CN111035619B - Gefitinib tablet and preparation method thereof - Google Patents
Gefitinib tablet and preparation method thereof Download PDFInfo
- Publication number
- CN111035619B CN111035619B CN201811191733.2A CN201811191733A CN111035619B CN 111035619 B CN111035619 B CN 111035619B CN 201811191733 A CN201811191733 A CN 201811191733A CN 111035619 B CN111035619 B CN 111035619B
- Authority
- CN
- China
- Prior art keywords
- gefitinib
- wetting agent
- surfactant
- preparation
- tablet
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a preparation method of gefitinib tablets. The preparation method comprises the following steps: uniformly mixing according to the prescription amount, granulating, drying, granulating and the like, controlling the concentration of the adhesive, the addition amount of the wetting agent and the addition mode to obtain gefitinib intermediate particles, and tabletting, coating and the like, so that the prepared gefitinib tablet has reliable quality, better dissolution effect, simple operation and good repeatability, and the preparation method is beneficial to industrial production.
Description
Technical Field
The invention belongs to the field of medicines, relates to a preparation method of an anti-tumor medicine, and particularly relates to a preparation method of a gefitinib tablet.
Background
Gefitinib, marketed as "iressa" and produced by AstraZeneca UK Limited, is an Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor, a small molecule compound that can enter cells and specifically inhibit the activity of the epidermal growth factor receptor tyrosine kinase by competitively binding to the ATP-binding domain. The chemical name of the N- (3-chloro-4-fluorophenyl) -7-methoxy-6- (3-morpholinopropoxy) quinazoline-4-amine is as follows:
in oral solid preparations, the absorption rate of a drug depends on the dissolution or release of the drug from the preparation, the dissolution of the drug under physiological conditions, and the permeability in the gastrointestinal tract. In vitro dissolution tests can predict in vivo behavior to some extent. In the classification of biological pharmaceutics, gefitinib belongs to class II medicines, and the dissolution of the class II medicines is the rate-limiting step of medicine absorption and has better in-vivo and in-vitro correlation. Therefore, the in vivo drug release process can be indirectly reflected or used as an important index for evaluating the curative effect of the drug by measuring the dissolution curve. At present, the problem of poor dissolution and the like generally exists in the imitation drugs of each research unit, and in order to solve the problem, the drug formulation, the micronization and the granulation of the drug are all tried to improve the dissolution of the drug by controlling the water content, and in order to solve the problem of difficult dissolution of gefitinib, a plurality of different test methods are tried. By researching the solubility of the gefitinib, the gefitinib is found to have obvious pH dependence, and the equilibrium solubility of the gefitinib under different pH conditions is measured, and the results are as follows:
gefitinib pH-solubility test result (37 ℃ C.)
Gefitinib has a high solubility at pH1.0, decreases in solubility with increasing pH, undergoes a sharp decrease in solubility between pH4.0 and 5.0, and is practically insoluble at pH6.0 to 6.8.
Oral administration is the most common mode of administration, and the absorption environment mainly lies in the stomach and small intestine, and the absorption of the drug is often influenced due to different pH environments in vivo.
According to the relationship between the solubility and the pH value of gefitinib, people hope that the gefitinib can achieve better dissolution in the stomach, namely, the dissolution curve measured in different in vitro media indirectly reflects the in vivo drug release process, so the pH values of dissolution media are selected to be 1.0 and 4.0, and the dissolution comparison of the gefitinib tablet and the iressa which is a product on the market of AstraZeneca company is measured to be used as an index for evaluating the curative effect of a drug.
For the insoluble drug gefitinib, a gefitinib preparation with good dissolution and stable release needs to be developed urgently through process design so as to ensure the safety, effectiveness and controllable quality of the product. In order to solve the problems that the dissolution rate of the existing gefitinib product is difficult to improve, the process stability is poor and the like, the invention provides a preparation method which has simple process operation and controllable parameters, and ensures that gefitinib tablets have stable dissolution efficiency and good release.
Disclosure of Invention
The invention aims to provide a preparation method capable of improving the dissolution rate of gefitinib tablets, and the method is simple to operate, and the obtained gefitinib tablets have stable drug effect, good dissolution and release and good process repeatability, and are beneficial to industrial production.
The preparation method of the gefitinib tablet core comprises the following steps:
(1) Uniformly mixing the gefitinib medicament, the filling agent and the disintegrating agent;
(2) Dissolving a bonding agent and a surfactant in a first wetting agent, adding the mixture obtained in the step (1), mixing and stirring, adding a second wetting agent, preparing a soft material, and granulating;
(3) Drying the wet granules, and finishing to obtain dry granules containing the medicine;
(4) Adding a lubricant into the dry granules containing the medicine obtained in the step (3), and uniformly mixing to obtain intermediate granules;
(5) And tabletting the intermediate granules to obtain the tablet core.
In certain embodiments of the present invention, the first wetting agent and the second wetting agent added in the preparation method of the gefitinib core are selected from water or ethanol/water mixture, preferably, the first wetting agent and the second wetting agent are both water.
In some embodiments of the present invention, the adhesive is preferably prepared in a mass concentration of 8-10% by dissolving a prescribed amount of the adhesive in a first wetting agent, preferably water, and after the first wetting agent is sufficiently dissolved, adding a prescribed amount of a surfactant, and sufficiently dissolving to obtain a mixed adhesive for later use.
In some embodiments of the present invention, the granulation method is wet granulation, the prepared mixed binder is added to the mixed powder of gefitinib, filler and disintegrant by spraying or injection method, the powder is wetted, after stirring, the second wetting agent, preferably water, is added to prepare a soft material, and the soft material is sieved to obtain wet granules.
When the first wetting agent and the second wetting agent are both water, the weight ratio of the total added wetting agent water to the gefitinib is 0.60-0.70.
In some embodiments of the present invention, the wet granules may be dried under reduced pressure or normal pressure, and after drying, the granules are sieved to obtain dry granules containing drug with moisture content less than or equal to 0.5%.
And (3) uniformly mixing the dry granules containing the medicine with a lubricant to obtain intermediate granules, measuring the bulk density to be 0.4-0.6g/ml, tabletting to obtain a tablet core, and optionally coating with a gastric-soluble coating material to obtain the gefitinib tablet.
The filler is selected from at least one of dextrin, lactose, sucrose, starch, pregelatinized starch and microcrystalline cellulose, preferably any combination of lactose and microcrystalline cellulose, and more preferably the weight ratio of the microcrystalline cellulose to the lactose is 1-5.
The binder is selected from at least one of polyvinylpyrrolidone, methylcellulose, carboxyl cellulose, hydroxypropyl cellulose and hydroxypropyl methylcellulose, preferably polyvinylpyrrolidone, and most preferably povidone K30.
The disintegrant is selected from at least one of croscarmellose sodium, crospovidone, low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch, starch and pregelatinized starch, and preferably is croscarmellose sodium.
The lubricant is selected from at least one of magnesium stearate, stearic acid, palmitic acid, calcium stearate, talcum powder, carnauba wax and sodium stearyl fumarate, and is preferably magnesium stearate.
The surfactant is at least one selected from sulfonate, sulfate ester salt and phosphate, and is preferably sodium dodecyl sulfate.
The gefitinib tablet core comprises the following components in percentage by weight: 0.8-1.2 parts of gefitinib, 0.2-1.2 parts of filling agent, 0.01-0.20 parts of surfactant, 0.02-0.06 parts of adhesive, 0.04-0.20 parts of disintegrant and 0.01-0.04 parts of lubricant.
In certain embodiments of the present invention, the gefitinib core comprises 0.8-1.2 parts by weight of gefitinib; 0.8-0.9 parts of a filler, preferably a mixture of lactose and microcrystalline cellulose, wherein the weight ratio of microcrystalline cellulose to lactose is 1; 0.01-0.03 parts of surfactant, preferably the surfactant is sodium dodecyl sulfate; 0.03-0.05 part of binder, preferably the binder is povidone K30;0.06-0.10 parts of disintegrant, preferably the disintegrant is croscarmellose sodium; 0.01-0.04 parts of lubricant, preferably the lubricant is magnesium stearate.
In certain embodiments of the invention, the gefitinib core comprises, by weight, 1 part gefitinib, 0.6-0.7 part lactose, 0.12-0.18 part microcrystalline cellulose, 0.01-0.03 part sodium lauryl sulfate, 0.03-0.05 part povidone K30,0.06-0.10 part croscarmellose sodium, 0.01-0.03 part magnesium stearate.
In certain embodiments of the present invention, the first wetting agent and the second wetting agent added in the preparation process of the gefitinib tablet core are both water, and the weight ratio of the total wetting agent, i.e. the total weight of the added water, to the gefitinib is 0.6-0.7. Taking the adhesive with the prescription amount, adding water to prepare 8-10% solution, and using the rest water as a second wetting agent.
The granularity D of the gefitinib raw material medicine provided by the invention 90 ≤10μm。
Compared with the prior art, the invention ensures that the bulk density of the intermediate particles is stable and controllable by controlling the concentration of the adhesive and the addition amount and the addition mode of the wetting agent in the preparation process, so that the in-vitro dissolution effect of the gefitinib tablet body obtained by the invention is better than that of the gefitinib tablet on the market, namely the in-vivo behavior can be predicted according to the in-vitro dissolution effect, and the gefitinib tablet prepared by the invention still has better dissolution effect when the pH value of the tail end of the stomach is about 4.0.
Detailed Description
The present invention will be described more specifically with reference to the following specific examples, but the present invention is not limited to the following examples.
The bulk density detection method of the intermediate particles comprises the following steps: about 100g of uncompacted test material was added to a dry 250mL measuring cylinder (readable to 2 mL), weighed to the nearest 0.1%, the sample was carefully screeded, not compressed, and the initial volume V read off 0 I.e. the most recent scale value, bulk density (g/ml), the calculation formula: m/V 0 。
The specific embodiment comprises the following components, wherein the proportion refers to the ratio of parts by weight.
Example 1
The preparation process of the components comprises the following steps:
(1) Taking gefitinib of a prescription amount to carry out jet milling micronization treatment, D 90 Sieving lactose, microcrystalline cellulose and croscarmellose sodium with 60 mesh sieve, and mixing well for use;
(2) Dissolving povidone K30 in the amount of the prescription in 0.46 part of water to prepare a solution with the concentration of 8%, adding sodium dodecyl sulfate, fully dissolving, performing wet granulation and the mixture obtained in the step (1), stirring and mixing, adding 0.16 part of water, stirring and mixing to prepare a soft material, sieving with a 24-mesh sieve, and granulating;
(3) Drying the wet granules until the water content is less than or equal to 0.5%, sieving and granulating to obtain medicine-containing dry granules;
(4) Adding magnesium stearate into the medicine-containing dry granules obtained in the step (3), uniformly mixing to obtain intermediate granules, and measuring the bulk density of the intermediate granules to be 0.50g/ml;
(5) Tabletting the intermediate granules to obtain a gefitinib tablet core;
(6) And (3) adding water into the gastric soluble Opadry II to prepare 20% coating solution, coating the tablet core obtained in the step (5), and finishing when the weight of the coating is increased to 2.5% -3.0%, thus obtaining the gefitinib tablet.
Example 2
The preparation process of the components comprises the following steps:
(1) The operation is as in example 1;
(2) Dissolving povidone K30 in the amount of the prescription in 0.46 part of water to prepare a solution with the concentration of 8%, adding sodium dodecyl sulfate, fully dissolving, performing wet granulation and the mixture obtained in the step (1), stirring and mixing, adding 0.20 part of water, stirring and mixing to prepare a soft material, sieving with a 24-mesh sieve, and granulating;
(3) The operation is as in example 1;
(4) The operation is the same as example 1, and the bulk density is measured to be 0.52g/ml;
(5) And (6) the same procedure as in example 1.
Example 3
The preparation process of the components comprises the following steps:
(1) The operation is as in example 1;
(2) Dissolving povidone K30 with the prescription amount in 0.46 part of water to prepare a solution with the concentration of 8%, adding sodium dodecyl sulfate, fully dissolving, performing wet granulation and the mixture obtained in the step (1), stirring and mixing, adding 0.22 part of water, mixing, stirring to prepare a soft material, sieving with a 24-mesh sieve, and granulating;
(3) The operation is as in example 1;
(4) The operation of example 1 was repeated to obtain a bulk density of 0.49g/ml;
(5) And (6) the same procedure as in example 1.
Example 4
The preparation process of the components comprises the following steps:
(1) The operation is as in example 1;
(2) Dissolving povidone K30 in the amount of the prescription in 0.36 part of water to prepare a solution with the concentration of 10%, adding sodium dodecyl sulfate, fully dissolving, performing wet granulation and the mixture obtained in the step (1), stirring, mixing, adding 0.32 part of water, mixing, stirring to prepare a soft material, sieving with a 24-mesh sieve, and granulating;
(3) The operation is as in example 1;
(4) The operation is the same as that of example 1, and the bulk density is measured to be 0.50g/ml;
(5) And (6) the same procedure as in example 1.
Comparative example 1
The preparation process according to the prescription amount is as follows:
(1) The operation is as in example 1;
(2) Dissolving povidone K30 with the formula amount in 0.76 part of water to prepare a solution with the concentration of 5%, adding sodium dodecyl sulfate, fully dissolving, performing wet granulation on the mixture obtained in the step (1), mixing and stirring to obtain a soft material, sieving by a 24-mesh sieve, and granulating;
(3) The operation is as in example 1;
(4) The operation of example 1 was repeated to obtain a bulk density of 0.65g/ml;
(5) And (6) the same procedure as in example 1.
Comparative example 2
The preparation process according to the prescription amount is as follows:
(1) The operation is as in example 1;
(2) Dissolving povidone K30 in the amount of the prescription in 0.36 part of water to prepare a solution with the concentration of 10%, adding sodium dodecyl sulfate, fully dissolving, performing wet granulation and the mixture obtained in the step (1), stirring and mixing, adding 0.39 part of water, stirring and mixing to prepare a soft material, sieving with a 24-mesh sieve, and granulating;
(3) The operation is as in example 1;
(4) The operation of example 1 was repeated to obtain a bulk density of 0.66g/ml;
(5) And (6) the same procedure as in example 1.
Comparative example 3
The preparation process according to the prescription amount is as follows:
(1) The operation is as in example 1;
(2) Dissolving povidone K30 in a prescribed amount in 0.36 part of water to prepare a solution with the concentration of 10%, adding sodium dodecyl sulfate, fully dissolving, performing wet granulation and the mixture obtained in the step (1), stirring, mixing, adding 0.14 part of water, mixing, stirring to obtain a soft material, sieving with a 24-mesh sieve, granulating
(3) The operation is as in example 1;
(4) The operation is the same as example 1, and the bulk density is measured to be 0.62g/ml;
(5) And (6) the same procedure as in example 1.
Test example 1
The in vitro dissolution rate of the gefitinib tablet prepared by the method is compared with that of the Iressa marketed by AstraZeneca company. The operation is performed according to a dissolution determination method (appendix X C of the second part of 2010 edition of chinese pharmacopoeia), 1000mL of dissolution medium (0.1 mol/L hydrochloric acid solution, ph4.0 acetate buffer solution) is measured respectively, and the measurement results of the average cumulative dissolution of iressa and gefitinib tablets prepared in the embodiments of the present invention are as follows:
TABLE 1 in vitro dissolution rate comparison of Gefitinib tablets prepared in accordance with the present invention with Iressa at pH1.0
TABLE 2 in vitro dissolution rate comparison of Gefitinib tablets prepared in the present invention and Iressa in dissolution medium with pH4.0
Table 1 shows that in the dissolution medium with pH of 1.0, the cumulative dissolution at 15min of examples 1, 2 and 4 is significantly better than that of comparative example 3, and compared with the iressa on the market, the cumulative dissolution at 15min is greater than 90%, and the gefitinib tablet of the embodiment of the present invention is better than that of the iressa on the market.
Table 2 shows that, in the dissolution medium with pH of 4.0, the gefitinib tablet of the embodiment of the present invention has significantly better cumulative dissolution at 10min than the comparative examples 1-3, and also has advantages compared with the marketed variety iressa, and the gefitinib tablets of the embodiment of the present invention have greater than 90% cumulative dissolution at 30min and are better than the marketed variety iressa.
Claims (7)
1. A preparation method of a gefitinib tablet core is characterized by comprising the following steps:
(1) Uniformly mixing the gefitinib medicament, the filler and the disintegrant;
(2) Dissolving a bonding agent and a surfactant in a first wetting agent, adding the mixture obtained in the step (1), mixing and stirring, adding a second wetting agent, preparing a soft material, and granulating;
(3) Drying the wet granules, and finishing to obtain dry granules containing the medicine;
(4) Adding a lubricant into the dry granules containing the medicine obtained in the step (3), and uniformly mixing to obtain intermediate granules;
(5) Tabletting the intermediate granules to obtain a tablet core;
wherein, the weight ratio of the total weight of the first wetting agent and the second wetting agent added in the step (2) to the gefitinib drug is 0.60-0.70;
dissolving the adhesive in a first wetting agent to prepare a solution with the mass concentration of 8-10%, adding a surfactant, uniformly mixing, and preparing a mixed adhesive for use;
the first wetting agent and the second wetting agent in the step (2) are both water;
the filler is a mixture of lactose and microcrystalline cellulose, the surfactant is sodium lauryl sulfate, the binder is povidone K30, the disintegrant is croscarmellose sodium, and the lubricant is magnesium stearate.
2. The process according to claim 1, wherein the gefitinib core comprises 0.8 to 1.2 parts by weight of gefitinib; 0.8-0.9 parts of filler, wherein the filler is a mixture of lactose and microcrystalline cellulose, and the weight ratio of the microcrystalline cellulose to the lactose is 1; 0.01-0.03 part of surfactant, wherein the surfactant is sodium dodecyl sulfate; 0.03-0.05 part of a binder, wherein the binder is povidone K30;0.06-0.10 parts of a disintegrating agent, wherein the disintegrating agent is croscarmellose sodium; 0.01-0.04 parts of a lubricant, wherein the lubricant is magnesium stearate.
3. The process according to claim 1 or 2, characterized in that the drug gefitinib of step (1) is micronized in particle size D 90 ≤10μm。
4. The method according to claim 1 or 2, wherein the moisture content of the dry particles containing drug in step (3) is not more than 0.5%.
5. The method according to claim 1 or 2, wherein the bulk density of the intermediate particles in the step (4) is 0.4 to 0.6g/ml.
6. Gefitinib tablets, which are prepared by coating tablet cores obtained by the preparation method of any one of claims 1 to 5.
7. Gefitinib tablet of claim 6, wherein said coating is a gastric coating.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811191733.2A CN111035619B (en) | 2018-10-12 | 2018-10-12 | Gefitinib tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811191733.2A CN111035619B (en) | 2018-10-12 | 2018-10-12 | Gefitinib tablet and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111035619A CN111035619A (en) | 2020-04-21 |
| CN111035619B true CN111035619B (en) | 2023-02-28 |
Family
ID=70229953
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811191733.2A Active CN111035619B (en) | 2018-10-12 | 2018-10-12 | Gefitinib tablet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111035619B (en) |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102631347A (en) * | 2012-05-03 | 2012-08-15 | 石药集团中奇制药技术（石家庄）有限公司 | Gefinitib medicinal composite and method for preparing same |
| CN104800175A (en) * | 2015-04-20 | 2015-07-29 | 珠海润都制药股份有限公司 | Gefitinib tablet preparation method |
| CN104887638A (en) * | 2015-06-19 | 2015-09-09 | 山东省药学科学院 | Preparation method of gefitinib tablets |
| CN105168169A (en) * | 2014-06-18 | 2015-12-23 | 山东新时代药业有限公司 | Gefitinib tablet and preparation method thereof |
| CN106913541A (en) * | 2015-12-25 | 2017-07-04 | 山东新时代药业有限公司 | A kind of Gefitinib tablet and preparation method thereof |
| CN106913544A (en) * | 2015-12-28 | 2017-07-04 | 山东新时代药业有限公司 | A kind of Gefitinib tablet of Fast Stripping and preparation method thereof |
| JP2017206488A (en) * | 2016-05-20 | 2017-11-24 | 高田製薬株式会社 | Gefitinib tablet and method for producing gefitinib tablet |
| JP2018002687A (en) * | 2016-07-08 | 2018-01-11 | 日本化薬株式会社 | Pharmaceutical tablet comprising gefitinib as active ingredient |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102266300B (en) * | 2011-07-14 | 2013-01-02 | 广东药学院 | Gefitinib dispersible tablet and preparation method and application thereof |
| CN103845335B (en) * | 2014-03-24 | 2016-07-13 | 江苏奥赛康药业股份有限公司 | Gefitinib pharmaceutical composition and the tablet containing this gefitinib pharmaceutical composition |
-
2018
- 2018-10-12 CN CN201811191733.2A patent/CN111035619B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102631347A (en) * | 2012-05-03 | 2012-08-15 | 石药集团中奇制药技术（石家庄）有限公司 | Gefinitib medicinal composite and method for preparing same |
| CN105168169A (en) * | 2014-06-18 | 2015-12-23 | 山东新时代药业有限公司 | Gefitinib tablet and preparation method thereof |
| CN104800175A (en) * | 2015-04-20 | 2015-07-29 | 珠海润都制药股份有限公司 | Gefitinib tablet preparation method |
| CN104887638A (en) * | 2015-06-19 | 2015-09-09 | 山东省药学科学院 | Preparation method of gefitinib tablets |
| CN106913541A (en) * | 2015-12-25 | 2017-07-04 | 山东新时代药业有限公司 | A kind of Gefitinib tablet and preparation method thereof |
| CN106913544A (en) * | 2015-12-28 | 2017-07-04 | 山东新时代药业有限公司 | A kind of Gefitinib tablet of Fast Stripping and preparation method thereof |
| JP2017206488A (en) * | 2016-05-20 | 2017-11-24 | 高田製薬株式会社 | Gefitinib tablet and method for producing gefitinib tablet |
| JP2018002687A (en) * | 2016-07-08 | 2018-01-11 | 日本化薬株式会社 | Pharmaceutical tablet comprising gefitinib as active ingredient |
Non-Patent Citations (2)
| Title |
|---|
| 吉非替尼片溶出度的测定方法;徐宁;《包头医学院学报》;20180331;第34卷(第3期);第117-121页 * |
| 吉非替尼片的制备工艺与质量研究;刘杰;《北京化工大学硕士学位论文》;20141230;第1-89页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111035619A (en) | 2020-04-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2017114227A1 (en) | Dapagliflozin and metformin complex extended release tablet and preparation method thereof | |
| JP2005526738A (en) | Dosage form for oral administration of drugs with low solubility | |
| WO2020249001A1 (en) | Oral solid tablet comprising bruton's tyrosine kinase inhibitor and preparation method therefor | |
| WO2006040779A2 (en) | Controlled release gastric floating matrix formulation containing imatinib | |
| CN112220770B (en) | Pharmaceutical composition of selepag and preparation method thereof | |
| CN112022825A (en) | Alvatripopa maleate tablet and preparation method thereof | |
| CN109789102A (en) | The preparation with improvement pH dependent drug release characteristics comprising esomeprazole or its pharmaceutically acceptable salt | |
| WO2023108895A1 (en) | Telmisartan oral solid preparation with stable product performance, and preparation method therefor | |
| JP2023509560A (en) | Pharmaceutical composition of sorafenib with high bioavailability and its application | |
| KR101421330B1 (en) | A disintegrating tablet | |
| CN111035619B (en) | Gefitinib tablet and preparation method thereof | |
| CN112516094A (en) | Topiroxostat tablet and preparation method thereof | |
| WO2013189305A1 (en) | Valsartan-amlodipine compound solid preparation and preparation method therefor | |
| WO2011161689A1 (en) | Imatinib mesilate pharmaceutical tablet | |
| US20230225977A1 (en) | Formulation comprising daprodustat | |
| WO2007090595A1 (en) | Solid formulations of valacyclovir hydrochloride | |
| JP4999297B2 (en) | High content terbinafine hydrochloride small tablets | |
| CN111888477B (en) | Bedaquinoline pharmaceutical preparation | |
| CN108096251B (en) | Gefitinib pharmaceutical composition and preparation method thereof | |
| CN109481410B (en) | Preparation method of domperidone tablets | |
| JP3746062B2 (en) | Solid preparation and method for producing the same | |
| CN112603898A (en) | Telmisartan tablet and preparation method thereof | |
| CN107744509B (en) | Mosapride citrate tablet and preparation method thereof | |
| WO2007033515A1 (en) | Oral formulation containing moxifloxacin and its preparation method | |
| WO2021136089A1 (en) | Anti-tumor pharmaceutical composition and method for increasing solubility of compound |
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 |