CN104490849A - High-density dimethyl fumarate enteric-coated granules and preparation method thereof - Google Patents
High-density dimethyl fumarate enteric-coated granules and preparation method thereof Download PDFInfo
- Publication number
- CN104490849A CN104490849A CN201410683477.4A CN201410683477A CN104490849A CN 104490849 A CN104490849 A CN 104490849A CN 201410683477 A CN201410683477 A CN 201410683477A CN 104490849 A CN104490849 A CN 104490849A
- Authority
- CN
- China
- Prior art keywords
- coated particles
- enteric
- enteric coated
- combination
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention discloses high-density dimethyl fumarate enteric-coated granules and a preparation method thereof. The density of the high-density dimethyl fumarate enteric-coated granules is 1.0g/mL or higher, or is 1.3g/mL or higher, or is 1.6g/mL or higher. Preparation size of the high-density dimethyl fumarate enteric-coated granules is small; the high-density dimethyl fumarate enteric-coated granules are convenient for administration, and are especially suitable for patients, elders, and children with swallowing difficulty, and are capable of increasing patient compliance; preparation content uniformity is high; rapid release is realized; stability is high; and the preparation method is simple, and is suitable for industrialized production.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of highdensity dimethyl fumarate enteric coated particles and preparation method thereof.
Background technology
Dimethyl fumarate, structure, as shown in the formula (I), is the medicine that one is used for the treatment of multiple sclerosis (MS).The dimethyl fumarate slow releasing capsule of BiogenIdec company, trade name Tecfidera, is ratified by FDA, is used for the treatment of multiple sclerosis (MS).
Multiple sclerosis is a kind of central nervous system disease, and typical evolution is chronic or intermittent, can develop into larger major function lose the impact of human body by the inconvenience of less body.Dimethyl fumarate plays a role by activating nuclear factor-2 sample path, and this path makes cells in vivo have the ability to resist the injury of inflammation and the oxidative stress come with diseases such as MS.Prior art CN99812388.9 discloses a kind of microplate or micropill of dimethyl fumarate, and the amount wherein containing dimethyl fumarate is 100 ~ 300mg, and said preparation finally can be prepared into the form of enteric coated capsule; CN200410051181.7 discloses a kind of microcapsule of dimethyl fumarate, and cyst material is fully refined paraffin wax; US20130295169 discloses a kind of preparation of dimethyl fumarate, and the amount comprising dimethyl fumarate is 43 ~ 95%, makes the form of microplate or micropill; CN201410194551.6 discloses a kind of enteric sustained-release pellet of dimethyl fumarate, comprises ball core, enteric layer and slow release layer, and wherein the content of dimethyl fumarate is 27 ~ 32%.
The dimethyl fumarate preparation of above-mentioned preparation has a common feature, and namely drug dose specification is large, if make final dosage form as capsule or tablet, size certainly will be caused to be difficult to greatly swallow, especially for the patient of difficulty of swallowing, old man or child.The product specification of existing listing is 240mg, adopts No. 0 capsule, and size is big to such an extent as to can not normally swallow, and affects patient's Compliance.Therefore the while of preparing a kind of high-load, size is little makes to swallow easily, and the dimethyl fumarate preparation improving patient compliance is necessary very much.
Summary of the invention
The present inventor is studying how to reduce dimethyl fumarate preparation size repeatedly, improve in the process of patient compliance, prepare a kind of highdensity dimethyl fumarate enteric coated particles, on the basis ensureing original active component high-load, by increasing the density of granule, prepare the preparation that a kind of volume is less, and pleasantly surprised discovery, while increasing the density of granule, still show the characteristic of Fast Stripping; Although the density variation of dimethyl fumarate and highdensity adjuvant is large in addition, the preparation obtained still has good uniformity of dosage units.
Summary of the invention
First aspect present invention provides a kind of highdensity dimethyl fumarate enteric coated particles, and this enteric coated particles has highdensity core, and the dosage form size finally prepared is little, and patient easily swallows, and improves compliance; The formulation content uniformity prepared is high, and release is quick, steady quality.
Second aspect present invention provides a kind of preparation method of dimethyl fumarate enteric coated particles, and the method preparation technology is simple, is applicable to suitability for industrialized production.
Term definition
Term " comprises " or " comprising " is 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 10%, as the difference of 1%, 2%, 3%, 4% or 5%.
Detailed Description Of The Invention
First aspect present invention provides a kind of dimethyl fumarate enteric coated particles, and the density of this granule is at least 1.0g/mL.
In some embodiments, the density of this granule is at least 1.3g/mL; In some embodiments, the density of this granule is at least 1.6g/mL.
When grain density is at least 1.0g/mL, No. 1 capsule (volume is 0.5ml) can be loaded according to minimum 50% cubage of granule drug content; When grain density is at least 1.3g/mL, No. 2 capsules (volume is 0.37ml) can be loaded according to minimum 50% cubage of granule drug content; When grain density is at least 1.6g/mL, No. 3 capsules (volume is 0.3ml) can be loaded according to minimum 50% cubage of granule drug content.
In some embodiments, this enteric coated particles is made up of core, intermediate coating layers and enteric coat layer, and wherein core comprises active component dimethyl fumarate and the pharmaceutically acceptable adjuvant of at least one.
In some embodiments, the active component contained in core, calculates according to percetage by weight, accounts for 55 ~ 85% of core weight.
In some embodiments, pharmaceutically acceptable accessory package is containing filler, disintegrating agent, binding agent, lubricant and fluidizer.
In order to prepare highdensity enteric coated particles, need to prepare highdensity core.In some embodiments, filler can comprise high density filler, low-density filler or its combination, and middle-high density filler of the present invention refers to that the bulk density scope of the filler recorded is more than or equal to 0.7g/mL; Low-density filler refers to that the bulk density scope of the filler recorded is less than 0.7g/mL.Its middle-high density filler is selected from calcium hydrogen phosphate, dicalcium phosphate dihydrate, calcium phosphate, calcium carbonate or its combination; Low-density filler is selected from microcrystalline Cellulose, silicified microcrystalline cellulose, mannitol, lactose monohydrate or its combination; In some embodiments, described filler, calculates according to percetage by weight, accounts for 5 ~ 60% of enteric coated particles core weight, or 10 ~ 40%.
The density of the granule described in the present invention and the density of filler all detect bulk density according to graduated cylinder method, concrete grammar is: amount and graduated cylinder size per sample, take sample (being accurate to 0.1%) and be placed in graduated cylinder, do not kowtow reality, it is 150 to 250mL that being chosen as of the quality of general sample does not kowtow real apparent volume, the not compacting of careful degradation sample powder, if needed, read apparent volume V0, calculate bulk density according to formula M/V0, unit is g/mL, and repeated measure is averaged for 3 times.
In some embodiments, disintegrating agent is selected from cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, polyvinylpolypyrrolidone or its combination; In some embodiments, described disintegrating agent, calculates according to percetage by weight, accounts for 0.5 ~ 20% of enteric coated particles core weight, or 3 ~ 10%.
In some embodiments, binding agent is selected from polyvinylpyrrolidone, pregelatinized Starch, methylcellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, carboxymethylcellulose calcium, hydroxyethyl-cellulose, ethylhydroxyethylcellulose, alginic acid, polyvinyl alcohol, polyacrylate, gelatin or its combination.In some embodiments, described binding agent, calculates according to percetage by weight, accounts for 1 ~ 20% of enteric coated particles core weight, or 2 ~ 15%.
In some embodiments, lubricant is selected from stearic acid, stearic alkaline metal salt as magnesium stearate, sodium stearyl fumarate or its combination; In some embodiments, described lubricant, calculates according to percetage by weight, accounts for 0.1 ~ 2% of enteric coated particles core weight, or 0.5 ~ 2%.
In some embodiments, fluidizer is selected from Pulvis Talci, micropowder silica gel, silicon dioxide, Polyethylene Glycol or its combination; In some embodiments, described fluidizer, calculates according to percetage by weight, accounts for 0.1 ~ 10% of enteric coated particles core weight, or 0.5 ~ 5%.
In some embodiments, the mean diameter of the core of enteric coated particles is no more than 2mm.Wherein particle diameter adopts rider point-score to measure, and concrete grammar is with reference to " Chinese Pharmacopoeia " 2010 editions annex IX: get the screen cloth that granule is placed in fixing respective model size, sieve is added a cover.Jolting at least 3 minutes is rotated according to horizontal aspect, and tapping sieve in the vertical direction frequently, get the granule that sieve is lower, weighed weight, calculating proportion scope is 40 ~ 60%.
In some embodiments, intermediate coating layers adopts non-water coating, and wherein coating material is propenoic acid resin series product; In some embodiments, coating material is acrylic resin L100 (commodity are called Eudragit L100).
In some embodiments, the coating material of enteric coat layer is selected from Hydroxypropyl Methylcellulose Phathalate, cellulose acetate-phthalate, carboxymethylethylcellulose, methyl acrylate-methyl acrylic copolymer, polyacrylic resin, methacrylic acid-acrylic acid ethyl ester, hydroxypropyl cellulose acetate succinate, polyvinyl acetate phthalic acid ester, Lac or its combination; In some embodiments, enteric-coating material is methacrylic acid-acrylic acid ethyl ester (commodity are called Eudragit L30D-55 or Eudragit L100-55).
Above-mentioned intermediate coating layers and enteric coat layer also comprise plasticizer, surfactant and fluidizer further.Described plasticizer is selected from propylene glycol, Polyethylene Glycol, triethyl citrate, Polysorbate, Oleum Ricini or its combination; Surfactant is selected from poly yamanashi esters, glyceryl monostearate, single glycerol distearate, polyoxyethylene 80 sorbitan monooleate, Myrj 45, polyoxyethylene 20 sorbitan monolaurate or its combination; Fluidizer is selected from Pulvis Talci, micropowder silica gel or its combination.
Second aspect present invention additionally provides the preparation method of dimethyl fumarate enteric coated particles; wherein core can adopt conventional criteria technique to prepare; such as powder vertical compression, dry granulation or powder lamination etc.; intermediate coating layers and enteric coat layer can adopt at the bottom of fluid bed sprays coating or high-efficiency coating machine art for coating, the enteric coated particles obtained.
Wherein dry granulation method is by being compressed by a large amount of mixture, is pulverized subsequently again and these fragments is made less granule to form granule, and then being filled to capsule or being compressed into large plain film or pill.
Powder direct pressure closing directly medicine and adjuvant is sieved without pelletization, and mix homogeneously, carries out filled capsules or tabletting.
Powder bed area method is in centrifugal granulator, and sprinkling powder and binding agent prepare the method for granule simultaneously.
In some embodiments, a kind of method preparing dimethyl fumarate enteric coated particles, comprises the following steps:
1) core preparation: dimethyl fumarate and other adjuvants are sieved, mixing, with Fitow tablet machine compacting microplate, obtains core;
2) intermediate coating layers preparation: coating material is configured to coating solution, adds other adjuvants, high speed shear emulsifying, Keep agitation; By step 1) in the core that obtains be placed in multifunctional fluidized bed, coating parameter is set, sprays into intermediate coating layers coating solution, complete coating, dry;
3) enteric coating preparation: by soluble in water for the adjuvant except coating material, prepare suspension; Slowly added in coating material by this suspension, Keep agitation obtains enteric coating liquid, by step 2) in the intermediate coating layers granule that obtains be placed in multifunctional fluidized bed, coating parameter is set, spray into above-mentioned enteric coat layer Coating Solution, complete coating, dry.
The enteric coated particles prepared can be prepared into capsule or mix other adjuvant and be prepared into tablet or mix other adjuvant and be prepared into suspensoid by filled capsules further.
The preparation that the present invention prepares uses USP second method (paddle method) 75rpm, and after 0.1M HCL is acidproof 2 hours, in pH6.8 medium, release in 30 minutes is no less than 75%.
The enteric coated particles that the present invention prepares has the high feature of density, effectively can reduce the size of final preparation, be easy to administration, is particularly useful for swallowing inconvenient old-age group and child patient, improves patient compliance; The formulation content uniformity of preparation is high, and release is quick, good stability; In addition, preparation method is simple, is applicable to suitability for industrialized production.
Detailed description of the invention
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, mg represents milligram, and mL represents milliliter, and h represents hour, and min represents minute
Prepared by embodiment 1 enteric coated particles
Be followed successively by core, intermediate coating layers, enteric coat layer from inside to outside, prescription is composed as follows:
Preparation technology:
1) core preparation:
Dimethyl fumarate, microcrystalline Cellulose PH102, silicified microcrystalline cellulose, calcium hydrogen phosphate, cross-linking sodium carboxymethyl cellulose and micropowder silica gel are crossed comill collator (032R screen cloth) successively, with rotating speed 10rpm mixing 10min in mixed-hopper, add magnesium stearate with rotating speed 10rpm mixing 5min.Use Fitow tablet machine compacting microplate, tablet die is of a size of 2mm, detects hardness and friability conforms with the regulations in tableting processes.
2) intermediate coating layers preparation:
Eudragit L100 is dissolved in recipe quantity 95% ethanol of 50%.Pulvis Talci and triethyl citrate add in remaining 50% recipe quantity 95% ethanol, are about 10min by high-speed shearing emulsion machine homogenize, then pour in Eudragit L100 solution, constantly stir in case on-slip stone powder precipitation in coating process.
It is multifunctional fluidized bed that the microplate core first step obtained is placed in GPCG2.0, arranges coating parameter, sprays into above-mentioned intermediate coating layers Coating Solution, complete coating, be dried to loss on drying and conform with the regulations.
3) enteric coat layer preparation:
Triethyl citrate, single glycerol distearate and Tween 80 are dissolved in 70 ~ 80 DEG C of appropriate hot water, stir 10min, add the purified water of residue recipe quantity, stir borehole cooling to room temperature, obtain milky suspension, this suspension is slowly added in Eudragit L30D-55, Keep agitation 30min, coating solution crosses 100 mesh sieves, obtains enteric layer coating solution.
It is multifunctional fluidized bed that the intermediate coating layers granule obtained by second step is placed in GPCG2.0, arranges coating parameter, sprays into above-mentioned enteric coat layer Coating Solution, complete coating, be dried to loss on drying and conform with the regulations.
4) capsule is loaded:
Obtained enteric coated particles is used NJP-2000 type capsule filling machine filled capsules, inspection outward appearance and content uniformity conform with the regulations.
Embodiment 2 uniformity of dosage units is investigated
According to " Chinese Pharmacopoeia 2010 editions annex XE Content uniformity tests ", investigate the finished product content uniformity prepared by prescription 1 ~ 3, result is as shown in the table.
Table 1. uniformity of dosage units
Wherein AVE represents meansigma methods; A represents the absolute value of the difference of labelled amount and average, and wherein labelled amount is 100; S represents standard deviation.
Discuss: data display from table 1, the formulation content uniformity of preparation meets quality standard.
Embodiment 3 discharges result and investigates
Enteric coated capsule in prescription 1 ~ 3 is loaded on respectively in HDPE bottle, 30 every bottle, sealing, place 6 months under 40 DEG C/75%RH, detect the release of 30min in the acid-resistant strength after the acidproof 2h of 0.1M HCL (by medicament contg checking in acidproof rear enteric coated particles) and PH6.8 buffer, shown in test result following table.
Table 2. dimethyl fumarate enteric coated capsule acceleration environment (40 DEG C/RH75%) drug release result (pH6.8 buffer, paddle method, 100rpm)
Discuss: it is visible that dimethyl fumarate enteric coated capsule prepared by prescription 1 ~ 3 places the acidproof rear content of medicine and 30min drug release result after June under acceleration conditions, the acidproof rear medicament contg of this product compared zero difference with 0 day, 30min drug release rate and 0 day no significant difference, 30min release is all greater than 75%, and the above results illustrates that the acidproof rear content of this product and drug release rate have good stability.
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 (11)
1. a dimethyl fumarate enteric coated particles, is characterized in that, the density of this granule is at least 1.0g/mL, or is at least 1.3g/mL, or is at least 1.6g/mL.
2. enteric coated particles according to claim 1, is made up of core, intermediate coating layers and enteric coat layer, and described core comprises active component dimethyl fumarate, filler, disintegrating agent, binding agent, lubricant and fluidizer.
3. enteric coated particles according to claim 2, described filler is selected from high density filler, low-density filler or its combination, its middle-high density filler refers to that the bulk density scope of the filler recorded is more than or equal to 0.7g/mL, and low-density filler refers to that the bulk density scope of the filler recorded is less than 0.7g/mL.
4. enteric coated particles according to claim 3, described high density filler is selected from calcium hydrogen phosphate, dicalcium phosphate dihydrate, calcium phosphate, calcium carbonate or its combination; Described low-density filler is selected from microcrystalline Cellulose, silicified microcrystalline cellulose, mannitol, lactose monohydrate or its combination.
5. enteric coated particles according to claim 2, described disintegrating agent is selected from cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, polyvinylpolypyrrolidone or its combination; Described binding agent is selected from polyvinylpyrrolidone, pregelatinized Starch, methylcellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, carboxymethylcellulose calcium, hydroxyethyl-cellulose, ethylhydroxyethylcellulose, alginic acid, polyvinyl alcohol, polyacrylate, gelatin or its combination; Described lubricant is selected from stearic acid, stearic alkaline metal salt as magnesium stearate, sodium stearyl fumarate or its combination; Described fluidizer is selected from Pulvis Talci, micropowder silica gel, silicon dioxide, Polyethylene Glycol or its combination.
6. enteric coated particles according to claim 2, calculate according to percetage by weight, core comprises dimethyl fumarate 55 ~ 85%, filler 5 ~ 60%, disintegrating agent 0.5 ~ 20%, binding agent 1 ~ 20%, lubricant 0.1 ~ 2% and fluidizer 0.1 ~ 10%.
7. enteric coated particles according to claim 2, the mean diameter of described core is no more than 2mm.
8. enteric coated particles according to claim 2, the coating material of described intermediate coating layers is acrylic resin L100, and commodity are called EudragitL100; Described enteric coat layer is selected from Hydroxypropyl Methylcellulose Phathalate, cellulose acetate-phthalate, carboxymethylethylcellulose, methyl acrylate-methyl acrylic copolymer, polyacrylic resin, methacrylic acid-acrylic acid ethyl ester, hydroxypropyl cellulose acetate succinate, polyvinyl acetate phthalic acid ester, Lac or its combination.
9. enteric coated particles according to claim 8, coatings also comprises plasticizer, surfactant and fluidizer further, and described plasticizer is selected from propylene glycol, Polyethylene Glycol, triethyl citrate, Polysorbate, Oleum Ricini or its combination; Surfactant is selected from poly yamanashi esters, glyceryl monostearate, single glycerol distearate, polyoxyethylene 80 sorbitan monooleate, Myrj 45, polyoxyethylene 20 sorbitan monolaurate or its combination; Fluidizer is selected from Pulvis Talci, micropowder silica gel or its combination.
10. the method for the enteric coated particles that preparation is as arbitrary in claim 1-9, comprises the following steps:
1) core core preparation: dimethyl fumarate and other adjuvants are sieved, mixing, suppresses microplate with tablet machine, obtains core;
2) intermediate coating layers preparation: coating material is configured to coating solution, adds other adjuvants, high speed shear emulsifying, Keep agitation; By step 1) in the core that obtains be placed in multifunctional fluidized bed, coating parameter is set, sprays into intermediate coating layers coating solution, complete coating, dry;
3) enteric coating preparation: by soluble in water for the adjuvant except coating material, prepare suspension; Slowly added in coating material by this suspension, Keep agitation obtains enteric coating liquid, by step 2) in the intermediate coating layers granule that obtains be placed in multifunctional fluidized bed, coating parameter is set, spray into above-mentioned enteric coat layer Coating Solution, complete coating, dry.
11. preparation methoies according to claim 10, the enteric coated particles obtained can obtain capsule by filled capsules further, or mixes additional adjuvant tabletting and obtain tablet, or mixing suspending granule obtains enteric suspensoid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410683477.4A CN104490849A (en) | 2014-11-24 | 2014-11-24 | High-density dimethyl fumarate enteric-coated granules and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410683477.4A CN104490849A (en) | 2014-11-24 | 2014-11-24 | High-density dimethyl fumarate enteric-coated granules and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104490849A true CN104490849A (en) | 2015-04-08 |
Family
ID=52932366
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410683477.4A Pending CN104490849A (en) | 2014-11-24 | 2014-11-24 | High-density dimethyl fumarate enteric-coated granules and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104490849A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108430462A (en) * | 2015-12-31 | 2018-08-21 | 波尔法玛制药工厂股份公司 | Enteric coating oral drug preparation including dimethyl fumarate |
| CN108472260A (en) * | 2015-12-31 | 2018-08-31 | 波尔法玛制药工厂股份公司 | The method for being used to prepare the enteric coating particle including dimethyl fumarate |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1323206A (en) * | 1998-10-20 | 2001-11-21 | 富玛法姆股份公司 | Fumaric acid microtablets |
| CN1325302A (en) * | 1998-11-19 | 2001-12-05 | 富马法姆股份公司 | Use of dialkylfumarates |
| WO2013119677A1 (en) * | 2012-02-07 | 2013-08-15 | Biogen Idec Ma Inc. | Pharmaceutical compositions containing dimethyl fumarate |
| CN104027311A (en) * | 2014-05-09 | 2014-09-10 | 万特制药(海南)有限公司 | Dimethyl fumarate-containing enteric slow-release pellet |
-
2014
- 2014-11-24 CN CN201410683477.4A patent/CN104490849A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1323206A (en) * | 1998-10-20 | 2001-11-21 | 富玛法姆股份公司 | Fumaric acid microtablets |
| CN1325302A (en) * | 1998-11-19 | 2001-12-05 | 富马法姆股份公司 | Use of dialkylfumarates |
| WO2013119677A1 (en) * | 2012-02-07 | 2013-08-15 | Biogen Idec Ma Inc. | Pharmaceutical compositions containing dimethyl fumarate |
| CN104027311A (en) * | 2014-05-09 | 2014-09-10 | 万特制药(海南)有限公司 | Dimethyl fumarate-containing enteric slow-release pellet |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108430462A (en) * | 2015-12-31 | 2018-08-21 | 波尔法玛制药工厂股份公司 | Enteric coating oral drug preparation including dimethyl fumarate |
| CN108472260A (en) * | 2015-12-31 | 2018-08-31 | 波尔法玛制药工厂股份公司 | The method for being used to prepare the enteric coating particle including dimethyl fumarate |
| CN108430462B (en) * | 2015-12-31 | 2021-08-06 | 波尔法玛制药工厂股份公司 | Enteric coated oral pharmaceutical formulation comprising dimethyl fumarate |
| CN108472260B (en) * | 2015-12-31 | 2021-08-10 | 波尔法玛制药工厂股份公司 | Process for preparing enteric coated granules comprising dimethyl fumarate |
| EP3397247B1 (en) * | 2015-12-31 | 2023-06-07 | Zaklady Farmaceutyczne Polpharma SA | Process for preparation of an enteric coated granulate comprising dimethyl fumarate |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20230240994A1 (en) | Medicament-containing hollow particle | |
| JP5948648B2 (en) | Sustained release formulation containing stabilized eperisone | |
| WO2022012172A1 (en) | Oral sustained-release composition for insoluble drug, and preparation method thereof | |
| CN104922086A (en) | Preparation method of proton pump inhibitor enteric-coated tablet | |
| JP7021108B2 (en) | Oral pharmaceutical composition of nicotinamide | |
| US10172878B2 (en) | Extended-release topiramate capsules | |
| CA2905011A1 (en) | Extended-release topiramate capsules | |
| CN101347413B (en) | Quetiapine sustained release tablets and method of preparing the same | |
| CN104523602B (en) | A kind of dimethyl fumarate enteric microplate and preparation method thereof | |
| SI22849A (en) | Ropinirole preparation | |
| WO2013123965A1 (en) | A fixed dose pharmaceutical formulation | |
| CN104490849A (en) | High-density dimethyl fumarate enteric-coated granules and preparation method thereof | |
| EP2409689B1 (en) | Prasugrel tablet formulations | |
| CA2781826A1 (en) | Controlled release pharmaceutical compositions of galantamine | |
| RU2435584C2 (en) | Prolonged pharmaceutical composition drug form and method of its production (versions) | |
| JP7117975B2 (en) | Pharmaceutical composition containing teneligliptin, method for producing pharmaceutical composition containing teneligliptin, tablet containing teneligliptin, and method for producing tablet containing teneligliptin | |
| TWI566786B (en) | Hydromorphone hydrochloride containing extended release solid preparation for oral use | |
| US11260055B2 (en) | Oral pharmaceutical composition of lurasidone and preparation thereof | |
| JP2016106129A (en) | Solid preparation comprising loxoprofen sodium and vitamin b1 | |
| JP6920564B1 (en) | Solid formulation | |
| CN103768034A (en) | Sustained or controlled release solid composition comprising bupropion hydrochloride | |
| EP3545951A1 (en) | Oral tablet composition comprising dexlansoprazole, oral tablet comprising same and method for manufacturing same | |
| JP5841257B2 (en) | Drug-containing hollow particles | |
| AU2021265311A1 (en) | Novel multiparticulate pharmaceutical composition of tamsulosin and solifenacin | |
| JP2020045367A (en) | Intraoral disintegrable tablet that includes flavoring agent-containing granules and can be more easily taken |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into 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: 20150408 |