CN113648327B - Pharmaceutical composition and preparation method thereof - Google Patents
Pharmaceutical composition and preparation method thereof Download PDFInfo
- Publication number
- CN113648327B CN113648327B CN202110976753.6A CN202110976753A CN113648327B CN 113648327 B CN113648327 B CN 113648327B CN 202110976753 A CN202110976753 A CN 202110976753A CN 113648327 B CN113648327 B CN 113648327B
- Authority
- CN
- China
- Prior art keywords
- citric acid
- magnesium oxide
- potassium bicarbonate
- sodium picosulfate
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
- A61K33/08—Oxides; Hydroxides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1611—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
Abstract
The invention belongs to the technical field of medicine preparation, and particularly relates to a pharmaceutical composition containing sodium picosulfate, magnesium oxide, citric acid and/or potassium bicarbonate and a preparation method thereof. The method comprises the steps of dissolving citric acid and magnesium oxide in water, and adjusting the pH value to obtain a magnesium citrate solution; and then obtaining solid magnesium citrate powder by a proper drying method, crushing potassium bicarbonate, further granulating the crushed solid magnesium citrate powder and the solid magnesium citrate powder by using a sodium picosulfate water solution, and adding other auxiliary materials to mix to obtain the pharmaceutical composition. The method avoids the step of magnesium oxide adsorption coating citric acid, and simultaneously obtains products with good uniformity and stable quality.
Description
Technical Field
The invention belongs to the technical field of medicine preparation, and particularly relates to a pharmaceutical composition containing sodium picosulfate, magnesium oxide, citric acid and/or potassium bicarbonate and a preparation method thereof.
Background
The compound sodium picosulfate particle is a new drug developed by the drug manufacturing company of huiling, and the trade name is as follows: PREPOPIK TM Petalite, for use in bowel cleansing preparations prior to colonoscopy, X-ray examination. The product is marketed in China in 2018 and 10 months. Specification: each bag contains active ingredients of sodium picosulfate 10mg, magnesium oxide 3.5g, citric acid 12.0g, and auxiliary material of potassium bicarbonate. After the product is dissolved, the magnesium oxide and the citric acid can react to generate the magnesium citrate to play a role in causing diarrhea. Sodium picosulfate is a prodrug that is converted to the active metabolite by bacteria in the colon after oral administration: bis (p-hydroxyphenyl) -pyridyl-2-methane (BHPM) for stimulating intestinal mucosa, promoting intestinal peristalsis, inhibiting water absorption in intestinal tract, and promoting catharsisAnd (4) acting. Compared with the traditional preparation such as the intestine clearing agent polyethylene glycol, the product has the advantages of small liquid amount, good effect and higher patient compliance.
The product contains sodium picosulfate, magnesium oxide, citric acid and potassium bicarbonate as an auxiliary material, and the sodium picosulfate content is lower and only accounts for 0.62 percent, and the materials are salts, are easy to dissolve in water, are difficult to obtain particles with uniform content by using a general preparation technology, and provide great challenges for the preparation technology. Patent CN101820859 "process for preparing a pharmaceutical product comprising citric acid, magnesium oxide, potassium bicarbonate and sodium picosulphate, pharmaceutical composition comprising granules obtained by the process and intermediates" discloses a formulation process: a. applying (in a spraying manner) a sodium picosulfate solution to the surface of the potassium bicarbonate to obtain particles 1; b. mixing magnesium oxide and citric acid, and adhering the magnesium oxide to the surface of the citric acid to obtain particles 2; c. mixing the granules 1 and 2 to obtain granules 3, and subpackaging the granules 3 to obtain the product. The method can obtain product meeting quality standard of medicine, but is unstable. The main reasons are: (1) The magnesium oxide is powder with adsorption property, which can be adhered to the surface of citric acid crystal, so as to isolate sodium picosulfate for stabilization, but in the product formula, the content of magnesium oxide is in the boundary of maximum adsorption capacity, and the difference of raw material source and production process of magnesium oxide production can cause the difference of citric acid adsorption capacity of magnesium oxide to be large. According to the experimental result, the adsorption quantity of the citric acid is 50-100%. This quality difference poses a great risk to the product. Firstly, magnesium oxide cannot be adsorbed on the surface of citric acid in a sufficient amount, and a large amount of unadsorbed fine powder magnesium oxide in the product causes poor mixing uniformity in the later process; secondly, the citric acid surface is not fully covered and coated by the magnesium oxide, so that the contact chance with the sodium picosulfate is increased, and the product is unstable. Although the apparent volumes, particle sizes, etc. of magnesia and other materials are fully studied and defined in patent CN101820859, the above risks cannot be circumvented.
Disclosure of Invention
In order to solve the existing problems, the invention provides a pharmaceutical composition containing sodium picosulfate, magnesium oxide, citric acid and/or potassium bicarbonate and a preparation method thereof, wherein the method comprises the following steps: dissolving citric acid and magnesium oxide in a solvent, and adjusting the pH value to obtain a magnesium citrate solution; and then obtaining the magnesium citrate solid powder by a proper drying method, and further mixing the magnesium citrate solid powder with sodium picosulfate and/or potassium bicarbonate to obtain the pharmaceutical composition.
The method comprises the following specific steps:
(1) Dissolving citric acid and magnesium oxide in a solvent, adjusting the pH value to obtain a magnesium citrate solution with the pH value = 6.5-7.5, and drying to obtain magnesium citrate solid powder;
(2) Crushing potassium bicarbonate to obtain potassium bicarbonate powder;
(3) Dissolving sodium picosulfate in water to obtain a sodium picosulfate solution;
(4) Adding magnesium citrate solid powder and potassium bicarbonate powder into a fluidized bed, atomizing sodium picosulfate solution, spraying into the fluidized bed, granulating the materials in the fluidized bed by one step, drying to the temperature of 45-50 ℃, and mixing with saccharin sodium and essence to obtain the pharmaceutical composition.
In the invention, the influence on the stability of sodium picosulfate is small because the pH of the magnesium citrate solution is close to neutral pH, wherein when the pH of the magnesium citrate solution is between 6.5 and 7.5, the sodium picosulfate is stable. The pH regulator is added to make the pH of the solution be 6.5-7.5, so that the stability of the sodium picosulfate can be improved. The potassium bicarbonate is used as an auxiliary material, and can be added in the subsequent process or not participate in the subsequent process. Variations on the above steps are within the scope of this patent.
The solution can be dried by lyophilization, spray drying or fluidized bed drying, and solid powder with good uniformity and stable quality can be obtained. This is accomplished by common commercial lyophilization equipment, spray equipment, and fluidized beds.
The solvent of the above solution, preferably water, has good solubility. The dissolution of citric acid and magnesium oxide may be carried out at a relatively high temperature to speed the dissolution process, e.g. 40-90 deg.C, preferably 40-70 deg.C, more preferably 65 deg.C. After the citric acid and the magnesium oxide are dissolved, a plurality of pH regulators can be used for regulating, and triethylamine is further optimized and selected for regulating the pH. In the process of dissolving sodium picosulfate, the temperature should be lowered moderately, generally 25 to 65 ℃, preferably 25 to 45 ℃, and more preferably 25 to 35 ℃. The sodium picosulfate generally dissolves rapidly due to its low content. In the dissolving process, the addition of some alcohol solvents has no obvious influence on the dissolving process, methanol or ethanol can be selected, 10-30% of alcohol by volume can be allowed to be added, and a good solution can be obtained.
The spray drying process is selected, the concentration of the solution is more critical, the concentration is higher, the forming or moisture content of the powder can be influenced, and if the concentration is too low, the time is longer and the efficiency is lower. The mass fraction of the magnesium citrate solution is generally selected to be 5 to 60%, preferably 5 to 35%, and more preferably 5 to 20%. The spray drying process is greatly influenced by the equipment and process parameters, such as reducing the spray feeding speed or increasing the air inlet temperature or other measures for improving the drying efficiency, can accept higher feeding concentration and still obtain qualified products. Adjustment of the above steps or parameters is within the scope of the claims.
The invention firstly prepares solution of citric acid and magnesium oxide, then adjusts pH value to 6.5-7.5, adds crushed potassium bicarbonate, uses sodium picosulfate water solution to carry out one-step granulation by utilizing a fluidized bed. The air inlet temperature, the rotating speed of the peristaltic pump and the drying end point temperature are critical, the granulation effect and speed are influenced by the air inlet temperature and the rotating speed of the peristaltic pump, and the moisture content of the granules is influenced by the drying end point temperature. The air inlet temperature is generally selected to be 40-80 ℃, and is further optimized to be 60-80 ℃. The rotation speed of the peristaltic pump is generally selected from 0.5-10 rpm, and is further optimized to 2-5 rpm. The drying end temperature is generally selected from 35-50 ℃, and is further optimized to 45-50 ℃. The one-step granulating process is greatly influenced by the equipment and process parameters, such as changing a nozzle of the granulator or increasing the frequency of a fan or other measures for improving the drying efficiency, can accept higher feeding concentration and can still obtain qualified products. Adjustment of the above steps or parameters is within the scope of the claims.
The medicine composition has unit taking dosage including sodium picosulfate 9-11 mg, magnesium oxide 3.15-3.85 g, citric acid 10.8-13.2 g and potassium bicarbonate 0.45-0.55 g or not.
The composition also contains saccharin sodium, essence and the like, and is also added in the total mixing process.
In the compositions of the present invention, the moisture content should be strictly controlled to maintain product stability. According to the research of the inventor, the moisture of more than 3 percent can cause serious instability of the product, and the moisture should be controlled to be less than 2 percent.
Compared with the prior art, the method has the advantages that citric acid and magnesium oxide are dissolved in the solvent, so that the step of adsorbing and coating citric acid by magnesium oxide is avoided; then, a proper pH value regulator is selected to regulate the pH value of the magnesium citrate solution, so that the stability of sodium picosulfate is improved; finally, a product with proper water content is obtained by adjusting granulation and finishing process parameters; the product obtained by the method has good uniformity and stable quality.
Detailed description of the preferred embodiment
The present invention is further described with reference to the following examples, but the present invention should not be construed as being limited thereto.
Comparative example 1
TABLE 1 composition of comparative example 1 (unit dose package, per bag)
| Comparative example 1 | |
| Material(s) | Weight(s) |
| Sodium picosulfate | 10mg |
| Magnesium oxide | 3.5g |
| Citric acid | 12g |
| Potassium bicarbonate | 0.5g |
| Saccharin sodium salt | 60mg |
| Essence | 60mg |
Comparative example 1 preparation method:
sieving 1kg potassium bicarbonate with 60 mesh sieve, adding into wet granulator, dissolving 20g sodium picosulfate with 2kg purified water, granulating potassium bicarbonate, drying the granules with fluidized bed, and grading with 0.6mm sieve to obtain premix granule 1.
In a three-dimensional mixer, 7kg of magnesium oxide and 24kg of citric acid (60 mesh sieve) were mixed to obtain premix pellets 2. Then 600g of saccharin sodium, 600g of essence and premixed granules 1 are added and mixed totally to obtain the composition. Filling into aluminum foil bags to obtain the product.
[ example 1]
TABLE 2 composition of example 1 (Unit dose Package, per bag)
| Example 1 | |
| Material(s) | Weight (D) |
| Sodium picosulfate | 10mg |
| Magnesium oxide | 3.5g |
| Citric acid | 12g |
| Potassium bicarbonate | 0.5g |
| Saccharin sodium salt | 60mg |
| Essence | 60mg |
Example 1 preparation method:
24kg of citric acid and 7kg of magnesium oxide were put into 10kg of water and heated at 65 ℃ to dissolve them into a clear solution. Drying with spray drying equipment at spray speed of 2.5 ml/min and drying temperature of 140 deg.C to obtain solid powder 1.
1kg of potassium hydrogencarbonate was pulverized using a pulverizer, and charged into a fluidized bed together with solid powder 1, and 20g of sodium picosulfate was dissolved in 4kg of purified water. Atomizing sodium picosulfate solution, and spraying into the fluidized bed to granulate the material in the fluidized bed. Drying to material temperature of 40 deg.C, and grading with 0.6mm screen to obtain granule 2.
Mixing the pre-mixed granule 2, saccharin sodium and essence in a three-dimensional mixer to obtain total mixed granule as medicinal composition, wherein the water content is 1.0%.
The content uniformity of the total blend compositions of comparative example 1 and example 1 was determined as follows:
| sample (I) | Uniformity of content of magnesium oxide% | Uniformity of content of pick sodium sulfate% |
| Comparative example 1 | 5.42 | 8.65 |
| Example 1 | 0.67 | 0.43 |
The above data illustrate that comparative example 1 results in a less uniform product content due to the differences in the amounts prescribed and particle sizes between the different materials; example 1 the problem of non-uniform magnesium oxide and sodium picosulphate content was solved by dissolving citric acid and magnesium oxide into a solution and crushing potassium bicarbonate and then granulating in one step.
[ examples 2 to 9]
TABLE 3 examples 2-9 specific compositions
Preparation of examples 2 to 9:
adding 12g of citric acid into 150g of purified water, stirring and dissolving, adding 3.5g of magnesium oxide, adding a pH regulator, and finally adding 10mg of sodium picosulfate to obtain a mixed solution.
Sodium picosulfate content stability study
The pH and content changes of the solutions of examples 2-9 were determined as follows:
sodium picosulfate content stability survey table
| Sample(s) | 0 | 1 month | 3 month |
| Example 2 | 93.3 | 89.1 | 79.6 |
| Example 3 | 94.6 | 91.5 | 85.9 |
| Example 4 | 98.5 | 97.6 | 97.5 |
| Example 5 | 98.9 | 98.6 | 98.5 |
| Example 6 | 98.7 | 98.1 | 97.9 |
| Example 7 | 86.3 | 85.3 | 84.7 |
| Example 8 | 90.1 | 89.7 | 89.4 |
| Example 9 | 95.4 | 93.1 | 91.8 |
The sodium picosulfate content is greatly influenced by adjusting to different pH values by using different pH regulators, wherein the product has better stability when the pH = 6.5-7.5, and the stability of triethylamine in the pH regulator is best.
[ examples 10 to 13]
TABLE 4 compositions of examples 10-13 (Unit dose Package, per bag)
| Example 10 | Example 11 | Example 12 | Example 13 | |
| Material(s) | Weight (D) | Weight (D) | Weight (D) | Weight(s) |
| Sodium picosulfate | 10mg | 10mg | 10mg | 10mg |
| Magnesium oxide | 3.5g | 3.5g | 3.5g | 3.5g |
| Citric acid | 12g | 12g | 12g | 12g |
| Potassium bicarbonate | 0.5g | 0.5g | 0.5g | 0.5g |
| Saccharin sodium salt | 60mg | 60mg | 60mg | 60mg |
| Essence | 60mg | 60mg | 60mg | 60mg |
| Triethylamine | 2.5mg | 2.5mg | 2.5mg | 2.5mg |
| Temperature of dried material | 35 | 40 | 45 | 50 |
Examples 10-13 methods of preparation:
24kg of citric acid, 7kg of magnesium oxide and 5g of triethylamine were added to 10kg of water and dissolved by heating at 65 ℃ to obtain a clear solution. Drying with spray drying equipment at spray speed of 2.5 ml/min and drying temperature of 140 deg.C to obtain solid powder 1.
1kg of potassium hydrogencarbonate was pulverized using a pulverizer, and charged into a fluidized bed together with solid powder 1, and 20g of sodium picosulfate was dissolved in 4kg of purified water. Atomizing sodium picosulfate solution, and spraying into the fluidized bed to granulate the material in the fluidized bed. Controlling the temperature of the materials to be between 28 and 35 ℃ in the granulating process, and after the granulating is finished, respectively drying the materials to the temperature of 35, 40, 45 and 50 ℃, and then taking 2kg of granules to carry out granule finishing by using a screen with the size of 0.6mm to obtain granules 2.
And mixing the granules 2 at different material temperatures and the saccharin sodium and essence in the prescribed amount in a three-dimensional mixer to obtain total mixed granules, namely the pharmaceutical compositions in different examples.
Stability results
The products obtained in examples 10 to 13 were subjected to moisture detection and stability studies (temperature 40. + -. 2 ℃ C., humidity 75. + -. 10%) and the results were as follows:
according to the data, the moisture content of the sample is more than 3%, and the stability of the sample is poor; the water content is less than 2%, and the stability is good.
Claims (2)
1. A method for preparing a pharmaceutical composition comprises the following raw materials of sodium picosulfate, magnesium oxide, citric acid, potassium bicarbonate, saccharin sodium and essence; it is characterized in that each bag of the unit dose of the pharmaceutical composition contains 9-11 mg of sodium picosulfate, 3.15-3.85 g of magnesium oxide, 10.8-13.2 g of citric acid and 0.45-0.55 g of potassium bicarbonate;
the method comprises the following specific steps:
(1) Dissolving citric acid and magnesium oxide in a solvent, adjusting the pH value to obtain a magnesium citrate solution with the pH value = 6.5-7.5, and performing spray drying to obtain magnesium citrate solid powder;
(2) Crushing potassium bicarbonate to obtain potassium bicarbonate powder;
(3) Dissolving sodium picosulfate in water to obtain a sodium picosulfate solution;
(4) Adding magnesium citrate solid powder and potassium bicarbonate powder into a fluidized bed, atomizing sodium picosulfate solution, spraying into the fluidized bed, granulating the materials in the fluidized bed by one step, drying to the temperature of 45-50 ℃, and mixing with saccharin sodium and essence to obtain the pharmaceutical composition.
2. The method of claim 1, wherein the magnesium citrate solution is present in an amount of about 5 to about 60% by weight.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110976753.6A CN113648327B (en) | 2021-08-24 | 2021-08-24 | Pharmaceutical composition and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110976753.6A CN113648327B (en) | 2021-08-24 | 2021-08-24 | Pharmaceutical composition and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113648327A CN113648327A (en) | 2021-11-16 |
| CN113648327B true CN113648327B (en) | 2023-03-28 |
Family
ID=78492690
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110976753.6A Active CN113648327B (en) | 2021-08-24 | 2021-08-24 | Pharmaceutical composition and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113648327B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115040512B (en) * | 2022-07-28 | 2023-06-20 | 苏州中化药品工业有限公司 | Pharmaceutical composition and preparation method thereof |
| CN115337271B (en) * | 2022-09-30 | 2023-07-21 | 山东创新药物研发有限公司 | Sodium picosulfate granule preparation and preparation process thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101820859B (en) * | 2007-10-12 | 2013-05-01 | 辉凌国际制药（瑞士）有限公司 | Process for the manufacure of pharmaceutical product comprising citric acid, magnesium oxide, potassium bicarbonate and sodium picosulfate, pharmaceutical composition comprising granules obtained by such process and intermediate |
| CN105456264B (en) * | 2015-12-03 | 2018-07-10 | 广州瑞尔医药科技有限公司 | Pharmaceutical composition of economic benefits and social benefits laxative and preparation method thereof |
| CN112603927A (en) * | 2020-12-21 | 2021-04-06 | 苏州二叶制药有限公司 | A pharmaceutical composition containing sodium picosulfate, magnesium oxide, citric acid and potassium bicarbonate, and its preparation method |
-
2021
- 2021-08-24 CN CN202110976753.6A patent/CN113648327B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN113648327A (en) | 2021-11-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN113648327B (en) | Pharmaceutical composition and preparation method thereof | |
| WO2021043227A1 (en) | Coated granule, solid dispersion, and preparation containing vortioxetine hydrobromide for oral taste masking | |
| CN108658817A (en) | A kind of preparation method of Florfenicol nanocrystal | |
| CN103705520A (en) | Method for preparing rivaroxaban solid composition | |
| CN112494434A (en) | Dry suspension containing oseltamivir phosphate and preparation method thereof | |
| CN103393617B (en) | Febustat tablet and preparation method thereof | |
| CN105030705B (en) | A kind of cancer therapy drug erlotinib Hydrochloride tablet and preparation method thereof | |
| CN112603927A (en) | A pharmaceutical composition containing sodium picosulfate, magnesium oxide, citric acid and potassium bicarbonate, and its preparation method | |
| CN106727396A (en) | A kind of II crystal linezolid piece and preparation method thereof | |
| CN110354086B (en) | Preparation method of candesartan cilexetil tablets | |
| CN105434386A (en) | Sustained release tablet containing high water-soluble active ingredients and preparation method thereof | |
| CN109718215A (en) | A kind of Ezetimibe piece | |
| CN106619572A (en) | Quinocetone sustained-release pellet and preparation method thereof | |
| JPH05262671A (en) | Raw material granule for medicinal coating liquid | |
| CN104116715A (en) | High-drug loading capacity oxcarbazepine controlled-release granule and preparation method thereof | |
| CN114042050A (en) | Preparation method of Venetu pull sheet | |
| CN111346064B (en) | Rivaroxaban tablet and preparation method thereof | |
| CN104208072A (en) | Megestrol acetate hot-melt extrusion preparation | |
| WO2009133774A1 (en) | Spherical granules and method of producing the same | |
| CN102949369B (en) | Preparation method of gemifloxacin mesylate medicinal composition | |
| CN110787130A (en) | 18 β -glycyrrhetinic acid solid dispersion and preparation method thereof | |
| CN114681404A (en) | Repaglinide granule pharmaceutical composition and preparation method thereof | |
| CN106924262A (en) | A kind of solid dispersions of unformed tropsch imatinib citrate and pharmaceutic adjuvant and preparation method thereof | |
| CN114392241B (en) | Ripide Wei Linpian and preparation method thereof | |
| EP3501497A1 (en) | Dispersion process of adapalene in a gel preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |