CN104622836A - Sofosbuvircoated tablet and preparation method thereof - Google Patents
Sofosbuvircoated tablet and preparation method thereof Download PDFInfo
- Publication number
- CN104622836A CN104622836A CN201410807131.0A CN201410807131A CN104622836A CN 104622836 A CN104622836 A CN 104622836A CN 201410807131 A CN201410807131 A CN 201410807131A CN 104622836 A CN104622836 A CN 104622836A
- Authority
- CN
- China
- Prior art keywords
- suo feibuwei
- tablet
- film coating
- coating tablet
- feibuwei
- 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.)
- Granted
Links
Abstract
The invention provides a sofosbuvircoated tablet and a preparation method thereof. The sofosbuvircoated tablet contains a tablet core and a thin-film coating layer, wherein the tablet core is prepared from sofosbuvir and at least one pharmaceutically acceptable auxiliary material. The sofosbuvircoated tablet is characterizedin thatthe tablet core is prepared through a dry granulation process; and the film forming material of the thin-film coating layer is ethyecellulose and hydroxypropyl methylcellulose at the weight ratio of (1:1) to (1:6). The sofosbuvircoated tablet prepared by the method has the characteristics of rapid dissolution and good stability.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, Suo Feibuwei coated tablet being specifically related to a kind of form stable and Fast Stripping and preparation method thereof.
Background technology
Suo Feibuwei sheet (trade name SovaldiTM, specification 400mg) obtain United States Food Drug Administration (FDA) and European Union's approval in Decembers, 2013 and in January, 2014 respectively, for oral nucleoside analog NS5B AG14361 once a day, as a part for antiviral therapy scheme, associating ribavirin, or ribavirin and Peg-IFN alpha-2b α are used for the treatment of chronic hepatitis C (Chronic Hepatitis C, CHC).Suo Feibuwei is a kind of nucleotide prodrug, is HCV NS5B RNA RNA-dependent AG14361, becomes the uridine analogs triphosphate with pharmacologically active at endocellular metabolism.SovaldiTM has been included into hepatopathy EASD of the U.S. (AASLD) hepatitis C treatment guidelines.
Hepatitis C is caused by hepatitis C virus (HCV), one group of general infectious disease based on liver injury.Its acute infection period symptom is not obvious, easy chronicity.Patients with chronic hepatitis C spontaneous recovery rate is very low, and the HCV infection person of about 10.0% ~ 20.0% develops into liver cirrhosis in infection in 20 years, and the case of about 5.0%-7.0% finally dies from liver cirrhosis or hepatocarcinoma.Hepatitis C has become major reason that is American-European and Japan and other countries End-stage liver disease, and hepatitis C relapse rate is high, and particularly chronic patients is higher, brings heavy financial burden to patient, family and society.The successful listing of Suo Feibuwei, when treating for specific gene type chronic hepatitis C, the demand to conventional injection interfering effects of drug element (IFN) can be eliminated, reduce the untoward reaction of patient and improve the compliance of patient, being widely regarded as the breakthrough medicine of chronic hepatitis c.
Suo Feibuwei (English name: Sofosbuvir; Molecular formula: C22H29FN3O9P; Molecular weight: 529.45) chemistry is by name: (S)-2-(((S)-(((2R; 3R; 4R; 5R)-5-(2; 4-dioxo-3; 4-dihydro-pyrimidin-1 (2H)-Ji)-4-fluoro-3-hydroxy-4-methyl oxolane-2-base) methoxyl group) (phenoxy group) phosphoryl) amino) isopropyl propionate, and there is following chemical constitution:
Suo Feibuwei is white to off-white color crystalline solid, and under 37 ° of C, pH is in the scope of 2-7.7, and dissolubility >=2mg/ml, is slightly soluble in water.
CN102459299A discloses Suo Feibuwei and preparation method, and comprises the purposes that hepatitis C virus is infected in treatment.
CN102858790A points out that Suo Feibuwei has polymorphic, and discloses 6 kinds of crystal formations (form 1 ~ form 6) and amorphous, and different crystal forms Suo Feibuwei has different XRPD TuPu method peaks.Wherein point out, form 1,2 and 3 is nonsolvated forms, 1:1DCM solvate and 1:1 chloroform compound respectively, and form 6 is anhydrous solid form.Form 4 and 5 is converted into form 1 after filtration.Form 2,3 is converted into form 1 through being separated.Form 1 is stable in sealed container.Under open condition, form 1 easily moisture absorption, can transfer form 6 to after certain approach.Form 1 at least two kinds of modes can transfer form 6 to, and namely form 1 is exposed to atmospheric humidity several days, forms plate-like monohydrate, is pulverized, and leaves standstill 6-10 week, can transfer form 6 in open container.Or by form 1 water in suspension, after experiencing several hours, transfer form 6 to.Phase co-conversion between the polymorphism of compound and polymorphic can affect safety and the effectiveness of medicine significantly, therefore must guarantee the stable crystal form of compound in formulation products.
Suo Feibuwei bitter in the mouth, coating can well cover bad abnormal smells from the patient, can improve the compliance that patient takes, and adopts the coating of different colours, also can well improve the identification of medicine, therefore be necessary to carry out coating to Suo Feibuwei sheet.In patent WO2013082003, disclose two kinds of tablets prepared by Suo Feibuwei form 1: tablet A is coated tablet, tablet B adds in label to add color lake but the tablet of non-coating.Tablet B can in 15 minutes Fast Stripping, the unexposed tablet A of patent stripping research.The present inventor experimental studies have found that through a large amount of, adopts packaging technique disclosed in patent WO2013082003 to the Suo Feibuwei tablet coating of form 1, can produce significant adverse effect to the stripping of product.Reason is, in coating process, tablet temperature remains on 46 ± 5 ° of C, and in the coated systems of aqueous solution, form 1 very easily forms hard plate-like solidification glue, and cause disintegration of tablet slack-off, drug-eluting speed obviously reduces.
Therefore, the object of this invention is to provide a kind of can Fast Stripping, stable Suo Feibuwei coated tablet.
Summary of the invention
Suo Feibuwei coated tablet that the invention provides Fast Stripping and stable form and preparation method thereof.Technical problem to be solved is to provide the preparation method of Fast Stripping type Suo Feibuwei coated tablet containing stable form and applicable industrialized great production.
It is accurate that tablet has drug dose, and medicament contg difference is little, steady quality, is convenient to transport, carries and store, patient's convenient drug administration, the advantages such as compliance is good.Coated tablet and capsule, can cover the bad smell of medicine.Suo Feibuwei bitter in the mouth, coated tablet is particularly applicable.
According to the present invention, Suo Feibuwei effective dose is 400mg.
According to the present invention, described Suo Feibuwei be with amorphous or in the form 1 form add.
Material owing to affecting by various factors, makes in molecule or intermolecular bonding mode changes when crystallization, cause molecule or atom different in lattice vacancy arrangement, form different crystal structures.Same substance has two or more spatial arrangements and cell parameter, and the phenomenon forming multiple crystal formation is called polymorphism (polymorphism).The medicine of identical chemical constitution can form the crystallization of different crystal forms, also can become the state of nodeless mesh, namely amorphous, and amorphous is not a type in polymorphic, and the microstructure of amorphous substance is the unordered set of molecule or atom.Amorphous drug may promote the quick absorption of medicine, increases the advantages such as the bioavailability of medicine, but also may have the shortcoming of less stable.The different crystal forms of same medicine may have remarkable difference in outward appearance, dissolubility, fusing point, dissolution, biological effectiveness etc.Therefore the Suo Feibuwei pharmaceutical preparation that stable crystal form form is provided is necessary.
According to the present invention, the Suo Feibuwei contained in described Suo Feibuwei coated tablet be with amorphous or in the form 1 form stable exist.
Particle size distribution/granularity (Particle Size Distribution, PSD): reflect that in powder sample, different-grain diameter granule accounts for the percent of granule total amount with specific instruments and methods.Represent several key indexs of particle property: particle diameter corresponding when 1. the cumulative particle sizes percentile of D50: one sample reaches 50%.Its physical significance is that the granule that particle diameter is greater than it accounts for 50%, and the granule being less than it also accounts for 50%, D50 and is also mean diameter or median particle diameter.2. particle diameter corresponding when the cumulative particle sizes distribution number of D90: one sample reaches 90%.Its physical significance be particle diameter be less than it granule account for 90%.Same, also have D10.Granularity of the present invention is measured by laser particle analyzer Mastersizer2000, and represents with the form of particle volume diameter.
According to the present invention, described Suo Feibuwei is micronized, its mean diameter D50≤90 μm; Preferred D50≤65 μm.
According to the present invention, the ratio (W/W) shared in oral solid pharmaceutical formulation of described Suo Feibuwei is 38% ~ 50%, preferably 40% ~ 45%.
According to Suo Feibuwei coated tablet provided by the invention, be made up of, as filler, disintegrating agent, fluidizer, lubricant Suo Feibuwei and one or more pharmaceutically acceptable adjuvants.
According to the present invention, described tablet label composition contains following weight percents:
As described herein, the Suo Feibuwei tablet of amorphous or form 1, in aqueous solution coated systems, by the effect of moisture and temperature, easily becomes plate-like thing or dope, reduces stripping.For suppressing amorphous or the Character change of the Suo Feibuwei of form 1 in coating process, the effect of moisture and/or temperature need be eliminated.
Common stomach dissolution type coating filmogen mainly contains polyvinyl alcohol (PVA) series and hypromellose (HPMC) series.Polyvinyl alcohol is solvable in water, insoluble in organic solvent, the preparation of the coating powder of this series and enrobing processes succinct, but need use water as coating solvent, and coating temperature needs to control at 45 ° of about C, even higher, as the coating adopted in patent WO2013082003.Hypromellose dissolves in cold water, almost insoluble in chloroform, ethanol and ether, and this serial coating powder also adopts water as coating solvent, and coating temperature needs to control at 40 ° of more than C.Coating powder containing these two kinds of filmogens is not suitable for Suo Feibuwei tablet coating that is amorphous or form 1.
Inventor is through a large amount of experimentatioies, be surprised to find, hypromellose (HPMC) and ethyl cellulose (EC) are combined the filmogen as coating, with the aqueous solution of different organic solvents or organic solvent as solvent, lower coating temperature can be adopted to carry out coating, the stripping of tablet is not by the impact of coating process, and within 15 minutes, dissolution can reach more than 90%.
Ethyl cellulose (EC) is water insoluble, is dissolved in the organic solvents such as ethanol, and ethyl cellulose has good film property, and the longer-term storage of its superior humidity resistance to form 1 and unbodied Suo Feibuwei is highly profitable.But because it is water insoluble, independent ethylcellulose coat is often used as extended release coatings film, the release of the great limit drug of meeting, this is disadvantageous for Suo Feibuwei coated tablet.Hypromellose (HPMC) is filmogen conventional in coating, water-soluble, and in the hydrous ethanol solution of different proportion.The present invention by ethyl cellulose and hypromellose conbined usage, double advantage of getting the two, and avoid bi-material shortcoming separately, by selecting suitable proportioning, reach balance in all fields, make Suo Feibuwei coated tablet have the characteristic of Fast Stripping, and good stability.
According to the present invention, in filmogen, the weight ratio of ethyl cellulose and hypromellose is 1:1 ~ 1:6; Preferred 1:2 ~ 1:5, is more preferably 1:4.
According to the present invention, except coating filmogen hypromellose (HPMC) and ethyl cellulose (EC), in coating, also antiplastering aid, opacifier, plasticizer, color lake etc. can be contained.
According to the present invention, the solvent of coating comprises the aqueous solution of organic solvent or organic solvent, and wherein organic solvent is selected from ethanol or acetone.
According to the present invention, organic solvent is selected from ethanol.
According to the present invention, the concentration of ethanol water is 75%-95%, is preferably 85%-95%.
According to the present invention, coating time slice bed tempertaure controls at 28-38 ° of C, preferred 30-35 ° C.
According to the present invention, coating weight gain scope is 1%-3%.
The preparation method being suitable for industrialized great production of the present invention is dry granulation.The selection of dry granulation process is through that experiment determines.
Due to the present invention's selection is Suo Feibuwei form 1 or amorphous, and it is unstable under the effect of moisture, and be easy to crystal conversion occurs, and it is agglomerating to be clamminess, cannot granulate, therefore wet granulation technology is excluded.
The good material of mobile performance can make the high speed tabletting of industrialized great production more easily realize, and reaches the object of time-saving energy-saving.In this oral solid pharmaceutical formulation preparation process, the index selected by mobility (Flowability) evaluating material is:
1) angle of repose (Angle of Repose): refer to angle of repose in gravitational field, the angle when Free Surface of powder accumulation body is in the limit state of balance between Free Surface and horizontal plane.Assay method has injection method, discharge method, inclination horn cupping etc.Angle of repose is less, and frictional force is less, and mobility is better, can meet the demand of production technology to mobility when it is generally acknowledged θ≤40 ° angle of repose.What the present invention adopted is injection method.
2) cake compressibility (Compressibility Index %): the important indicator being powder fluidity.In recent years, cake compressibility has become a kind of method that simple, quick and popular method predicts the flow feature judging powder body, the bulk density of its large I reflection powder body, granular size and form, surface area, coherency, doughy state etc.When it is generally acknowledged that cake compressibility is greater than 26%, mobility is poor, and when being greater than 38%, mobility is extremely poor.When being less than 20%, it is generally acknowledged that mobility is fine, the requirement of production can be met.
Inventors performed contrast experiment, namely undressed Suo Feibuwei is measured, Suo Feibuwei granule after dry granulation, Suo Feibuwei and vertical compression type microcrystalline Cellulose Type112(1:1) mixed powder, the mobility of the mixed powder of Suo Feibuwei and vertical compression type Parteck deltaM (1:1) and bulk density.Result is as follows:
As can be seen from result:
Suo Feibuwei powder fluidity is not good and bulk density is too little, and the good vertical compression type adjuvant of selective flow performance is as microcrystalline Cellulose Type112 and Parteck deltaM, and mobility is still not good.If select directly to mix powder tablet forming technique, the problem such as weight differential can be caused defective, is not suitable for industrialized great production.Therefore vertical compression technique is not suitable for.
Suo Feibuwei after dry granulation, mobility is obviously improved, and bulk density is moderate, and these character are conducive to carrying out smoothly of tablet forming technique.
According to the present invention, dry granulation process feature comprises dry granulation independent for Suo Feibuwei, or Suo Feibuwei and pharmaceutically acceptable adjuvant mixing carry out dry granulation.
Preparation method of the present invention specifically comprises the following steps:
1. the mixed powder containing adjuvant acceptable on Suo Feibuwei or Suo Feibuwei and pharmaceutics is suppressed to obtain block, bar or tablet at running roller top roll.
2. the block obtained, bar or tablet are smashed the particulate matter sieving and obtain containing Suo Feibuwei.
3. particulate matter is mixed with one or more in additional filler, disintegrating agent, fluidizer, lubricant, obtain mixed granule.
4. the mixed granule in 3 is pressed into tablet.
5. the tablet obtained in 4 is carried out coating.
Above-mentioned dry granulation process carries out on Alexanderwerk dry granulation equipment.Material is delivered between running roller with the speed of 50-80rpm by feed auger bar, roller speed 4-12rpm, running roller pressure 20 ~ 70bar, by the tablet, block or the bar that obtain after extruding.After cutter are smashed, cross the preliminary granulate of screen cloth of 2mm, obtain the granule containing Suo Feibuwei after the screen cloth granulate of 0.63mm.Granule is mixed 5 ~ 15 minutes with additional adjuvant in total mixed bucket.Mixed granule carries out high speed tabletting on tablet machine.Coating is carried out to the tablet obtained.
According to the present invention, the Suo Feibuwei contained in coated tablet prepared by above-mentioned preparation method is with stable amorphous or exist with amorphous or form 1, does not change in long term storage.
According to the present invention, coated tablet prepared by above-mentioned preparation method, disintegration is within 3 minutes.
According to the present invention, coated tablet prepared by above-mentioned preparation method, 15 minutes stripping quantities reach 90% or more, and in long term storage, stripping can not reduce, and its stripping is little by the impact of temperature and humidity, has good effectiveness.
According to the present invention, coated tablet prepared by above-mentioned preparation method, has good stability, and maximum single impurity is no more than 0.1%, and total impurities is no more than 0.5%, and long term storage increases hardly, has good safety.
According to the present invention, prepared by above-mentioned preparation method contains Suo Feibuwei coated tablet, is used for the treatment of chronic hepatitis C.
Detailed description of the invention
Below by way of specific embodiment, the invention will be further described, but these embodiments do not mean that any limitation of the invention.
Embodiment 1:
Suo Feibuwei granularity: D90=185 μm, D50=90 μm, D10=25 μm
Preparation process:
1) dry granulation part:
Dry granulation partial material rotates after pelletizing machine sieves through Ф 2.0mm screen cloth and mixes.
Start Alexanderwerk WP120 dry granulating machine, adjustment charging rate is 70rpm, running roller pressure 40bar, roller speed 5rpm, running roller gap 2.0mm.Dry granulation is added, is rolled into lamellar, strip or block.After cutter are smashed, thick 2.0mm screen cloth excessively, after the screen cloth of 0.63mm, forms Suo Feibuwei granule.
2) Extra Section:
The microcrystalline Cellulose Type112 of Suo Feibuwei granule and Extra Section, cross-linking sodium carboxymethyl cellulose, micropowder silica gel are added in total mixed bucket and mix.Later, add magnesium stearate, remix, obtain mixed granule.
3) high speed tabletting:
Mixed granule carries out high speed tabletting on tablet machine, controls the scope of weight at 1050.0mg ± 3.0%.
4) coating:
Coating powder containing ethyl cellulose and hypromellose (1:4) is made into 8%(w/w with 95% ethanol) solid content.The slice, thin piece obtained in step 3 is carried out coating in coating pan, coated tablet bed tempertaure 28-38 ° of C.Coating weight gain scope is at 1%-3%.
The plain sheet that said method obtains and the testing result of coated tablet as follows:
Embodiment 2:
Suo Feibuwei form 1 in embodiment 1 is changed to Suo Feibuwei amorphous (Suo Feibuwei granularity: D90=138 μm, D50=65 μm, D10=14 μm), the preparation method with embodiment 1 prepares plain sheet.Coating steps is carried out as follows:
Coating powder containing ethyl cellulose and hypromellose (1:1) is made into 8%(w/w with 75% ethanol) solid content.The slice, thin piece obtained in step 3 is carried out coating in coating pan, coated tablet bed tempertaure 30-35 ° of C.Coating weight gain scope is at 1%-3%.
The result obtained is as follows:
Embodiment 3:
Preparation process is with embodiment 1.Suo Feibuwei granularity: D90=87 μm, D50=26 μm, D10=7 μm.Coating steps is carried out as follows:
Coating powder containing ethyl cellulose and hypromellose (1:6) is made into 8%(w/w with 85% ethanol) solid content.The slice, thin piece obtained in step 3 is carried out coating in coating pan, coated tablet bed tempertaure 30-35 ° of C.Coating weight gain scope is at 1%-3%.
Testing result is as follows:
Comparative example:
The label preparation of comparative example is with embodiment 1.Coating changes the coating powder (Opadry 03B620018) that coating powder (Opadry 85G62511) that filmogen is PVA or filmogen are HPMC into, and be solvent with purified water, testing result is as follows:
Dissolution testing result shows, and adopt independent PVA or HPMC as filmogen coating, the dissolution of coated tablet obviously reduces, and causes active component can not Fast Stripping.
Claims (10)
1. Yi Zhong Suo Feibuwei film coating tablet, containing the label that Suo Feibuwei and the pharmaceutically acceptable adjuvant of at least one make, and based calcium, it is characterized in that described label is prepared by dry granulation process, the filmogen of based calcium is ethyl cellulose and hypromellose, and part by weight is 1:1 ~ 1:6 between the two.
2. Suo Feibuwei film coating tablet as claimed in claim 1, is characterized in that the part by weight of ethyl cellulose and hypromellose is 1:2 ~ 1:5.
3. Suo Feibuwei film coating tablet as claimed in claim 1, is characterized in that the part by weight of ethyl cellulose and hypromellose is 1:4.
4. Suo Feibuwei film coating tablet as claimed in claim 1, is characterized in that described Suo Feibuwei is micronized, mean diameter D50≤90 μm.
5. Suo Feibuwei film coating tablet as claimed in claim 4, is characterized in that mean diameter D50≤65 μm of Suo Feibuwei.
6. Suo Feibuwei film coating tablet as claimed in claim 1, is characterized in that Suo Feibuwei is with amorphous existence.
7. Suo Feibuwei film coating tablet as claimed in claim 1, is characterized in that Suo Feibuwei 1 existence in the form.
8. prepare a method for Suo Feibuwei film coating tablet as claimed in claim 1, comprise the steps:
1) by Suo Feibuwei micronization; Micronized Suo Feibuwei roll-in separately or together with pharmaceutically acceptable adjuvant is granulated; Add the mixing of pharmaceutically acceptable adjuvant and tabletted;
2) film coating agent that is filmogen containing ethyl cellulose and hypromellose being dissolved or dispersed in concentration is obtain coating solution in the ethanol water of 75%-95%;
3) label preheating in high-efficiency coating machine, control strip bed tempertaure is 28 ° of C-38 ° of C, and coating solution even spraying is also fully dry to sheet wicking surface, obtains Suo Feibuwei film coating tablet.
9. the method for Suo Feibuwei film coating tablet as claimed in claim 8, is characterized in that ethanol water concentration is 85%-95%.
10. the method for Suo Feibuwei film coating tablet as claimed in claim 8, is characterized in that sheet bed tempertaure is 30 ° of C-35 ° of C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410807131.0A CN104622836B (en) | 2014-12-23 | 2014-12-23 | Sofosbuvir coated tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410807131.0A CN104622836B (en) | 2014-12-23 | 2014-12-23 | Sofosbuvir coated tablet and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104622836A true CN104622836A (en) | 2015-05-20 |
| CN104622836B CN104622836B (en) | 2020-02-21 |
Family
ID=53202401
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410807131.0A Active CN104622836B (en) | 2014-12-23 | 2014-12-23 | Sofosbuvir coated tablet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104622836B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104906062A (en) * | 2015-06-30 | 2015-09-16 | 浙江天顺生物科技有限公司 | Sofosbuvir tablet and preparation method thereof |
| CN105380922A (en) * | 2015-12-18 | 2016-03-09 | 北京华禧联合科技发展有限公司 | Sofosbuvir film-coated tablets and preparation method thereof |
| CN106667936A (en) * | 2016-12-31 | 2017-05-17 | 杭州康本医药科技有限公司 | Sofosbuvir tablet and preparation method thereof |
| CN106880609A (en) * | 2015-12-15 | 2017-06-23 | 北大方正集团有限公司 | A kind of Suo Feibuwei dispersible tablets and preparation method thereof |
| CN107041873A (en) * | 2017-02-17 | 2017-08-15 | 杭州青玥医药科技有限公司 | The preparation method of rope fluorine cloth Wei coated tablet |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013082003A1 (en) * | 2011-11-29 | 2013-06-06 | Gilead Pharmasset Llc | Compositions and methods for treating hepatitis c virus |
-
2014
- 2014-12-23 CN CN201410807131.0A patent/CN104622836B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013082003A1 (en) * | 2011-11-29 | 2013-06-06 | Gilead Pharmasset Llc | Compositions and methods for treating hepatitis c virus |
Non-Patent Citations (2)
| Title |
|---|
| 刘蜀宝等: "《药剂学》", 31 August 2004 * |
| 姚日生等: "《药用高分子材料》", 31 March 2008 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104906062A (en) * | 2015-06-30 | 2015-09-16 | 浙江天顺生物科技有限公司 | Sofosbuvir tablet and preparation method thereof |
| CN104906062B (en) * | 2015-06-30 | 2018-05-25 | 浙江天顺生物科技有限公司 | A kind of tablet of Suo Feibuwei and preparation method thereof |
| CN106880609A (en) * | 2015-12-15 | 2017-06-23 | 北大方正集团有限公司 | A kind of Suo Feibuwei dispersible tablets and preparation method thereof |
| CN105380922A (en) * | 2015-12-18 | 2016-03-09 | 北京华禧联合科技发展有限公司 | Sofosbuvir film-coated tablets and preparation method thereof |
| CN106667936A (en) * | 2016-12-31 | 2017-05-17 | 杭州康本医药科技有限公司 | Sofosbuvir tablet and preparation method thereof |
| CN107041873A (en) * | 2017-02-17 | 2017-08-15 | 杭州青玥医药科技有限公司 | The preparation method of rope fluorine cloth Wei coated tablet |
| CN107041873B (en) * | 2017-02-17 | 2020-02-28 | 杭州青玥医药科技有限公司 | Preparation method of sofosbuvir coated tablet |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104622836B (en) | 2020-02-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5775464B2 (en) | Delayed release oral dosage composition containing amorphous CDDO-ME | |
| JP6876758B2 (en) | Dosage form composition comprising an inhibitor of Bruton's tyrosine kinase | |
| US10166234B2 (en) | Pharmaceutical preparation comprising phenylalanine derivative | |
| WO2019010092A1 (en) | Compositions and methods for treatment of cystic fibrosis | |
| CN104622836A (en) | Sofosbuvircoated tablet and preparation method thereof | |
| WO2020249001A1 (en) | Oral solid tablet comprising bruton's tyrosine kinase inhibitor and preparation method therefor | |
| EP2568964B1 (en) | Pharmaceutical dosage form comprising one or more antiretroviral active ingredients | |
| EP3087989B1 (en) | Solid preparations comprising tofogliflozin and method for producing the same | |
| CN103142494A (en) | Ornidazole oral preparation and preparation method thereof | |
| WO2011101862A1 (en) | Stabilized fluconazole polymorph iii formulation | |
| EP3923914B1 (en) | Afabicin formulation, method for making the same | |
| US10583087B2 (en) | Pharmaceutical composition for oral administration | |
| JP2020518611A (en) | Compositions with improved water solubility and bioavailability | |
| CN103845332A (en) | Medicinal dasatinib composition and preparation method thereof | |
| CN108210509A (en) | New composition of nucleosides phosphoramidic acid compound and preparation method thereof | |
| CN103271908B (en) | Oral tablet and preparation method thereof containing Telmisartan and Amlodipine Besylate Tablet | |
| CN102641253A (en) | Valsartan sustained release tablet and preparation method thereof | |
| WO2015199115A1 (en) | Pharmaceutical composition for oral administration | |
| WO2012062691A1 (en) | Pharmaceutical compositions for treating hcv infections | |
| CN105380922A (en) | Sofosbuvir film-coated tablets and preparation method thereof | |
| EP3928771A1 (en) | Pharmaceutical compositions of 1,2-benzisoxazole-3-methanesulfonamide | |
| JP2024016309A (en) | solid dispersion |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | 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 |