CN105919957A - Idelalisib dispersible tablet and preparation method thereof - Google Patents
Idelalisib dispersible tablet and preparation method thereof Download PDFInfo
- Publication number
- CN105919957A CN105919957A CN201610417860.4A CN201610417860A CN105919957A CN 105919957 A CN105919957 A CN 105919957A CN 201610417860 A CN201610417860 A CN 201610417860A CN 105919957 A CN105919957 A CN 105919957A
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- CN
- China
- Prior art keywords
- dailalisi
- dispersible tablet
- mixture
- idelalisib
- preparation
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- 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.)
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- 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
- A61K31/52—Purines, e.g. adenine
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses an idelalisib dispersible tablet which is used for treating recurrent follicular B-cell non-hodgkin lymphoma (FL) and recurrent small lymphocytic lymphoma (SLL). Idelalisib is used as a raw material and is added with adjuvant to obtain the idelalisib dispersible tablet. The dispersible tablet is disintegrated and absorbed quickly, is high in bioavailability, convenient to take, small in intestinal residue and few in side effects, is sweet and has fragrance, the drug therapy compliance of a patient is improved quite easily, the taste of a preparation is improved, sticking can be avoided in a pelleting and tabletting process, and implementation of industrial production is facilitated.
Description
Technical field
The present invention relates to a kind of Ai Dailalisi novel form, particularly to be Ai Dailalisi dispersible tablet and preparation side thereof
Method.
Background technology
Ai Dailalisi Idelalisib is oral, the selective phosphoinositide 3-kinase delta of first listing
(PI3K-delta, P110-delta) inhibitor.P110-delta participates in changing the immune environment of bone-marrow-derived lymphocyte, to this kind of swollen
The activation of oncocyte, breed, survive and migrate (trafficking) and play pivotal role.Ai Dailalisi Idelalisib's
Accelerating approval is based on a single armed, multicenter, the actively second phase clinical effectiveness of open label.This clinical experiment has recruited 123
The 'inertia' non-Hodgkin lymphoma (iNHL) of position recurrent and small lymphocyte lymphoma (SLL) patient.Patient accepts every day
Twice, each 150 milligrams of Chinese mugworts are for this treatment of Larry, and one-level experimental endpoints is total response rate (ORR), and two grades of experimental endpoints are responses
Time and Progression free survival phase.Wherein total response rate of FL and SLL patient is respectively 54% and 58%.The middle position of the latter's response time
Number is 11.9 months.This result is compared quite with the usual curative effect of standard treatment or more preferably.Ai Dailalisi
(Idelalisib) granted listing, the treatment for chronic lymphocytic leukemia (CLL) brings again one after ibrutinib
Individual new selection.In the U.S., chronic lymphocytic leukemia (CLL) number in Patients With Adult Leukemia ranked second, it is contemplated that
Within 2014, can increase more than 15000 new patients.CLL new drug development including Idelalisib and ibrutinib, is expected to
CLL is developed into a kind of controllable chronic disease from death sentence.Certainly, correspondingly CLL market the most gradually expands, Bloomberg News
Analyst thinks will rise 9,000,000,000 dollars soon in CLL market.
Dispersible tablet is a kind of quick-effective preparation, due to its distinctive advantage, is the most increasingly paid close attention to by people.Can add
Solubilizing agent；The dissolution of Ai Dailalisi insoluble drug can be improved, be suitable for taking.Medicine for disintegrate difficulty is made
Sheet can beneficially absorb.The feature of sheet: 1. disintegrate is fast, it is fast to absorb, bioavailability is high；2. taking convenience 3. intestinal residual is few,
Few side effects.
Summary of the invention
It is an object of the invention to provide a kind of Ai Dailalisi dispersible tablet and preparation method thereof.
Objects of the present invention are achieved through the following technical solutions.
Ai Dailalisi dispersible tablet of the present invention is become to be grouped into (percentage by weight) by following:
| Ai Dailalisi | 5-35% |
| Filler | 10-50% |
| Disintegrating agent | 10-25% |
| Binding agent | 0.1-5% |
| Solubilizing agent | 0.1-5% |
| Lubricant | 0.5-5%。 |
It is more than the basic prescription of the present invention, can the most suitably regulate and delete.
Ai Dailalisi is active component, preferred content scope 10-35%, further preferred scope 10-30%.Unit formulation
Middle Ai Dailalisi dosage 50-150mg, preferred dose is 50-100mg, preferred dosage is 100,50,150mg.
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 pharmaceutic adjuvant and the consumption thereof of Ai Dailalisi 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 9.5-30%, 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 bad strange taste of Ai Dailalisi 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 preparation method of Ai Dailalisi dispersible tablet.Ai Dailalisi dispersible tablet of the present invention can be with powder
Prepared by end direct compression process.Direct powder compression preparation process is: by Ai Dailalisi and filler (such as lactose), disintegrate
After agent, solubilizing agent, binding agent and mix lubricant are uniform, direct powder compression.
Ai Dailalisi dispersible tablet disintegrate of the present invention is fast, it is fast to absorb, bioavailability is high；Taking convenience；Intestinal residual is few,
Few side effects；Taste is sweet, does not has Ai Dailalisi off-odor and has fragrance, is particularly easy to improve patient's drug compliance.
Detailed description of the invention
Embodiment l
Prescription:
Preparation method:
(1) Ai Dailalisi powder (200 mesh) is mixed homogeneously with cane sugar powder (150 mesh) equal increments, 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) Ai Dailalisi powder (200 mesh) is mixed homogeneously with lactose powder (150 mesh) equal increments, 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) Ai Dailalisi powder (200 mesh) is mixed homogeneously with lactose powder (150 mesh) equal increments, 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) Ai Dailalisi powder (200 mesh) is mixed homogeneously with lactose powder (150 mesh) equal increments, 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.
Ai Dailalisi raw material used by above example is that Pfizer's Pharmaceutical produces；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. Yi Zhong Ai Dailalisi dispersible tablet, is made up of following weight percent composition:
。
Ai Dailalisi dispersible tablet the most according to claim 1, 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.
Ai Dailalisi dispersible tablet the most according to claim 2, wherein said Ai Dailalisi content range 5-30%.
Ai Dailalisi dispersible tablet the most according to claim 2, wherein said filler loading scope 10-45%.
Ai Dailalisi dispersible tablet the most according to claim 2, wherein said disintegrating agent amount ranges 10-20%.
Ai Dailalisi dispersible tablet the most according to claim 2, wherein said binder dosage scope 0.5-2%.
7. according to the Ai Dailalisi dispersible tablet described in any claim in claim 3-6, wherein: Ai Dailalisi content
Scope 10-30%；Filler loading 30-50%；Disintegrating agent consumption 10-20%；Binder dosage 0.5-2%, solubilizing agent consumption 0.5-
2%。
Ai Dailalisi dispersible tablet the most according to claim 1, wherein said Ai Dailalisi unit dose 10-80mg.
9. the preparation method of Ai Dailalisi dispersible tablet described in claim 1, uses direct powder compression, by Ai Dailalisi
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 |
|---|---|---|---|
| CN201610417860.4A CN105919957A (en) | 2016-06-13 | 2016-06-13 | Idelalisib dispersible tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610417860.4A CN105919957A (en) | 2016-06-13 | 2016-06-13 | Idelalisib dispersible tablet and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105919957A true CN105919957A (en) | 2016-09-07 |
Family
ID=56833811
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610417860.4A Pending CN105919957A (en) | 2016-06-13 | 2016-06-13 | Idelalisib dispersible tablet and preparation method thereof |
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| Country | Link |
|---|---|
| CN (1) | CN105919957A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014046617A1 (en) * | 2012-09-19 | 2014-03-27 | Agency For Science, Technology And Research | Compositions and methods for treating cancer |
| WO2015014315A1 (en) * | 2013-08-01 | 2015-02-05 | 杭州普晒医药科技有限公司 | Inhibitor crystalline form and preparation method and use thereof |
| CN104780913A (en) * | 2012-09-14 | 2015-07-15 | 赛诺菲 | Tablet formulation of a phosphatidylinositol 3-kinase inhibitor |
| CN105380956A (en) * | 2015-11-04 | 2016-03-09 | 张陆军 | Medicine composition which is used for treating leukemia and contains idelalisi and application |
| WO2016051374A1 (en) * | 2014-10-03 | 2016-04-07 | Novartis Ag | Pharmaceutical compositions comprising alpelisib |
-
2016
- 2016-06-13 CN CN201610417860.4A patent/CN105919957A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104780913A (en) * | 2012-09-14 | 2015-07-15 | 赛诺菲 | Tablet formulation of a phosphatidylinositol 3-kinase inhibitor |
| WO2014046617A1 (en) * | 2012-09-19 | 2014-03-27 | Agency For Science, Technology And Research | Compositions and methods for treating cancer |
| WO2015014315A1 (en) * | 2013-08-01 | 2015-02-05 | 杭州普晒医药科技有限公司 | Inhibitor crystalline form and preparation method and use thereof |
| WO2016051374A1 (en) * | 2014-10-03 | 2016-04-07 | Novartis Ag | Pharmaceutical compositions comprising alpelisib |
| CN105380956A (en) * | 2015-11-04 | 2016-03-09 | 张陆军 | Medicine composition which is used for treating leukemia and contains idelalisi and application |
Non-Patent Citations (1)
| Title |
|---|
| 元英进主编: "《现代制药工艺学 下册》", 31 January 2006 * |
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Application publication date: 20160907 |