CN107468665A - A kind of olaparib composition capsule - Google Patents
A kind of olaparib composition capsule Download PDFInfo
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- CN107468665A CN107468665A CN201710699342.0A CN201710699342A CN107468665A CN 107468665 A CN107468665 A CN 107468665A CN 201710699342 A CN201710699342 A CN 201710699342A CN 107468665 A CN107468665 A CN 107468665A
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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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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- 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
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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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
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Abstract
The present invention relates to field of medicine preparations, specifically discloses a kind of olaparib composition capsule.Olaparib composition capsule of the present invention includes olaparib, starch, toluene di-tert-butyl phenol, sodium alginate, Compritol 888 ATO.The preferably composition of olaparib, starch, toluene di-tert-butyl phenol, sodium alginate, Compritol 888 ATO as olaparib capsule of the invention, mutually synergy improves stability, mobility and the dissolution rate of olaparib, moisture is reduced, is advantageous to the safe handling of clinical medicine and long-term storage.
Description
Technical field
The present invention relates to field of medicine preparations, and in particular to a kind of olaparib composition capsule.
Background technology
Olaparib, chemical name are 4- [3- (4- cyclopropane carboxyl-piperazine -1- carboxyls) the fluoro- benzyls of -4-] -2H- phenol
Piperazine -1- ketone, available for providing poly- ADP- ribose polymerases (PARP) inhibitory action.This effect can be used for treating cancer, such as breast
Gland cancer or oophoroma, it particularly effective can treat its cell and be repaiied in homologous recombination (HR) dependent DNA double bond fracture (DSB)
Defective cancer in multiple path, such as BRCA1+ and/or BRCA2+ve cancers.
Disclosed in International Patent Application Publication No. WO 2004/080976 (compound 168) and illustrate 4- [3- (4- rings
Propane carboxyl-piperazine -1- carboxyls) the fluoro- benzyls of -4-] -2H- phenol piperazine -1- ketone, it has having structure：
Olaparib is the low bioavailability medicine of low-solubility, and the preparation method result of extraction using routine is poor, quality
Stability is bad, and bioavailability is low；And compound has polymorphic, including crystal formation L and crystal formation A, change in production process
Compound is also possible to be converted into crystal formation H, and crystal formation may change during preparation preserves, it is impossible to ensure the stabilization of medicine
Property.
Insoluble drug is absorbed by organisms because being not easy, and a definite limitation is received in clinical practice.Using solid dispersions
Technology, high degree of dispersion homogeneous state can be made up to, so as to ensure the absorption and utilization of made preparation.Solid dispersions have
Dramatically increase the dissolution rate of insoluble drug, improve its bioavilability and postpone to absorb, reduce medication dose the features such as, such as specially
Sharp CN102238945A, CN104434809A, CN106137998A, CN106074409A, which are disclosed, is prepared into olaparib admittedly
Preparation is prepared into after body dispersion.But solid dispersion preparation has as a drawback that：(1) it is not suitable for the big medicine of dosage；
(2) its carrier dosage is big, and the stability of medicine dispersity is not high, and storage long is also easy to produce aging phenomenon, i.e., solid dispersions is hard
Degree becomes big, separates out crystal or overgrowth of crystal, so as to reduce the bioavilability of medicine.(3) some carriers are in solid dispersions
Thermodynamic phase, time to time change is presented.(4) solid dispersion preparation preparation technology is complicated, to support requirement
Compare high, quality control is relatively difficult.
Due to the easy moisture absorption of olaparib, its less stable, relevant material increase is very big under the conditions of hot and humid, so
The selection of drug ingedient and the selection of dosage and preparation method become particularly important.Drug ingedient choose at random it is also possible that
Olaparib capsule dissolubility is deteriorated, relevant material increases, moisture rises etc. is obtained, or even can not granulating.
CN106551916A discloses a kind of olaparib conventional capsule preparation and preparation method thereof.Its olaparib glue
Capsule, wet granulation is used comprising active component olaparib and as disintegrant and the hydroxypropylcellulose of adhesive, preparation method
Filling capsule afterwards；It reduces product by selecting the small hydroxypropylcellulose of hygroscopicity to be used as disintegrant instead of PVP class
Draw moist so that product quality in prolonged storage is more stable；By being controlled to the particle diameter of olaparib, use is small
In the olaparib of 200 mesh particle diameters, it can make product that there is good dissolution rate in the case of without using super-disintegrant.
Although influence factor experiment, long term test and the accelerated test result of the patent notes show that the capsule has certain quality,
But in terms of olaparib capsule quality, still need further to be improved.The inventors discovered that using prescription disclosed in this application
The poor fluidity of the olaparib capsule prepared with preparation method, content uniformity is obvious, and its moisture is higher, and dissolution rate needs
Improve.
The suitably species of preparation method and process conditions, filler, disintegrant, lubricant etc. and dosage and filling
Agent, disintegrant, the appropriate combination of lubricant are most important to the result of extraction of capsule, mobility, content uniformity and stability.Often
Filler has starch, lactose etc., and conventional disintegrant has microcrystalline cellulose, sodium carboxymethyl starch etc., conventional lubricant
There are talcum powder, magnesium stearate, silica, superfine silica gel powder, sodium stearyl fumarate, lauryl sodium sulfate etc..But how to lead to
Cross suitable prescription, technique obtains more excellent dissolution rate, improves its mobility and content uniformity, reduce its moisture,
Its stability is further improved, prior art does not all provide further prompting, and in view of this, spy proposes this invention.
It is contemplated that overcoming, the mobility of existing olaparib capsule is bad, dissolution rate is low, content uniformity is obvious, moisture
The problems such as content is high, gained olaparib capsule stability is high, good fluidity, and content uniformity is low, and dissolution rate is high, moisture
It is low, substantially increase the security and validity of medication.
The content of the invention
In view of this, it is an object of the invention to provide a kind of olaparib composition capsule so that the olaparib
Capsule can improve the stability of olaparib, mobility, reduce content uniformity and moisture, improve dissolution rate, carry significantly
The security and validity of high medication.
To achieve the above object, the present invention provides following technical scheme：
A kind of olaparib composition capsule, described pharmaceutical composition include olaparib, starch, di-t-butyl to toluene
Phenol, sodium alginate, Compritol 888 ATO.
Preferably, with weight, the composition includes：Olaparib 30%-35%, starch
50.4%-53.5%, toluene di-tert-butyl phenol 0.1%-0.3%, sodium alginate 14%-18%, Compritol 888 ATO
0.4%-0.6%.
It is highly preferred that with weight, the composition includes：Olaparib 30%, starch 53.5%, two uncles
Butyl p-cresol 0.2%, sodium alginate 15.8%, Compritol 888 ATO 0.5%.
It is highly preferred that the amount ratio of the Compritol 888 ATO and sodium alginate is 0.1:2.5-4.5.
Olaparib composition of the present invention can be prepared according to any rational method of prior art.This area skill
The prior art that art personnel grasp according to it, and by simple experiment, can prepare meet national drug quality requirement completely
This composition.That is the realization of foregoing invention purpose can not also be limited by its preparation method.But in order to further improve
The quality of the composition, present invention preferably provides following preparation method：
Described preparation method comprises the following steps：
Drug ingedient olaparib, starch, toluene di-tert-butyl phenol, sodium alginate, Compritol 888 ATO are crushed respectively,
80 mesh sieves are crossed, well mixed be sent into dry granulating machine is pelletized, 18 mesh whole grains, and capsule is filling.
Preferably, with weight, each Ingredients Weight percentage composition is：Olaparib 30%-35%, starch
50.4%-53.5%, toluene di-tert-butyl phenol 0.1%-0.3%, sodium alginate 14%-18%, Compritol 888 ATO
0.4%-0.6%.
It is highly preferred that with weight, each Ingredients Weight percentage composition is：Olaparib 30%, starch
53.5%th, toluene di-tert-butyl phenol 0.2%, sodium alginate 15.8%, Compritol 888 ATO 0.5%.
It is highly preferred that the amount ratio of the Compritol 888 ATO and sodium alginate is 0.1:2.5-4.5.
It is easily tacky after olaparib raw material moisture absorption, cause hardness to become big, cause disintegration difficult, dissolution rate is slack-off.So
If auxiliary material selects bad, easy moisture absorption, quality is unstable during causing finished product storage.It is made in pharmaceutical composition, leads to
The auxiliary material of often more likely few selection, and the stripping quantity of active component is bigger, so can be with the reduction auxiliary material of maximum possible to work
The influence of property composition, simplifies preparation technology, while reduce cost.But specifically which auxiliary material it can reach above-mentioned mesh from
, it is necessary to which paying performing creative labour could realize, the present invention olaparib composition prescription has been carried out largely
Screening, refers to experimental example 1, and the composition of the olaparib composition of the present invention is finally determined.
In olaparib capsule prescription disclosed in CN106551916A.Its olaparib capsule, includes active component Aura
Pa Ni and as disintegrant and the hydroxypropylcellulose of adhesive.Because the mobility of olaparib and starch is poor, therefore cause
The bad control of loading amount, makes troubles to production.The inventors discovered that when assembling application using hydroxypropylcellulose and starch or lactose,
Dissolution rate is bad, and when especially hydroxypropylcellulose and starch assemble application, poor fluidity, content uniformity is obvious；Inventor passes through
Substantial amounts of experiment screening is found：Sodium alginate cooks disintegrant, while adds Compritol 888 ATO and do lubricant, and it is significantly improved
It mobility, ensure that content uniformity is small in large-scale production process, while find that it can improve the molten of olaparib capsule by experiment
Out-degree；In order to improve its stability in preparation process, a small amount of toluene di-tert-butyl phenol, obtained olaparib are added
Good fluidity, content uniformity is small, and moisture is low, and dissolution rate and stability significantly improve.
Wherein the amount ratio of Compritol 888 ATO and sodium alginate has a great impact to the mobility and dissolution rate of medicine,
Experimental example 2 is Compritol 888 ATO, the dosage screening experiment of sodium alginate, when Compritol 888 ATO and the amount ratio of sodium alginate
Control is 0.1:During 2.5-4.5, its mobility is best, and content uniformity is low, and dissolution rate is high.
The dosage of starch also has a great impact to the performance of medicine, and experimental example 3 is the dosage screening experiment of starch, if
The dosage of starch very little, easily causes content uniformity and becomes big；And dosage is too many, its dissolution rate can be affected again, starch of the present invention
Dosage be total recipe quantity 50.4-53.5% (weight percentage).
For existing olaparib capsule poor fluidity, dissolution rate and moisture are low, stability is not high the defects of, this hair
It is bright to be furtherd investigate by long-term, the influence between various composition has been considered, has optimized the compositing formula of olaparib capsule, has been selected
Olaparib, starch, toluene di-tert-butyl phenol, sodium alginate, Compritol 888 ATO combination prepare olaparib capsule, mutually
Synergy improves curative effect, and good fluidity, the content uniformity of the olaparib capsule provided are small, moisture is low, molten
Out-degree is high, stability is good, substantially increases the security and validity of medication.
Embodiment
The invention discloses a kind of olaparib composition capsule, those skilled in the art can use for reference present disclosure, fit
When modified technique parameter is realized.In particular, all similar replacements and change for a person skilled in the art
It is it will be apparent that they are considered as being included in the present invention.The method of the invention is carried out by preferred embodiment
Description, related personnel can substantially not depart from present invention, composition as described herein changed in spirit and scope
It is dynamic or suitably change with combining, to realize and using the technology of the present invention.
With reference to embodiment, the present invention is expanded on further.
The weight percentage (%) of embodiment 1-5 each components
| Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 | |
| Olaparib | 35 | 30 | 30 | 30 | 30 |
| Starch | 50.4 | 53.5 | 53.4 | 53.5 | 51.4 |
| Toluene di-tert-butyl phenol | 0.1 | 0.2 | 0.3 | 0.1 | 0.2 |
| Sodium alginate | 14 | 15.8 | 16 | 15.8 | 18 |
| Compritol 888 ATO | 0.5 | 0.5 | 0.4 | 0.6 | 0.4 |
The preparation method of olaparib capsule：
Drug ingedient olaparib, starch, toluene di-tert-butyl phenol, sodium alginate, Compritol 888 ATO are crushed respectively,
80 mesh sieves are crossed, well mixed be sent into dry granulating machine is pelletized, 18 mesh whole grains, and capsule is filling.
Test method：
1st, mobility-detected is tested：
The mobility of solid can not be expressed with single characteristic value, commonly use angle of repose (angle of repose) and represent.
Typically refer to the maximum angular that the free inclined-plane of powder accumulation horizon and horizontal plane are formed.Angle of repose is smaller, and frictional force is smaller, flowing
Property is better, it is considered that good fluidity during θ≤30 degree, the need for liquidity in production process can be met during θ≤40 degree.Powder
Mobility the weight differential of the preparations such as granule, capsule, tablet and normal operating are had a great influence.
Inventor uses injection method：Powder is slowly added into above funnel, the material spilt from funnel bottom is in level
The inclination angle of coniform accumulation body is formed on face.Determine 3 times altogether, average, the results are shown in Table 1.
2nd, content uniformity detects
Reference《Chinese Pharmacopoeia》The detection method detection about content uniformity, takes for trying under 2005 editions annex capsule items
Product 10, respectively accurately weighed weight pours out content (must not lose softgel shell), hard shell capsules softgel shell with small brush or other suitably
Apparatus is wiped only；Soft capsule shell is cleaned with ether equal solvent, and putting ventilation makes solvent wave to the greatest extent, respectively accurately weighed softgel shell weight,
Obtain the tolerant loading amount of every intragranular.(all labelled amounts are indicated every loading amount with certain component amount, should be with compared with sign loading amount
Average loading amount compares), content uniformity limit should must not be more than 2 within ± 10.0% beyond content uniformity limit.And
There must not be 1 one times of overrun.
3rd, dissolution rate detects
Elution test method：Using basket method, under 37 DEG C and 100rpm mixing speeds, the 0.3%SDS for being placed in 900ml is molten
In liquid.After 90 min, 1ml samples are taken, and olaparib content is detected by HPLC.
Experimental example 1：Prescription screening is tested
Due to the easy moisture absorption of olaparib, to damp and hot unstable, therefore pay the utmost attention to dry granulation method preparation, prevent moisture
Influence of the agent temperature to supplementary material, specific preparation method are as follows：Supplementary material is crushed respectively, crosses 80 mesh sieves, is well mixed to be sent into and is done
Granulation, 18 mesh whole grains, capsule are filling in method granulator.
Screening experiment overabundance of data, only lists the important experimental data in part herein, and inventor passes through substantial amounts of experiment screening
It was found that when hydroxypropylcellulose assembles application with starch or lactose, dissolution rate is bad, and especially hydroxypropylcellulose is assembled with starch and answered
Used time, mobility is very poor, and content uniformity is obvious；When lubricant is changed into Compritol 888 ATO, it significantly improves mobility,
But its dissolution rate is not high；When using sodium alginate as disintegrant, its dissolution rate not only increases, and its mobility is also notable
Improve, content uniformity substantially reduces.
Experimental example 2：The dosage screening experiment of Compritol 888 ATO, sodium alginate
This experimental example is when preparing olaparib capsule, and the dosage as Compritol 888 ATO, sodium alginate is screened real
Test, control each supplementary material weight percentage：Olaparib 30%-35%, starch 50.4%-53.5%, di-t-butyl are to first
Phenol 0.1%-0.3%, Compritol 888 ATO, sodium alginate weight percentage are adjusted on this basis.
The dosage of disintegrant sodium alginate has a great influence to disintegration time and dissolution rate, and its dosage is too small, can not meet and collapses
Solution and the requirement of dissolution.Sodium alginate aqueous solution is the disintegrant of viscosity, and its dosage is bigger, and the speed of disintegration and dissolution is slower.
Therefore inventor passes through substantial amounts of experiment screening, selects its weight percentage to be advisable for 14%-18%.
The dosage screening experiment of the Compritol 888 ATO of table 2, sodium alginate
Method preparation is prepared as follows in above-mentioned prescription：Drug ingedient olaparib, starch, di-t-butyl are crushed respectively
P-cresol, sodium alginate, Compritol 888 ATO, 80 mesh sieves are crossed, well mixed be sent into dry granulating machine is pelletized, and 18 mesh are whole
Grain, capsule are filling.
Screening experiment overabundance of data, only lists the important experimental data in part herein, and inventor passes through substantial amounts of experiment screening
It was found that the amount ratio of Compritol 888 ATO and sodium alginate has a great impact to the mobility and dissolution rate of medicine, work as behenyl
The amount ratio of acid glyceride and sodium alginate is controlled 0.1:During 2.5-4.5, its mobility is best, and content uniformity is low, dissolution rate
It is high.
Experimental example 3：The dosage screening experiment of starch
This experimental example be when preparing olaparib capsule, as the screening experiment of the dosage of the starch of filler, wherein
The prescription of capsule is such as embodiment 2 in addition to starch, and its preparation technology is in addition to the amount change of starch, remaining equal reference implementation example 2,
The taken amount of starch is shown in Table 3.
The dosage screening experiment (weight percentage %) of the starch of table 3
Screening experiment overabundance of data, only lists the important experimental data in part herein, and inventor passes through substantial amounts of experiment screening
It was found that the dosage of starch also has a great impact to the performance of medicine, experimental example 3 is the dosage screening experiment of starch, if formed sediment
The dosage of powder very little, easily causes content uniformity and becomes big；And dosage is too many, its mobility, dissolution rate are created a great impression, present invention warp
Substantial amounts of experiment screening is crossed, determine the dosage of starch is advisable for the 50.4-53.5% (weight percentage) of total recipe quantity.
Experimental example 4：Performance detection
The olaparib capsule and prior art olaparib glue prepared according to prescription provided by the invention and preparation method
The comparison of capsule performance is shown in Table 4：
The performance test results of table 4
As can be seen from the above table, dissolution rate height, the good fluidity of olaparib capsule of the invention, content uniformity is low, water
Point content significantly reduces, and its performance is significantly better than existing preparation olaparib capsule.
Experimental example 5：High wet test
The sample of the embodiment of the present invention 2 and the product of CN106551916A patent Examples 1 (control sample) are taken, puts sealing respectively
In clean container, place 10 days under conditions of 25 DEG C, relative humidity 92.5% ± 5%, sampled in the 5th day and the 10th day,
Detected by stability high spot reviews project, result of the test the results are shown in Table 5 compared with 0 day.
The high humidity testing inspection result of table 5
Identical experiment has been carried out to other embodiments of the invention, has obtained the result similar to the embodiment of the present invention 2；It is right
CN106551916A patents other embodiment has carried out identical experiment, has obtained similar to CN106551916A patent Examples 1
Result；Product of the embodiment of the present invention under conditions of high humidity, in character, moisture, dissolution rate and has it can be seen from experimental result
Material etc. is closed to be intended to than control sample stabilization.
Experimental example 6：Accelerated test
Take the sample of the embodiment of the present invention 2 with the product of CN106551916A patent Examples 1 (control sample) respectively in temperature
40 DEG C ± 2 DEG C, relative humidity is placed 6 months under conditions of being 75% ± 5%, sampled once respectively at the 1st, 2,3,6 the end of month,
It is measured by stability high spot reviews project.Result of the test is shown in Table 6.
The accelerated test result of table 6
Identical experiment has been carried out to other embodiments of the invention, has obtained the result similar to the embodiment of the present invention 2；It is right
CN106551916A patents other embodiment has carried out identical experiment, has obtained similar to CN106551916A patent Examples 1
Result；Product of the embodiment of the present invention is 75% ± 5% in 40 DEG C ± 2 DEG C of temperature, relative humidity it can be seen from experimental result
Under conditions of, it is intended to accelerating 3 than control sample stabilization, control sample in character, moisture, dissolution rate and relevant material etc.
Occur as soon as caking phenomenon within individual month or so, it is very sensitive to humidity.
Embodiment 7：Long term test
It is respectively 25 DEG C in temperature to take the embodiment of the present invention 1, the sample of embodiment 2, and relative humidity is 60% ± 10% bar
Place 24 months under part, respectively at the 3rd, 6,9,12,18,24 the end of month sampling once, carried out by stability high spot reviews project
Measure.Result of the test is shown in Table 7.
The long-term test results of table 7
Identical experiment has been carried out to other embodiments of the invention, obtained similar to the embodiment of the present invention 1, embodiment 2
As a result；Product of the present invention is in 40 DEG C ± 2 DEG C of temperature, the condition that relative humidity is 75% ± 5% it can be seen from experimental result
Under, it is respectively provided with character, moisture, dissolution rate and about material etc. higher stability.
Claims (9)
1. a kind of olaparib composition capsule, it is characterised in that described pharmaceutical composition includes olaparib, starch, two uncles
Butyl p-cresol, sodium alginate, Compritol 888 ATO.
2. olaparib composition capsule according to claim 1, it is characterised in that described with weight
Composition includes：Olaparib 30%-35%, starch 50.4%-53.5%, toluene di-tert-butyl phenol 0.1%-0.3%, sea
Mosanom 14%-18%, Compritol 888 ATO 0.4%-0.6%.
3. olaparib composition capsule according to claim 2, it is characterised in that with weight, described group
Compound includes：Olaparib 30%, starch 53.5%, toluene di-tert-butyl phenol 0.2%, sodium alginate 15.8%, behenic acid
Glyceride 0.5%.
4. olaparib composition capsule according to claim 2, it is characterised in that the Compritol 888 ATO and alginic acid
The amount ratio of sodium is 0.1:2.5-4.5.
5. a kind of preparation method of olaparib composition capsule, it is characterised in that comprise the following steps：
Drug ingedient olaparib, starch, toluene di-tert-butyl phenol, sodium alginate, Compritol 888 ATO are crushed respectively, cross 80
Mesh sieve, well mixed be sent into dry granulating machine are pelletized, 18 mesh whole grains, and capsule is filling.
6. preparation method according to claim 5, it is characterised in that with weight, each Ingredients Weight percentage
Content is：Olaparib 30%-35%, starch 50.4%-53.5%, toluene di-tert-butyl phenol 0.1%-0.3%, alginic acid
Sodium 14%-18%, Compritol 888 ATO 0.4%-0.6%.
7. preparation method according to claim 6, it is characterised in that with weight, each Ingredients Weight percentage
Content is：Olaparib 30%, starch 53.5%, toluene di-tert-butyl phenol 0.2%, sodium alginate 15.8%, behenic acid are sweet
Grease 0.5%.
8. preparation method according to claim 6, it is characterised in that the dosage of the Compritol 888 ATO and sodium alginate
Than for 0.1:2.5-4.5.
9. olaparib composition capsule prepared by preparation method described in claim 5-8 any one.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN117298062A (en) * | 2022-06-17 | 2023-12-29 | 北京阳光诺和药物研究股份有限公司 | PARP (PARP inhibitor) capsule and preparation method thereof |
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| CN117298062B (en) * | 2022-06-17 | 2024-03-26 | 北京阳光诺和药物研究股份有限公司 | PARP (PARP inhibitor) capsule and preparation method thereof |
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| CN107468665B (en) | 2019-11-08 |
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