CN109381438A - A kind of olaparib tablet composition - Google Patents
A kind of olaparib tablet composition Download PDFInfo
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- CN109381438A CN109381438A CN201811310951.3A CN201811310951A CN109381438A CN 109381438 A CN109381438 A CN 109381438A CN 201811310951 A CN201811310951 A CN 201811310951A CN 109381438 A CN109381438 A CN 109381438A
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- Prior art keywords
- olaparib
- recipe quantity
- lactose
- cyclodextrin
- mannitol
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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
-
- 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
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/502—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
-
- 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
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
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- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to a kind of olaparib tablet compositions, belong to pharmaceutical technology field.The technical scheme is that a kind of olaparib tablet composition, in every thousand, contain D90For 32-60 microns of olaparib 100g, pregelatinized starch 26-48g, lactose 12-25g, beta-cyclodextrin 3-6g, disodium ethylene diamine tetraacetate 10-18g, mannitol 6-12g, lauryl sodium sulfate 1.0-1.5g.The present invention is adjusted by reasonable prescription, in conjunction with corresponding preparation method, provides a kind of olaparib tablet composition of qualification.
Description
Technical field
The present invention relates to a kind of olaparib tablet compositions, belong to pharmaceutical technology field.
Background technique
Olaparib, English name: olaparib is researched and developed by Astrazeneca AB.For treating and BRCA gene defect
Relevant women's advanced ovarian cancer and the metastatic breast cancer of system genitale BRCA gene mutation (gBRCAm), HER2 feminine gender.
Olaparib daily 2 times, each 200mg, marketed tablet specification is 100g, capsule 50mg, due to glue
Wafer needs to take 4 every time, and therefore, patient is easier to receive tablet.
Olaparib belongs to insoluble drug, dissolves out to improve, Chinese patent CN102238945A,
CN106074409A, CN104434809A are prepared as olaparib dispersion, are then prepared as tablet composition.Due to
Olaparib tablet format is 100mg, belongs to larger specification, and test proves the stability of olaparib drug dispersity not
It is good, during storage and easily occur dispersion hardness become larger, overgrowth of crystal phenomena such as, dropped so as to cause the dissolution rate of tablet
It is low, related substance increase phenomena such as.In short, solid dispersion preparation preparation process is complicated, matter more demanding to support
Amount control is difficult to the quality control of ordinary tablet.
Since olaparib is on the one hand not soluble in water, it is on the other hand also easy to moisture absorption, related substance under the conditions of high temperature and humidity
It increases obviously, adds many factors for needing to overcome to the preparation of conventional tablet.
Summary of the invention
The present invention is directed to clinical demand, overcomes the characteristic of olaparib bulk pharmaceutical chemicals, provides a kind of Austria for meeting pharmacopoeial requirements
La Pani tablet composition.
Applicant has unexpectedly invented technical solution of the present invention.
The technical scheme is that a kind of olaparib tablet composition, in every thousand, contain D90It is 32-60 microns
Olaparib 100g, pregelatinized starch 26-48g, lactose 12-25g, beta-cyclodextrin 3-6g, disodium ethylene diamine tetraacetate 10-
18g, mannitol 6-12g, lauryl sodium sulfate 1.0-1.5g.
In technical solution of the present invention, what beta-cyclodextrin was cooperateed with disodium ethylene diamine tetraacetate improves olaparib
Stability.In stability test, stable product quality does not change substantially in relation to content of material and dissolution rate.
What mannitol was cooperateed with lauryl sodium sulfate improves the dissolution of olaparib, in conjunction with the granularity control of olaparib
System, present invention obtains the olaparib tablet compositions of higher dissolution.
Preferably, olaparib tablet composition of the present invention in every thousand, contains D90For 38-50 microns of Aura
Pa Buddhist nun 100g, pregelatinized starch 32-40g, lactose 15-20g, beta-cyclodextrin 4-5g, disodium ethylene diamine tetraacetate 12-16g, sweet dew
Alcohol 8-10g, lauryl sodium sulfate 1.2-1.4g.
Preferably, olaparib tablet composition of the present invention in every thousand, contains D90For 40 microns of olaparib
100g, pregelatinized starch 38g, lactose 18g, beta-cyclodextrin 4.5g, disodium ethylene diamine tetraacetate 14g, mannitol 9g, dodecyl
Sodium sulphate 1.3g.
The preparation method of olaparib tablet composition of the present invention, comprising the following steps:
The first step presses prescription requirements, and by olaparib air-flow crushing to the granularity needed, other auxiliary materials cross 60 meshes；
The olaparib of second step recipe quantity is uniformly mixed with the beta-cyclodextrin of recipe quantity, adds half recipe quantity
Mannitol, the lactose of recipe quantity are uniformly mixed, pre- tabletting, then by precompressed slice lapping to 60 meshes excessively；
Obtained by third step second step, be added the pregelatinized starch of recipe quantity, disodium ethylene diamine tetraacetate, remaining recipe quantity it is sweet
Reveal alcohol to be uniformly mixed；
The lauryl sodium sulfate of recipe quantity, direct tablet compressing is added by obtained by third step in 4th step.
Preparation method of the present invention increases pre- tableting step, compared with a step direct tablet compressing technique, stability and dissolution rate
There is a little raising.
The utility model has the advantages that adjusting by reasonable prescription, in conjunction with corresponding preparation method, the present invention provides a kind of Aura pas
Buddhist nun's tablet composition provides qualified olaparib tablet for clinic, provides good selection for patient.
1. D of embodiment90For 32 microns of olaparib 100g, pregelatinized starch 26g, lactose 25g, beta-cyclodextrin 3g, second
Edetate disodium 18g, mannitol 6g, lauryl sodium sulfate 1.5g, the preparation of by specification technical solution part description
Method prepares 1000.
2. D of embodiment90For 60 microns of olaparib 100g, pregelatinized starch 48g, lactose 12g, beta-cyclodextrin 6g, second
Edetate disodium 10g, mannitol 12g, lauryl sodium sulfate 1.0g, the preparation of by specification technical solution part description
Method prepares 1000.
The olaparib 100g, pregelatinized starch 38g, lactose 18g that 3. D90 of embodiment is 40 microns, beta-cyclodextrin
4.5g, disodium ethylene diamine tetraacetate 14g, mannitol 9g, lauryl sodium sulfate 1.3g, the description of by specification technical solution part
Preparation method prepare 1000.
The prescription of 1. embodiment 3 of reference examples, removes beta-cyclodextrin and disodium ethylene diamine tetraacetate, corresponding quality is by lactose
Supplement.It is specific as follows:
The olaparib 100g, pregelatinized starch 38g, lactose 36.5g that D90 is 40 microns, mannitol 9g, lauryl sodium sulfate
1.3g prepares 1000 by following preparation methods.
The first step presses prescription requirements, and by olaparib air-flow crushing to the granularity needed, other auxiliary materials cross 60 meshes；
The olaparib of second step recipe quantity is uniformly mixed with the lactose for entering the mannitol of half recipe quantity, recipe quantity,
Pre- tabletting, then by precompressed slice lapping to 60 meshes excessively；
Obtained by third step second step, the mannitol of pregelatinized starch, remaining recipe quantity that recipe quantity is added is uniformly mixed；
The lauryl sodium sulfate of recipe quantity, direct tablet compressing is added by obtained by third step in 4th step.
The prescription of 2. embodiment 3 of reference examples, removes mannitol and lauryl sodium sulfate, and corresponding quality is mended by lactose
It fills.It is specific as follows
The olaparib 100g, pregelatinized starch 38g, lactose 28g that D90 is 40 microns, beta-cyclodextrin 4.5g, ethylenediamine tetra-acetic acid
The preparation method of disodium 14g, the description of by specification technical solution part prepare 1000
The first step presses prescription requirements, and by olaparib air-flow crushing to the granularity needed, other auxiliary materials cross 60 meshes；
The olaparib of second step recipe quantity is uniformly mixed with the beta-cyclodextrin of recipe quantity, adds the lactose mixing of recipe quantity
Uniformly, pre- tabletting, then by precompressed slice lapping to 60 meshes excessively；
Obtained by third step second step, pregelatinized starch, the disodium ethylene diamine tetraacetate that recipe quantity is added are uniformly mixed, directly press
Piece.
The prescription of 3. embodiment 3 of reference examples, supplementary material directly mixes film-making, specific as follows:
The olaparib 100g, pregelatinized starch 38g, lactose 18g that D90 is 40 microns, beta-cyclodextrin 4.5g, ethylenediamine tetra-acetic acid
Disodium 14g, mannitol 9g, lauryl sodium sulfate 1.3g, the preparation method preparation of by specification technical solution part description
1000
The first step presses prescription requirements, and by olaparib air-flow crushing to the granularity needed, other auxiliary materials cross 60 meshes；
The olaparib of second step recipe quantity, beta-cyclodextrin, mannitol, lactose, pregelatinized starch, ethylenediamine with recipe quantity
Tetraacethyl disodium is uniformly mixed；
The lauryl sodium sulfate of recipe quantity, direct tablet compressing is added by obtained by third step in 4th step.
Test example distinguishes each 100, tablet of Example 1-3 and reference examples 1-3, aluminum-plastic packaged, is placed in constant temperature and humidity
In case, 25 DEG C, relative humidity 75% is stored 8 months, measure respectively 0 day, August end in relation to content of material and dissolution rate, data note
It records in table 1.
Table 1
1 data of table explanation: product of the embodiment of the present invention does not change during storage in relation to substance and dissolution rate substantially, and
The related content of material of 1 product of reference examples is increased significantly, and 2 product dissolution rate of reference examples is not up to standard, and is stored process and summarized dissolution
Degree decline is obvious, and 3 product dissolution rate of reference examples has certain decline, and related substance has a degree of raising.
It is positive to illustrate that prescription of the present invention and preparation method play the role of the stability and dissolution rate that improve tablet.
Other indexs of product of the embodiment of the present invention meet the related request of pharmacopeia and product standard.
Claims (4)
1. a kind of olaparib tablet composition, which is characterized in that in every thousand, contain D90For 32-60 microns of olaparib
100g, pregelatinized starch 26-48g, lactose 12-25g, beta-cyclodextrin 3-6g, disodium ethylene diamine tetraacetate 10-18g, mannitol 6-
12g, lauryl sodium sulfate 1.0-1.5g.
2. olaparib tablet composition according to claim 1, which is characterized in that in every thousand, contain D90It is micro- for 38-50
The olaparib 100g, pregelatinized starch 32-40g, lactose 15-20g, beta-cyclodextrin 4-5g, disodium ethylene diamine tetraacetate 12- of rice
16g, mannitol 8-10g, lauryl sodium sulfate 1.2-1.4g.
3. olaparib tablet composition according to claim 1, which is characterized in that be 40 microns containing D90 in every thousand
Olaparib 100g, pregelatinized starch 38g, lactose 18g, beta-cyclodextrin 4.5g, disodium ethylene diamine tetraacetate 14g, mannitol
9g, lauryl sodium sulfate 1.3g.
4. the preparation method of olaparib tablet composition described in claim 1, which comprises the following steps:
The first step presses prescription requirements, and by olaparib air-flow crushing to the granularity needed, other auxiliary materials cross 60 meshes；
The olaparib of second step recipe quantity is uniformly mixed with the beta-cyclodextrin of recipe quantity, adds half recipe quantity
Mannitol, the lactose of recipe quantity are uniformly mixed, pre- tabletting, then by precompressed slice lapping to 60 meshes excessively；
Obtained by third step second step, be added the pregelatinized starch of recipe quantity, disodium ethylene diamine tetraacetate, remaining recipe quantity it is sweet
Reveal alcohol to be uniformly mixed；
The lauryl sodium sulfate of recipe quantity, direct tablet compressing is added by obtained by third step in 4th step.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811310951.3A CN109381438A (en) | 2018-11-06 | 2018-11-06 | A kind of olaparib tablet composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811310951.3A CN109381438A (en) | 2018-11-06 | 2018-11-06 | A kind of olaparib tablet composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109381438A true CN109381438A (en) | 2019-02-26 |
Family
ID=65428377
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811310951.3A Withdrawn CN109381438A (en) | 2018-11-06 | 2018-11-06 | A kind of olaparib tablet composition |
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| Country | Link |
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| CN (1) | CN109381438A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113288859A (en) * | 2020-02-21 | 2021-08-24 | 上海宣泰医药科技股份有限公司 | Olaparib pharmaceutical composition, preparation method and application thereof |
| CN113350349A (en) * | 2020-03-04 | 2021-09-07 | 中国科学院上海药物研究所 | Olaparib dissolution enhancing composition |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106074409A (en) * | 2016-06-13 | 2016-11-09 | 佛山市腾瑞医药科技有限公司 | A kind of Aura handkerchief Buddhist nun's preparation and application thereof |
-
2018
- 2018-11-06 CN CN201811310951.3A patent/CN109381438A/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106074409A (en) * | 2016-06-13 | 2016-11-09 | 佛山市腾瑞医药科技有限公司 | A kind of Aura handkerchief Buddhist nun's preparation and application thereof |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113288859A (en) * | 2020-02-21 | 2021-08-24 | 上海宣泰医药科技股份有限公司 | Olaparib pharmaceutical composition, preparation method and application thereof |
| EP4108236A4 (en) * | 2020-02-21 | 2024-03-27 | Sinotherapeutics Inc | Olaparib pharmaceutical composition, preparation thereof, preparation method therefor and use thereof |
| CN113350349A (en) * | 2020-03-04 | 2021-09-07 | 中国科学院上海药物研究所 | Olaparib dissolution enhancing composition |
| WO2021175274A1 (en) * | 2020-03-04 | 2021-09-10 | 中国科学院上海药物研究所 | Olaparib dissolution enhancing composition |
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Application publication date: 20190226 |
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