CN105748435A - Palbociclib pharmaceutical composition and preparation method thereof - Google Patents
Palbociclib pharmaceutical composition and preparation method thereof Download PDFInfo
- Publication number
- CN105748435A CN105748435A CN201610250321.6A CN201610250321A CN105748435A CN 105748435 A CN105748435 A CN 105748435A CN 201610250321 A CN201610250321 A CN 201610250321A CN 105748435 A CN105748435 A CN 105748435A
- Authority
- CN
- China
- Prior art keywords
- former times
- pabuk former
- times profit
- profit cloth
- pharmaceutical composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- 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
Landscapes
- 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 a palbociclib pharmaceutical composition, comprising palbociclib or its medicinal salt and a pharmaceutically acceptable auxiliary material, wherein the palbociclib or its medicinal salt is 50-150 Mum, and the medicinal salt includes isethionates, hydrochlorides, sulfates or benzene sulfonates.Direct mixing and capsuling process of raw and auxiliary materials is used for the pharmaceutical composition provided herein, the biological availability is high, product quality stability is good, the technical process is easy to control, inter-batch reproducibility is good, and the composition is easy to industrialize.
Description
Technical field
The invention belongs to technical field of medicine, relate to the pharmaceutical composition of a kind of Pabuk former times profit cloth, more particularly to Pabuk former times profit cloth pharmaceutical composition prepared by a kind of direct hybrid technique and preparation method thereof.
Background technology
Breast carcinoma is one of modal malignant tumor of women, and sickness rate accounts for the 7%～10% of the various malignant tumor of whole body, is only second to uterus carcinoma, it has also become threaten the Etiological of WomanHealth.Its morbidity is often relevant with heredity, and the women's sickness rate before and after 40～60 years old menopause is higher.It is that one usually occurs in breast glandular epithelium tissue, having a strong impact on one of physically and mentally healthy even life-threatening malignant tumor of women, in recent years, its sickness rate is in the trend risen year by year, having leapt to the first place of female malignant, the sickness rate of China has exceeded world average level.
The whole world there are about 1,200,000 women every year and suffers from breast cancer, and 500,000 people die from breast carcinoma.In the developed country such as West Europe, North America, breast cancer incidence accounts for female malignant first place.2010, Chinese population association announced " China mastopathy investigation report ", China main cities over 10 years breast cancer incidence increase 37%；Sickness rate is just with the speed increase of annual 3%.2003-2009 years, in China city, the mortality rate of breast carcinoma increased 38.91%.In patient with breast cancer, the ratio of ErbB-2 (HER2) breast cancer patients with positive accounts for 20%, and HER2 negative patient accounts for 80%.HER2 Breast Cancer Patients with Negative Axillary relative populations is more, and progress is slow.
Pabuk former times profit cloth (English name: Palbociclib), structural formula is as follows:
Formula I.
Pabuk former times profit cloth is the inhibitor of a kind of cell cycle protein dependent kinase (CDK) 4 and 6.Cyclin D1 and CDK4/6 is the downstream causing cell proliferation signals path.In vitro, Pabuk former times profit cloth enters the S phase from the cell cycle G1 phase thus the cell proliferation of the estrogen receptor that slows down (ER)-positive breast cancer cells strain by blocking cell.It is compared to independent medication, Pabuk former times profit cloth associating estrogen antagonist treatment breast carcinoma cell strain, cause that its Retinoblastoma Protein (Rb) phosphorylation slows down, result E2F expresses and signal transmission is slowed down and growth inhibited is accelerated.In vitro, the associating estrogen antagonist treatment ER-positive breast cancer cells strain of Pabuk former times profit cloth causes that its cell ageing is accelerated, and can last up to 6 days after drug withdrawal.Multinomial In vivo study shows, combines letrozole with Pabuk former times profit cloth and treats the ER-positive breast cancer heteroplastic transplantation model in a kind of patient source, is compared to independent medication, can accelerate to suppress the transmission of Rb phosphorylation, downstream signal and tumor growth.
Pfizer Products Inc and domestic minority enterprise have applied for the synthetic method patent of this medicine in China, Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd has applied for formulation patent, name is called pharmaceutical composition prepared by a kind of dry granulation process, application number 201510732916.0, this patent adopts the preparation technology of dry granulation, particle diameter mainly due to crude drug is too little, specific surface area is too big, raw material large percentage in prescription, about 28%, crude drug physical state is caused to affect bigger on the material properties of whole prescription mixture, it is greatly reduced the mobility of prescription mixture material, therefore employing dry method granulation processes.But there is many shortcomings in dry method granulation processes at present: first China's dry granulating machine manufacturing firm is a lot; but stabilization of equipment performance is compared more poor; fault rate is higher, and subject matter includes that roll is bad, leaks, roll dislocation, dust-producing amount is big, yield rate is low, difficult cleaning, pressure transient etc.；Secondly equipment price is expensive；It is important that volume of production is little, first-time qualification rate is low, and the granule prepared is irregular, and its mobility of particle is good not as wet granulation.The present invention, by controlling the recrystallizing technology of crude drug, obtains that size is moderate, the good crude drug of mobility, uses this crude drug and selects the good adjuvant of mobility, and can reach direct mixing supplementary material can the effect of fill capsule.
Formulation patent Pabuk former times profit cloth intra-gastric floating tablet of Shanghai Lu Yuan Pharmaceutical Technology Co., Ltd application and preparation method thereof, application number is 201510162791.2, this invention provides a kind of high bioavailability, in slow releasing trend, effectively reducing the Pabuk former times profit cloth intra-gastric floating tablet of medication total amount, obtained tablet can keep the flotation time of more than 10 hours in gastric juice.The former medicine that grinds of Pfizer listing is quick-release capsules agent, dissolution test in the 0.1mol/L hydrochloric acid solution of in-vitro simulated gastric juice shows 15 minutes mistakes and leachable more than 95%, gastric emptying time is 1.5 ~ 2 hours, ensure that medicine has time enough to absorb at gastric, clinical trial simultaneously confirms that therapeutic effect is very good, illustrates that the Pabuk former times fabric one-tenth capsule of profit is proper.Additionally, stomach floating preparation design success or failure it is critical only that whether it can reach intended floating effect under one's belt, gastric transit time can be extended, if floating state can not be become, can only being equivalent to a common sustained-release matrix tablets, owing to Pabuk former times profit cloth is when pH value is more than 4.0, dissolubility significantly reduces, like this instead result in medicine can not be fully absorbed, lessen the curative effect.
Summary of the invention
The technical problem to be solved in the present invention is to provide one and prepares simple, the Pabuk former times profit cloth pharmaceutical composition that constant product quality is good.
For solving above-mentioned technical problem, the technical solution used in the present invention is:
A kind of Pabuk former times profit cloth pharmaceutical composition, it comprises Pabuk former times profit cloth or its pharmaceutical salts and pharmaceutically acceptable adjuvant, wherein, the particle diameter of described Pabuk former times profit cloth or its pharmaceutical salts is 50 μm ~ 150 μm, and described pharmaceutical salts includes isethionate, hydrochlorate, sulfate or benzene sulfonate.
Particle diameter mentioned by the present invention all represents with D90, well known to those skilled in the art, and D90 refers to that drug particle cumulative particle sizes distribution number reaches particle diameter corresponding when 90%.
Further, Pabuk former times profit cloth pharmaceutical composition of the present invention, wherein, comprise the Pabuk former times profit cloth of percentage by weight 20 ~ 40% or the adjuvant of its pharmaceutical salts and percentage by weight 60% ~ 80%, described adjuvant includes filler, disintegrating agent, fluidizer and lubricant.
Further, Pabuk former times profit cloth pharmaceutical composition of the present invention, wherein, it is 45 ~ 70% that described filler accounts for the percentage ratio of Pabuk former times profit cloth pharmaceutical composition gross weight；It is 3 ~ 8% that described disintegrating agent accounts for the percentage ratio of Pabuk former times profit cloth pharmaceutical composition gross weight；It is 1 ~ 4% that described fluidizer accounts for the percentage ratio of Pabuk former times profit cloth pharmaceutical composition gross weight；It is 0.5 ~ 4% that described lubricant accounts for the percentage ratio of Pabuk former times profit cloth pharmaceutical composition gross weight.
It is further preferred that Pabuk former times profit cloth pharmaceutical composition of the present invention, wherein, it is 57 ~ 65% that described filler accounts for the percentage ratio of Pabuk former times profit cloth pharmaceutical composition gross weight.
Further, Pabuk former times profit cloth pharmaceutical composition of the present invention, wherein, described filler is microcrystalline Cellulose and lactose, and wherein, the mass ratio of described microcrystalline Cellulose and lactose is (0.5 ~ 3): 1.
It is further preferred that Pabuk former times profit cloth pharmaceutical composition of the present invention, wherein, described filler is microcrystalline Cellulose and lactose, and wherein, the mass ratio of described microcrystalline Cellulose and lactose is 2:1.
Further, Pabuk former times profit cloth pharmaceutical composition of the present invention, wherein, described disintegrating agent is selected from carboxymethylstach sodium, polyvinylpolypyrrolidone or cross-linking sodium carboxymethyl cellulose, it is preferable that carboxymethylstach sodium.
Further, Pabuk former times profit cloth pharmaceutical composition of the present invention, wherein, described fluidizer is selected from silica sol, silicon dioxide or Pulvis Talci, it is preferable that silica sol or silicon dioxide.
Further, Pabuk former times profit cloth pharmaceutical composition of the present invention, wherein, described lubricant is selected from magnesium stearate or sodium stearyl fumarate, it is preferable that magnesium stearate.
The present invention also provides for a kind of Pabuk former times profit cloth preparation.
A kind of Pabuk former times profit cloth preparation prepared by Pabuk former times profit cloth pharmaceutical composition of the present invention, it is encapsulated after directly being mixed by described Pabuk former times profit cloth pharmaceutical composition is prepared from.
Further, Pabuk former times profit cloth preparation of the present invention, wherein, described preparation method comprises the following steps: take Pabuk former times profit cloth or its pharmaceutical salts, addition filler, disintegrating agent, fluidizer carry out premixing, add lubricant and always mix after mix homogeneously, until mix homogeneously, always mixed material is put capsule filling machine and carries out capsule filling, inner packing.
Another object of the present invention is to, it is provided that the preparation method of described Pabuk former times profit cloth preparation.
The preparation method of Pabuk former times profit cloth preparation of the present invention, it comprises the steps:
Taking Pabuk former times profit cloth or its pharmaceutical salts, addition filler, disintegrating agent, fluidizer carry out premixing, add lubricant and always mix after mix homogeneously, until mix homogeneously, always mixed material is put capsule filling machine and carries out capsule filling, inner packing.
Adopt and have the beneficial effects that produced by technique scheme:
The present inventor finds by conventional method of granulating in the development process of Pabuk former times profit cloth preparation; whether dry granulation or wet granulation; all it is unable to reach and grinds quite or dissolution release profiles faster with former, thus cannot obtain and the former product grinding same or higher bioavailability.Owing to Pabuk former times profit cloth is very little more than the dissolubility in pH4.0 solution, and the medicine time of staying under one's belt is shorter, therefore medicine is very crucial at the dissolution rate of gastric, which determine the bioavailability of medicine, but prior art such as CN201510732916.0 with former grind reference preparation compared with, dissolution before 30min is considerably slower than reference preparation, and dissolution rate then shortens the medicine soak time at gastric slowly, consequently, it is possible to affect Clinical efficacy.
The present inventor has been surprisingly found that in test; by controlling Pabuk former times profit cloth raw material particle size size, in conjunction with adopting the good adjuvant of mobility, and screen rational prescription proportioning; supplementary material is adopted directly to mix encapsulated technique; the preparation suitable with Yuan Yan company reference preparation dissolved corrosion can be obtained, and, compared with dry granulation or wet granulation; technical process is easily controllable; constant product quality is good, favorable reproducibility between batch, it is easy to industrialization.The patient taking this product is generally long-term prescription, have selected most widely used general, most popular capsule formulation, it is easy to accept for patient.The present invention adopts and grinds consistent dosage form capsule with former, it is ensured that the effectiveness of clinical application and safety.
Detailed description of the invention
With detailed description of the invention, the present invention is further detailed explanation below.Following example are only used for explaining technical solution of the present invention, but not as a limitation of the invention.
Embodiment 1(1000 preparation unit)
Pabuk former times profit cloth free alkali, silica sol, microcrystalline Cellulose, carboxymethylstach sodium, lactose are joined and carry out premixing 10min in mixer, adds magnesium stearate and always mix 4min, discharging, join and capsule filling machine carries out capsule filling.
Embodiment 2(1000 preparation unit)
Pabuk former times profit cloth free alkali, silica sol, microcrystalline Cellulose, carboxymethylstach sodium, lactose are joined and carry out premixing 12min in mixer, adds magnesium stearate and always mix 5min, discharging, join and capsule filling machine carries out capsule filling.
Embodiment 3(1000 preparation unit)
Pabuk former times profit cloth free alkali, silica sol, microcrystalline Cellulose, carboxymethylstach sodium, lactose are joined and carry out premixing 12min in mixer, adds magnesium stearate and always mix 6min, discharging, join and capsule filling machine carries out capsule filling.
Embodiment 4(1000 preparation unit)
Pabuk former times profit cloth free alkali, silica sol, microcrystalline Cellulose, carboxymethylstach sodium, lactose are joined and carry out premixing 15min in mixer, adds magnesium stearate and always mix 4min, discharging, join and capsule filling machine carries out capsule filling.
Embodiment 5(1000 preparation unit)
Pabuk former times profit cloth isethionate, silica sol, microcrystalline Cellulose, carboxymethylstach sodium, lactose are joined and carry out premixing 12min in mixer, add magnesium stearate and always mix 4min, discharging, joins and carries out capsule filling in capsule filling machine.
Embodiment 6(1000 preparation unit)
Pabuk former times profit cloth free alkali, silica sol, microcrystalline Cellulose, carboxymethylstach sodium, lactose are joined and carry out premixing 12min in mixer, adds magnesium stearate and always mix 4min, discharging, join and capsule filling machine carries out capsule filling.
Embodiment 7(1000 preparation unit)
Pabuk former times profit cloth free alkali, silica sol, microcrystalline Cellulose, carboxymethylstach sodium, lactose are joined and carry out premixing 12min in mixer, adds magnesium stearate and always mix 4min, discharging, join and capsule filling machine carries out capsule filling.
Embodiment 8(1000 preparation unit)
Pabuk former times profit cloth free alkali, silica sol, microcrystalline Cellulose, carboxymethylstach sodium, lactose are joined and carry out premixing 12min in mixer, adds magnesium stearate and always mix 4min, discharging, join and capsule filling machine carries out capsule filling.
Embodiment 9(1000 preparation unit)
Pabuk former times profit cloth hydrochlorate, silica sol, microcrystalline Cellulose, carboxymethylstach sodium, lactose are joined and carry out premixing 12min in mixer, adds magnesium stearate and always mix 6min, discharging, join and capsule filling machine carries out capsule filling.
Embodiment 10(1000 preparation unit)
Pabuk former times profit cloth free alkali, silica sol, microcrystalline Cellulose, carboxymethylstach sodium, lactose are joined and carry out premixing 10min in mixer, adds magnesium stearate and always mix 4min, discharging, join and capsule filling machine carries out capsule filling.
Embodiment 11(1000 preparation unit)
Pabuk former times profit cloth free alkali, silica sol, microcrystalline Cellulose, carboxymethylstach sodium, lactose are joined and carry out premixing 10min in mixer, adds magnesium stearate and always mix 4min, discharging, join and capsule filling machine carries out capsule filling.
Comparative example 1
Pabuk former times profit cloth compositions (1000 preparation unit) is prepared according to the embodiment 1 disclosed in patent 201510732916.0
By Pabuk former times profit cloth free alkali, add silica sol, microcrystalline Cellulose, carboxymethylstach sodium, magnesium stearate (inside adding), lactose, mix homogeneously.Granulating in material addition dry granulating machine after mixing, device parameter is: oil pressure 35-50Kg/cm2, feeding 8Hz, tabletting 18Hz, granulation 10Hz, granulation aperture 1mm.After taking granulation, granule and powder add magnesium stearate (additional), mixing, and capsule is filled.
Comparative example 2
Pabuk former times profit cloth compositions (1000 preparation unit) is prepared according to the embodiment 9 disclosed in patent 201510732916.0
By Pabuk former times profit cloth isethionate, silica sol, it is sufficiently mixed.Add microcrystalline Cellulose, carboxymethylstach sodium, magnesium stearate (inside adding), lactose, mix homogeneously.Granulating in material addition dry granulating machine after mixing, device parameter is: oil pressure 35-50Kg/cm2, feeding 8Hz, tabletting 18Hz, granulation 10Hz, granulation aperture 1mm.After taking granulation, granule and powder add magnesium stearate (additional), mixing, and capsule is filled.
Comparative example 3
Pabuk former times profit cloth compositions (1000 preparation unit) is prepared according to the embodiment 10 disclosed in patent 201510732916.0
By Pabuk former times profit cloth hydrochlorate, silica sol, it is sufficiently mixed.Add microcrystalline Cellulose, carboxymethylstach sodium, magnesium stearate (inside adding), lactose, mix homogeneously.Granulating in material addition dry granulating machine after mixing, device parameter is: oil pressure 35-50Kg/cm2, feeding 8Hz, tabletting 18Hz, granulation 10Hz, granulation aperture 1mm.After taking granulation, granule and powder add magnesium stearate (additional), mixing, and capsule is filled.
Comparative example 4
(1000 preparation unit)
Pabuk former times profit cloth free alkali, silica sol, microcrystalline Cellulose, carboxymethylstach sodium, lactose are joined and carry out premixing 10min in mixer, adds magnesium stearate and always mix 4min, discharging, join and capsule filling machine carries out capsule filling.
Comparative example 5
(1000 preparation unit)
Pabuk former times profit cloth free alkali, silica sol, microcrystalline Cellulose, carboxymethylstach sodium, lactose are joined and carry out premixing 10min in mixer, add magnesium stearate and always mix 4min, discharging, join and capsule filling machine carries out capsule filling, but find that the filling weight of capsule is lower than 450mg, does not reach sign weight, and capsule content uniformity excessive (± 13.2%, exceed well over four general rules 0103 regulations of Chinese Pharmacopoeia version in 2015 ± 7.5%), cause test failure.May determine that particle diameter is too little and cause that material density reduces, and material fluidity is remarkably decreased, cause that capsule loading amount is on the low side and differs greatly.
Embodiment 13
Embodiment 1-11, the made preparation of comparative example 1-4 and Pfizer Inc. former grind reference preparation stripping curve comparative test, concrete operations: take this product, according to dissolution method (Chinese Pharmacopoeia version four general rules 0,931 second method in 2015), with the hydrochloric acid 900ml of 0.1mol/L for dissolution medium, rotating speed is 50 turns per minute, operate in accordance with the law, through 5, 10, 15, 30, when 45 minutes, take solution 10ml respectively, blank dissolution medium 10ml is supplemented immediately after sampling, the filter membrane that via hole diameter is 0.45 μm filters, discard just filtrate 5ml, take in subsequent filtrate 1ml to 10ml volumetric flask, it is diluted to scale as need testing solution with the hydrochloric acid solution of 0.1mol/L；Another precision weighs Pabuk former times profit cloth reference substance and is about in 14.0mg to 10ml volumetric flask, dissolves with the hydrochloric acid solution of 0.1mol/L and is diluted to scale, shaking up, precision measures in 1ml to 100ml volumetric flask, it is diluted to scale with the hydrochloric acid solution of 0.1mol/L, shakes up, as reference substance solution.Taking above two solution, according to ultraviolet visible spectrophotometry (Chinese Pharmacopoeia four general rules 0401 of version in 2015), measure trap in the wavelength place of 250nm, calculate accumulation dissolution, dissolution data are shown in following table.
Table 1 embodiment 1-11, comparative example 1-4 preparation and the former stripping curve measurement result grinding reference preparation
Data shown in table can be seen that, the example of formulations 1-11 prepared according to the method for the present invention is in 30min, all basically identical with the dissolution data of reference preparation, thus improving the success rate that clinical trial is consistent with reference preparation, reduce the drug cost of compatriots, bring benefit to the people.And according to preparation prepared by prescription (comparative example 1-3) published in prior art, dissolution before 30min is considerably slower than reference preparation, because Pabuk former times profit cloth is very little more than the dissolubility in pH4.0 solution, the medicine time of staying under one's belt is 1.5～2 hours, therefore medicine is very crucial at the dissolution rate of gastric, which determining the bioavailability of medicine, dissolution rate then shortens the medicine soak time at gastric slowly, consequently, it is possible to affect Clinical efficacy.Additionally, under same prescription and process condition, it is slack-off that Pabuk former times profit cloth particle diameter D90 also results in dissolution more than 150 μm, and dissolution data and reference preparation have notable difference, illustrate that bioavailability is had considerable influence by particle diameter, raw material particle size should be controlled in 50～150 μ m.
Embodiment 14 embodiment 1,3,4,5,9, the accelerated test of comparative example 1,2,3 and reference preparation
According to material medicine and preparation stability test direction principle (Chinese Pharmacopoeia four general rules 9000 of version in 2015) to embodiment 1,3,4,5,9, comparative example 1,2,3 and reference preparation be accelerated test, by estimating commercially available back, place 6 months under acceleration environment 40 DEG C ± 2 DEG C/75%RH ± 5%RH, sampling time point is 1,2,3 and June, then detect, and compare with the former reference preparation Ibrace that grinds, result is in Table 2.
Table 2 embodiment 1,3,4,5,9, the accelerated test result of comparative example 1,2,3 and reference preparation
Continuous
Embodiment 1,3,4,5,9 stability test of accelerated 6 months, comparing with 0 month and reference preparation, every inspection has no significant change, and illustrates that described compositions has good stability, and comparative example 1,2,3 has the trend of increase at accelerated test Process Impurity content, dissolution has a declining tendency.
Claims (12)
1. a Pabuk former times profit cloth pharmaceutical composition, it is characterized in that: it comprises Pabuk former times profit cloth or its pharmaceutical salts and pharmaceutically acceptable adjuvant, wherein, the particle diameter of described Pabuk former times profit cloth or its pharmaceutical salts is 50 μm ~ 150 μm, and described pharmaceutical salts includes isethionate, hydrochlorate, sulfate or benzene sulfonate.
2. Pabuk former times profit cloth pharmaceutical composition according to claim 1, it is characterized in that: Pabuk former times profit cloth that it comprises percentage by weight 20 ~ 40% or the adjuvant of its pharmaceutical salts and percentage by weight 60% ~ 80%, described adjuvant includes filler, disintegrating agent, fluidizer and lubricant.
3. Pabuk former times profit cloth pharmaceutical composition according to claim 2, it is characterised in that: it is 45 ~ 70% that described filler accounts for the percentage ratio of Pabuk former times profit cloth pharmaceutical composition gross weight；It is 3 ~ 8% that described disintegrating agent accounts for the percentage ratio of Pabuk former times profit cloth pharmaceutical composition gross weight；It is 1 ~ 4% that described fluidizer accounts for the percentage ratio of Pabuk former times profit cloth pharmaceutical composition gross weight；It is 0.5 ~ 4% that described lubricant accounts for the percentage ratio of Pabuk former times profit cloth pharmaceutical composition gross weight.
4. Pabuk former times profit cloth pharmaceutical composition according to claim 3, it is characterised in that: it is 57 ~ 65% that described filler accounts for the percentage ratio of Pabuk former times profit cloth pharmaceutical composition gross weight.
5. Pabuk former times profit cloth pharmaceutical composition according to claim 3, it is characterised in that: described filler is microcrystalline Cellulose and lactose, and wherein, the mass ratio of described microcrystalline Cellulose and lactose is (0.5 ~ 3): 1.
6. Pabuk former times profit cloth pharmaceutical composition according to claim 5, it is characterised in that: the mass ratio of described microcrystalline Cellulose and lactose is 2:1.
7. Pabuk former times profit cloth pharmaceutical composition according to claim 4, it is characterised in that: described disintegrating agent is selected from carboxymethylstach sodium, polyvinylpolypyrrolidone or cross-linking sodium carboxymethyl cellulose.
8. Pabuk former times profit cloth pharmaceutical composition according to claim 4, it is characterised in that: described fluidizer is selected from silica sol, silicon dioxide or Pulvis Talci.
9. Pabuk former times profit cloth pharmaceutical composition according to claim 4, it is characterised in that: described lubricant is selected from magnesium stearate or sodium stearyl fumarate.
10. the Pabuk former times profit cloth preparation that prepared by the Pabuk former times profit cloth pharmaceutical composition according to any one of claim 1 ~ 9, it is characterised in that: it is encapsulated after directly being mixed by described Pabuk former times profit cloth pharmaceutical composition is prepared from.
11. Pabuk former times profit cloth preparation according to claim 10, it is characterized in that: described preparation method comprises the following steps: take Pabuk former times profit cloth or its pharmaceutical salts, addition filler, disintegrating agent, fluidizer carry out premixing, add lubricant after mix homogeneously always to mix, until mix homogeneously, always mixed material is put capsule filling machine and carries out capsule filling, inner packing.
12. the preparation method of Pabuk former times profit cloth preparation according to claim 10, it is characterized in that: it comprises the steps: to take Pabuk former times profit cloth or its pharmaceutical salts, addition filler, disintegrating agent, fluidizer carry out premixing, add lubricant after mix homogeneously always to mix, until mix homogeneously, always mixed material is put capsule filling machine and carries out capsule filling, inner packing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610250321.6A CN105748435B (en) | 2016-04-21 | 2016-04-21 | A kind of Pabuk former times benefit cloth pharmaceutical composition and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610250321.6A CN105748435B (en) | 2016-04-21 | 2016-04-21 | A kind of Pabuk former times benefit cloth pharmaceutical composition and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105748435A true CN105748435A (en) | 2016-07-13 |
| CN105748435B CN105748435B (en) | 2019-03-29 |
Family
ID=56324657
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610250321.6A Active CN105748435B (en) | 2016-04-21 | 2016-04-21 | A kind of Pabuk former times benefit cloth pharmaceutical composition and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105748435B (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108066312A (en) * | 2017-12-29 | 2018-05-25 | 山东裕欣药业有限公司 | A kind of Pa Boxini pharmaceutical compositions and 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 |
| CN113750063A (en) * | 2021-09-16 | 2021-12-07 | 江苏食品药品职业技术学院 | Solid preparation of piperazine isethionate cetirizine and preparation method thereof |
| CN114246841A (en) * | 2020-09-24 | 2022-03-29 | 南京济群医药科技股份有限公司 | Composition and medicine of piperazine isethionate and quinapride |
| WO2022062096A1 (en) * | 2020-09-24 | 2022-03-31 | 南京济群医药科技股份有限公司 | Process method for improving fluidity of palbociclib isethionate and composition |
| US11464779B2 (en) | 2016-03-29 | 2022-10-11 | Shenzhen Pharmacin Co., Ltd. | Pharmaceutical formulation of palbociclib and a preparation method thereof |
| US11471418B2 (en) | 2020-09-29 | 2022-10-18 | Shenzhen Pharmacin Co., Ltd. | Pharmaceutical compositions of amorphous solid dispersions and methods of preparation thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
-
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 (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11464779B2 (en) | 2016-03-29 | 2022-10-11 | 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 |
| CN110997666A (en) * | 2017-09-19 | 2020-04-10 | 浙江华海药业股份有限公司 | N-formyl palbociclib, preparation method and application thereof, palbociclib preparation and quality control method thereof |
| CN108066312A (en) * | 2017-12-29 | 2018-05-25 | 山东裕欣药业有限公司 | A kind of Pa Boxini pharmaceutical compositions and preparation method thereof |
| CN114246841A (en) * | 2020-09-24 | 2022-03-29 | 南京济群医药科技股份有限公司 | Composition and medicine of piperazine isethionate and quinapride |
| WO2022062096A1 (en) * | 2020-09-24 | 2022-03-31 | 南京济群医药科技股份有限公司 | Process method for improving fluidity of palbociclib isethionate and composition |
| CN114246841B (en) * | 2020-09-24 | 2024-02-02 | 南京济群医药科技股份有限公司 | Composition and medicine of isethionic acid piperdine Bai Xi |
| US11471418B2 (en) | 2020-09-29 | 2022-10-18 | Shenzhen Pharmacin Co., Ltd. | Pharmaceutical compositions of amorphous solid dispersions and methods of preparation thereof |
| CN113750063A (en) * | 2021-09-16 | 2021-12-07 | 江苏食品药品职业技术学院 | Solid preparation of piperazine isethionate cetirizine and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105748435B (en) | 2019-03-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105748435A (en) | Palbociclib pharmaceutical composition and preparation method thereof | |
| SA517390473B1 (en) | Solid dosage forms of palbociclib | |
| CN108697803A (en) | The pharmaceutical composition of transmucosal administration | |
| CN105213322A (en) | Pharmaceutical composition prepared by a kind of dry granulation process | |
| CN106667952A (en) | Palbociclib pharmaceutical composition and preparation method thereof | |
| CN104586804B (en) | A kind of preparation method of the Letrozole piece of good stability | |
| CN108066312A (en) | A kind of Pa Boxini pharmaceutical compositions and preparation method thereof | |
| CN110179796B (en) | Benzofuran derivative composition and preparation method thereof | |
| WO2013189305A1 (en) | Valsartan-amlodipine compound solid preparation and preparation method therefor | |
| WO2014075583A1 (en) | Stable oral solid drug composition of abiraterone and preparation method therefor | |
| CN112190583B (en) | Levatinib pharmaceutical composition and preparation method thereof | |
| CN106456640A (en) | Ceritinib formulation | |
| CN110934848B (en) | Telmisartan capsule and preparation method thereof | |
| WO2022062096A1 (en) | Process method for improving fluidity of palbociclib isethionate and composition | |
| CN104415034A (en) | Imidafenacin pharmaceutical composition and preparation method thereof | |
| CN110960501A (en) | Norfloxacin capsule and preparation method thereof | |
| CN102370629B (en) | Entecavir liquid capsule and preparation method thereof | |
| CN106562968A (en) | Pharmaceutical composition containing tamsulosin hydrochloride and solifenacin succinate | |
| CN102772377B (en) | A kind of ultra micro pulverizes the preparation method of levonorgestrel altogether | |
| CN113134007B (en) | Abiraterone acetate oral preparation and preparation method thereof | |
| CN105078913B (en) | A kind of Irbesartan Tablets and preparation method thereof | |
| WO2022063119A1 (en) | Composition and drug of palbociclib isethionate | |
| CN109925288A (en) | A kind of glucocorticoid medicine tablet and preparation method thereof | |
| CN104644558A (en) | Solid dispersion of cilnidipine and preparation method thereof | |
| CN101780054A (en) | Compound sustained-release preparation and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information | ||
| CB02 | Change of applicant information |
Address after: 050035 Building No. 3, A District, No. 313, Fang billion science park, Yuhua District, Shijiazhuang, Hebei Applicant after: SHIJIAZHUANG HAIRUI PHARMACEUTICAL TECHNOLOGY CO., LTD. Address before: 050011 room 420, room 4, Hebei University Of Science and Technology, 70 Yuhua East Road, Shijiazhuang, Hebei Applicant before: SHIJIAZHUANG HAIRUI PHARMACEUTICAL TECHNOLOGY CO., LTD. |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20200617 Address after: 050011 3-706 Dongcheng International Business Plaza, No. 98, Huanghe Avenue, hi tech Zone, Shijiazhuang City, Hebei Province Patentee after: Hebei Zeyun Biomedical Technology Co., Ltd Address before: 050035 Building No. 3, A District, No. 313, Fang billion science park, Yuhua District, Shijiazhuang, Hebei Patentee before: SHIJIAZHUANG HAIRUI PHARMACEUTICAL TECHNOLOGY Co.,Ltd. |
|
| CP02 | Change in the address of a patent holder | ||
| CP02 | Change in the address of a patent holder |
Address after: 050090 room 2711, unit 1, block C, shangfenghui building, No. 218, Youyi South Street, Qiaoxi District, Shijiazhuang City, Hebei Province Patentee after: Hebei Zeyun Biomedical Technology Co., Ltd Address before: 050011 3-706, Dongcheng International Business Plaza, 98 Huanghe Avenue, high tech Zone, Shijiazhuang City, Hebei Province Patentee before: Hebei Zeyun Biomedical Technology Co., Ltd |