CN105384649A - Fingolimod hydrochloride with specific particle diameter and solid composition thereof - Google Patents
Fingolimod hydrochloride with specific particle diameter and solid composition thereof Download PDFInfo
- Publication number
- CN105384649A CN105384649A CN201510519837.1A CN201510519837A CN105384649A CN 105384649 A CN105384649 A CN 105384649A CN 201510519837 A CN201510519837 A CN 201510519837A CN 105384649 A CN105384649 A CN 105384649A
- Authority
- CN
- China
- Prior art keywords
- particle diameter
- fingolimod hydrochloride
- temperature
- fingolimod
- hydrochloride
- 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
Abstract
The invention provides a fingolimod hydrochloride with specific particle diameter and a solid composition thereof, and belongs to the technical field of pharmacy. The particle diameter D90 of the fingolimod hydrochloride with specific particle diameter is not greater than 62 microns and not smaller than 15 microns, and the particle diameter D50 is not greater than 14 microns and not smaller than 6 microns. When the fingolimod hydrochloride in the particle diameter range is used, a solid preparation with an uniform content and a high dissolution rate can be prepared, and the dissolution and in vivo absorption of the medicine can be effectively increased. The preparation technology of the fingolimod hydrochloride with specific particle diameter and the solid preparation thereof provided by the invention is simple and practicable; the cost is low; and the fingolimod hydrochloride and the solid preparation thereof are suitable for industrial production.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of fingolimod hydrochloride of specified particle diameter, its solids composition, and preparation method.
Background technology
FTY720 (Fingolimod), chemistry 2-amino-2-[2-(4-octyl phenyl) ethyl]-1,3-PD by name, structure as shown in the formula:
FTY720 can impel lymphocyte to move back to lymphoglandula (away from central nervous system), regulates the S1P acceptor of neurocyte; Be first can the neotype immunosuppressant being used for the treatment of relapsing remitting multiple sclerosis disease of oral administration administration.FTY720 capsule preparations is gone on the market in the U.S. in 2010 by Novartis Co., Ltd.
The oral dosage specification of FTY720 is 0.5mg, and content is extremely low in the formulation, easily causes the problem that formulation content is uneven.Generally speaking, the problem of uniformity of dosage units can be improved by the particle diameter controlling bulk drug; But, for the solid preparation of FTY720, predict the bulk drug of suitable particle diameter, so that it is extremely difficult for controlling formulation content uniformity coefficient and not affecting stripping homogeneity simultaneously.
Summary of the invention
Summary of the invention
First aspect present invention provides a kind of fingolimod hydrochloride with specified particle diameter and preparation method thereof, and the fingolimod hydrochloride of this particle diameter can make the solid preparation content that obtains even, and dissolution rate is fast.
The present invention provides on the other hand and a kind ofly includes solids composition of the fingolimod hydrochloride of specified particle diameter and preparation method thereof, and solids composition content is even, and dissolution rate is fast, steady quality; Its preparation method is simple, and cost is lower, is applicable to suitability for industrialized production.
Term definition
Particle diameter corresponding when term " D90 " refers to that the cumulative particle sizes distribution number of a sample reaches 90%.Its physical significance is that the particle that particle diameter is less than it accounts for 90%, such as " such as should be not more than 62 grains of answering then represent " be not more than 62 answer particle account for 90% ".Particle diameter corresponding when D10 refers to that the cumulative particle sizes distribution number of a sample reaches 10%.Particle diameter corresponding when D50 refers to that the cumulative particle sizes distribution number of a sample reaches 50%.
Term " optionally " or " optionally " refer to the event that describes subsequently or situation can but not necessarily occur, and this description comprises situation that wherein said event or situation occur and wherein its absent variable situation.Such as, " optionally other pharmaceutically acceptable vehicle " refer to that other pharmaceutically acceptable vehicle can exist or can not exist.
Term " comprises " for open language, namely comprises the content specified by the present invention, but does not get rid of otherwise content.
Above of the present invention, no matter whether use the wording such as " approximately " or " about ", all numerals disclosed at this are approximation.The numerical value of each numeral likely there will be difference or the rational difference thought of those skilled in the art of less than 5%, as the difference of 0.1%, 0.5%, 1%, 2%, 3%, 4% or 5%.
Detailed Description Of The Invention
The present inventor is to improving fingolimod hydrochloride uniformity of dosage units in the formulation and dissolution rate conducts in-depth research, find under study for action, when using particle diameter D90 to be not more than the fingolimod hydrochloride of 62 μm, especially particle diameter D90 is used to be not more than 62 μm and to be not less than 15 μm, when particle diameter D50 is not more than 14 μm and is not less than the fingolimod hydrochloride of 6 μm, the content of preparation-obtained solids composition is even and dissolution rate is fast, the fingolimod hydrochloride of this specified particle diameter scope is conducive to increasing stripping and the absorption in vivo of medicine, is conducive to preparing solid preparation.
Therefore, the invention provides a kind of particle diameter D90 and be not more than 62 μm and be not less than 15 μm, particle diameter D50 is not more than 14 μm and is not less than the fingolimod hydrochloride of 6 μm.
Present invention also offers a kind of method preparing described fingolimod hydrochloride, the method comprises: dissolved in ethanol by fingolimod hydrochloride, separates out to there being solid first temperature underpressure distillation; Ethyl acetate is added, cooling second temperature; The 3rd temperature stirring and crystallizing; Then except desolventizing, after gained solid drying and get final product.
Described first temperature is 50 DEG C-70 DEG C.In some embodiments, described first temperature is 55 DEG C-65 DEG C.
Described second temperature is 50 DEG C-70 DEG C.In some embodiments, described second temperature is 55 DEG C-65 DEG C.
Described 3rd temperature is-10 DEG C-10 DEG C.In some embodiments, described 3rd temperature is-5 DEG C-5 DEG C.In some embodiments, described 3rd temperature is 0 DEG C-5 DEG C.
The mass ratio of fingolimod hydrochloride and ethanol is 1:3-1:10.
The mass ratio of fingolimod hydrochloride and ethyl acetate is 1:5-1:40.In some embodiments, the mass ratio of fingolimod hydrochloride and ethyl acetate is 1:8-1:35.In some embodiments, the mass ratio of fingolimod hydrochloride and ethyl acetate is 1:10-1:35.In some embodiments, the mass ratio of fingolimod hydrochloride and ethyl acetate is 1:8-1:30.In some embodiments, the mass ratio of fingolimod hydrochloride and ethyl acetate is 1:10-1:30.
The time of described crystallization is 1 hour-10 hours.In some embodiments, the time of described insulation crystallization is 3 hours-7 hours.
Describedly can adopt filtration except desolventizing, centrifugally wait conventional solid-liquid separation method.
Described drying can adopt vacuum-drying, and forced air drying etc. can except the method for desolventizing.Dry temperature-controllable is built in 10 DEG C-30 DEG C.
In some embodiments, fingolimod hydrochloride being dissolved in 3 times-10 times (mass ratio) ethanol, separating out to there being solid 50 DEG C of-70 DEG C of underpressure distillation; Add 8 times-35 times (mass ratio) ethyl acetate at 50 DEG C-70 DEG C, cooling, stir insulation crystallization 3 hours-7 hours at-5 DEG C-5 DEG C; Then except desolventizing, gained solid is 10 DEG C of-30 DEG C of vacuum-dryings, and obtain D90 and be not more than 62 μm and be not less than 15 μm, particle diameter D50 is not more than 14 μm and is not less than the fingolimod hydrochloride of 6 μm.
Present invention also offers a kind of solids composition comprising the fingolimod hydrochloride of described specified particle diameter, this solids composition can be granule, also can be capsule.
Described solids composition also comprises other pharmaceutically acceptable auxiliary materials, comprises thinner and lubricant.
Described thinner is selected from but is not limited to N.F,USP MANNITOL, lactose, composite starch, maltose alcohol, Sorbitol Powder, Xylitol, dextrose, maltose, sucrose, glucose, fructose, maltodextrin, starch, pregelatinized Starch, Solka-floc, Microcrystalline Cellulose, silicified microcrystalline Mierocrystalline cellulose, secondary calcium phosphate, calcium carbonate, sodium carbonate, sodium phosphate or its combination.In some embodiments, described thinner is composite starch.
Described lubricant is selected from but is not limited to Magnesium Stearate, calcium stearate, Zinic stearas, stearic acid, fumaric acid, sodium stearyl fumarate, polyoxyethylene glycol, Glyceryl Behenate or its combination.In some embodiments, described lubricant is Magnesium Stearate.
In some embodiments, the described solids composition comprising the fingolimod hydrochloride of described specified particle diameter comprises: particle diameter D90 is not more than 62 μm and is not less than 15 μm, particle diameter D50 is not more than 14 μm and is not less than the fingolimod hydrochloride of 6 μm, thinner and lubricant.
In some embodiments, be 100 parts of calculating with the solids composition comprising the fingolimod hydrochloride of described specified particle diameter, the described solids composition comprising the fingolimod hydrochloride of described specified particle diameter comprises particle diameter D90 and is not more than 62 μm and is not less than 15 μm, and particle diameter D50 is not more than 14 μm and is not less than the fingolimod hydrochloride 0.5 part-10 parts of 6 μm; Thinner 55 parts-99 parts; Lubricant 0.5 part-10 parts.
In some embodiments, be 100 parts of calculating with the solids composition comprising the fingolimod hydrochloride of described specified particle diameter, the described solids composition comprising the fingolimod hydrochloride of described specified particle diameter comprises particle diameter D90 and is not more than 62 μm and is not less than 15 μm, and particle diameter D50 is not more than 14 μm and is not less than the fingolimod hydrochloride 0.5 part-10 parts of 6 μm; Composite starch 55 parts-99 parts; Magnesium Stearate 0.5 part-10 parts.
In some embodiments, the described solids composition comprising the fingolimod hydrochloride of described specified particle diameter comprises particle diameter D90 and is not more than 62 μm and is not less than 15 μm, particle diameter D50 is not more than 14 μm and is not less than the fingolimod hydrochloride of 6 μm, composite starch and Magnesium Stearate.
In some embodiments, calculate according to mass ratio, the described solids composition comprising the fingolimod hydrochloride of described specified particle diameter comprises particle diameter D90 and is not more than 62 μm and is not less than 15 μm, particle diameter D50 is not more than 14 μm and is not less than the fingolimod hydrochloride 0.62% of 6 μm, composite starch 97.38%, Magnesium Stearate 2%.
In some embodiments, the solids composition comprising the fingolimod hydrochloride of described specified particle diameter of the present invention can be the form of particle, also can be the preparation being finally prepared into capsule, described solids composition, except above-mentioned composition composition, also comprises capsule shell, opalizer and pigment.
Described capsule shell material is selected from gelatin; Described opalizer is selected from titanium dioxide; Described pigment be selected from red No. 3 of FD & C, red No. 20 of FD & C, yellow No. 6 of FD & C, blue No. 2 of FD & C, green No. 5 of D & C, red No. 8 of orange No. 5 of D & C, D & C, caramel, red iron oxide, iron oxide yellow one or more.
Comprise the preparation method of the solids composition of the fingolimod hydrochloride solid of described specified particle diameter described in the present invention additionally provides on the other hand, the method comprises the following steps: mixing of fingolimod hydrochloride and thinner being sieved; Add after lubricant mixes further again, prepare solid particulate, optionally solid particulate is filled in gelatin hollow capsule, prepares capsule.
The fingolimod hydrochloride with specified particle diameter provided by the invention, the solids composition content that obtains can be made even, and dissolution rate is fast; Effectively can increase stripping and the absorption in vivo of medicine.Solids composition content provided by the invention is even, and dissolution rate is fast, and good stability, may be used for useful in preparing drug formulations.Preparation is simple for fingolimod hydrochloride solid preparation provided by the invention, and cost is low, is suitable for suitability for industrialized production.
Embodiment
In order to make those skilled in the art understand technical scheme of the present invention better, below disclose further some non-limiting embodiments the present invention is described in further detail.
Reagent used in the present invention all can be buied from the market or can be obtained by method described in the invention preparation.
In the present invention, kg represents kilogram, and g represents gram, and mL represents milliliter, μm represents micron, and nm represents nanometer, and rpm represents rev/min, and mol/L represents mol/L.
Embodiment 1: fingolimod hydrochloride preparation method
In dissolution kettle, drop into dehydrated alcohol 1200g, fingolimod hydrochloride 200g, still temp 35 DEG C, is stirred to clearly molten, filtered while hot, and filtrate steams ethanol 60 DEG C of underpressure distillation and separates out to there being solid, stops underpressure distillation; System temperature control 60 DEG C, drips ethyl acetate 7kg.4 DEG C of crystallizatioies are cooled to, insulated and stirred crystallization 6 hours after dropwising.After crystallization terminates, filter, filter cake 600g ethyl acetate drip washing.Be laid on drip pan by gained solid homogeneous, temperature control 10 DEG C of-30 DEG C of vacuum-dryings are to moisture≤0.15%, and drying terminates.Dried product is crossed 40 eye mesh screens, obtains product 170g, detect size distribution, D90:29.351 μm, D50:9.890 μm; D10:3.156 μm.
Embodiment 2: fingolimod hydrochloride preparation method
In dissolution kettle, drop into dehydrated alcohol 2kg, fingolimod hydrochloride 200g, still temp 35 DEG C, is stirred to clearly molten, filtered while hot, and filtrate steams ethanol 65 DEG C of underpressure distillation and separates out to there being solid, stops underpressure distillation; System temperature control 55 DEG C, drips ethyl acetate 8kg.-3 DEG C of crystallizatioies are cooled to, insulated and stirred crystallization 6 hours after dropwising.After crystallization terminates, filter, filter cake 600g ethyl acetate drip washing.Be laid on drip pan by gained solid homogeneous, temperature control 10 DEG C of-30 DEG C of vacuum-dryings are to moisture≤0.15%, and drying terminates.Dried product is crossed 40 eye mesh screens, obtains product 160g, detect size distribution, D90:62.035 μm, D50:14.134 μm; D10:3.798 μm.
Embodiment 3: fingolimod hydrochloride preparation method
In dissolution kettle, drop into dehydrated alcohol 800g, fingolimod hydrochloride 200g, still temp 35 DEG C, is stirred to clearly molten, filtered while hot, and filtrate steams ethanol 55 DEG C of underpressure distillation and separates out to there being solid, stops underpressure distillation; System temperature control 60 DEG C, drips ethyl acetate 2kg.0 DEG C of crystallization is cooled to, insulated and stirred crystallization 6 hours after dropwising.After crystallization terminates, filter, filter cake 600g ethyl acetate drip washing.Be laid on drip pan by gained solid homogeneous, temperature control 10 DEG C of-30 DEG C of vacuum-dryings are to moisture≤0.15%, and drying terminates.Dried product is crossed 40 eye mesh screens, obtains product 180g, detect size distribution, D90:20.201 μm, D50:5.432 μm; D10:2.341 μm.
Embodiment 4: prescription and preparation technology
Prescription:
In prescription, the per-cent of each component is mass percent.
Preparation technology:
I) method of reference embodiment 1-embodiment 3 obtains the bulk drug of three kinds of different-grain diameters;
II) adopted by composite starch U5 dry method pelletizing machine to sieve (rotating speed: 1440rpm), first take out the composite starch separately use of about 1/3 recipe quantity, residual content is crossed 170 mesh sieves, material is contained in mixed-hopper, obtain material 1;
III) by mistake 40 mesh sieves after the composite starch mixing 30min of the fingolimod hydrochloride of recipe quantity and its 5 times amount (by weight), be loaded on Step II) mixed-hopper in; Remaining composite starch crosses 40 mesh sieves, is loaded on Step II) mixed-hopper in, guarantee that on screen cloth, fingolimod hydrochloride is without adhesion; Obtain material 2;
IV) above-mentioned material 2 mixes in mixed-hopper, rotating speed 10rpm, mixing 30min;
V) by the step IV of recipe quantity Magnesium Stearate and its 3 times amount (by weight)) gained material after manual mixing, crosses 40 mesh sieves and adds step IV in PE bag) mixed-hopper in, rotating speed 10rpm, mixing 30min.
VI) adopt NJP-500 Autocapsulefillingmachine filled capsules, the heavy 90mg of capsule 's content, is filled in No. 3 gelatin hollow capsule.
Embodiment 5: uniformity of dosage units and dissolution rate
1) uniformity of dosage units detects
The sample of prescription 1-prescription 3 preparation respectively in Example 4, uniformity of dosage units detects with reference to Chinese Pharmacopoeia 2010 editions " annex XE Content uniformity test ", the results are shown in Table 1.
Table 1: uniformity of dosage units
Remarks: AVE represents mean value; A represents the absolute value of the difference of labelled amount and average, and wherein labelled amount is 100; S represents standard deviation.
According to the above results, the filling rear uniformity of dosage units of capsule prepared when bulk drug particle diameter bulk drug D90 is not more than 62 μm meets quality criteria requirements.
2) dissolution rate detects
The sample of prescription 1-prescription 3 preparation in Example 4, according to Chinese Pharmacopoeia 2010 editions, " " first method measures the stripping of 5min, 10min, 15min, 20min, 30min and 45min, the results are shown in Table 2 annex XC dissolution method respectively.
Table 2: the dissolution rate of capsule prepared by different-grain diameter bulk drug
SDS is sodium lauryl sulphate.
Can find out according to In Vitro Dissolution data, along with the increase dissolution rate of particle diameter is in the trend that slows down, but dissolution rate is all very fast in this particle diameter, and in 15min, stripping is all more than 90%.
Embodiment 6: prescription and technique
Preparation technology is with embodiment 4.
Embodiment 7: study on the stability
1) acceleration for stabilization experiment related substance and content
Experimental technique is with reference to two the annex XIXC medicine stability test governing principle designs of " Chinese Pharmacopoeia " version in 2010.
Detection method: choose sample prepared by the embodiment of the present invention 6 respectively at 40 DEG C, place 6 months under 75%RH (relative humidity) condition, in the 1st, sampling in 3,6 months detects indices stability.The detection method of related substance (single assorted and total assorted) is HPLC method, and content and related substance detected result are in table 4.
Wherein, HPLC testing conditions and parameter as follows:
Chromatographic column: WatersXterra
tMmSC8; 4.6 × 50mm, 2.5 μm;
Flow velocity: 1.5mL/min;
Column temperature: 30 DEG C;
Sample disc temperature: 8 DEG C;
Determined wavelength: 215nm;
Sampling volume: 10 μ L;
Working time: 35min;
Damping fluid: phosphate aqueous solution;
Moving phase: mobile phase A (pH2.6 damping fluid: methyl alcohol=93:7) and Mobile phase B (acetonitrile) gradient elution, elution program sees the following form 3:
Table 3: elution program
Time (min) | A phase (%) | B phase (%) |
0→1 | 70 | 30 |
1→15 | 70→58 | 30→42 |
15→28 | 58→5 | 42→95 |
28→30 | 5 | 95 |
30→30.1 | 5→70 | 95→30 |
30.1→35 | 70 | 30 |
Table 4: content and related substance detected result
Remarks: E, F, G, H are known impurities; RRT (relative retention time) be 1.58,1.66,1.71,1.84 peak be auxiliary material peak, be not counted in total assorted.
2) stripping experiment
6, sample in Example 6, according to Chinese Pharmacopoeia 2010 editions, " " first method, measures placement 0 day, January to annex XC dissolution method respectively, and the stripping after March and June, the results are shown in Table 5.
Table 5: dissolution rate result (0.1mol/L hydrochloric acid+0.2%SDS, 500mL, basket method, 100rpm)
Can find out according to detected result: acceleration environment 6 months, preparation related substance is without increase trend, and always mixing is 0; Place the dissolution rate in vitro after 6 months and 0 day compare without considerable change.
Embodiment 8: droplet measurement method
The detection method of the particle diameter of fingolimod hydrochloride is: instrument and sampler: Malvern ParticleSizer, Scirocco2000 (A) sampler; Analytical model: universal former (fine powder); Sample tray: general tray; Background Measuring Time: 12 seconds; The sample measurement time: 10 seconds; Obscurity: 0.5%-0.6%; Sample rate: 50%; Dispersion air pressure: 2.5 bar, add screen cloth.
Method of the present invention is described by preferred embodiment, and related personnel obviously can change methods and applications as herein described or suitably change and combination in content of the present invention, spirit and scope, realizes and applies the technology of the present invention.Those skilled in the art can use for reference present disclosure, and suitable improving technique parameter realizes.Special needs to be pointed out is, all similar replacements and change apparent to those skilled in the art, they are all deemed to be included in the present invention.
Claims (10)
1. a fingolimod hydrochloride, its particle diameter D90 is not more than 62 μm and is not less than 15 μm, and particle diameter D50 is not more than 14 μm and is not less than 6 μm.
2. solids composition, comprise D90 and be not more than 62 μm and be not less than 15 μm, particle diameter D50 is not more than 14 μm and is not less than the fingolimod hydrochloride of 6 μm, thinner and lubricant.
3. solids composition according to claim 2, is 100 parts of calculating with solids composition, comprises fingolimod hydrochloride 0.5 part-10 parts; Thinner 55 parts-99 parts; Lubricant 0.5 part-10 parts.
4. solids composition according to claim 2, calculates according to mass ratio, comprises fingolimod hydrochloride 0.62%, composite starch 97.38%, Magnesium Stearate 2%.
5. solids composition according to claim 2, described thinner is composite starch.
6. prepare the method for fingolimod hydrochloride according to claim 1, comprising: fingolimod hydrochloride is dissolved in ethanol, separating out to there being solid first temperature underpressure distillation; Ethyl acetate is added, cooling second temperature; Insulation crystallization is stirred the 3rd temperature; Then except desolventizing, obtained fingolimod hydrochloride after gained solid drying; Described first temperature is 50 DEG C-70 DEG C, and described second temperature is 50 DEG C-70 DEG C, and described 3rd temperature is-10 DEG C-10 DEG C; The mass ratio of fingolimod hydrochloride and ethanol is 1:3-1:10.
7. method according to claim 6, described first temperature is 55 DEG C-65 DEG C; Described second temperature is 55 DEG C-65 DEG C; Described 3rd temperature is-5 DEG C-5 DEG C.
8. method according to claim 6, wherein the mass ratio of fingolimod hydrochloride and ethyl acetate is 1:8-1:35.
9. method according to claim 6, the time of described insulation crystallization is 3 hours-7 hours.
10. method according to claim 6, the temperature of described drying controls at 10 DEG C-30 DEG C.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510519837.1A CN105384649A (en) | 2014-08-22 | 2015-08-21 | Fingolimod hydrochloride with specific particle diameter and solid composition thereof |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410419567 | 2014-08-22 | ||
CN2014104195672 | 2014-08-22 | ||
CN201510519837.1A CN105384649A (en) | 2014-08-22 | 2015-08-21 | Fingolimod hydrochloride with specific particle diameter and solid composition thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
CN105384649A true CN105384649A (en) | 2016-03-09 |
Family
ID=55417477
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201510519837.1A Pending CN105384649A (en) | 2014-08-22 | 2015-08-21 | Fingolimod hydrochloride with specific particle diameter and solid composition thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN105384649A (en) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130034603A1 (en) * | 2011-08-01 | 2013-02-07 | Julia Hrakovsky | Process for preparing pharmaceutical compositions of fingolimod |
US20130095177A1 (en) * | 2010-04-22 | 2013-04-18 | Ratiopharm Gmbh | Method of preparing an oral dosage form comprising fingolimod |
CN104193626A (en) * | 2014-09-18 | 2014-12-10 | 广东东阳光药业有限公司 | Method for preparing Fingolimod particles |
-
2015
- 2015-08-21 CN CN201510519837.1A patent/CN105384649A/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130095177A1 (en) * | 2010-04-22 | 2013-04-18 | Ratiopharm Gmbh | Method of preparing an oral dosage form comprising fingolimod |
US20130034603A1 (en) * | 2011-08-01 | 2013-02-07 | Julia Hrakovsky | Process for preparing pharmaceutical compositions of fingolimod |
CN104193626A (en) * | 2014-09-18 | 2014-12-10 | 广东东阳光药业有限公司 | Method for preparing Fingolimod particles |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105055359B (en) | (S) pyrrolidine acetamide sustained release tablets of 4 hydroxyl, 2 oxo 1 and preparation method thereof | |
AU2002334413C1 (en) | Low hygroscopic aripiprazole drug substance and processes for the preparation thereof | |
JP7090674B2 (en) | Chinese herbal medicine compositions, their formulations and uses | |
CN1320926C (en) | Ginkgo leaf extract composition and its prepn | |
US20160143976A1 (en) | Traditional chinese medicine composition, and preparation and application thereof | |
AU2002334413A1 (en) | Low hygroscopic aripiprazole drug substance and processes for the preparation thereof | |
CN105828827A (en) | Solid preparation comprising tofogliflozin and method for producing same | |
CN105384649A (en) | Fingolimod hydrochloride with specific particle diameter and solid composition thereof | |
CN102188392B (en) | Stabilized divalproex sodium coated granules, preparation method and solid preparation thereof | |
WO2014036865A1 (en) | Method for preparing fingolimod mucate and crystal thereof and application of fingolimod mucate and crystal thereof | |
CN101491528A (en) | Anti-hepatitis b virus medicine dispersion combination at non-crystal state and medicine preparation thereof | |
CN112076190B (en) | Solid preparation containing insoluble thienopyridine composition and preparation method thereof | |
CN104447292A (en) | 2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropionic acid polymorph as well as preparation method and pharmaceutical composition thereof | |
CN101579323B (en) | Butylphenyl phthaleine sustained release tablet and preparation method thereof | |
WO1997010810A2 (en) | Pharmaceutical granules | |
CN105435239A (en) | Use of microcrystalline cellulose in Meisuoshuli preparation, auxiliary material used for Meisuoshuli, Meisuoshuli preparation and preparation method of Meisuoshuli preparation | |
CN107245054A (en) | A kind of amorphous bulleyaconitine A compound and preparation method thereof | |
CN114533677A (en) | Solid dispersion, preparation method and application thereof | |
CN103845332A (en) | Medicinal dasatinib composition and preparation method thereof | |
CN115671054A (en) | Mannitol pellet core and preparation method and application thereof | |
CN103655571A (en) | Lopinavir and ritonavir compound high-uniformity nano co-dispersion body and preparation method thereof | |
CN109157523B (en) | Orlistat dripping pill and its prepn | |
CN101991859A (en) | Beta-cyclodextrin inclusion compound of huperzine A, and preparation method and preparation thereof | |
CN105055353B (en) | A kind of Entecavir tablet and preparation method thereof | |
CN111249241B (en) | Solid preparation containing insoluble thienopyridine composition and preparation method thereof |
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 | ||
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160309 |