxide is greatly different in Example 1 and Comparative Examples 1-5.

Test Method 4-Disintegration Suspension and Passability Test of Tablet of the Present Invention Measurement of Applicable Quantity (1) Pull out the piston part of the dispenser, put an arbitrary number of tablets into the dispenser, return the piston, and put 55 in the dispenser. Absorb 20 mL of hot water at 0 ° C., cap the tip of the tube, and shake until the tablet disintegrates and suspends. The obtained suspension was injected from the injection end of a tube feeding tube having an inner diameter of 2.7 mm at a rate of about 2 to 3 mL / second, and the permeability was observed. It was investigated how many tablets could be administered without obstructing the tube feeding tube.

The tablets of Example 1 could be administered by tube up to 18 tablets.
(2) The thickness of the tube feeding tube was changed to an inner diameter of 6.0 mm, and the others were tested under the same conditions as in (1).

  The tablets of Example 1 could be administered by tube up to 24 tablets.

Claims (13)

In order to administer by a tube feeding tube comprising an aqueous dispersion containing 1 to 30% by weight of magnesium oxide particles having an average secondary particle diameter of 0.5 to 10 μm measured by a laser diffraction scattering method An antacid / loose water dispersion. The aqueous dispersion for antacid / relaxation according to claim 1, wherein the aqueous dispersion is obtained by dispersing a tablet comprising magnesium oxide particles satisfying the following requirements (i) to (iii) in water. .
(I) Magnesium oxide particles have an average secondary particle diameter of 0.5 to 10 μm measured by a laser diffraction scattering method.
(Ii) The tablet has a content of magnesium oxide particles of 88 to 97% by weight.
(Iii) Disintegration time in water is 10 seconds or less. The aqueous dispersion for antacid / relaxation according to claim 1, wherein the tube feeding tube for tube administration has an inner diameter of 2.7 to 4.0 mm. The antacid / relaxing aqueous dispersion according to claim 2, wherein the tablet contains 1 to 10% by weight of crystalline cellulose or starch as a binder. The tablet contains 1 to 3.5% by weight of at least one member selected from the group consisting of croscarmellose sodium, carmellose calcium, carboxy starch sodium, low-substituted hydroxypropyl cellulose and polyvinylpyrrolidone as a disintegrant. 2. An aqueous dispersion for antacid / relaxation according to 2. An aqueous dispersion containing 1 to 30% by weight of magnesium oxide particles having an average secondary particle diameter of 0.5 to 10 μm measured by a laser diffraction scattering method is administered to a human through a tube feeding tube. Administration of antacid / relaxed water dispersion. The aqueous dispersion for antacid / relaxation according to claim 6, wherein the aqueous dispersion is obtained by dispersing a tablet comprising magnesium oxide particles satisfying the following requirements (i) to (iii) in water. Administration method.
(I) Magnesium oxide particles have an average secondary particle diameter of 0.5 to 10 μm measured by a laser diffraction scattering method.
(Ii) The tablet has a content of magnesium oxide particles of 88 to 97% by weight.
(Iii) Disintegration time in water is 10 seconds or less. 7. The method of administering an aqueous dispersion for antacid / relaxation according to claim 6, wherein the inner diameter of the tube feeding tube for tube administration is 2.7 to 4.0 mm. The method of administering an aqueous dispersion for antacid / relaxation according to claim 7, wherein the tablet contains 1 to 10% by weight of crystalline cellulose or starch as a binder. The tablet contains 1 to 3.5% by weight of at least one member selected from the group consisting of croscarmellose sodium, carmellose calcium, carboxy starch sodium, low-substituted hydroxypropyl cellulose and polyvinylpyrrolidone as a disintegrant. 7. A method for administering an antacid / relaxing aqueous dispersion according to 7. An antacid / relaxing tablet containing magnesium oxide particles for administration through a tube feeding tube as an aqueous dispersion dispersed in water, the tablet satisfying the following requirements (i) to (iii) A tablet characterized by that.
(I) Magnesium oxide particles have an average secondary particle diameter of 0.5 to 10 μm measured by a laser diffraction scattering method.
(Ii) The tablet has a content of magnesium oxide particles of 88 to 97% by weight.
(Iii) Disintegration time in water is 10 seconds or less. The tablet according to claim 11, wherein the tablet contains 1 to 10% by weight of crystalline cellulose or starch as a binder. The tablet contains 1 to 3.5% by weight of at least one member selected from the group consisting of croscarmellose sodium, carmellose calcium, carboxy starch sodium, low-substituted hydroxypropyl cellulose and polyvinylpyrrolidone as a disintegrant. 11. The tablet according to 11.