KR100467146B1 - Process for preparing coated tablet with antiacid - Google Patents

Abstract

The present invention relates to a method for preparing a coated tablet having a coating layer, specifically, a bio-diasterase, a lipase, and a scopolyax, which is an enzyme component, is mixed into tablets and tableted into uncoated tablets, and sodium bicarbonate and magnesium aluminate silicate as antacid components in the coating solution. , Which is a mixture of magnesium carbonate and aldioxa (allantoin), wherein the antacid component contained in the coating layer maintains the pH of the gastric acid at 3.5-7.0 when dissolving in the stomach of the uncoated tablet containing the enzyme component. It is a repellent gastrointestinal drug showing a rapid digestive effect in the stomach, characterized by maximizing enzymatic power.

The present invention is designed so that the enzyme layer disintegrates after the disintegration of the antacid layer as a coating layer is completed, and the enzyme shows activity under optimum conditions in the stomach and can be manufactured without using a special tableting machine.

Description

Process for preparing coated tablet with coating layer

The present invention relates to a method for preparing a coated tablet having a coating layer, specifically, a bio-diasterase, a lipase, and a scopolyax, which is an enzyme component, is mixed into tablets and tableted into uncoated tablets, and sodium bicarbonate and magnesium aluminate silicate as antacid components in the coating solution. , Which is a mixture of magnesium carbonate and aldioxa (allantoin), wherein the antacid component contained in the coating layer maintains the pH of the gastric acid at 3.5-7.0 when dissolving in the stomach of the uncoated tablet containing the enzyme component. The present invention relates to a method for preparing a repellent gastrointestinal drug having a rapid digestion effect in the stomach, characterized by maximizing enzymatic power.

In Korean Patent Publication No. 217308, a double core tablet is known, which is composed of an outer layer and an enteric core, but the enteric portion is first compressed into a central core, followed by an enteric coating, followed by the top coating into an outer coated core. There is a hassle in the process of manufacturing a double-nucleated tablet by coating a conventional outer shell in, and the digestive agent is difficult to expect rapid digestive effect because the enteric-coated tablet is dissolved after the stomach-soluble part is first dissolved. In addition, Korean Patent Publication No. 165920 discloses a triplet containing an antacid in the upper layer and a lower layer and a digestive enzyme in the middle layer, but the outer layer of the upper layer and the lower layer containing the antacid is dissolved first to adjust pH in the stomach. Although it promotes the physiological activity of digestive enzymes, such triple tablets require the use of expensive special tableting machines, and the triple tablets are uncoated tablets, and the intermediate layer containing enzymes and the upper and lower layers containing antacids are in direct contact with each other. There is a problem of preservation stability in which the potency of the enzyme is lowered.

The present invention has been made to solve the above problems, the coating layer containing the antacid component is first dissolved to protect the gastric mucosa and adjust the acidity of the digestive enzyme layer (uncoated layer) is dissolved to promote digestion The present invention relates to a repellent gastrointestinal drug having a coating layer. More specifically, the coating layer contains sodium carbonate, magnesium metasilicate aluminate, magnesium carbonate, aldioxa (allantoin), which are antacid and gastrointestinal protective agents. The present invention relates to a repellent gastrointestinal drug containing Scofolia X, which has an antimycotic and secretory effect.

Unlike the prior art of tableting tablets first and then coating the coated tablets in the present invention, the tablet tablet does not need to use a special tableting machine, and the antacid layer as a coating layer is dissolved first to protect the gastric mucosa and gastric acidity. By maintaining the pH at 3.5 to 7.0, the digestive enzymes of the uncoated layer were designed to work optimally in the stomach.

In other words, the conventional digestive enzyme is made of enteric tablets to prevent inactivation of the stomach, and the digestive effect of the enzyme is expressed after 2 to 3 hours after moving to the intestine through the stomach. Instead, the pH of the stomach is maintained at 3.5 to 7.0 at the time when the uncoated tablet containing the digestive enzyme is dissolved so that the digestive enzyme is not inactivated in the stomach. have.

Figure 1 is a measure of the enzyme activity of biodiastatase in each pH-specific buffer.

Figure 2 measures the enzyme activity of lipase in each pH buffer.

The repellent gastrointestinal drug of the present invention contains sodium bicarbonate, magnesium metasilicate aluminate, magnesium carbonate and aldioxa (allantoin) as antacid components in the coating layer, and biodiastatase and lipase as an enzyme component in the uncoated layer It contains scofolia extract, preferably 200 mg of sodium bicarbonate, 125 mg of magnesium aluminate silicate, 65 mg of magnesium carbonate, 25 mg of dioxa, 5 mg of scofolia, or 1000 mg of biodiastat. And 5 mg of lipase AP-6. First, 10 times acid of biodiastatase, lipase, and scofolia X to be contained in uncoated tablets is prepared to prepare an enzyme powder or granules, and then uncoated tablets and metasilicate as an antacid component. It is prepared by coating with a coating solution containing magnesium aluminate, sodium hydrogen carbonate, magnesium carbonate and aldioxa (allantoin).

As the coating agent used in the present invention, hydroxypropyl methyl cellulose, polyvinyl alcohol, methyl cellulose, gelatin, gum arabic and the like can be used.

In addition, crystalline cellulose, polyvinylpyrrolidone, lactose, and the like, which are conventional excipients, can be added in an acceptable amount, and flavorings such as peppermint oil can be added as necessary.

Gastrointestinal gastrointestinal digestive tablets of the present invention is a coating layer containing an antacid and a gastrointestinal protective agent is first dissolved to surround the stomach wall to suppress the secretion of gastric acid, while the pH of the stomach is maintained at 3.5 to 7.0 while the enzyme-containing uncoated layer is dissolved It is designed to increase the physiological activity of the enzyme to the best, it has the advantage that the digestive action by the enzyme appears quickly by creating an environment in the stomach so that the digestive enzyme can work in the stomach.

The present invention is preferably a prescription design to take two tablets once.

Hereinafter, examples and experimental examples of the present invention will be described, but are not intended to be limited thereto.

Example 1

[Preparation of uncoated enzyme]

15 g of biodiastatase, 5 g of lipase AP-6, and 1 g of magnesium stearate are passed through a No. 40 sieve and then transferred to a debulcon mixer. Next, 5 g of scopolyax and 45 g of lactose are mixed and distributed, passed through a No. 40 sieve, and then transferred to a debulcon mixer and mixed for 30 minutes to prepare an enzyme powder.

[coating]

100 ml of purified water, 10 g of gum arabic powder, 20 g of gelatin, and 250 g of white sugar were added sequentially to a preparation container, followed by stirring at 80 ° C. for 30 minutes to dissolve completely. 200 g of sodium bicarbonate, 125 g of magnesium aluminate silicate, 65 g of magnesium carbonate, and 25 g of dioxa are mixed. Spread the uncoated tablet in a sugar pen, sprinkle the prepared liquid and sprinkle the mixture evenly over it. After coating the antacid in this way, it was dried at 40 ° C. and purified water 100ml, gelatin 11g, titanium oxide 5g, yellow No. 5, red No. 40 and yellow No. 203 were placed in the preparation container and stirred for 20 minutes to completely dissolve the antacid. Sprinkle evenly on the coated tablets for coloring.

Finally, use carnauna lead to polish and dry

The repellent gastrointestinal drug of the present invention is preferably taken two tablets once per adult, three times a day after meals or between meals.

In the present invention, the content of the antacid contained in the coating layer so that the digestive enzyme shows an optimal pH range (per tablet) is as follows.

1) Sodium bicarbonate 260mg

2) 160 mg magnesium carbonate

3) Sodium Hydrogen Carbonate 200mg

Magnesium Carbonate 65mg

Magnesium Metasilicate Magnesium 125mg

Experimental Example

A stability test was carried out with three Lot no ANT 101, 102, 103 samples prepared according to Example 1 (manufacture date: 1999.2.01).

I. Main equipment used for stability test

1) Thermo-hygrostat-Constant temperature and humidity

2) UV-Spectrophotometer

3) HPLC-For content test

4) Atomic Absorption Spectrometer-for content test

II. Test Methods

1) Appearance: Observe directly with the naked eye.

2) Disintegration test: Should follow the disintegration test of the general test method of the KP.

3) Confirmation test

(1) Magnesium metasilicate

According to KFDA Notification No. 98-127, Identification of Methyl Aluminate Metasilicate Aluminate, Sodium Hydrogen Carbonate, or Pancreatin Tablet.

(2) sodium bicarbonate

According to KFDA Notification No. 98-127, Identification of Methyl Aluminate Metasilicate Aluminate, Sodium Hydrogen Carbonate, or Pancreatin Tablet.

(3) magnesium carbonate

It is tested according to the Magnesium Identification Test in (1).

(4) Aldioxa

Grind about 5 tablets finely, powder it, add 10 ml of diluted hydrochloric acid, and boil for 5 minutes. Add 10 ml of phenyl hydrazine solution (1 → 100), cool, add 0.5 ml of potassium ferricyanide solution, mix well, and add 1 ml of hydrochloric acid. When shaken, the liquid appears red.

(5) Scopolia X

This drug is used as a powder and is weighed in an equivalent amount of about 50 mg. The drug is tested according to the Korean Test No. 98-127, Methyl Aluminate Metasilicate Aluminate, Sodium Hydrogen Carbonate, or Pancreatin Tablet.

(6) biodiastatase 1000, lipase AP6

Positive test when tested according to the Assay.

Enzyme Activity Test

◎ biodiasta

Enzyme activity was measured in each pH buffer under each digestibility test condition (FIG. 1).

◎ lipase

Enzyme activity is measured in each pH buffer (Fig. 2).

4) Antacid Test

Take about 20 tablets or more of this solution and weigh it to get the average weight of 2 tablets. Use 45 powder (350㎛) to make an average powder. Mix equally and add 550mg to 100 ml of 0.1N hydrochloric acid. Shake for 1 hour at ± 2 ℃, mix, filter and cool. If necessary, filter again to accurately extract 50 ml of the filtrate, and titrate the excess hydrochloric acid with 0.1 N sodium hydroxide solution. The end point of the titration is pH 3.5. Do a blank test in the same way.

f: Regulatory coefficient coefficient of 0.1N sodium hydroxide solution

a: consumption amount of 0.1 N sodium hydroxide solution (ml)

b: Consumption of 0.1 N sodium hydroxide solution (ml)

t: weight of 6 tablets

s: amount of sample (mg)

5) Content test

(1) Silicates of silica (SiO ₂ ), aluminum oxide (Al ₂ O ₃ ), magnesium oxide (MgO): Methanol alumina metasilicate in magnesium bisulfate metasilicate alumina, sodium bicarbonate, pancreatin Test according to Magnesium Nitrate assay.

(2) Aldioxa (Allantoin)

Take at least 20 tablets of this solution and make it powder. Take 1 mg of an allantoin and add water to make exactly 100 ml. Use this solution as the sample solution. Separately, weigh 100 mg of alatoine (105 ℃, 3 hours, dry) accurately and add water to make exactly 100ml. Take 1ml of this solution and add water to make 100ml. Take 5 ml of each sample and standard solution into a test tube with brown stoppers, add 1 ml of 0.5 N sodium hydroxide, close the stopper, warm for 8 minutes in a water bath, cool, and add 5 ml of 0.4 N potassium hydrogen phosphate solution. Diacetyl monooxime, acetic acid solution (1: 200) and 5 ml each of antipyriline and ferric sulfate solution were added at a 1: 1 ratio, and the solution was warmed in a water bath for about 40 minutes and ice-cooled. Leave it. Separately, about 5 ml of each diluted 100-fold sample and standard solution are accurately taken, and 1 ml of 0.5 N sodium hydroxide and 5 ml of 0.4 M potassium dihydrogen phosphate are added in the same manner.

Absorbance AT and AS are measured at a wavelength of 460 nm using the blank as a control.

◎ Diacetyl monooxime and acetic acid solution (1: 200): Dilute acetic acid (1 → 20) is added to 0.5 g of diacetyl monooxime to make 100 ml.

◎ Antipyrine and Ferric Sulfate Sulfate Solution: Dilute sulfuric acid (1 → 5) into 0.4g of antipyrine and 0.005g of ferric sulfate to make 100ml.

(3) aluminum

① Preparation of Test Solution

Take about 20 tablets or more, powder it, weigh 1 g precisely, place it in a ceramic crucible, loosen the lid, and heat it slightly to carbonize it. After cooling, 4 ml of nitric acid and 1 ml of sulfuric acid are added and carefully heated until white smoke is not formed. When the carbide is left again, it is wet with a small amount of nitric acid and sulfuric acid after cooling and heated again, and then carbonized by heating at 600 ° C. for 4-5 hours. After cooling, 2 ml of aqua regia was added and evaporated to dryness in a water bath. 10 ml of boiling water and 5 drops of hydrochloric acid were added to the residue, followed by heating for 5 minutes. If necessary, filter by cold phase, wash the residue as water, add filtrate and tax solution, and add water to make exactly 100 ml. Take 5 ml of this solution accurately and add 0.5 ml of hydrochloric acid and water to make exactly 100 ml. Use this solution as the sample solution.

② Preparation of Standard Solution

Take an appropriate amount of aluminum standard stock solution and add water to make 0.2 ppm, 0.4 ppm, and 0.6 ppm aluminum standards.

③ operation

The test solution and the standard solution are tested according to the KP Atomic Absorption Spectrophotometry under the following conditions, and the aluminum concentration in the test solution is determined by the calibration curve obtained from the absorbance of the standard solution.

④ Condition

Gas used: flammable gas-acetylene, delayed gas-nitrous oxide

Lamp: Aluminum Hollow Cathode Lamp

Wavelength: 309.2 nm

(4) sodium bicarbonate

Take about 20 tablets of this solution and weigh it precisely to make a powder. Take about 300mg of sodium bicarbonate and dissolve it in 30ml of water. Filter the residue over 2 times with 10ml of water and combine the filtrate and the tax solution with methyl orange. Add 2-3 drops and titrate with 0.1 N sulfuric acid.

1 ml of 0.1 N sulfuric acid = 8.402 mg NaHCO ₃

(5) Hiyosushiamine in scofolia extract

① Preparation of Standard Solution

Accurately take 33 mg of L-hiyosushiamine standard (in terms of dry weight loss), place it in a 100 ml volumetric flask, completely dissolve in 30 ml of methanol: water (70:30), and fill it to the mark with methanol: water (70:30). 10 ml of this solution is taken into a 100 ml volumetric flask and filled with methanol: water (70:30) to the mark, filtered through a 0.45 μm membrane filter to obtain a standard solution.

② Preparation of Test Solution

Take 20 tablets or more and calculate the average weight. Use powder to make 3.3 mg of Hiyosushiamine. Add 100 ml volumetric flask and fill with methanol: water (70:30) to the mark and stir for 30 minutes. After filtration with a membrane filter to the sample solution.

③ operation

Under the following conditions, the liquid chromatograph method of the pharmacopoeia general test method for 10µl of the standard solution and the sample solution, and then the area QS, QT of the standard solution and the sample solution.

⑤ Condition

Column: Spectraphysics Spherisorb 10 Si (L: 25 cm, I.D: 4.6 cm)

Detector: UV Absorbance Spectrometer (210nm)

Flow rate: 1.5 ml / min

Temperature: Constant temperature around 30 ℃

Chart Speed: 0.5cm / min

Mobile phase: Methanol containing sodium lauryl sulfate 0.1w / v%, tetramethylammonium chloride 0.33w / v%, sodium perchlorate 0.05w / v%, pH 6.8 phosphate buffer mixture (55:45)

Sensitivity: 0.01 Aufs

(6) starch sugar power (pH 5.0)

Take about 20 tablets of this solution, weigh it, powder it, accurately weigh 1.0 g, add 50 ml of acetic acid and sodium acetate buffer solution (pH 5.0), shake for 10 minutes, mix, and centrifuge. Take 10 ml of this supernatant and add water to make 100 ml.

Take 10 ml of 1% solution of potato starch, leave at 37 ± 0.5 ° C for 10 minutes, and accurately add 1 ml of sample solution and shake. Leave this solution for 10 minutes at 37 ± 0.5 ℃, add 2 ml of alkaline tin stannate solution of ferring solution, shake well, add 2 ml of copper solution of ferring solution, shake gently, place a funnel in a test tube, and heat for 15 minutes in a water bath. After cooling to 2 ° C, add 2 ml of potassium iodide solution and 2 ml of dilute sulfuric acid (1 → 6), titrate the free iodine with 0.05 N sodium thiosulfate (b ml), and dissolve 1 ~ 2 drops of soluble starch solution when the end point of titration is close. The end point is when the blue-purple color formed by the color becomes colorless.

10 ml of water instead of 10 ml of potato starch 1% solution was added and titrated as above.

f: Regulatory coefficient coefficient of 0.05N sodium thiosulfate solution

W1: Average weight per tablet

W2: Amount of sample taken

Inverse assumption: When amylase acts on potato starch at 37 ° C, the amount of enzyme that leads to an increase in reducing power corresponding to 1 mg of glucose in 1 minute of the initial reaction is called 1 unit of starch saccharification capacity.

[Hours]

Acetic acid, sodium acetate (pH 5.0)-13.6 g of sodium acetate is added to make 100 ml, and diluted acetic acid is adjusted to pH 5.0.

Potassium iodide TS-Dissolve 70 ml of water in 30 g of potassium iodide. Shade preservation, prepare when using.

1% solution of potato starch-1 g of potato starch is dried at 105 ° C for 2 hours, and then the weight loss is measured. Accurately weigh the dried potato starch corresponding to 1.0 g of the dried product, add 20 ml of water, dissolve, shake, add 5.0 ml of 2N sodium hydroxide solution, heat for 3 minutes in a water bath, add 25 ml of water, cool, neutralize with 2N hydrochloric acid solution, and acetic acid and acetic acid. Add 10 ml of sodium buffer solution (pH 5.0) and add water to make 100 ml. Manufactured when writing.

(7) starch purification power (pH 5.0)

Take about 20 tablets of this solution, weigh it to make powder, and weigh 2.6 g accurately, add 100 ml of acetic acid and sodium acetate buffer solution (pH 5.0), shake gently for 10 minutes, mix, and centrifuge to add 5 ml of supernatant. What is done is the test liquid. Take 10 ml of 1% solution of potato starch and leave it at 37 ± 0.5 ℃ for 10 minutes, shake 1 ml of sample solution, and shake the solution at 37 ± 0.5 ℃ for 10 minutes. Take 1 ml of this solution, add 10 ml of 0.1 N hydrochloric acid, and shake. Mix 0.5 ml of this solution, add 10 ml of 0.0004 N iodine solution, shake, and measure absorbance AT at 660 nm. Separately, add water instead of the test solution, and operate in the same manner as the test solution to measure the absorbance AB.

W1: average weight per tablet

W2: Amount of sample taken

Inverse assumption: When amylase acts at 100 mg of potato starch and 37 ° C, the amount of enzyme that reduces the blue color of potato starch by iodine 10% in one minute of the initial reaction is 1 unit of starch purification capacity.

(8) protein digest (pH 6.0)

Take about 20 tablets of this solution, weigh it, powder it, weigh precisely 2.6 g, add 50 ml of cooled 0.1 N phosphate buffer at pH 6.0, shake gently for 20 minutes, mix, and filter the filtrate as a sample solution.

Take exactly 5.0 ml of casein solution (pH 6.0), leave it at 37 ± 0.5 ° C for 10 minutes, add 1 ml of the sample solution, and shake. Leave this solution at 37 ± 0.5 ℃ for 10 minutes, add 5.0ml of trichloroacetic acid solution, shake and mix, and filter again after standing at 37 ± 0.5 ℃ for 30 minutes.

Accurately take 2.0 ml of the filtrate, add 5.0 ml of 0.55 M sodium carbonate TS and 1.0 ml of diluted polyline TS (1 → 3), and leave at 37 ± 0.5 ° C. for 30 minutes. Measure the absorbance AT at 660 nm.

Separately, 1.0 ml of the sample solution is accurately taken, 5.0 ml of trichloroacetic acid solution is added, shaken, and 5.0 ml of casein solution is added. The solution is allowed to stand at 37 ± 0.5 ° C. for 30 minutes, and the absorbance AB is measured as described below.

W1: Average weight per tablet (mg)

W2: Amount of sample taken (mg)

F: It is calculated | required by the tyrosine calibration curve as the quantity (microgram) of tyrosine corresponding to an absorbance difference of 1.000.

Inverse assumption: When the protease acts on casein at 37 ° C, the amount of enzyme that leads to an increase in the nonproteinaceous polychromate corresponding to 1 µg of tyrosine in the first minute of the reaction is called 1 unit of protein digestibility.

Preparation of tyrosine calibration curve: Accurately weigh 500.0 mg of tyrosine standard dried at 105 ° C. for 3 hours, add 0.2 N hydrochloric acid solution to make 500 ml. Take 1.0 ml, 2.0 ml, 3.0 ml and 4.0 ml of this solution and add 0.2N hydrochloric acid to make 100.0 ml.

Accurately take 2.0 ml of each solution, add 5.0 ml of 0.55 M sodium carbonate TS and 1.0 ml of diluted polyline TS (1 → 3), and leave at 37 ± 0.5 ° C for 30 minutes, and immediately absorb absorbances A1, A2, A3 and Measure A4.

Separately, 2.0 ml of 0.2 N hydrochloric acid solution was operated in the same manner to measure absorbance AB.

A calibration curve is prepared with the difference in absorbance on the vertical axis and the amount of tyrosine on the horizontal axis.

[Hours]

Trichloroacetic acid solution-Add 1.80g of trichloroacetic acid and 1.80g of anhydrous sodium acetate, add 5.5ml of 6N acetic acid and water to make 100ml.

Casein solution (pH 6.0)-1 g of emulsion casein was dried at 105 ° C for 2 hours to calculate the weight loss, and 1.2 g of the corresponding amount of emulsion casein was added. Add hydrochloric acid or 1N sodium hydroxide solution to adjust pH to 6.0, and add water to make 200ml. Prepare when writing.

0.55 M sodium carbonate TS-Dissolve in 58.3 g of anhydrous sodium carbonate and dissolve to 1000 ml.

(9) Fat Digestion (pH 6.0)

Take about 20 tablets of this solution and weigh it to make 4.5 g of fine powder, add water to dissolve it, and make 50 ml of the filtrate.

5.0 ml of olive oil emulsion and 4.0 ml of 0.1M phosphate buffer solution are mixed and left to stand for 10 minutes in a constant temperature water bath at 37 ° C. Then, 1 ml of sample solution is added and shaken every 10 minutes to react for 20 minutes at 37 ° C. 1) Add 10 ml to stop the enzyme reaction, add 10 ml of 0.05 N sodium hydroxide solution and 10 ml of acetone-ethanol mixture (1: 1), titrate 0.05 N hydrochloric acid solution with excess sodium hydroxide (A ml).

(Indicator: 2 drops of phenolphthalein solution)

Separately, add 10 ml of acetone and ethanol mixture (1: 1) to 1 ml of the test solution, and titrate it in the same manner as above (B ml).

F: Regulatory coefficient of 0.05N hydrochloric acid

Inverse assumption: The amount of enzyme which liberates the free acid corresponding to 0.6 ml of 0.05 N sodium hydroxide solution at 37 ° C. for 30 minutes is 10 units of fat digestion capacity.

(The amount of enzyme that liberates an acid corresponding to 1 μeq for 1 minute under the above conditions is referred to as a 10-digestion capacity).

[Hours]

Olive oil emulsion: Take 75 ml of olive oil and 225 ml of 2% polyvinyl alcohol solution, emulsify in an ice cold bath at 3 ~ 10 ℃ for 10 minutes, and use.

2% polyvinyl alcohol solution: 5 g of polyvinyl alcohol is suspended in 250 ml of water and heated to 80 ° C with shaking.

After cooling, leave this solution until cleared and filter.

Phosphate buffer (pH 6.0): 0.1M potassium dihydrogen phosphate (KH ₂ PO ₄ ) 0.1M sodium dihydrogen phosphate (Na ₂ HPO ₄ ) is adjusted to pH 6.0.

Ⅲ, Test Result Data: (Refer to Table 1a to Table 1f)

Ⅳ Observation of Results

As a result of the long-term preservation test results according to Table 1, the repellent gastrointestinal drug of the present invention maintained the titer of the digestive enzyme for three years of use, the storage stability was recognized, and the production of degradation products could not be confirmed.

The present invention is a gastrointestinal drug showing a rapid digestion effect in the stomach characterized in that the antacid component contained in the coating layer to maintain the pH of the gastric acidity to 3.5 ~ 7.0 when dissolving in the stomach to maximize the enzymatic power of the enzyme in the stomach to be.

The present invention is designed so that the enzyme layer disintegrates after the disintegration of the antacid layer as a coating layer is completed, and the enzyme shows activity under optimum conditions in the stomach and can be manufactured without using a special tableting machine.

Claims (2)

In the preparation of a coating repellent gastrointestinal drug having a coating layer, by mixing biodiastatase, lipase and scopolyax, tableting uncoated tablet, and at least one antacid selected from sodium hydrogen carbonate, magnesium aluminate silicate and magnesium carbonate in the coating solution and aldi A method for preparing a repellent gastrointestinal drug, comprising mixing and coating oxa (allantoin). delete