CN112137990A - Epalrestat sustained-release preparation and preparation method thereof - Google Patents
Epalrestat sustained-release preparation and preparation method thereof Download PDFInfo
- Publication number
- CN112137990A CN112137990A CN202011214487.5A CN202011214487A CN112137990A CN 112137990 A CN112137990 A CN 112137990A CN 202011214487 A CN202011214487 A CN 202011214487A CN 112137990 A CN112137990 A CN 112137990A
- Authority
- CN
- China
- Prior art keywords
- release
- sustained
- epalrestat
- coating
- preparation
- 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.)
- Pending
Links
Images
Classifications
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/426—1,3-Thiazoles
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
- A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hematology (AREA)
- Medicinal Preparation (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Biomedical Technology (AREA)
- Obesity (AREA)
Abstract
The invention belongs to the field of pharmaceutical preparations, and provides an epalrestat sustained-release preparation and a preparation method thereof. The sustained release preparation of epalrestat consists of 64 to 92 percent of drug-containing sustained release pellets, 1.0 to 8.0 percent of gastric-soluble isolation coating layer, 5.0 to 20 percent of enteric coating layer and 2.0 to 8.0 percent of protective coating layer. The epalrestat sustained-release preparation can effectively avoid the peak valley phenomenon of the blood concentration of a common preparation, reduce the times of taking medicines, reduce the incidence rate of adverse reactions and increase the compliance of patients; the possible drug burst effect of the single-unit sustained release preparation can be avoided, the toxicity and the side effect of the drug are reduced, and the safety of clinical medication is further ensured; the selected auxiliary materials are common, the preparation process is simple, the technical difficulty is low, the industrial mass production is easy to realize, and the market potential is large.
Description
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to an epalrestat sustained-release preparation and a preparation method thereof.
Background
Epalrestat (Epalrestat) is a phenylpropenyl thiazolidine carboxylic acid, structurally a carboxylic acid derivative, the only non-competitive ARIs currently commercially available, for use in the treatment of diabetic neuropathy. Epalrestat was first discovered to inhibit AR and possibly ameliorate delayed complications of diabetes, was then prepared during development as an oral formulation and first marketed in Japan in 1992 under the trade name
(ONO-2235) for the treatment of neuropathy and retinopathy. Since the market, epalrestat is used as a therapeutic drug for diabetic neuropathy, can obviously improve the symptoms of the neuropathy and improve the life quality of patients, has obvious clinical curative effect and less side effect, can be clinically used alone or combined with other drugs, such as alprostadil, can obviously improve the symptoms and obviously improve the conduction speed of peripheral nerves; the pharmaceutical composition is combined with alpha-zinc sulfate and mecobalamin, has obvious clinical curative effect on DPN, is better than that of epalrestat which is used alone, and has clinical popularization value.
The chemical name of the epalrestat raw material medicine is 5- [ (1Z,2E) -2-methyl-3-phenyl-2-propylene subunit ] -4-oxo-2-thio-thiazolidine acetic acid, the molecular formula is C15H13NO3S2, the molecular weight is 319.4, the character is yellow to orange, and the epalrestat raw material medicine is crystal or crystalline powder, is easily soluble in DMF and is almost insoluble in water. The Tsrlinc website shows log P2.23 and clog P2.43 and is assigned to BCS class ii, formula:
the sustained-release preparation is a preparation which can slowly release the medicine in the body after being taken so that the medicine can maintain effective blood concentration for a longer time; the enteric preparation is not dissolved in the stomach, so that the damage of the medicament to the stomach can be avoided, and the damage of gastric acid to the medicament activity can be avoided; the enteric sustained-release preparation can reduce the fluctuation of the blood concentration of the medicine in vivo, reduce the times of taking the medicine, reduce the incidence rate of adverse reactions and increase the compliance of patients.
The multi-unit sustained-release preparation represented by the pellet has more advantages in the aspect of curative effect. The pellet has small volume, is easy to swallow, is not influenced by food delivery rhythm during the transportation in the gastrointestinal tract, can pass through a closed pylorus, is not generally influenced by gastric emptying during the absorption, has the advantages of high absorption rate, uniform absorption mode, less administration frequency, capability of being taken together with fluid, increased medicine stability, improved curative effect, reduced adverse reaction, convenient quality control and content measurement during the production and the like.
According to different drug release mechanisms and structures, the sustained-release pellets comprise skeleton sustained-release pellets, film-controlled sustained-release pellets and skeleton and film-controlled combined sustained-release pellets. The multi-unit pellet sustained release preparation can overcome the performance difference generated by the gastrointestinal tract transfer time and irregular gastric emptying difference, can be dispersed into a plurality of small units in the gastrointestinal tract, has good drug release uniformity, improves the contact time between the drug and the gastrointestinal tract, improves the bioavailability and reduces the stimulation to the gastrointestinal tract mucous membrane. The slow release pellets are filled into capsules, which belongs to a multi-unit slow release preparation, avoids the burst release effect of single-unit slow release preparation, reduces the toxicity and side effect of the medicine, and ensures the safety of clinical medication. The preparation process of the capsule for preparing the sustained-release pellets is simple, the technical difficulty is low, and the industrial mass production is easy to realize.
CN201510313451.5 provides an epalrestat enteric-coated sustained-release tablet, which adopts sustained-release framework material to prepare a single-layer sustained-release tablet core and carries out enteric-coated, and the tablet core also has sustained-release effect, but the single-layer sustained-release tablet core still has the risk of drug burst release caused by the damage of gastrointestinal tract environment or the careless bite of patients.
Therefore, the epalrestat is prepared into the sustained release preparation, belongs to a multi-unit sustained release preparation, can ensure that the medicine can continuously exert curative effect in the body of a patient for a long time, simultaneously reduces the adverse reaction rate of the medicine, has large market potential, and can obtain certain economic and social benefits.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides an epalrestat sustained-release preparation and a preparation method thereof. The invention is realized by the following technical scheme.
A sustained release preparation of epalrestat is characterized in that the sustained release preparation consists of 64 to 92 percent of drug-containing sustained release pellets, 1.0 to 8.0 percent of gastric-soluble isolation coating layer, 5.0 to 20 percent of enteric coating layer and 2.0 to 8.0 percent of protective coating layer; the drug-containing sustained-release pellet contains epalrestat, a sustained-release framework material, a release regulator, a filling agent and an adhesive; the isolation coating layer and the protection coating layer contain gastric-soluble film coating materials; the enteric coating layer contains an enteric film coating material.
As a preferred technical scheme of the invention, the sustained-release preparation consists of 77-88 percent of drug-containing sustained-release pellets, 2.0-4.0 percent of gastric-soluble isolation coating layer, 8.0-15 percent of enteric coating layer and 2.0-4.0 percent of gastric-soluble protection coating layer.
The epalrestat sustained-release preparation is characterized in that sustained-release framework materials contained in the drug-containing sustained-release pellets are selected from one or more of methylcellulose, hydroxyethyl cellulose, sodium carboxymethylcellulose, hydroxypropyl methylcellulose, sodium alginate, polyvinylpyrrolidone, polyvinyl alcohol and acrylic acid polymers, and preferably one or more of hydroxypropyl methylcellulose, polyvinylpyrrolidone and acrylic acid polymers.
The epalrestat sustained-release preparation provided by the invention has the advantages that the filler contained in the drug-containing sustained-release pellet is selected from one or more of lactose, mannitol, starch, microcrystalline cellulose, pregelatinized starch, sucrose, sorbitol and dextrin, and preferably one or more of lactose, microcrystalline cellulose and mannitol.
According to the epalrestat sustained-release preparation, the adhesive contained in the drug-containing sustained-release pellet is selected from one or more of hydroxypropyl methylcellulose, povidone, copovidone, hydroxypropyl cellulose, sodium carboxymethyl cellulose, methyl cellulose, shellac, carbomer and tragacanth, and is preferably povidone K30.
According to the epalrestat sustained-release preparation, the release regulator contained in the drug-containing sustained-release pellet is hydroxypropyl methylcellulose E5.
According to the epalrestat sustained-release preparation, the sustained-release framework material contained in the drug-containing sustained-release pellet is hydroxypropyl methylcellulose K15M, the release regulator is hydroxypropyl methylcellulose E5, the weight ratio of hydroxypropyl methylcellulose K15M to hydroxypropyl methylcellulose E5 is 1: 2-11: 1, and the preferable weight ratio of hydroxypropyl methylcellulose K15M to hydroxypropyl methylcellulose E5 is 3: 1-5: 1.
According to the epalrestat sustained-release preparation, gastric-soluble film coating materials contained in the isolation coating layer and the protection coating layer are Opadry YS-1-7003.
The epalrestat sustained-release preparation comprises an enteric coating layer and an enteric film coating material, wherein the enteric film coating material contained in the enteric coating layer is selected from one or more of Sureteic (Suteric) and ACRYL-EZE (Yake Yi), and preferably Sureteic (Suteric).
The invention also provides a preparation method of the epalrestat sustained-release preparation, which is characterized by comprising the following steps:
(1) micronizing epalrestat raw material;
(2) mixing epalrestat, filler, release regulator and slow-release framework material uniformly, and adding adhesive to prepare soft material;
(3) preparing pellets by using an extrusion spheronizer: extruding at the speed of 10-25 rpm, rolling at the speed of 500-1700 rpm for 2-5 min, and screening pellets of 18-40 meshes to obtain epalrestat drug-containing pellets;
(4) fluidized bed drying: setting the drying temperature to be 50 ℃, and drying for 25-35 minutes;
(5) coating an isolation layer: preparing coating liquid with solid content of 10%, and performing isolated layer coating by a fluidized bed;
(6) coating with an enteric layer: preparing coating liquid with solid content of 15%, and performing enteric coating on the coating liquid by a fluidized bed;
(7) coating a protective layer: preparing coating liquid with solid content of 10%, and performing protective layer coating by a fluidized bed;
(8) the prepared enteric sustained-release pellets are filled into hard capsules.
The epalrestat sustained-release preparation and the preparation method thereof have the following beneficial effects:
(1) the medicine is prepared into the enteric sustained-release pellet preparation, so that the peak-valley phenomenon of the blood concentration of the common preparation can be effectively avoided, the medicine taking times are reduced, the incidence rate of adverse reactions is reduced, and the compliance of patients is improved;
(2) the sustained-release preparation belongs to a multi-unit sustained-release preparation, can avoid possible drug burst effect of a single-unit sustained-release preparation, reduces the toxicity and side effect of the drug, and further ensures the safety of clinical medication;
(3) the dosage is convenient to be divided, and the medicine is convenient to take;
(4) the selected auxiliary materials are common, the preparation process is simple, the technical difficulty is low, the industrial mass production is easy to realize, and the market potential is large.
Drawings
FIG. 1 is a graph comparing in vitro cumulative release profiles of sustained release formulations of epalrestat of examples 1-5;
FIG. 2 is a graph comparing in vitro cumulative release profiles of sustained release formulations of epalrestat of examples 1 and 6;
FIG. 3 is a graph showing the comparison of in vitro cumulative release profiles of the sustained release formulations of epalrestat of examples 1, 7 to 10.
Detailed Description
The paliperidone sustained-release composition and the preparation method thereof according to the present invention will be further explained and illustrated by examples. It should be understood that: the embodiments of the present invention are given for illustration only and not for limitation, and any simple modification of the present invention based on the technical solution of the present invention falls within the protection scope of the present invention.
Example 1
(1) Medicine-containing slow-release pill core (1000 pieces per pill)
(2) Isolation coating layer (1000 granules each)
Opadry YS-1-700317.1 g
154g of purified water
The coating weight gain was about 3%.
(3) Enteric coating layer (1000 granules each)
Sureteic 58.56g
Antifoam emulsion 0.19g
331g of purified water
The coating weight gain was about 10%.
(4) Protective coating layer (1000 granules each)
Opadry YS-1-700319.3 g
174g of purified water
The coating weight gain was about 3%.
Example 1-example 10 epalrestat sustained release formulation preparation process:
micronizing epalrestat raw material to obtain particle diameter D90About 50 μm, sieving the adjuvant with 40 mesh sieve;
preparing a soft material: respectively weighing epalrestat, a filling agent, a release regulator and a slow-release framework material according to the prescription amount, placing the materials in a wet granulator, uniformly mixing, spraying a proper amount of adhesive aqueous solution with a certain concentration, and starting a stirring knife to prepare a soft material;
preparing the pellets: and (3) placing the soft material in an extrusion spheronizer to prepare the pellets. Setting the aperture of the screen mesh to be 0.8mm, the extrusion speed to be 10-25 rpm, the rolling speed to be 500-1700 rpm, and the rolling time to be 2-5 min. Sieving, taking pellets of 18-40 meshes, drying by a fluidized bed, setting the drying temperature to be 60 ℃, and drying for 20-25 minutes;
coating with an isolation layer in a fluidized bed: preparing an isolation layer coating solution with solid content of 5%, setting the material temperature of a fluidized bed to be 40-45 ℃, the atomization pressure to be 0.15-0.3 MPa, and increasing the weight of the coating to be 1-8%;
coating with an enteric layer on a fluidized bed: preparing enteric coating solution with the solid content of 15%, setting the material temperature of a fluidized bed to be 30-35 ℃, the atomization pressure to be 0.2-0.35 MPa, and the weight gain of the coating to be 5-20%;
coating the protective layer by a fluidized bed: preparing an isolation layer coating solution with solid content of 5%, setting the material temperature of a fluidized bed to be 40-45 ℃, the atomization pressure to be 0.15-0.3 MPa, and the coating weight increase to be 2-8%;
filling the prepared pellets into hard capsules.
Example 1-example 10 determination of the Release Rate of Epalrestat sustained Release formulations:
according to the first method of the method for measuring the dissolution rate and the release degree of 0931 in the four general guidelines of the Chinese pharmacopoeia 2015 edition, the epasi sustained-release preparation is placed in a dissolution cup, 900mL of degassed 0.1mol/L hydrochloric acid solution is used as a release medium, the rotating speed is 100rpm, the temperature is (37 +/-0.5) DEG C, the operation is carried out according to the method, after 2h, the acidic medium is discarded, the residual hydrochloric acid on the surfaces of the pellets is washed by purified water, then pH6.8 phosphate buffer solution is poured into the dissolution cup as the release medium, and the release test is continued. Taking 10mL of release solution in 1h, 2h, 4h, 6h, 8h, 12h and 24h respectively, simultaneously supplementing fresh medium with the same amount and temperature, filtering with 0.45 μm microporous membrane, diluting the filtrate, and measuring the absorbance at 398nm by using an ultraviolet spectrophotometer; in addition, a proper amount of reference substance is precisely weighed, the cumulative release percentage is calculated by the same method, and the requirement is met.
Example 2
Medicine-containing slow-release pill core (1000 pieces per pill)
Hydroxypropyl methylcellulose E5 (release regulator) 15g
Lactose G200 (Filler) 90G
Microcrystalline cellulose PH101 (Filler) 90g
Povidone K30 (Binder) 8g
Proper amount of purified water
The types and the amounts of other auxiliary materials and the preparation process are the same as those of the example 1.
Example 3
Medicine-containing slow-release pill core (1000 pieces per pill)
The types and the amounts of other auxiliary materials and the preparation process are the same as those of the example 1.
Example 4
Medicine-containing slow-release pill core (1000 pieces per pill)
The types and the amounts of other auxiliary materials and the preparation process are the same as those of the example 1.
Example 5
Medicine-containing slow-release pill core (1000 pieces per pill)
The types and the amounts of other auxiliary materials and the preparation process are the same as those of the example 1.
The release rate curves of the epalrestat sustained-release formulations of examples 1-5 are shown in the graph of FIG. 1. The result shows that the release rate of the preparation is in a descending trend along with the increase of the proportion of the hydroxypropyl methylcellulose K15M, on the contrary, the release rate is faster along with the increase of the proportion of the hydroxypropyl methylcellulose E5, and when the proportion of the hydroxypropyl methylcellulose K15M to the hydroxypropyl methylcellulose E5 is within the range of 3: 1-5: 1, the release curve of the preparation is more appropriate.
Example 6
Enteric coating layer (1000 granules each)
ACRYL-EZE (Yake Yi) 63.06g
Antifoam emulsion 0.22g
357g of purified water
The coating weight gain was about 10%.
The types and the amounts of other auxiliary materials and the preparation process are the same as those of the example 1.
The release profiles of the epalrestat sustained release formulations of examples 1 and 6 are shown in fig. 2. The results show no significant difference in pellet release profiles after coating with the two enteric materials, but it was found in the experiments that the coating efficiency was about 5% lower with ACRYL-EZE (yacley) than with Sureteric (sutly).
Example 7
Enteric coating layer (1000 granules each)
Sureteric (Suteric) 29.28g
Defoaming emulsion 0.1g
166g of purified water
The coating weight gain was about 5%.
The types and the amounts of other auxiliary materials and the preparation process are the same as those of the example 4.
Example 8
Enteric coating layer (1000 granules each)
Sureteic 46.85g
Antifoam emulsion 0.16g
266g of purified water
The coating weight gain was about 8%.
The types and the amounts of other auxiliary materials and the preparation process are the same as those of the example 4.
Example 9
Enteric coating layer (1000 granules each)
Sureteic 87.84g
Defoaming emulsion 0.3g
498g of purified water
The coating weight gain was about 15%.
The types and the amounts of other auxiliary materials and the preparation process are the same as those of the example 4.
Example 10
Enteric coating layer (1000 granules each)
Sureteic 117.12g
Defoaming emulsion 0.4g
Purified Water 664g
The coating weight gain was about 20%.
The types and the amounts of other auxiliary materials and the preparation process are the same as those of the example 4.
The release rate curves of the epalrestat sustained release formulations of example 1 and examples 7-10 are compared and shown in FIG. 3. The result shows that when the weight of the enteric coating is increased by 5 percent, the release amount in acid is larger; when the weight of the enteric coating is increased by 8-20%, the enteric coating is almost not released in acid, but the release degree is reduced along with the increase of the weight in phosphate buffer solution with pH 6.8.
While the preferred embodiments and principles of this invention have been described in detail, it will be apparent to those skilled in the art that variations may be made in the embodiments based on the teachings of the invention and such variations are considered to be within the scope of the invention.
Claims (10)
1. A sustained release preparation of epalrestat is characterized in that the sustained release preparation consists of 64 to 92 percent of drug-containing sustained release pellets, 1.0 to 8.0 percent of gastric-soluble isolation coating layer, 5.0 to 20 percent of enteric coating layer and 2.0 to 8.0 percent of protective coating layer; the drug-containing sustained-release pellet contains epalrestat, a sustained-release framework material, a release regulator, a filling agent and an adhesive; the isolation coating layer and the protection coating layer contain gastric-soluble film coating materials; the enteric coating layer contains an enteric film coating material.
2. The sustained-release preparation of epalrestat of claim 1, wherein the sustained-release preparation consists of 77-88% of drug-containing sustained-release pellets, 2.0-4.0% of gastric-soluble isolation coating layer, 8.0-15% of enteric coating layer and 2.0-4.0% of gastric-soluble protection coating layer.
3. The epalrestat sustained-release preparation according to claim 1, wherein the sustained-release matrix material contained in the drug-containing sustained-release pellets is selected from one or more of methylcellulose, hydroxyethyl cellulose, sodium carboxymethylcellulose, hypromellose, sodium alginate, polyvinylpyrrolidone, polyvinyl alcohol and acrylic acid polymer, preferably one or more of hypromellose, polyvinylpyrrolidone and acrylic acid polymer.
4. The sustained-release epalrestat preparation according to claim 1, wherein the drug-containing sustained-release pellets contain one or more fillers selected from lactose, mannitol, starch, microcrystalline cellulose, pregelatinized starch, sucrose, sorbitol and dextrin, preferably one or more fillers selected from lactose, microcrystalline cellulose and mannitol.
5. The sustained-release epalrestat preparation according to claim 1, wherein the drug-containing sustained-release pellets contain a binder selected from one or more of hypromellose, povidone, copovidone, hydroxypropyl cellulose, sodium carboxymethyl cellulose, methyl cellulose, shellac, carbomer and tragacanth, preferably povidone K30.
6. The sustained-release epalrestat formulation of claim 1, wherein the sustained-release drug-containing pellet comprises a release modifier hypromellose E5.
7. The epalrestat sustained-release preparation according to claim 1, wherein the sustained-release skeleton material of the drug-containing sustained-release pellet is hypromellose K15M, the release regulator is hypromellose E5, and the weight ratio of hypromellose K15M to hypromellose E5 is 1: 2-11: 1, preferably the weight ratio of hypromellose K15M to hypromellose E5 is 3: 1-5: 1.
8. The sustained-release epalrestat formulation of claim 1, wherein the gastric-soluble film coating material contained in the barrier coating layer and the protective coating layer is opalatic YS-1-7003.
9. The sustained-release epalrestat formulation of claim 1, wherein the enteric coating layer comprises an enteric film coating material selected from one or more of Sureteric (Suteric), ACRYL-EZE (Yakeyi), preferably Sureteric (Suteric).
10. The process for preparing a sustained release formulation of epalrestat according to any of claims 1 to 9, comprising the steps of:
(1) micronizing epalrestat raw material;
(2) mixing epalrestat, filler, release regulator and slow-release framework material uniformly, and adding adhesive to prepare soft material;
(3) preparing pellets by using an extrusion spheronizer: extruding at the speed of 10-25 rpm, rolling at the speed of 500-1700 rpm for 2-5 min, and screening pellets of 18-40 meshes to obtain epalrestat drug-containing pellets;
(4) fluidized bed drying: setting the drying temperature to be 50 ℃, and drying for 25-35 minutes;
(5) coating an isolation layer: preparing coating liquid with solid content of 10%, and performing isolated layer coating by a fluidized bed;
(6) coating with an enteric layer: preparing coating liquid with solid content of 15%, and performing enteric coating on the coating liquid by a fluidized bed;
(7) coating a protective layer: preparing coating liquid with solid content of 10%, and performing protective layer coating by a fluidized bed;
(8) the prepared enteric sustained-release pellets are filled into hard capsules.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011214487.5A CN112137990A (en) | 2020-11-04 | 2020-11-04 | Epalrestat sustained-release preparation and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011214487.5A CN112137990A (en) | 2020-11-04 | 2020-11-04 | Epalrestat sustained-release preparation and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112137990A true CN112137990A (en) | 2020-12-29 |
Family
ID=73953882
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011214487.5A Pending CN112137990A (en) | 2020-11-04 | 2020-11-04 | Epalrestat sustained-release preparation and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112137990A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113143880A (en) * | 2021-03-10 | 2021-07-23 | 河北化工医药职业技术学院 | Sustained-release tablet for treating diabetic complications and preparation method thereof |
| CN113925838A (en) * | 2021-11-11 | 2022-01-14 | 乐普制药科技有限公司 | Compound sustained-release tablet of epalrestat and sitagliptin or pharmaceutically acceptable salt thereof and preparation method thereof |
| CN115245496A (en) * | 2022-09-21 | 2022-10-28 | 北京惠之衡生物科技有限公司 | Preparation method of stable epalrestat tablets |
| CN115444831A (en) * | 2022-10-25 | 2022-12-09 | 南京康川济医药科技有限公司 | Epalrestat gastric floating tablet and preparation method thereof |
Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006282526A (en) * | 2005-03-31 | 2006-10-19 | Taiyo Yakuhin Kogyo Kk | Designing of simple and stable preparation of 5-[(1z,2e)-2-methyl-3-phenyl-2-propenylidene]-4-oxo-2-thioxo-3-thiazolidineacetic acid |
| CN101277684A (en) * | 2005-09-30 | 2008-10-01 | 弗拉梅技术公司 | Microparticles with modified release of at least one active principle and oral galenic form comprising same |
| CN101378736A (en) * | 2006-02-16 | 2009-03-04 | 弗拉梅技术公司 | Multimicroparticulate pharmaceutical forms for oral administration |
| CN103142552A (en) * | 2013-02-22 | 2013-06-12 | 广州科的信医药技术有限公司 | Lovastatin enteric coated sustained-release pellet capsule and preparation method thereof |
| CN103356489A (en) * | 2013-08-05 | 2013-10-23 | 谢斌 | Proton pump inhibitor enteric coated pellet and preparation and preparation method thereof |
| CN104922052A (en) * | 2015-06-09 | 2015-09-23 | 扬子江药业集团南京海陵药业有限公司 | Epalrestat sustained-release preparation as well as preparation method and application thereof |
| CN104940156A (en) * | 2015-06-09 | 2015-09-30 | 扬子江药业集团南京海陵药业有限公司 | Epalrestat enteric-coated and sustained-release tablets and preparation method thereof |
| CN105982863A (en) * | 2015-02-27 | 2016-10-05 | 湖南千金湘江药业股份有限公司 | Esomeprazole magnesium enteric-pellet capsules and preparation method thereof |
| CN107837271A (en) * | 2017-11-07 | 2018-03-27 | 中国药科大学 | Epalrestat is preparing the application in treating medicine for treating diabetic nephropathy |
| CN109966269A (en) * | 2017-12-27 | 2019-07-05 | 江苏万邦生化医药集团有限责任公司 | A kind of Memantine hydrochloride slow-release pellet preparation and preparation method thereof |
| CN110214007A (en) * | 2017-06-14 | 2019-09-06 | 江苏恒瑞医药股份有限公司 | A kind of controlled release pharmaceutical compositions and preparation method thereof |
-
2020
- 2020-11-04 CN CN202011214487.5A patent/CN112137990A/en active Pending
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006282526A (en) * | 2005-03-31 | 2006-10-19 | Taiyo Yakuhin Kogyo Kk | Designing of simple and stable preparation of 5-[(1z,2e)-2-methyl-3-phenyl-2-propenylidene]-4-oxo-2-thioxo-3-thiazolidineacetic acid |
| CN101277684A (en) * | 2005-09-30 | 2008-10-01 | 弗拉梅技术公司 | Microparticles with modified release of at least one active principle and oral galenic form comprising same |
| CN101378736A (en) * | 2006-02-16 | 2009-03-04 | 弗拉梅技术公司 | Multimicroparticulate pharmaceutical forms for oral administration |
| CN103142552A (en) * | 2013-02-22 | 2013-06-12 | 广州科的信医药技术有限公司 | Lovastatin enteric coated sustained-release pellet capsule and preparation method thereof |
| CN103356489A (en) * | 2013-08-05 | 2013-10-23 | 谢斌 | Proton pump inhibitor enteric coated pellet and preparation and preparation method thereof |
| CN105982863A (en) * | 2015-02-27 | 2016-10-05 | 湖南千金湘江药业股份有限公司 | Esomeprazole magnesium enteric-pellet capsules and preparation method thereof |
| CN104922052A (en) * | 2015-06-09 | 2015-09-23 | 扬子江药业集团南京海陵药业有限公司 | Epalrestat sustained-release preparation as well as preparation method and application thereof |
| CN104940156A (en) * | 2015-06-09 | 2015-09-30 | 扬子江药业集团南京海陵药业有限公司 | Epalrestat enteric-coated and sustained-release tablets and preparation method thereof |
| CN110214007A (en) * | 2017-06-14 | 2019-09-06 | 江苏恒瑞医药股份有限公司 | A kind of controlled release pharmaceutical compositions and preparation method thereof |
| CN107837271A (en) * | 2017-11-07 | 2018-03-27 | 中国药科大学 | Epalrestat is preparing the application in treating medicine for treating diabetic nephropathy |
| CN109966269A (en) * | 2017-12-27 | 2019-07-05 | 江苏万邦生化医药集团有限责任公司 | A kind of Memantine hydrochloride slow-release pellet preparation and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 鄢海燕: "《高职高专"十三五"规划教材 药剂学 第2版》", 31 January 2018, 南京：江苏科学技术出版社 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113143880A (en) * | 2021-03-10 | 2021-07-23 | 河北化工医药职业技术学院 | Sustained-release tablet for treating diabetic complications and preparation method thereof |
| CN113143880B (en) * | 2021-03-10 | 2022-07-12 | 河北化工医药职业技术学院 | Sustained-release tablet for treating diabetic complications and preparation method thereof |
| CN113925838A (en) * | 2021-11-11 | 2022-01-14 | 乐普制药科技有限公司 | Compound sustained-release tablet of epalrestat and sitagliptin or pharmaceutically acceptable salt thereof and preparation method thereof |
| CN113925838B (en) * | 2021-11-11 | 2022-11-11 | 乐普制药科技有限公司 | Compound sustained-release tablet of epalrestat and sitagliptin or pharmaceutically acceptable salt thereof and preparation method thereof |
| CN115245496A (en) * | 2022-09-21 | 2022-10-28 | 北京惠之衡生物科技有限公司 | Preparation method of stable epalrestat tablets |
| CN115444831A (en) * | 2022-10-25 | 2022-12-09 | 南京康川济医药科技有限公司 | Epalrestat gastric floating tablet and preparation method thereof |
| CN115444831B (en) * | 2022-10-25 | 2023-08-22 | 南京康川济医药科技有限公司 | Epalrestat gastric floating tablet and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112137990A (en) | Epalrestat sustained-release preparation and preparation method thereof | |
| CN101574323B (en) | Migltol microcapsule tablet and preparation method thereof | |
| CN113925838B (en) | Compound sustained-release tablet of epalrestat and sitagliptin or pharmaceutically acceptable salt thereof and preparation method thereof | |
| CN113616624B (en) | Empagliflozin metformin sustained release preparation and preparation method thereof | |
| CN112641742B (en) | Sacubitril valsartan sodium sustained-release tablet and preparation method thereof | |
| WO2014040548A1 (en) | Metoprolol sustained-release drug and preparation method therefor | |
| CN112315927A (en) | Paliperidone sustained-release orally disintegrating tablet and preparation method thereof | |
| CN112402392A (en) | Dabigatran etexilate mesylate sustained release preparation and preparation method thereof | |
| CN111494328A (en) | Osmotic pump tablet containing acarbose and dapagliflozin and preparation method thereof | |
| CN109646417B (en) | Trimetazidine sustained release tablet and preparation method thereof | |
| CN102755310A (en) | Composition drug preparation containing levodopa | |
| CN112999182B (en) | Metformin hydrochloride dual sustained and controlled release composition and preparation method and application thereof | |
| WO2021197376A1 (en) | A febuxostat tablet | |
| CN1985823A (en) | Slow released preparation containing metformin hydrochloride and rosiglitazone and its preparing process | |
| WO2018185669A1 (en) | Effervescent compositions comprising saxagliptin or salt thereof | |
| WO2015196956A1 (en) | Metoprolol sustained-release composition and preparation method thereof | |
| CN112057429B (en) | Lei Xina Deg controlled release pharmaceutical composition | |
| CN112353784A (en) | Aspirin enteric-coated micro-tablet capsule and preparation method thereof | |
| CN112472677A (en) | Renin-resistant preparation and preparation method thereof | |
| CN112190564A (en) | Compound pellet preparation and preparation method thereof | |
| CN1985819A (en) | Slow released preparation containing metformin hydrochloride and gliclazide and its preparing process | |
| CN112294777B (en) | Ivabradine hydrochloride sustained-release preparation and preparation method and application thereof | |
| CN114903863B (en) | Sitagliptin and metformin hydrochloride sustained-release tablet and preparation method thereof | |
| CN103446062A (en) | Preparing method of compound metformin hydrochloride and pioglitazone hydrochloride slow-release micro-pellet preparation | |
| CN115671070B (en) | Desloratadine citrate osmotic pump controlled release tablet and preparation method thereof |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20201229 |
|
| RJ01 | Rejection of invention patent application after publication |