Search

CN-122005479-A - Pharmaceutical composition for gastroesophageal reflux disease and preparation method thereof

CN122005479ACN 122005479 ACN122005479 ACN 122005479ACN-122005479-A

Abstract

The invention provides a composition for gastroesophageal reflux disease and a preparation method thereof, belonging to the field of pharmaceutical preparations. The composition provided by the invention comprises a tablet core and a coating layer, wherein the tablet core comprises a plurality of components added in two modes of internal addition and external addition. The composition has the advantages of uniform content of active ingredients, better dissolution and extremely high stability, no sticking and pressing roller problem in the preparation process, simple and easy process and suitability for industrial production.

Inventors

  • CHEN XIAOYU
  • ZHOU YUEGUANG
  • YANG ZHIJUN
  • GU YINAN
  • HE XUNGUI
  • HU QIANG

Assignees

  • 珠海莱奇生物科技有限公司

Dates

Publication Date
20260512
Application Date
20260317

Claims (10)

  1. 1. The oral tablet comprises a tablet core and a coating layer, wherein the tablet core comprises the following components of tigorase, microcrystalline cellulose, mannitol, croscarmellose sodium, hydroxypropyl cellulose, silicon dioxide and magnesium stearate, and the preparation method of the tablet core comprises a dry granulation process, wherein the microcrystalline cellulose, the croscarmellose sodium, the silicon dioxide and the magnesium stearate are respectively added by adopting an internal adding mode and an external adding mode.
  2. 2. The oral tablet according to claim 1, wherein the tablet core comprises, by weight, 23 to 27 parts of tigorason, 35 to 41 parts of microcrystalline cellulose, 23 to 27 parts of mannitol, 6 to 8 parts of croscarmellose sodium, 2.5 to 3.5 parts of hydroxypropyl cellulose, 0.8 to 1.2 parts of colloidal silicon dioxide and 0.8 to 1.2 parts of magnesium stearate.
  3. 3. The oral tablet according to claim 1 or 2, wherein the mass ratio of the added microcrystalline cellulose to the added microcrystalline cellulose is 1:0.8-1:1.
  4. 4. The oral tablet of claim 1 or 2, wherein the mass ratio of the added croscarmellose sodium to the added croscarmellose sodium is 1:0.6-1:1.
  5. 5. The oral tablet according to claim 1 or 2, wherein the mass ratio of the internally added silica to the externally added silica is 1:0.8-1:1.2, and/or the mass ratio of the internally added magnesium stearate to the externally added magnesium stearate is 1:0.8-1:1.2.
  6. 6. The oral tablet according to claim 1 or 2, wherein the coating layer is prepared from a gastric-soluble film coating premix, and the mass of the coating layer is 2% -8% of the mass of the tablet core.
  7. 7. The oral tablet of claim 1, wherein the tablet core comprises, by weight, 25 parts of tigorase, 36-39 parts of microcrystalline cellulose, 24-26 parts of mannitol, 7 parts of croscarmellose sodium, 3 parts of hydroxypropyl cellulose, 1 part of colloidal silicon dioxide and 1 part of magnesium stearate, wherein the mass ratio of the added microcrystalline cellulose to the added microcrystalline cellulose is 1:0.8-1:0.9, the mass ratio of the added croscarmellose sodium to the added croscarmellose sodium is 1:0.7-1:1, the mass ratio of the added colloidal silicon dioxide to the added colloidal silicon dioxide is 1:1, the mass ratio of the added magnesium stearate to the added magnesium stearate is 1:1, the coating layer raw material is a gastric-soluble film coating premix, and the mass ratio of the coating layer is 2% -4% of the mass of the tablet core.
  8. 8. The oral tablet according to any one of claims 1 to 7, wherein the tablet core is prepared by mixing microcrystalline cellulose, croscarmellose sodium, silicon dioxide and magnesium stearate, and hydroxypropyl cellulose, mannitol and tigorason, granulating by dry method, grading, adding microcrystalline cellulose, croscarmellose sodium, silicon dioxide and magnesium stearate, mixing, and tabletting.
  9. 9. A method of preparing the oral tablet of any one of claims 1-7, comprising: 1) Sieving silicon dioxide for standby; 2) Mixing hydroxypropyl cellulose, internally added microcrystalline cellulose, internally added croscarmellose sodium, internally added silicon dioxide, mannitol and agoraphite to obtain a premix 1 material; 3) Dispersing, sieving and uniformly mixing the material in the premixing mode 1 to obtain a material in the premixing mode 2; 4) Adding internally added magnesium stearate, and uniformly mixing to obtain a premixed material 3; 5) Granulating the premixed material 3 by a dry method, then finishing the granules, and uniformly mixing to obtain a granulated material; 6) Adding the added microcrystalline cellulose, the added croscarmellose sodium and the added silicon dioxide into the granulated material, and uniformly mixing; 7) Tabletting the total mixed material to obtain tablet cores; 8) Coating the tablet core to weight gain of 2% -8% by adopting coating liquid with the solid content of 10% -15%, and drying to obtain the tablet.
  10. 10. The preparation method according to claim 9, comprising at least one of the following conditions: in the step 1), the silicon dioxide is sieved by a sieve with 25-50 meshes; In the step 3), a screen with 0.5mm to 1.5mm is used for dispersing and sieving; In the step 5), in the process of finishing grains, the aperture of the screen is 0.3 mm-1.5 mm; in step 6), the total mixture does not pass through a 50 mesh screen more than 25wt%, and In the step 8), water and a gastric-soluble film coating premix are uniformly mixed, a coating solution with the solid content of 10% -15% is obtained through filtering by a 80-mesh screen, a tablet core with the temperature of 35 ℃ -50 ℃ is coated to weight gain of 2% -5% by using the coating solution, and then the tablet core is dried at 38 ℃ -45 ℃ until the weight loss on drying is not more than 3%, so that the oral tablet is obtained.

Description

Pharmaceutical composition for gastroesophageal reflux disease and preparation method thereof Technical Field The invention relates to a pharmaceutical composition for gastroesophageal reflux disease and a preparation method thereof, belonging to the field of pharmaceutical preparations. Background In the field of pharmaceutical formulations, pharmaceutical formulations comprising the same ingredients may also exhibit large differences in certain pharmaceutical properties, such as dissolution characteristics, stability, etc. of the active ingredient contained in the formulation, which differences are associated with the ingredients, content, impurities, and/or manufacturing process of the formulation, etc. Therefore, the development of the prescription, process, etc. of the pharmaceutical preparation is also extremely important. Tegoratron, which is known under the chemical name (S) -4- [ (5, 7-difluorochroman-4-yl) oxy ] -N, N, 2-trimethyl-1H-benzo [ d ] imidazole-6-carboxamide, is a potassium competitive acid blocker (P-CAB) useful in the treatment of diseases mediated by acid pump antagonistic activity, such as gastroesophageal reflux disease, reflux esophagitis, duodenal ulcer, helicobacter pylori infection, and the like. According to the prior studies, it is known that tigoramin is a very poorly water-soluble drug and is prone to cause instability of the drug action over the storage time. In patent CN110121333B et al, a method for obtaining tablets by wet granulation process is described, but due to the influence of the properties of tigoracle, the wet granulation process has very high requirements on the quality of the tigoracle, and for the tigoracle with relatively low stability under high temperature or high humidity conditions, such as metastable crystal form, amorphous form or other forms, the wet granulation process is difficult to control and implement, so that the selection of the tigoracle is limited, and the difficulty and cost of the preparation are also increased. Tablets are commonly used dosage forms for oral administration. Therefore, it is still difficult and necessary to develop an oral tablet of tigorason which can keep the pharmaceutical effect stable and is suitable for industrial mass production and which meets the requirements or better in all aspects such as dissolution behavior. Disclosure of Invention The invention provides a tablet composition for oral administration, which has better dissolution, stable drug action and no bitter taste. The oral tablet comprises a tablet core and a coating layer, wherein the tablet core consists of agoraphobia, microcrystalline cellulose, mannitol, croscarmellose sodium, hydroxypropyl cellulose, silicon dioxide and magnesium stearate, and the preparation method of the tablet core comprises a dry granulation process, wherein the microcrystalline cellulose, the croscarmellose sodium, the silicon dioxide and the magnesium stearate are respectively added in an internal adding mode and an external adding mode. According to the invention, the tablet core can be composed of 23-27 parts of tigorason, 35-41 parts of microcrystalline cellulose, 23-27 parts of mannitol, 6-8 parts of croscarmellose sodium, 2.5-3.5 parts of hydroxypropyl cellulose, 0.8-1.2 parts of silicon dioxide and 0.8-1.2 parts of magnesium stearate in parts by weight. In some preferred embodiments, the tablet core consists of, by weight, 24-26 parts of tigorason, 36-40 parts of microcrystalline cellulose, 24-26 parts of mannitol, 6-8 parts of croscarmellose sodium, 2.7-3.3 parts of hydroxypropyl cellulose, 0.9-1.1 parts of silicon dioxide and 0.9-1.1 parts of magnesium stearate. In some preferred embodiments, the tablet core is composed of 25 parts by weight of tigorason, 36-39 parts by weight of microcrystalline cellulose, 24-26 parts by weight of mannitol, 7 parts by weight of croscarmellose sodium, 3 parts by weight of hydroxypropyl cellulose, 1 part by weight of silicon dioxide and 1 part by weight of magnesium stearate. In some preferred embodiments, the tablet core consists of, in parts by weight, 25 parts of tigorason, 38 parts of microcrystalline cellulose, 25 parts of mannitol, 7 parts of croscarmellose sodium, 3 parts of hydroxypropyl cellulose, 1 part of silicon dioxide and 1 part of magnesium stearate. In some preferred embodiments, the tablet core consists of, in parts by weight, 25 parts of tigorason, 39 parts of microcrystalline cellulose, 24 parts of mannitol, 7 parts of croscarmellose sodium, 3 parts of hydroxypropyl cellulose, 1 part of silicon dioxide and 1 part of magnesium stearate. In some preferred embodiments, the tablet core consists of, in parts by weight, 25 parts of tigorason, 39 parts of microcrystalline cellulose, 25 parts of mannitol, 7 parts of croscarmellose sodium, 3 parts of hydroxypropyl cellulose, 1 part of silicon dioxide and 1 part of magnesium stearate. According to the invention, the preparation method of the tablet core comprises a dry granul