CN105902508A - Ruxolitinib dispersible tablet and preparation method thereof - Google Patents
Ruxolitinib dispersible tablet and preparation method thereof Download PDFInfo
- Publication number
- CN105902508A CN105902508A CN201610418360.2A CN201610418360A CN105902508A CN 105902508 A CN105902508 A CN 105902508A CN 201610418360 A CN201610418360 A CN 201610418360A CN 105902508 A CN105902508 A CN 105902508A
- Authority
- CN
- China
- Prior art keywords
- buddhist nun
- dispersible tablet
- luso profit
- luso
- profit
- 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
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
Abstract
The invention discloses a ruxolitinib dispersible tablet used for treating patients suffering from intermediate or high-risk myelofibrosis including chronic idiopathic myelofibrosis, myelofibrosis after polycythemia vera and myelofibrosis after primary thrombocythemia. Ruxolitinib serves as the raw material, auxiliary materials are added, and the ruxolitinib dispersible tablet is prepared. The ruxolitinib dispersible tablet is quick in disintegration and absorbing, high in bioavailability, convenient to take, little in intestinal residues, small in side effect, sweet in taste and fragrant, can easily improve medication compliance of the patients, improves the taste of preparation, has no sticking phenomenon in the granulation and tabletting process, and is beneficial to industrial production.
Description
Technical field
The present invention relates to a kind of Luso profit for Buddhist nun's novel form, particularly to be that Luso profit is for Buddhist nun's dispersible tablet and preparation side thereof
Method.
Background technology
Ruxolitinib (reed can replace Buddhist nun, also known as Luso profit for Buddhist nun) is a kind of inhibitors of kinases, be used for treating centre or
High-risk myelofibrosis, including PMF, after polycythemia vera, myelofibrosis and constitutional blood are little
Myelofibrosis patient after plate increase disease.Reed can replace Buddhist nun (ruxolitinib, Jakavi) to be a kind of oral JAK1 and JAK2 cheese ammonia
Acid kinase inhibitor, obtains European Union's approval in August, 2012, is used for treating intermediate or high-risk myelofibrosis, including constitutional bone
Marrow fibrosis, myelofibrosis after myelofibrosis and primary thrombocytosis after polycythemia vera.At present, Shandong
Suo Li has obtained more than 50 state approval in the whole world for Buddhist nun Jakavi, including European Union, Canada and some Asia, Latin America and South America
Continent country.Novartis obtains Luso profit from the mandate of Incyte company and replaces Buddhist nun Ruxolitinib exploitation beyond the U.S. and commercialization
Right.EU Committee and FDA have authorized the Luso profit Orphan drug status for Buddhist nun Ruxolitinib treatment myelofibrosis the most.
At present, Incyte sells with trade name Jakafi in the U.S., for the treatment of intermediate or high-risk myelofibrosis.True property is red
Cytosis (polycythemia vera, PV) is a kind of chronic, the hematologic cancers that cannot cure, and this disease is raw with hemocyte
Producing surplus relevant, cause blood thickening, blood clotting risk increases.These blood clots may result in serious cardiovascular complication, as
Apoplexy and heart attack, thus increase disease and send out rate and mortality rate.Erythrocytosis patient, often has spleen enlargement and additionally declines
Weak symptom.Many patients can become not tolerate or resist after conventional therapy, and this is relevant with the risk rising that sb.'s illness took a turn for the worse.
Dispersible tablet is a kind of quick-effective preparation that development in recent years is got up, due to its distinctive advantage, the most increasingly by people
Concern.Solubilizing agent can be added；The Luso profit dissolution for Buddhist nun's insoluble drug can be improved, be suitable for taking.For
The medicine of disintegrate difficulty is made sheet and can beneficially be absorbed.The feature of sheet: 1. disintegrate is fast, it is fast to absorb, bioavailability is high；2. take
Convenient 3. intestinal residual is few, few side effects.
Summary of the invention
It is an object of the invention to provide a kind of Luso profit for Buddhist nun's dispersible tablet and preparation method thereof.
Objects of the present invention are achieved through the following technical solutions.
Luso profit of the present invention is become to be grouped into (percentage by weight) by following for Buddhist nun's dispersible tablet:
| Luso profit replaces Buddhist nun | 5-45% |
| Filler | 10-30% |
| Disintegrating agent | 10-25% |
| Binding agent | 0.1-6% |
| Solubilizing agent | 0.1-6% |
| Lubricant | 0.5-5%。 |
It is more than the basic prescription of the present invention, can the most suitably regulate and delete.
Luso profit is active component for Buddhist nun, preferred content scope 10-40%, further preferred scope 10-30%.Unit formulation
Middle Luso profit replaces Buddhist nun dosage 5-100mg, and preferred dose is 5-50mg, preferred dosage is 5,10,15,20,50mg.
Due to dispersible tablet require in water can rapidly disintegrate dispersed, have taking convenience, disintegrate rapidly, absorb soon and
Bioavailability high.Therefore the selection to supplementary product kind and performance thereof is the key preparing sheet.Inventor is through repeatedly
Test, it is determined that be suitable for Luso profit and replace pharmaceutic adjuvant and the consumption thereof of Buddhist nun's dispersible tablet.
Filler selects the weight and volume being used for increasing sheet, in order to the molding of preparation and divided dose.The present invention fills out
Fill the agent mixture of one or more in lactose, sucrose, microcrystalline Cellulose, pregelatinized Starch, dextrin etc..Amount ranges
Preferably 10-30%, particularly preferred 15-25%.
Disintegrating agent is selected from the pharmaceutic adjuvant such as low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone.The preferred 10-25% of consumption, the most excellent
Select 15-20%.
The kind of solubilizing agent and the selection of consumption are most important for the dissolution of this preparation.Dodecane is selected in the solubilizing agent of the present invention
One of base sodium sulfate, polyethylene glycol 6000, Macrogol 4000, Tween 80, polysorbate40, sorbester p18, span 40 or the most several
The mixture planted, masks the Luso profit bad strange taste for Buddhist nun further, improves the mouthfeel of sheet.
The lubricant mixture of one or more in micropowder silica gel, magnesium stearate, Pulvis Talci.
Present invention also offers the Luso profit preparation method for Buddhist nun's dispersible tablet.Luso profit of the present invention can be with powder for Buddhist nun's dispersible tablet
Prepared by end direct compression process.Direct powder compression preparation process is: by Luso profit for Buddhist nun and filler (such as lactose), disintegrate
After agent, solubilizing agent, binding agent and mix lubricant are uniform, direct powder compression.
Luso profit of the present invention is fast for Buddhist nun's dispersible tablet disintegrate, it is fast to absorb, bioavailability is high；Taking convenience；Intestinal residual is few,
Few side effects；Taste is sweet, does not has Luso profit for Buddhist nun's off-odor and to have fragrance, is particularly easy to improve patient's drug compliance.
Detailed description of the invention
Embodiment l
Prescription:
Preparation method:
(1) Luso profit is mixed homogeneously with cane sugar powder (150 mesh) equal increments for Buddhist nun's powder (200 mesh), obtain mixture A；
(2) after remaining adjuvant being crossed 200 mesh sieves, equal increments mix homogeneously, obtain mixture B；
(3) after mixture A and mixture B being pressed equal increments method mix homogeneously, direct compression.
Embodiment 2
Prescription:
Preparation method:
(1) Luso profit is mixed homogeneously with lactose powder (150 mesh) equal increments for Buddhist nun's powder (200 mesh), obtain mixture A；
(2) after remaining adjuvant being crossed 200 mesh sieves, equal increments mix homogeneously, obtain mixture B；
(3) after mixture A and mixture B being pressed equal increments method mix homogeneously, direct compression.
Embodiment 3
Prescription:
Preparation method:
(1) Luso profit is mixed homogeneously with lactose powder (150 mesh) equal increments for Buddhist nun's powder (200 mesh), obtain mixture A；
(2) after remaining adjuvant being crossed 200 mesh sieves, equal increments mix homogeneously, obtain mixture B；
(3) after mixture A and mixture B being pressed equal increments method mix homogeneously, direct compression.
Embodiment 4
Prescription:
Preparation method:
(1) Luso profit is mixed homogeneously with lactose powder (150 mesh) equal increments for Buddhist nun's powder (200 mesh), obtain mixture A；
(2) after remaining adjuvant being crossed 200 mesh sieves, equal increments mix homogeneously, obtain mixture B；
(3) after mixture A and mixture B being pressed equal increments method mix homogeneously, direct compression.
Invention formulation and technology prepares the study on the stability of sample:
Sample prepared by embodiment 1, embodiment 2, embodiment 3 and embodiment 4 is respectively placed in stability test case, arranges
Temperature 40 DEG C, carry out under the conditions of relative humidity 75%RH three months accelerating to investigate.
Using disintegration as inspection target, it was demonstrated that the science of the tablet recipe technique invented.
Luso profit used by above example is that Pfizer's Pharmaceutical produces for Buddhist nun's raw material；Adjuvant supply producer be Ka Lekang pharmacy,
Degussa pharmacy, Le Jiawen pharmacy, International Specialty Products pharmaceutical Co. Ltd and the mountains and rivers, Huainan pharmaceutical Co. Ltd.
Claims (9)
1. Luso profit replaces Buddhist nun's dispersible tablet, is made up of following weight percent composition:
。
Luso profit the most according to claim 1 replaces Buddhist nun's dispersible tablet, wherein said:
The filler mixture of one or more in microcrystalline Cellulose, lactose, sucrose, pregelatinized Starch, dextrin etc.；
Disintegrating agent is in low-substituted hydroxypropyl methylcellulose, polyvinylpolypyrrolidone, carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose
One of or the most several mixture；
Binding agent is selected from polyvidone, height replaces one of hydroxypropylcellulose, gelatine size, starch slurry, sodium carboxymethyl cellulose or it
In several mixture；
The lubricant mixture of one or more in micropowder silica gel, magnesium stearate, Pulvis Talci.
Luso profit the most according to claim 2 replaces Buddhist nun's dispersible tablet, and wherein said Luso profit replaces Buddhist nun content range 10-45%.
Luso profit the most according to claim 2 replaces Buddhist nun's dispersible tablet, wherein said filler loading scope 10-30%.
Luso profit the most according to claim 2 replaces Buddhist nun's dispersible tablet, wherein said disintegrating agent amount ranges 15-20%.
Luso profit the most according to claim 2 replaces Buddhist nun's dispersible tablet, wherein said binder dosage scope 0.5-2%.
7. according to the Luso profit described in any claim in claim 3-6 for Buddhist nun's dispersible tablet, wherein: Luso profit replaces Buddhist nun's content
Scope 10-40%；Filler loading 10-30%；Disintegrating agent consumption 15-20%；Binder dosage 0.5-2%, solubilizing agent consumption 0.5-
2%。
Luso profit the most according to claim 1 replaces Buddhist nun's dispersible tablet, and wherein said Luso profit replaces Buddhist nun's unit dose 5-100mg.
9. Luso profit described in claim 1 is for the preparation method of Buddhist nun's dispersible tablet, uses direct powder compression, by Luso profit for Buddhist nun
After uniform with filler, disintegrating agent, solubilizing agent, binding agent and mix lubricant, direct powder compression.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610418360.2A CN105902508A (en) | 2016-06-13 | 2016-06-13 | Ruxolitinib dispersible tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610418360.2A CN105902508A (en) | 2016-06-13 | 2016-06-13 | Ruxolitinib dispersible tablet and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105902508A true CN105902508A (en) | 2016-08-31 |
Family
ID=56750074
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610418360.2A Pending CN105902508A (en) | 2016-06-13 | 2016-06-13 | Ruxolitinib dispersible tablet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105902508A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104496904A (en) * | 2014-11-28 | 2015-04-08 | 上海北卡医药技术有限公司 | Synthesis method of ruxolitinib intermediate |
| CN104586798A (en) * | 2015-01-04 | 2015-05-06 | 成都恒瑞制药有限公司 | Gefitinib dispersible tablet and preparation method thereof |
| CN105007901A (en) * | 2012-11-15 | 2015-10-28 | 因赛特公司 | Sustained-release dosage forms of ruxolitinib |
-
2016
- 2016-06-13 CN CN201610418360.2A patent/CN105902508A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105007901A (en) * | 2012-11-15 | 2015-10-28 | 因赛特公司 | Sustained-release dosage forms of ruxolitinib |
| CN104496904A (en) * | 2014-11-28 | 2015-04-08 | 上海北卡医药技术有限公司 | Synthesis method of ruxolitinib intermediate |
| CN104586798A (en) * | 2015-01-04 | 2015-05-06 | 成都恒瑞制药有限公司 | Gefitinib dispersible tablet and preparation method thereof |
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| PB01 | Publication | ||
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| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20160831 |
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| WD01 | Invention patent application deemed withdrawn after publication |