CN105748435B - A kind of Pabuk former times benefit cloth pharmaceutical composition and preparation method thereof - Google Patents
A kind of Pabuk former times benefit cloth pharmaceutical composition and preparation method thereof Download PDFInfo
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- CN105748435B CN105748435B CN201610250321.6A CN201610250321A CN105748435B CN 105748435 B CN105748435 B CN 105748435B CN 201610250321 A CN201610250321 A CN 201610250321A CN 105748435 B CN105748435 B CN 105748435B
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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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
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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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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Abstract
The invention discloses a kind of Pabuk former times benefit cloth pharmaceutical compositions, it includes Pabuk former times benefit cloth or its pharmaceutical salts and pharmaceutically acceptable auxiliary materials, wherein, the Pabuk former times benefit cloth or the partial size of its pharmaceutical salts are 50 μm ~ 150 μm, and the pharmaceutical salts include isethionate, hydrochloride, sulfate or benzene sulfonate.Pharmaceutical composition provided by the invention directly mixes encapsulated technique using supplementary material, and bioavilability is high, and stable product quality is good, and technical process is easily controllable, and favorable reproducibility between batch is easy to industrialization.
Description
Technical field
The invention belongs to technical field of medicine, are related to a kind of pharmaceutical composition of Pabuk former times benefit cloth, more particularly to one
The Pabuk former times benefit cloth pharmaceutical composition and preparation method thereof of the direct hybrid technique preparation of kind.
Background technique
Breast cancer is one of the most common malignant tumors in women, and disease incidence accounts for the 7%~10% of the various malignant tumours of whole body, only
Inferior to uterine cancer, it has also become threaten the Etiological of WomanHealth.Its morbidity is often related with heredity, and menopause in 40~60 years old
Women's disease incidence before and after phase is higher.It is that one kind usually occurs to seriously affect women's physical and mental health in breast galandular epithelium tissue
Even one of the malignant tumour of threat to life, in recent years, disease incidence shows an increasing trend year by year, and it is pernicious swollen to have leapt to women
The disease incidence of the first place of tumor, China has been higher by world average level.
There are about 1,200,000 women to suffer from breast cancer every year in the whole world, and 500,000 people die of breast cancer.In the flourishing state such as West Europe, North America
Family, breast cancer incidence account for female malignant first place.2010, Chinese population association announced " Chinese mammary gland disease investigation report
Accuse ", China main cities over 10 years breast cancer incidence increase 37%；Disease incidence is just with annual 3% speed increase.2003
Years -2009 years, the death rate of breast cancer increased 38.91% in China city.In patient with breast cancer, human epidermal growth because
Sub- receptor 2(HER2) ratio of breast cancer patients with positive accounts for about 20%, HER2 negative patient and accounts for about 80%.HER2 negative breast cancer is suffered from
Person's relative populations are more, and progress is slow.
Pabuk former times benefit cloth (English name: Palbociclib), structural formula is as follows:
Formula I.
Pabuk former times benefit cloth is a kind of inhibitor of cell cycle protein dependent kinase (CDK) 4 and 6.Cyclin D1 and
CDK4/6 is the downstream for leading to cell proliferation signals access.In vitro, Pabuk former times benefit cloth is by blocking cell from cell cycle G1
Phase enters the S phase to slow down estrogen receptor (ER)-positive breast cancer cells strain cell Proliferation.Independent medication is compared to,
Pabuk former times benefit cloth combines estrogen antagonist and treats breast carcinoma cell strain, leads to its Retinoblastoma Protein (Rb) phosphorylation
Slow down, as a result E2F expression and signal transmitting slow down and growth inhibition acceleration.In vitro, Pabuk former times benefit cloth combines estrogen antagonism
Agent treatment ER- positive breast cancer cells strain causes its cell ageing to accelerate, and 6 days can be lasted up to after drug withdrawal.It is multinomial internal
Studies have shown that treating a kind of ER- positive breast cancer heteroplastic transplantation model in patient source, phase with Pabuk former times benefit cloth joint Letrozole
It is compared to for independent medication, can accelerate to inhibit Rb phosphorylation, downstream signal transmitting and tumour growth.
A small number of enterprises of Pfizer Products Inc and the country have applied for the synthetic method patent of the drug, the honest day in Nanjing in China
Fine pharmaceutical Co. Ltd has applied for formulation patent, a kind of entitled pharmaceutical composition of dry granulation process preparation, application number
201510732916.0, which uses the preparation process of dry granulation, mainly since the partial size of bulk pharmaceutical chemicals is too small, specific surface
Too big, large percentage of the raw material in prescription of product, about 28%, cause bulk pharmaceutical chemicals physical state to the material of entire prescription mixture
Property is affected, and greatly reduces the mobility of prescription mixture material, therefore uses dry method granulation processes.But current dry method
There are many disadvantages for prilling: there are many China's dry granulating machine manufacturing firm first, but stabilization of equipment performance is compared to more poor, therefore
Barrier rate is higher, and main problem includes bad roll, leak, roll dislocation, dust-producing amount is big, yield rate is low, difficult cleaning, pressure transient
Deng；Secondly equipment price is expensive；It is important that output is small, first-time qualification rate is low, and particle obtained is irregular, particle flow
Property it is good not as good as wet granulation.The present invention by the recrystallizing technologies of control bulk pharmaceutical chemicals, obtain particle size is moderate, mobility compared with
Good bulk pharmaceutical chemicals, using the bulk pharmaceutical chemicals and select the preferable auxiliary material of mobility, and can reach directly mixing supplementary material can filling glue
The effect of capsule.
The formulation patent Pabuk former times benefit cloth gastric floating tablet and preparation method thereof of Shanghai Lu Yuan Pharmaceutical Technology Co., Ltd application,
Application No. is 201510162791.2, which provides a kind of high bioavilability, is in slow release trend, medication is effectively reduced
The Pabuk former times benefit cloth gastric floating tablet of total amount, obtained tablet can keep 10 hours or more flotation times in gastric juice.The U.S.
It is quick-release capsules agent that the original of Pfizer's listing, which grinds drug, and the dissolution test in the 0.1mol/L hydrochloric acid solution of in-vitro simulated gastric juice shows
I.e. leachable 95% or more is crossed within 15 minutes, the gastric emptying time is 1.5 ~ 2 hours, guarantee that drug has time enough to absorb in stomach,
Clinical test simultaneously confirms that therapeutic effect is very good, illustrate Pabuk former times benefit it is fabric at capsule be proper.In addition, stomach floats
Can the key of floating formulation design success or failure be whether it can reach expected floating effect under one's belt, when extending Entogastric lingering
Between, if a common sustained-release matrix tablets cannot can only be equivalent at floating state, since Pabuk former times benefit cloth is greater than in pH value
When 4.0, solubility is significantly reduced, and in this case instead resulting in drug cannot be fully absorbed, and lessen the curative effect.
Summary of the invention
Simple and easy, stable product quality good Pabuk former times is prepared the technical problem to be solved in the present invention is to provide a kind of
Sharp cloth pharmaceutical composition.
In order to solve the above technical problems, the technical solution used in the present invention is:
A kind of Pabuk former times benefit cloth pharmaceutical composition, it includes Pabuk former times benefit cloth or its pharmaceutical salts and pharmaceutically acceptable
Auxiliary material, wherein the Pabuk former times benefit cloth or the partial size of its pharmaceutical salts are 50 μm ~ 150 μm, and the pharmaceutical salts include isethionic acid
Salt, hydrochloride, sulfate or benzene sulfonate.
Partial size mentioned by the present invention is indicated with D90, well known to those skilled in the art, and D90 refers to that drug particle is tired
Meter size distribution number reaches partial size corresponding when 90%.
Further, Pabuk former times benefit cloth pharmaceutical composition of the present invention is comprising weight percent 20 ~ 40%
The auxiliary material of Pabuk former times benefit cloth or its pharmaceutical salts and weight percent 60% ~ 80%, the auxiliary material include filler, disintegrating agent, help stream
Agent and lubricant.
Further, Pabuk former times benefit cloth pharmaceutical composition of the present invention, wherein the filler accounts for Pabuk former times benefit cloth
The percentage of pharmaceutical composition total weight is 45 ~ 70%；The disintegrating agent accounts for the percentage of Pabuk former times benefit cloth pharmaceutical composition total weight
Than being 3 ~ 8%；The percentage that the glidant accounts for Pabuk former times benefit cloth pharmaceutical composition total weight is 1 ~ 4%；The lubricant accounts for pa
The percentage of cloth former times benefit cloth pharmaceutical composition total weight is 0.5 ~ 4%.
It is further preferred that Pabuk former times benefit cloth pharmaceutical composition of the present invention, wherein the filler accounts for Pabuk former times
The percentage of sharp cloth pharmaceutical composition total weight is 57 ~ 65%.
Further, Pabuk former times benefit cloth pharmaceutical composition of the present invention, wherein the filler is microcrystalline cellulose
And lactose, wherein the mass ratio of the microcrystalline cellulose and lactose is (0.5 ~ 3): 1.
It is further preferred that Pabuk former times benefit cloth pharmaceutical composition of the present invention, wherein the filler is that crystallite is fine
Dimension element and lactose, wherein the mass ratio of the microcrystalline cellulose and lactose is 2:1.
Further, Pabuk former times benefit cloth pharmaceutical composition of the present invention, wherein the disintegrating agent is selected from carboxymethylstarch
Sodium, crospovidone or croscarmellose sodium, preferably carboxyrnethyl starch sodium.
Further, Pabuk former times benefit cloth pharmaceutical composition of the present invention, wherein the glidant is selected from colloid dioxy
SiClx, silica or talcum powder, preferably colloidal silicon dioxide or silica.
Further, Pabuk former times benefit cloth pharmaceutical composition of the present invention, wherein the lubricant is selected from magnesium stearate
Or sodium stearyl fumarate, preferred magnesium stearate.
The present invention also provides a kind of Pabuk former times benefit cloth preparations.
A kind of Pabuk former times benefit cloth preparation prepared by Pabuk former times benefit cloth pharmaceutical composition of the present invention, by the pa
Cloth former times benefit cloth pharmaceutical composition is encapsulated after directly mixing to be prepared.
Further, Pabuk former times benefit cloth preparation of the present invention, wherein the preparation method comprises the following steps: taking
Pabuk former times benefit cloth or its pharmaceutical salts are added filler, disintegrating agent, glidant and are pre-mixed, add lubrication after mixing
Agent is always mixed, until being uniformly mixed, total mix material is set capsule filling machine and carries out capsule filling, inner packing.
Another object of the present invention is to provide the preparation methods of the Pabuk former times benefit cloth preparation.
The preparation method of Pabuk former times benefit cloth preparation of the present invention comprising following steps:
Pabuk former times benefit cloth or its pharmaceutical salts are taken, filler, disintegrating agent, glidant is added and is pre-mixed, after mixing
It adds lubricant always to be mixed, until being uniformly mixed, total mix material is set into capsule filling machine and carries out capsule filling, interior packet
Dress.
The beneficial effects of adopting the technical scheme are that
The present inventor has found the method for granulating by routine in the development process of Pabuk former times benefit cloth preparation, no matter
It is dry granulation or wet granulation, is unable to reach and grinds suitable with original or faster dissolve out release profiles, to can not obtain
The product of same or higher bioavilability is ground with original.Since Pabuk former times benefit cloth is non-in the solubility being greater than in pH4.0 solution
It is often small, and the residence time is shorter under one's belt for drug, therefore dissolution rate of the drug in stomach is very crucial, which determine the lifes of drug
Object availability, but dissolution rate of the prior art such as CN201510732916.0 compared with original grinds reference preparation, before 30min
Considerably slower than reference preparation, dissolution rate then shortens soak time of the drug in stomach slowly, clinical effective so as to influence
Property.
The present inventor has been surprisingly found that in test, by controlling Pabuk former times benefit cloth raw material particle size size, in conjunction with adopting
With the preferable auxiliary material of mobility, and reasonable prescription proportion is screened, encapsulated technique is directly mixed using supplementary material, can be obtained
With the comparable preparation of Yuan Yan company reference preparation dissolved corrosion, also, compared with dry granulation or wet granulation, technical process is easy
In control, stable product quality is good, and favorable reproducibility between batch is easy to industrialization.The patient for taking this product is generally long-term administration,
Most widely used, most popular capsule formulation has been selected, has been easy to as patient's receiving.The present invention, which is used, grinds consistent dosage form with original
Capsule guarantees the validity and safety of clinical application.
Specific embodiment
With specific embodiment, the present invention is described in further detail below.Following embodiment is only used for explaining this hair
Bright technical solution, but it is not as a limitation of the invention.
1(1000 preparation unit of embodiment)
Pabuk former times benefit cloth free alkali, colloidal silicon dioxide, microcrystalline cellulose, carboxyrnethyl starch sodium, lactose are added to mixing
Premixing 10min is carried out in machine, and magnesium stearate is added and carries out total mixing 4min, discharging is added in capsule filling machine and carries out glue
Capsule filling.
2(1000 preparation unit of embodiment)
Pabuk former times benefit cloth free alkali, colloidal silicon dioxide, microcrystalline cellulose, carboxyrnethyl starch sodium, lactose are added to mixing
Premixing 12min is carried out in machine, and magnesium stearate is added and carries out total mixing 5min, discharging is added in capsule filling machine and carries out glue
Capsule filling.
3(1000 preparation unit of embodiment)
Pabuk former times benefit cloth free alkali, colloidal silicon dioxide, microcrystalline cellulose, carboxyrnethyl starch sodium, lactose are added to mixing
Premixing 12min is carried out in machine, and magnesium stearate is added and carries out total mixing 6min, discharging is added in capsule filling machine and carries out glue
Capsule filling.
4(1000 preparation unit of embodiment)
Pabuk former times benefit cloth free alkali, colloidal silicon dioxide, microcrystalline cellulose, carboxyrnethyl starch sodium, lactose are added to mixing
Premixing 15min is carried out in machine, and magnesium stearate is added and carries out total mixing 4min, discharging is added in capsule filling machine and carries out glue
Capsule filling.
5(1000 preparation unit of embodiment)
Pabuk former times benefit cloth isethionate, colloidal silicon dioxide, microcrystalline cellulose, carboxyrnethyl starch sodium, lactose are added
Premixing 12min is carried out into mixing machine, and magnesium stearate is added and carries out total mixing 4min, discharging is added in capsule filling machine
Carry out capsule filling.
6(1000 preparation unit of embodiment)
Pabuk former times benefit cloth free alkali, colloidal silicon dioxide, microcrystalline cellulose, carboxyrnethyl starch sodium, lactose are added to mixing
Premixing 12min is carried out in machine, and magnesium stearate is added and carries out total mixing 4min, discharging is added in capsule filling machine and carries out glue
Capsule filling.
7(1000 preparation unit of embodiment)
Pabuk former times benefit cloth free alkali, colloidal silicon dioxide, microcrystalline cellulose, carboxyrnethyl starch sodium, lactose are added to mixing
Premixing 12min is carried out in machine, and magnesium stearate is added and carries out total mixing 4min, discharging is added in capsule filling machine and carries out glue
Capsule filling.
8(1000 preparation unit of embodiment)
Pabuk former times benefit cloth free alkali, colloidal silicon dioxide, microcrystalline cellulose, carboxyrnethyl starch sodium, lactose are added to mixing
Premixing 12min is carried out in machine, and magnesium stearate is added and carries out total mixing 4min, discharging is added in capsule filling machine and carries out glue
Capsule filling.
9(1000 preparation unit of embodiment)
Pabuk former times benefit cloth hydrochloride, colloidal silicon dioxide, microcrystalline cellulose, carboxyrnethyl starch sodium, lactose are added to mixing
Premixing 12min is carried out in machine, and magnesium stearate is added and carries out total mixing 6min, discharging is added in capsule filling machine and carries out glue
Capsule filling.
10(1000 preparation unit of embodiment)
Pabuk former times benefit cloth free alkali, colloidal silicon dioxide, microcrystalline cellulose, carboxyrnethyl starch sodium, lactose are added to mixing
Premixing 10min is carried out in machine, and magnesium stearate is added and carries out total mixing 4min, discharging is added in capsule filling machine and carries out glue
Capsule filling.
11(1000 preparation unit of embodiment)
Pabuk former times benefit cloth free alkali, colloidal silicon dioxide, microcrystalline cellulose, carboxyrnethyl starch sodium, lactose are added to mixing
Premixing 10min is carried out in machine, and magnesium stearate is added and carries out total mixing 4min, discharging is added in capsule filling machine and carries out glue
Capsule filling.
Comparative example 1
Pabuk former times benefit cloth composition (1000 systems are prepared according to embodiment 1 disclosed in patent 201510732916.0
Agent unit)
By Pabuk former times benefit cloth free alkali, it is (interior that colloidal silicon dioxide, microcrystalline cellulose, carboxyrnethyl starch sodium, magnesium stearate is added
Add), lactose, be uniformly mixed.Material is added in dry granulating machine and pelletizes after mixing, device parameter are as follows: oil pressure 35-50Kg/
cm2, feeding 8Hz, tabletting 18Hz, pelletize 10Hz, and pelletize aperture 1mm.Take particle and powder after pelletizing that magnesium stearate is added (outside
Add), it mixes, capsule filling.
Comparative example 2
Pabuk former times benefit cloth composition (1000 systems are prepared according to embodiment 9 disclosed in patent 201510732916.0
Agent unit)
By Pabuk former times benefit cloth isethionate, colloidal silicon dioxide, it is sufficiently mixed.Microcrystalline cellulose is added, carboxylic first is formed sediment
Powder sodium, magnesium stearate (interior to add), lactose, are uniformly mixed.Material is added in dry granulating machine and pelletizes after mixing, device parameter
Are as follows: oil pressure 35-50Kg/cm2, feeding 8Hz, tabletting 18Hz, pelletize 10Hz, and pelletize aperture 1mm.Particle and powder after pelletizing is taken to add
Enter magnesium stearate (additional), mixes, capsule filling.
Comparative example 3
Pabuk former times benefit cloth composition (1000 systems are prepared according to embodiment 10 disclosed in patent 201510732916.0
Agent unit)
By Pabuk former times benefit cloth hydrochloride, colloidal silicon dioxide, it is sufficiently mixed.Microcrystalline cellulose, carboxyrnethyl starch sodium, hard is added
Fatty acid magnesium (interior to add), lactose, are uniformly mixed.Material is added in dry granulating machine and pelletizes after mixing, device parameter are as follows: oil pressure
35-50Kg/cm2, feeding 8Hz, tabletting 18Hz, pelletize 10Hz, and pelletize aperture 1mm.Take particle and powder after pelletizing that tristearin is added
Sour magnesium (additional) mixes, capsule filling.
Comparative example 4
(1000 preparation units)
Pabuk former times benefit cloth free alkali, colloidal silicon dioxide, microcrystalline cellulose, carboxyrnethyl starch sodium, lactose are added to mixing
Premixing 10min is carried out in machine, and magnesium stearate is added and carries out total mixing 4min, discharging is added in capsule filling machine and carries out glue
Capsule filling.
Comparative example 5
(1000 preparation units)
Pabuk former times benefit cloth free alkali, colloidal silicon dioxide, microcrystalline cellulose, carboxyrnethyl starch sodium, lactose are added to mixing
Premixing 10min is carried out in machine, and magnesium stearate is added and carries out total mixing 4min, discharging is added in capsule filling machine and carries out glue
Capsule filling, but find that the filling weight of capsule is lower than 450mg, is not achieved mark weight, and capsule content uniformity it is excessive (±
13.2%, far more than ± 7.5% as defined in Chinese Pharmacopoeia four general rules 0103 of version in 2015), lead to test failure.It may determine that grain
Diameter is too small to cause material density to reduce, and material fluidity is remarkably decreased, and causes capsule loading amount relatively low and differs greatly.
Embodiment 13
Embodiment 1-11, the made preparation of comparative example 1-4 and Pfizer Inc.'s original grind the dissolution curve ratio of reference preparation
Compared with test, concrete operations: taking this product, according to dissolution method (four general rules of Chinese Pharmacopoeia version in 2015,0,931 second method),
Using the hydrochloric acid 900ml of 0.1mol/L as dissolution medium, revolving speed is 50 turns per minute, is operated according to methods, through 5,10,15,30,45 minutes
When, solution 10ml is taken respectively, supplements blank dissolution medium 10ml after sampling immediately, and the filter membrane that via hole diameter is 0.45 μm filters, and abandons
Primary filtrate 5ml is removed, takes subsequent filtrate 1ml into 10ml volumetric flask, the hydrochloric acid solution of 0.1mol/L is used to be diluted to scale as examination
Product solution；Another precision weighs Pabuk former times benefit cloth reference substance about 14.0mg into 10ml volumetric flask, with the hydrochloric acid solution of 0.1mol/L
Scale is dissolved and be diluted to, is shaken up, precision measures 1ml into 100ml volumetric flask, is diluted to quarter with the hydrochloric acid solution of 0.1mol/L
Degree, shakes up, as reference substance solution.Above two solution is taken, according to UV-VIS spectrophotometry (Chinese Pharmacopoeia version in 2015
Four general rules 0401), trap is measured at the wavelength of 250nm, calculates accumulation dissolution rate, and dissolution data see the table below.
1 embodiment 1-11 of table, comparative example 1-4 preparation and the former dissolution curve measurement result for grinding reference preparation
The example of formulations 1-11 that it can be seen from the data shown in table prepared by the method according to the invention is in 30min,
It is almost the same with the dissolution data of reference preparation, to improve clinical test and the consistent success rate of reference preparation, reduce compatriots
Drug cost, bring benefit to the people.And according to the preparation of published prescription (comparative example 1-3) preparation in the prior art, in 30min
Dissolution rate before is considerably slower than reference preparation, because Pabuk former times benefit cloth is very small in the solubility being greater than in pH4.0 solution, medicine
The residence time of object under one's belt is 1.5~2 hours, therefore dissolution rate of the drug in stomach is very crucial, and which determine drugs
Bioavilability, dissolution rate then shortens soak time of the drug in stomach slowly, so as to influence Clinical efficacy.Separately
Outside, under same prescription and process condition, Pabuk former times benefit cloth partial size D90 is also resulted in greater than 150 μm dissolves out slack-off, dissolution data
There is notable difference with reference preparation, illustrate that partial size has larger impact to bioavilability, raw material particle size should be controlled at 50~150 μm
In range.
14 embodiment 1 of embodiment, 3,4,5,9, the accelerated test of comparative example 1,2,3 and reference preparation
It is right according to material medicine and preparation stability test direction principle (four general rules 9000 of Chinese Pharmacopoeia version in 2015)
Embodiment 1,3,4,5,9, comparative example 1,2,3 and reference preparation carry out accelerated test, by estimated commercially available back, in acceleration environment 40
It places 6 months, sampling time point 1,2,3 and June, is then detected, and grind ginseng with original under DEG C ± 2 DEG C/75%RH ± 5%RH
It is compared than preparation Ibrace, the results are shown in Table 2.
2 embodiment 1 of table, 3,4,5,9, the accelerated test result of comparative example 1,2,3 and reference preparation
It is continuous
The accelerated stability test in 6 months of embodiment 1,3,4,5,9, compared with 0 month and reference preparation, items check equal
Without significant change, illustrate that the composition has good stability, and comparative example 1,2,3 has increase in accelerated test Process Impurity content
Trend, dissolution rate has a declining tendency.
Claims (8)
1. a kind of Pabuk former times benefit cloth pharmaceutical composition, it is characterised in that: it includes Pabuk former times benefit cloth or its pharmaceutical salts and pharmacy
Upper acceptable auxiliary material, it is encapsulated after directly being mixed by ingredient in the Pabuk former times benefit cloth pharmaceutical composition to be prepared,
In, the partial size of the Pabuk former times benefit cloth or its pharmaceutical salts is 50 μm~150 μm, and the pharmaceutical salts include isethionate, salt
Hydrochlorate, sulfate or benzene sulfonate, it includes the Pabuk former times benefit cloth of weight percent 20~40% or its pharmaceutical salts and weight hundred
Divide the auxiliary material than 60%~80%, the auxiliary material includes filler, disintegrating agent, glidant and lubricant, wherein the filler
The percentage for accounting for Pabuk former times benefit cloth pharmaceutical composition total weight is 57~65%；The disintegrating agent accounts for Pabuk former times benefit cloth pharmaceutical composition
The percentage of object total weight is 3~8%；The glidant account for Pabuk former times benefit cloth pharmaceutical composition total weight percentage be 1~
4%；The percentage that the lubricant accounts for Pabuk former times benefit cloth pharmaceutical composition total weight is 0.5~4%, wherein the filler
For microcrystalline cellulose and lactose, the mass ratio of the microcrystalline cellulose and lactose is (0.5~3): 1.
2. Pabuk former times benefit cloth pharmaceutical composition according to claim 1, it is characterised in that: the microcrystalline cellulose and lactose
Mass ratio be 2:1.
3. Pabuk former times benefit cloth pharmaceutical composition according to claim 1 or 2, it is characterised in that: the disintegrating agent is selected from carboxylic
First sodium starch, crospovidone or croscarmellose sodium.
4. Pabuk former times benefit cloth pharmaceutical composition according to claim 1 or 2, it is characterised in that: the glidant is selected from two
Silica or talcum powder.
5. Pabuk former times benefit cloth pharmaceutical composition according to claim 4, it is characterised in that: the silica is colloid two
Silica.
6. Pabuk former times benefit cloth pharmaceutical composition according to claim 1 or 2, it is characterised in that: the lubricant is selected from hard
Fatty acid magnesium or sodium stearyl fumarate.
7. Pabuk former times benefit cloth preparation according to claim 1 or 2, it is characterised in that: preparation method is the following steps are included: take
Pabuk former times benefit cloth or its pharmaceutical salts are added filler, disintegrating agent, glidant and are pre-mixed, add lubrication after mixing
Agent is always mixed, until being uniformly mixed, total mix material is set capsule filling machine and carries out capsule filling, inner packing.
8. the preparation method of Pabuk former times benefit cloth preparation according to claim 1 or 2, it is characterised in that: it includes following step
It is rapid: to take Pabuk former times benefit cloth or its pharmaceutical salts, filler, disintegrating agent, glidant is added and is pre-mixed, adds after mixing
Lubricant is always mixed, until being uniformly mixed, total mix material is set capsule filling machine and carries out capsule filling, inner packing.
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| WO2022063119A1 (en) * | 2020-09-24 | 2022-03-31 | 南京济群医药科技股份有限公司 | Composition and drug of palbociclib isethionate |
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| US10449195B2 (en) | 2016-03-29 | 2019-10-22 | Shenzhen Pharmacin Co., Ltd. | Pharmaceutical formulation of palbociclib and a preparation method thereof |
| WO2019056163A1 (en) * | 2017-09-19 | 2019-03-28 | 浙江华海药业股份有限公司 | N-formyl palbociclib and preparation method therefor and use thereof, and palbociclib preparation and quality control method therefor |
| CN108066312B (en) * | 2017-12-29 | 2020-03-20 | 山东裕欣药业有限公司 | Palbociclib pharmaceutical composition and preparation method thereof |
| CN114246872B (en) * | 2020-09-24 | 2024-02-06 | 南京济群医药科技股份有限公司 | Technological method and composition for improving fluidity of isethionic acid piperazine Bai Xili |
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| CN105213322A (en) * | 2015-10-30 | 2016-01-06 | 南京正大天晴制药有限公司 | Pharmaceutical composition prepared by a kind of dry granulation process |
| WO2016030439A1 (en) * | 2014-08-28 | 2016-03-03 | Ratiopharm Gmbh | Method of producing palbociclib and pharmaceutical compositions comprising the same |
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2016
- 2016-04-21 CN CN201610250321.6A patent/CN105748435B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016030439A1 (en) * | 2014-08-28 | 2016-03-03 | Ratiopharm Gmbh | Method of producing palbociclib and pharmaceutical compositions comprising the same |
| CN105213322A (en) * | 2015-10-30 | 2016-01-06 | 南京正大天晴制药有限公司 | Pharmaceutical composition prepared by a kind of dry granulation process |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2022063119A1 (en) * | 2020-09-24 | 2022-03-31 | 南京济群医药科技股份有限公司 | Composition and drug of palbociclib isethionate |
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