CN104523574A - Apremilast solid dispersoid and preparation method thereof - Google Patents
Apremilast solid dispersoid and preparation method thereof Download PDFInfo
- Publication number
- CN104523574A CN104523574A CN201510062970.9A CN201510062970A CN104523574A CN 104523574 A CN104523574 A CN 104523574A CN 201510062970 A CN201510062970 A CN 201510062970A CN 104523574 A CN104523574 A CN 104523574A
- Authority
- CN
- China
- Prior art keywords
- apremilast
- preparation
- solid dispersion
- poloxamer
- colloidal silica
- 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 an apremilast solid dispersoid and a preparation method thereof. The apremilast solid dispersoid is characterized by having a prescription comprising the following components in percentage by weight: 5-35% of apremilast, 5-70% of a carrier material and 2-30% of an adsorbing agent. The apremilast solid dispersoid has the advantages that drug releasing rate is increased, pharmaceutical function can be realized in short time, and pharmaceutical bioavailability is improved. The apremilast solid dispersoid is prepared by adopting a melting method, steps are simple, technological parameters are easy to control, and the apremilast solid dispersoid is applicable to large-scale production.
Description
Technical field
The invention belongs to field of medicine preparations, be specifically related to a kind of Apremilast solid dispersion and preparation method thereof.
Background technology
Psoriatic arthritis (PsA) is a kind of inflammatory arthropathy relevant to psoriasis, has psoriasis erythra and with joint and surrounding soft tissue's pain, swelling, tenderness, the stiff and dyskinesia.Some patients can have sacroiliitis and (or) spondylitis, and the course of disease is delayed, and easily recurs.Can there be ankylosis in late period.Before patient's erythra of about 75% appears at arthritis, do not occur person about 15% simultaneously, erythra appears at meta-arthritic patient about 10%.This disease can betide any age, and the peak age is 30 ~ 50 years old, asexuality difference, but spinal column is got involved more with male.Primary disease often has family controller to be inclined to, and one-level sickness in the family rate is up to 30%, and monovular twins onset risk is 72%.Domestic report has family history person to be 10% ~ 23.8%, is reported as 10% ~ 80% abroad.Primary disease is autosomal dominant inheritance, AD, and with incomplete penetrance, but also someone thinks autosomal recessive inheritance, AR or the heredity of property connection.
Apremilast is the medicament for treating arthritis developed by Celgene biotech company, and FDA in 2014 ratifies its oral drugs as treatment psoriasis arthropathica and goes on the market.Apremilast, as the oral phosphodiesterase-4 of a kind of new small molecule (PDE-4) inhibitor, can regulate in born of the same parents proinflammatory with anti-inflammatory factors effect, alleviates arthroncus and improves the physiological function of joint part.Three III clinical trial phases participated in by 1493 active type psoriasis arthropathica patients demonstrate safety and the effectiveness of Apremilast.The overall well-tolerated of research display Apremilast, demonstrates acceptable safety.And domestic relevant report and the patent having no Apremilast solid dispersion.
Apremilast belongs to insoluble drug, and its stripping, bioavailability are so limited.And solid dispersion technology solve insoluble drug preparation difficult in have great advantage, in the solid dispersion that insoluble drug and suitable carrier are formed, medicine exists with crystallite state, unformed shape, colloidal dispersions state or molecular dispersion state, there is very large dispersion, after contacting with gastro-intestinal Fluid, the dissolution rate of medicine is accelerated, and can promote the absorption of medicine, improves bioavailability.Find that Apremilast has hydrophobicity after deliberation, the half-life is longer, is applicable to being prepared into solid dispersion, thus accelerates medicine release in vivo, reduces drug dose, reduces toxicity, improves bioavailability.
Summary of the invention
The present invention aims to provide that a kind of bioavailability is high, the simple Apremilast solid dispersion of preparation technology and preparation method thereof,
For achieving the above object, a kind of Apremilast solid dispersion of the present invention and preparation method thereof, concrete scheme is:
A kind of Apremilast solid dispersion of the present invention and preparation method thereof, is characterized in that said preparation prescription percentage by weight is: Apremilast 5-35%, carrier material 5-70%, adsorbent 2-30%.
A kind of Apremilast solid dispersion of the present invention and preparation method thereof, is characterized in that said preparation prescription percentage by weight is: Apremilast 5-35%, poloxamer 5-60%, polyethylene glycol 6000 5-60%, colloidal silica 2-30%.
A kind of Apremilast solid dispersion of the present invention and preparation method thereof, is characterized in that described carrier is wherein one or more combinations of Macrogol 4000, polyethylene glycol 6000 and PEG 8000, polyvinylpyrrolidone, poloxamer, polyethylene oxide, mannitol, xylitol, sorbitol, galactose.
A kind of Apremilast solid dispersion of the present invention and preparation method thereof, is characterized in that described adsorbent is wherein one or more combinations of colloidal silica, microcrystalline Cellulose, aluminium-magnesium silicate.
Described a kind of Apremilast solid dispersion of the present invention and preparation method thereof, is characterized in that said preparation preparation method is fusion method.
A kind of Apremilast solid dispersion of the present invention and preparation method thereof, is characterized in that said preparation preparation method is specially:
1) by Apremilast, poloxamer, polyethylene glycol 6000, colloidal silica porphyrize crosses 80-100 mesh sieve respectively;
2) recipe quantity poloxamer is taken, polyethylene glycol 6000, colloidal silica heating and melting.3) 2) in add recipe quantity Apremilast, stirring makes fully to be uniformly dispersed, mix and blend speed 300-900r/min, mixing time 1-10min, mixing temperature is 60-100 DEG C, cool rapidly afterwards, chilling temperature is-20-0 DEG C, and cool time is 10-60min, treat to solidify completely, taking-up is put in vacuum drying oven, pulverizes after brittle, crosses 150 mesh sieves and get final product.
A kind of Apremilast solid dispersion of the present invention and preparation method thereof, Apremilast and carrier material mix and blend speed 400-700r/min, mixing time 3-7min when it is characterized in that prepared by said preparation, mixing temperature is 75-95 DEG C.
A kind of Apremilast solid dispersion of the present invention and preparation method thereof, it is characterized in that said preparation is prepared chilling temperature and is-10-0 DEG C, cool time is 15-45min.
Beneficial effect of the present invention: Apremilast solid dispersion of the present invention accelerates drug releasing rate, can play drug effect at short notice, improve drug bioavailability.The present invention prepares Apremilast solid dispersion and adopts fusion method, and step is simple, and technological parameter is easily controlled, and is applicable to large-scale production.
Detailed description of the invention
Embodiment is only for further illustrating the present invention below, does not limit the present invention in any form.
embodiment 1:
Prescription (weight percent meter):
Apremilast 30%
Poloxamer 25%
Polyethylene glycol 6000 30%
Colloidal silica 15%
Preparation method:
1) by Apremilast, poloxamer, polyethylene glycol 6000, colloidal silica porphyrize crosses 80-100 mesh sieve respectively;
2) recipe quantity poloxamer is taken, polyethylene glycol 6000, colloidal silica heating and melting.3) 2) in add recipe quantity Apremilast, stir make fully to be uniformly dispersed, mix and blend speed 450r/min, mixing time 4min, mixing temperature is 80 DEG C, cools rapidly afterwards, and chilling temperature is-5 DEG C, and cool time is 30min.Treat to solidify completely, take out and put in vacuum drying oven, pulverize after brittle, cross 150 mesh sieves and get final product.
embodiment 2:
Prescription (weight percent meter):
Apremilast 30%
Poloxamer 28%
PVP K30 27%
Colloidal silica 15%
Preparation method:
1) by Apremilast, poloxamer, PVP K30, colloidal silica porphyrize crosses 80-100 mesh sieve respectively;
2) recipe quantity poloxamer is taken, PVP K30, colloidal silica heating and melting.
3) 2) in add recipe quantity Apremilast, stir make fully to be uniformly dispersed, mix and blend speed 500r/min, mixing time 7min, mixing temperature is 85 DEG C, cools rapidly afterwards, and chilling temperature is-8 DEG C, and cool time is 35min.Treat to solidify completely, take out and put in vacuum drying oven, pulverize after brittle, cross 150 mesh sieves and get final product.
embodiment 3:
Prescription (weight percent meter):
Apremilast 30%
Poloxamer 25%
Polyethylene glycol 6000 30%
Colloidal silica 15%
Preparation method:
1) by Apremilast, poloxamer, polyethylene glycol 6000, colloidal silica porphyrize crosses 80-100 mesh sieve respectively;
2) recipe quantity poloxamer is taken, polyethylene glycol 6000, colloidal silica heating and melting.3) 2) in add recipe quantity Apremilast, stir make fully to be uniformly dispersed, mix and blend speed 300r/min, mixing time 5min, mixing temperature is 90 DEG C, cools rapidly afterwards, and chilling temperature is 0 DEG C, and cool time is 30min.Treat to solidify completely, take out and put in vacuum drying oven, pulverize after brittle, cross 150 mesh sieves and get final product.
Embodiment 4(ordinary preparation)
Prescription (weight percent meter):
Apremilast 30%
Lactose 25%
Microcrystalline Cellulose 25%
Low-substituted hydroxypropyl cellulose 10%
Carboxymethyl starch sodium 10%
1) get the Apremilast of recipe quantity, add binding agent lactose, microcrystalline Cellulose mix homogeneously, for subsequent use.
2) to 1) in add disintegrating agent carboxymethyl base Starch Sodium, low-substituted hydroxypropyl cellulose, fully mix, cross 80 mesh sieves, ethanol soft material, cross 14 mesh sieves granulations.
3) dry, granulate and get final product.
Embodiment of the present invention 1-3 and embodiment 4(ordinary preparation) Dissolution experiments Data Comparison:
| Time (min) | Embodiment 1 (%) | Embodiment 2 (%) | Embodiment 3 (%) | Embodiment 4 (%) |
| 0 | 0 | 0 | 0 | 0 |
| 5 | 55.74 | 45.74 | 43.14 | 28.45 |
| 10 | 67.15 | 63.44 | 62.75 | 39.64 |
| 20 | 84.25 | 80.11 | 78.62 | 45.28 |
| 30 | 86.51 | 84.75 | 82.47 | 68.51 |
| 45 | 92.33 | 89.61 | 90.41 | 80.62 |
| 60 | 98.64 | 96.12 | 99.08 | 81.68 |
Seen by experimental result, Apremilast solid dispersion rate of release, obviously faster than ordinary preparation, discharges balance substantially at about 45min, and dissolution is also apparently higher than ordinary preparation.
Claims (8)
1. Apremilast solid dispersion and preparation method thereof, is characterized in that said preparation prescription percentage by weight is: Apremilast 5-35%, carrier material 5-70%, adsorbent 2-30%.
2. a kind of Apremilast solid dispersion and preparation method thereof according to claim 1, is characterized in that described carrier is wherein one or more combinations of Macrogol 4000, polyethylene glycol 6000 and PEG 8000, polyvinylpyrrolidone, poloxamer, polyethylene oxide, mannitol, xylitol, sorbitol, galactose.
3. a kind of Apremilast solid dispersion and preparation method thereof according to claim 1, is characterized in that described adsorbent is wherein one or more combinations of colloidal silica, microcrystalline Cellulose, aluminium-magnesium silicate.
4. a kind of Apremilast solid dispersion and preparation method thereof according to claim 1-3, is characterized in that said preparation prescription percentage by weight is: Apremilast 5-35%, poloxamer 5-60%, polyethylene glycol 6000 5-60%, colloidal silica 2-30%.
5. a kind of Apremilast solid dispersion and preparation method thereof according to claim 1-4, is characterized in that said preparation preparation method is fusion method.
6. a kind of Apremilast solid dispersion and preparation method thereof according to claim 5, is characterized in that said preparation preparation method is specially:
1) by Apremilast, poloxamer, polyethylene glycol 6000, colloidal silica porphyrize crosses 80-100 mesh sieve respectively;
2) recipe quantity poloxamer is taken, polyethylene glycol 6000, colloidal silica heating and melting; 3) 2) in add recipe quantity Apremilast, stirring makes fully to be uniformly dispersed, mix and blend speed 300-900r/min, mixing time 1-10min, mixing temperature is 60-100 DEG C, cool rapidly afterwards, chilling temperature is-20-5 DEG C, treats to solidify completely, takes out and puts in vacuum drying oven, pulverize after brittle, cross 150 mesh sieves and get final product.
7. a kind of Apremilast solid dispersion and preparation method thereof according to claim 6, when it is characterized in that prepared by said preparation, Apremilast and carrier material mix and blend speed are 400-700r/min, mixing time 3-7min, and mixing temperature is 75-95 DEG C.
8. a kind of Apremilast solid dispersion and preparation method thereof according to claim 6, it is characterized in that said preparation is prepared chilling temperature and is-10-0 DEG C, cool time is 15-45min.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510062970.9A CN104523574B (en) | 2015-02-08 | 2015-02-08 | A kind of Apremilast solid dispersions |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510062970.9A CN104523574B (en) | 2015-02-08 | 2015-02-08 | A kind of Apremilast solid dispersions |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104523574A true CN104523574A (en) | 2015-04-22 |
| CN104523574B CN104523574B (en) | 2017-11-24 |
Family
ID=52839337
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510062970.9A Active CN104523574B (en) | 2015-02-08 | 2015-02-08 | A kind of Apremilast solid dispersions |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104523574B (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105919927A (en) * | 2015-12-18 | 2016-09-07 | 重庆两江药物研发中心有限公司 | Apremilast oral liquid and preparation method thereof |
| WO2017076987A1 (en) * | 2015-11-03 | 2017-05-11 | Ratiopharm Gmbh | Composition comprising apremilast in amorphous form |
| CN106727344A (en) * | 2015-11-19 | 2017-05-31 | 常州爱诺新睿医药技术有限公司 | A kind of solid dispersions of unformed Apremilast and preparation method thereof |
| CN107405311A (en) * | 2015-12-24 | 2017-11-28 | 江苏恒瑞医药股份有限公司 | Apremilast sustained release preparation |
| CN109310624A (en) * | 2016-06-15 | 2019-02-05 | 托伦特药物有限公司 | The topical composition of Apremilast |
| CN113081967A (en) * | 2019-12-19 | 2021-07-09 | 康普药业股份有限公司 | Kidney-tonifying life-prolonging preparation and preparation method thereof |
| WO2022075760A1 (en) * | 2020-10-08 | 2022-04-14 | 주식회사 네비팜 | Pharmaceutical composition including apremilast |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110028510A1 (en) * | 2009-02-18 | 2011-02-03 | Combinatorx (Singapore) Pte. Ltd. | Compositions, Methods, and Kits for Treating Influenza Viral Infections |
| CN102188398A (en) * | 2010-03-12 | 2011-09-21 | 上海天龙药业有限公司 | Solid preparation containing highly dispersed fenofibrate |
| CN102781443A (en) * | 2009-11-19 | 2012-11-14 | 细胞基因公司 | Apremilast For The Treatment Of Sarcoidosis |
-
2015
- 2015-02-08 CN CN201510062970.9A patent/CN104523574B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110028510A1 (en) * | 2009-02-18 | 2011-02-03 | Combinatorx (Singapore) Pte. Ltd. | Compositions, Methods, and Kits for Treating Influenza Viral Infections |
| CN102781443A (en) * | 2009-11-19 | 2012-11-14 | 细胞基因公司 | Apremilast For The Treatment Of Sarcoidosis |
| CN102188398A (en) * | 2010-03-12 | 2011-09-21 | 上海天龙药业有限公司 | Solid preparation containing highly dispersed fenofibrate |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017076987A1 (en) * | 2015-11-03 | 2017-05-11 | Ratiopharm Gmbh | Composition comprising apremilast in amorphous form |
| CN106727344A (en) * | 2015-11-19 | 2017-05-31 | 常州爱诺新睿医药技术有限公司 | A kind of solid dispersions of unformed Apremilast and preparation method thereof |
| CN105919927A (en) * | 2015-12-18 | 2016-09-07 | 重庆两江药物研发中心有限公司 | Apremilast oral liquid and preparation method thereof |
| CN105919927B (en) * | 2015-12-18 | 2019-01-22 | 重庆两江药物研发中心有限公司 | A kind of Apremilast oral solution and preparation method thereof |
| CN107405311A (en) * | 2015-12-24 | 2017-11-28 | 江苏恒瑞医药股份有限公司 | Apremilast sustained release preparation |
| CN109310624A (en) * | 2016-06-15 | 2019-02-05 | 托伦特药物有限公司 | The topical composition of Apremilast |
| CN113081967A (en) * | 2019-12-19 | 2021-07-09 | 康普药业股份有限公司 | Kidney-tonifying life-prolonging preparation and preparation method thereof |
| CN113081967B (en) * | 2019-12-19 | 2024-05-07 | 康普药业股份有限公司 | Kidney-tonifying life-prolonging preparation and preparation method thereof |
| WO2022075760A1 (en) * | 2020-10-08 | 2022-04-14 | 주식회사 네비팜 | Pharmaceutical composition including apremilast |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104523574B (en) | 2017-11-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104523574A (en) | Apremilast solid dispersoid and preparation method thereof | |
| EP2258394B1 (en) | Oral dosage form comprising a PDE 4 inhibitor as an active ingredient and polyvinylpyrrolidon as excipient | |
| NZ530040A (en) | Solid pharmaceutical formulations comprising modafinil | |
| WO2012045282A1 (en) | Applications of arctigenin in formulating medicines for preventing or treating diseases related to red blood cell reduction | |
| WO2008017216A1 (en) | The application of marine steroid in preparing the medicine of treating neurons damaging | |
| JPH0597672A (en) | Amide derivative-containing solid preparation and its production | |
| CN107753458B (en) | Nimodipine tablet medicine composition and preparation method thereof | |
| CN102406626B (en) | Pramipexole hydrochloride slow release tablet and preparation method thereof | |
| CN108201534A (en) | A kind of Rui Kapabu takes orally sustained and controlled release medicament composition and application thereof | |
| EP1556026B1 (en) | Novel pharmaceutical formulations of modafinil | |
| AU2011276450A1 (en) | Pharmaceutical compositions containing vanoxerine | |
| KR102095536B1 (en) | Oral formulation for improved dissolution rate and disintegrability of herbal extract | |
| CN110960499A (en) | Posaconazole gastric floating tablet and preparation method thereof | |
| CN103432570A (en) | Thymalfasin sustained-release microspheres and preparation method thereof | |
| WO2007108463A1 (en) | Solid preparation having improved solubility | |
| CN105853367B (en) | The preparation method and its pharmaceutical preparation of Deferasirox solid dispersions | |
| CN103239417A (en) | Preparation method of trimetazidine dihydrochloride tablet | |
| CN101190937B (en) | Compound with liver-protecting activity | |
| CN101269067B (en) | Antibacterial gynecology externally used pharmaceutical combination | |
| CN111821277A (en) | Pimavanserin nanocrystalline capsule and preparation method thereof | |
| CN102423317A (en) | Diosmin-containing medicinal composition | |
| Kumar et al. | Solid Dispersed Fast Dissolving Tablets-More Complaint Dosage Forms | |
| CN108014097B (en) | Temozolomide sustained-release capsule and preparation method thereof | |
| CN106729730B (en) | slow-release medicine and preparation method thereof | |
| CN100411637C (en) | Chinese animal medicine for treating mammitis and its preparation method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| EXSB | Decision made by sipo to initiate substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |