CN104546745A - Tablet combination of abiraterone acetate and preparation method of tablet combination - Google Patents
Tablet combination of abiraterone acetate and preparation method of tablet combination Download PDFInfo
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- CN104546745A CN104546745A CN201310478345.3A CN201310478345A CN104546745A CN 104546745 A CN104546745 A CN 104546745A CN 201310478345 A CN201310478345 A CN 201310478345A CN 104546745 A CN104546745 A CN 104546745A
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- abiraterone acetate
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Abstract
The invention discloses a tablet combination of abiraterone acetate and a preparation method of the tablet combination. The tablet combination comprises an active component, namely abiraterone acetate micropowder, and auxiliary components, namely a filler, a surfactant, an adhesive, a disintegrating agent, a flow aid and a lubricating agent, wherein the particle diameter of the abiraterone acetate micropowder is as follows: D90 is 5-60 microns and D50 is 3-15 microns.
Description
Technical field
The invention belongs to medical art, be specifically related to a kind of Abiraterone acetate preparation compositions and preparation technology thereof.
Background technology
Abiraterone acetate is a kind of oral prodrug thing, and de-acetyl changes into active component abiraterone in vivo, can suppress the key enzyme CYP17 of synthetic androgen in prostata tissue, is mainly used in treating advanced prostate cancer or breast carcinoma etc.Abiraterone acetate is soluble in organic solvent as oxolane, dichloromethane, alcohols; But water-soluble hardly under the condition of pH2 ~ 12, be slightly soluble in the hydrochloric acid of 0.1N, BCS classification belongs to IV class (low dissolving, hypotonicity).
There is polymorphic in Abiraterone acetate, Chinese patent CN200910189173.1 discloses its A, B, C, the preparation method of form D and character, also individually discloses the form being called crystal form E and I crystal being different from above-mentioned four kinds of crystal formations in addition at patent CN201110299046.4 and CN201110338041.8.But above-mentioned no matter that crystal formation, all cannot meet the dissolubility required by preparation and dissolution.Therefore, raising drug solubility and dissolution rate are the keys of this drug development.
According to pharmaceutics Noyes-Whitney equation, it is the effective ways improving insoluble drug dissolution characteristic that the particle diameter of pulverizing reduction medicine increases drug-eluting area, namely usually alleged micronization technology.According to material properties, reaching micronized object can be achieved by ball mill or comminution by gas stream.
Publication No. CN102743393A(mono-kind is containing the pharmaceutical composition of Abiraterone acetate and preparation technology) application for a patent for invention mention Abiraterone acetate and hydrophilicity condiment be about 0.1-50 μm of wish improve stripping as starch, pregelatinized Starch, mannitol, lactose, maltose, glucose etc. are crushed to particle diameter altogether.Method as pressed CN102743393A is implemented, although control the particle diameter of common ground product, is difficult to monitor the particle diameter of raw material and define accurately, is unfavorable for the quality control of preparation.The shortcoming pulverized altogether is also the handled thing doses significantly increasing pulverizing process, economically consider it is also unworthy, and the loss amount of principal agent and adjuvant or system residual also may be different in crushing process, this will cause feeding deviation, and prescription forms and changes.
Summary of the invention
An object of the present invention is to provide a kind of Abiraterone acetate oral tablet, comprise the component of following weight proportion:
Wherein, described Abiraterone acetate powder compounds particle diameter be 5<D
90<60 μm and 3<D
50<15 μm.
Particularly, described filler comprises lactose and microcrystalline Cellulose, and the weight proportion of lactose and microcrystalline Cellulose is 1:1-3:1.The mobility of the medicine after general micronization processes and compressibility are all poor, for these physical imperfections making up raw material should have lactose and the microcrystalline Cellulose model of good fluidity and compressibility by prioritizing selection.Such as, lactose can select vertical compression lactose, Lactis Anhydrous, spray-dried lactose etc.In the present invention, because contained medication amount is higher, the amount of filler lactose and microcrystalline Cellulose is subject to certain restrictions, in unit formulation their amount can be based on sheet heavy 55% or less, more especially about 50% or less.The content of preferred lactose and microcrystalline Cellulose be based on sheet heavy 40% to 55%.
Lactose and microcrystalline Cellulose consumption proportion to preparation nature also important, the more particularly impact of the consumption proportion of granulation sections lactose and microcrystalline Cellulose.These impacts include but not limited to following aspect: graininess (such as fine powder amount, frangible degree, hardness), and viscosity when compressibility, friability, granulation and wetting agent are uniformly dispersed degree, the tablet moisture absorption etc.Applicant finds, the ratio of lactose should be greater than or at least equal microcrystalline Cellulose, and the ratio of such as lactose and microcrystalline Cellulose can be 1:1 or 2:1 or 3:1 or larger.This is because lactose is higher relative to the ratio of microcrystalline Cellulose, and pellet hardness also will improve, and compressibility during preparation, mobility etc. also significantly improve.On the contrary, if the ratio of microcrystalline Cellulose is higher relative to lactose, then the frangible not molding of granule.But for the present invention, the ratio of lactose is also not more high better, in fact between lactose and microcrystalline Cellulose combination, there is complementary effect, too high galactose ratio improves making the friability of preparation, wear-resisting impact resistant degradation, the content at this moment suitably improving microcrystalline Cellulose then can reduce friability.For obtaining comprehensive gratifying result, the preferred 1:1 to 3:1 of ratio of lactose and microcrystalline Cellulose, specifically 1.5:1 to 2:1.
Described surfactant is sodium lauryl sulphate.For the present invention, Abiraterone acetate is extremely hydrophobic, is not easy and hydrophilic adjuvant, and as the wet adhesive such as filler (microcrystalline Cellulose and lactose), binding agent, disintegrating agent, the loose particles made is frangible, and the sheet disintegrate not containing sodium lauryl sulphate is rapid.The effect of sodium lauryl sulphate in prescription added makes medicine easily wetted, a small amount of medicine dissolution out played the effect of self adhesive simultaneously, makes powder granulation better and granule has certain degree of hardness.So determine that the consumption of sodium lauryl sulphate in prescription is with graininess, disintegrate speed is leading indicator.According to the present invention, in unit formulation the consumption of sodium lauryl sulphate can be based on sheet heavy 6% or less, more especially about 4% or less.The content of preferably sodium dodecyl sulfate is 2% to 6%, specifically 3% to 5%, most preferably 4%.
In the present invention, selectable binding agent includes but not limited to: polyvidone, HPMC, HPC, starch or used in combination, preferred PVP K30 or K90.About the use of binding agent, can be that dry powder adds or with slurryly adds two kinds of modes, they have respective pluses and minuses.For the present invention, dry powder adds more excellent, because the viscosity of soft material is comparatively large, the mode added with slurry is unfavorable for being uniformly distributed of binding agent, more easily causes the particle adherence of local too.
Disintegrating agent of the present invention includes but not limited to: cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, crosslinked carboxymethyl fecula sodium or their mixture, the amount of disintegrating agent can be based on sheet heavy 3% to 7%, and disintegrating agent divide interior additional be better than independent in add or additional.
Described lubricant is for being selected from magnesium stearate, stearic acid, sodium stearyl fumarate; Described fluidizer is micropowder silica gel.
Another object of the present invention is to provide the preparation method of described Abiraterone acetate oral tablet, and described preparation method comprises phase in formation, then adds all the other foreign ministers (Extra Section) and is mixed together, compacting.Wherein, inside comprise active component Abiraterone acetate powder compounds and filler, disintegrating agent, binding agent, surfactant mutually, foreign minister comprises additional disintegrating agent, fluidizer and lubricant.The amount of interior phase is about 75% ~ 95%, preferably to 80% ~ 95%, and more preferably 85% ~ 95%; Interior phase mixture need in high-shearing granulation mix homogeneously, add purified water or a certain proportion of alcohol water mixed solution moistening and granulate, then obtain more homogeneous granule through oscillating granulator, then wet granular is carried out drying, such as forced air drying or fluid bed drying.Concrete steps are as follows:
(1) Abiraterone acetate being crushed to particle diameter is 5<D
90<60 μm and 3<D
50<15 μm, obtains Abiraterone acetate powder compounds;
Particularly, the method obtaining the abiraterone powder compounds of described particle diameter is comminution by gas stream, and its required pulverizing stream pressure controlled is 0.3-0.6MPa.
(2) disintegrating agent of the filler of Abiraterone acetate powder compounds and formula ratio, surfactant, binding agent and 1%-3% is mixed;
(3) wet granulation;
(4) disintegrating agent of dried granule and fluidizer, lubricant and 4%-6% is mixed to form mixture;
(5) mixture that obtains of pressing step (4) is to form tablet.
Usually, the tablet of various shape can be suppressed by the punch die of definite shape, such as circle, similar round, ellipse, rhombus or the shape of appointing him to be applicable to.The confined state of powder when being pressed into difformity of identical weight is different, the tightness degree combined between granule, the weight, surface area etc. of unit volume all there are differences, and these differences may affect the characteristic of preparation in some cases, such as dissolution characteristic, friability etc.In the present invention, preferred figure of tablet, such as long 15 to 20mm, preferably 16 to 19mm; Wide 6 to 12mm, preferably 8.5 to 10mm.
Accompanying drawing explanation
Fig. 1 is the structural formula of compound Abiraterone acetate.
Detailed description of the invention
Embodiment provided by the invention can be understood more fully with the following Examples.These embodiments intention is described pharmaceutical composition provided by the invention and dosage form, but limits never in any form.
The size of drug particle determines other character of medicament powder, such as dissolubility, adsorptivity, mobility, compressibility, apparent density, hygroscopicity, stability etc. important physical chemical property.The diameter of spheroidal particle of rule and the characteristic length such as the length of side of cube granule can the sizes of direct representation granule.But in common powder body, most cases is the different and irregularity of each particle shape of composition, be difficult to represent its size as regular particles such as spherical, cubes with characteristic length.For same irregular granules, the assay method in its particle footpath (particle diameter) is different, and its physical significance is just different, and measured value is also probably different.The particle footpath method for expressing describing particle footpath assay methods different in practical application and correspondence thereof in the chapter 13 (micromeritis basis) of " pharmaceutics " (Cui Fude, People's Health Publisher .5 version, Beijing, 2003) can be for reference.In practical application, people are it is of concern that particle size distribution (particle size distribution) situation of whole population (powder body), and be also the uniformity coefficient of particle size, frequency distribution and cumulative distribution are the representations of conventional particle size distribution.Frequency distribution represents the percent that the particle corresponding with each particle diameter is shared in wholegrain subgroup.Cumulative distribution represents the percent of particle shared by wholegrain subgroup being less than or greater than certain particle diameter, such as D90 represents that the percent of particle shared by population being less than this particle diameter is 90%, in like manner D50, represents the particle size distribution situation of powder body usually simultaneously with D90 and D50.The benchmark of percent can use number benchmark, quality criteria, area benchmark, volume reference, length standard etc.Assay standard is different, and size distribution curve is made a world of difference, and must indicate assay standard when therefore representing particle size distribution.The particle size distribution of different benchmark can convert mutually in theory.Current, the method measuring diameter of particle based on laser light diffraction principle is used widely, such as Malvern laser particle analyzer Mastersizer2000 can carry out Accurate Measurement to the particle of 0.02-20000 μm of size, and the diameter of particle result good stability obtained, accuracy is high.Unless otherwise indicated, diameter of particle of the present invention is all based on the volume equivalent diameter measured by laser light diffraction principle.
The screening of [embodiment 1] Abiraterone acetate particle size range
The crystallization of Abiraterone acetate is flakelike powder, and its profile is unfavorable for Flow of Goods and Materials, mixing, and the compressibility of raw material when tabletting of lamellar is also bad.In addition, the particle size distribution range of the crystalline powder of Abiraterone acetate is from several microns to hundreds of micron, and wide particle size distribution makes dissolution rate widely different.The dissolution of preparation when the present invention compares different-grain diameter scope, result is as shown in table 1.Abiraterone acetate crude material is pulverized on jet mill, regulates the stream pressure size pulverized can obtain the Abiraterone acetate powder compounds of different-grain diameter.
The dissolution of table 1. Abiraterone acetate particle size range and preparation (formula is shown in embodiment 4)
From the stripping curve of the Abiraterone acetate powder compounds of table 1 five groups of different-grain diameters, at 5<D
90<30 μm and 3<D
50stripping optimum during <10 μm of scope (when the stripping of Quality Control point 30min is greater than 90%, 60min, stripping is substantially complete); And as particle diameter D
90increase to 54.2 μm and D
50when increasing to 15.4 μm stripping some reduce, particle diameter is increased to D again
90125.0 μm and D
50when 29.5 μm, stripping has not met the prescription (Quality Control point stripping <75%, final stripping is incomplete) of quick-release tablet.Therefore the size controlling of the Abiraterone acetate powder compounds in the present invention is 5<D
90<60 μm and 3<D
50<15 μm, preferred 5<D
90<30 μm and 3<D
50<10 μm, for obtaining the raw material of above-mentioned particle diameter, the pulverizing stream pressure of jet mill need control at about 0.3 ~ 0.6MPa.
The proportioning of [embodiment 2] lactose and microcrystalline Cellulose is screened
In the present invention, lactose and microcrystalline Cellulose consumption proportion have material impact to preparation nature, more particularly the impact of the consumption proportion of granulation sections lactose and microcrystalline Cellulose.These impacts include but not limited to following aspect: graininess (such as fine powder amount, frangible degree, hardness), and viscosity when compressibility, friability, granulation and wetting agent are uniformly dispersed degree, the tablet moisture absorption etc.As table 2, when the amount of fixing filler total amount and other excipient is fixing, the major effect rule of lactose and microcrystalline Cellulose proportioning when disclosing granulation: the amount of (1) microcrystalline Cellulose, higher than kneaded and formed difference of granulating during lactose, increases this trend with crystallite consumption more obvious; Contrary lactose yield raising contributes to molding, and increase molding with lactose yield better, pellet hardness is harder, and the amount of lactose exists partially soft, the granule risk causing stripping low really up to the mark higher than soft material after microcrystalline Cellulose 3 times.(2) there is positive correlation with lactose/microcrystalline Cellulose ratio in friability, and increasing obviously than improving friability with lactose/microcrystalline Cellulose, easily weares and teares in tablet corner.Therefore, consider the prescription of tablet manufacture and finished product, in prescription, the proportioning of lactose and microcrystalline Cellulose should be 1:1 to 3:1, preferred 1.5:1 to 2:1.
The proportioning of table 2 lactose and microcrystalline Cellulose affects to be tested
The consumption screening of [embodiment 3] sodium lauryl sulphate
Sodium lauryl sulphate, as surfactant, has the effect of solubilising and moistening to insoluble drug.But the solubilising power of sodium lauryl sulphate Dichlorodiphenyl Acetate abiraterone is limited, expect that the medicine that can be realized solubilising unit dose by the sodium lauryl sulphate in prescription is impossible.In prescription, sodium lauryl sulphate is by solubilising and moistening, and final embodied effect contributes to granulating and Drug controlled release and stripping.
By table 3, inventor finds, not adding surfactant relies on separately binding agent polyvidone to be not easy to make granule, significantly improved by the consumption pelletizing forming increasing sodium lauryl sulphate, the increase of whatever you like also will make soft material occur partially soft partially sticky character, illustrate that the wettability that sodium lauryl sulphate improves raw material and adjuvant is convenient to molding.Observe the pellet hardness increase that sodium lauryl sulphate raising can make to make from another point of view, when this is sodium lauryl sulphate granulation, some drugs is dissolved, after drying, play the effect of bonding of building bridge.Can see from the embodiment of different amounts, when consumption is 0, disintegrate is exceedingly fast, but medicine dissolution needs the time, so the fine drug powder discharged fast is not easy stripping because of hydrophobic aggregation, so final 30min stripping is on the low side, but consumption excessive as 6% or more time can make to dissolve during granulation and appear many medicines and form medicine duricrust or hard bridge joint at particle surface, this also can cause stripping on the low side.So the suitable consumption of sodium lauryl sulphate is 2%-6%, preferred 3%-5%.
The consumption of table 3 sodium lauryl sulphate
[embodiment 4] Abiraterone acetate preparation prescription composition and preparation method
| Component | （w/w）% |
| Abiraterone acetate (micronization) | 35.0 |
| Lactose | 28.0 5 |
| Microcrystalline Cellulose | 21.0 |
| Cross-linking sodium carboxymethyl cellulose (inside adding) | 2.0 |
| Cross-linking sodium carboxymethyl cellulose (additional) | 4.0 |
| Polyvidone | 4.0 |
| Sodium lauryl sulphate | 4.0 10 |
| Micropowder silica gel | 1.0 |
| Magnesium stearate | 1.0 |
Preparation method: first, the Abiraterone acetate crude material of synthesis is pulverized separately on jet mill, and regulating and pulverizing stream pressure is 0.55MPa, and finally pulverizing the Abiraterone acetate powder compounds particle size parameters obtained is: its D
90be about 7 μm, D
50be about 4 μm, D
10be about 1.5 μm, use in this, as preparation.
80 mesh sieve pretreatment crossed by adjuvant, get the microcrystalline Cellulose after screening, lactose, cross-linking sodium carboxymethyl cellulose (inside adding), polyvidone and sodium lauryl sulphate and above-mentioned active component Abiraterone acetate powder compounds ground 80 mesh sieves altogether.In after sieve is mixed, phase mixture mixes in wet granulation mixer, adds water-wet soft material.18 eye mesh screens are granulated, with 16 mesh sieve granulate after drying.Interior phase granule and remaining adjunct ingredient (i.e. cross-linking sodium carboxymethyl cellulose (additional), micropowder silica gel and magnesium stearate) are mixed to form foreign minister, at the oval tablet of 14-16KN pressure system.
[embodiment 5] Abiraterone acetate preparation prescription composition and preparation method
| Component | （w/w）% |
| Abiraterone acetate (micronization) | 33.0 |
| Lactose | 28.0 |
| Microcrystalline Cellulose | 25.0 |
| Cross-linking sodium carboxymethyl cellulose (inside adding) | 2.5 |
| Cross-linking sodium carboxymethyl cellulose (additional) | 1.5 |
| Polyvidone | 2.0 |
| Sodium lauryl sulphate | 6.0 |
| Micropowder silica gel | 1.0 |
| Magnesium stearate | 1.0 |
Preparation method: first, the Abiraterone acetate crude material of synthesis is pulverized separately on jet mill, and regulating and pulverizing stream pressure is 0.55MPa, and finally pulverizing the Abiraterone acetate powder compounds particle size parameters obtained is: its D
90be about 7 μm, D
50be about 4 μm, D
10be about 1.5 μm, use in this, as preparation.
80 mesh sieve pretreatment crossed by adjuvant, get the microcrystalline Cellulose after screening, lactose, cross-linking sodium carboxymethyl cellulose (inside adding), polyvidone and sodium lauryl sulphate and above-mentioned active component Abiraterone acetate powder compounds ground 80 mesh sieves altogether.In after sieve is mixed, phase mixture mixes in wet granulation mixer, adds water-wet soft material.18 eye mesh screens are granulated, with 16 mesh sieve granulate after drying.Interior phase granule and remaining adjunct ingredient (i.e. cross-linking sodium carboxymethyl cellulose (additional), micropowder silica gel and magnesium stearate) are mixed to form foreign minister, at the oval tablet of 14-16KN pressure system.
[embodiment 6] Abiraterone acetate preparation prescription composition and preparation method
| Component | （w/w）% |
| Abiraterone acetate (micronization) | 36.0 |
| Lactose | 35.0 |
| Microcrystalline Cellulose | 12.0 |
| Cross-linking sodium carboxymethyl cellulose (inside adding) | 2.5 |
| Cross-linking sodium carboxymethyl cellulose (additional) | 4.5 |
| Polyvidone | 6.0 |
| Sodium lauryl sulphate | 2.0 |
| Micropowder silica gel | 1.0 |
| Magnesium stearate | 1.0 |
Preparation method: first, the Abiraterone acetate crude material of synthesis is pulverized separately on jet mill, and regulating and pulverizing stream pressure is 0.55MPa, and finally pulverizing the Abiraterone acetate powder compounds particle size parameters obtained is: its D
90be about 7 μm, D
50be about 4 μm, D
10be about 1.5 μm, use in this, as preparation.
80 mesh sieve pretreatment crossed by adjuvant, get the microcrystalline Cellulose after screening, lactose, cross-linking sodium carboxymethyl cellulose (inside adding), polyvidone and sodium lauryl sulphate and above-mentioned active component Abiraterone acetate powder compounds ground 80 mesh sieves altogether.In after sieve is mixed, phase mixture mixes in wet granulation mixer, adds water-wet soft material.18 eye mesh screens are granulated, with 16 mesh sieve granulate after drying.Interior phase granule and remaining adjunct ingredient (i.e. cross-linking sodium carboxymethyl cellulose (additional), micropowder silica gel and magnesium stearate) are mixed to form foreign minister, at the oval tablet of 14-16KN pressure system.
The stripping curve of [embodiment 7] Abiraterone acetate preparation
Optimum prescription disclosed in CN102743393A is embodiment one, preferred raw material particle size (0.1-20 μm) and preferred Abiraterone acetate-lactose powder thing particle diameter (0.1-50 μm) altogether.Select the Abiraterone acetate raw material (D50 is about 4 μm) of particle diameter suitable for the present invention, in Abiraterone acetate: the ratio of lactose (1:1) is the common powder thing of 29.7 μm (namely D50 equals 29.7 μm) at high speed disintegrator cpc powder broken acquisition particle diameter, carry out again granulating and tabletting, in this, as control formulation 1; Alternative selects the Abiraterone acetate raw material of about 20 μm of particle diameters, the samely obtains by pulverizing altogether with lactose 1:1 the common powder thing that particle diameter is 48.3 μm, then carries out granulating and tabletting, obtains control formulation 2.Under following leaching condition: paddle board method, the PBS of the pH 4.5 of 900mL adds 0.25%SDS solution as dissolution medium, the stripping curve % of the preparation under rotating speed 50rpm comparative control preparation and compositions of the present invention and preparation technology.
Through contrast, the stripping feature of control formulation 1,2 is that leading portion discharges quickly, but back segment stripping is not enough, in whole process in leaching, stripping is incomplete, the stripping quantity of Quality Control point 30min is also less than 90%, may be distributed in medium with drug particles is too fast, and the dissolution velocity of medicine itself is unhappy, makes superfine drug powder hydrophobic aggregation under high local concentrations become grow up and make final stripping incomplete.Comparatively speaking, invention formulation can good Drug controlled release speed, ensure that the stripping of final Quality Control point reach more than 90% and final stripping substantially complete.
The stripping curve %(pH4.5PBS of table 4 embodiment and control formulation)
| Time (min) | Embodiment 4 | Embodiment 5 | Embodiment 6 | Control formulation 1 | Control formulation 2 |
| 5 | 23.34 | 20.79 | 21.12 | 48.61 | 44.87 |
| 10 | 44.76 | 42.03 | 40.45 | 75.94 | 69.14 |
| 20 | 81.94 | 77.17 | 74.79 | 87.59 | 85.33 |
| 30 | 95.41 | 91.31 | 90.02 | 88.45 | 86.21 |
| 45 | 97.28 | 93.76 | 91.23 | 87.71 | 86.15 |
| 60 | 97.47 | 94.21 | 93.04 | 87.34 | 86.24 |
The impact of [embodiment 8] sheet shape
By the prescription of embodiment 4, be pressed into difform tablet with two kinds of punch dies respectively, one 13mm monocline punch die is pressed into circular piece, and another suppresses elliptical piece with the oval punch die of 19.8mm*8.5mm, both stripping curve reflections difference is measured with stripping, as shown in table 5.Circular piece is worse than elliptical piece in stripping.
The stripping curve (pH4.5PBS) of the different flap-type of table 5
| Time (min) | Elliptical piece (stripping quantity %) | Circular piece (stripping quantity %) |
| 5 | 23.34 | 23.32 |
| 10 | 44.76 | 47.83 |
| 20 | 81.94 | 79.64 |
| 30 | 95.41 | 87.08 |
| 45 | 97.28 | 88.06 |
| 60 | 97.47 | 87.93 |
Claims (12)
1. an Abiraterone acetate oral tablet, comprises the component of following weight proportion:
Wherein, the particle diameter of described Abiraterone acetate powder compounds is 5<D
90<60 μm and 3<D
50<15 μm.
2. Abiraterone acetate oral tablet as claimed in claim 1, it is characterized in that, the particle diameter of described Abiraterone acetate powder compounds is preferably 5<D
90<30 μm and 3<D
50<10 μm.
3. Abiraterone acetate oral tablet as claimed in claim 1, it is characterized in that, described filler comprises lactose and microcrystalline Cellulose, and the weight proportion of lactose and microcrystalline Cellulose is 1:1-3:1.
4. Abiraterone acetate oral tablet as claimed in claim 3, it is characterized in that, described filler comprises lactose and microcrystalline Cellulose, and the weight proportion of lactose and microcrystalline Cellulose is 1.5:1-2:1.
5. Abiraterone acetate oral tablet as claimed in claim 1, it is characterized in that, described surfactant is sodium lauryl sulphate, and consumption is 3%-5%.
6. Abiraterone acetate oral tablet as claimed in claim 1, it is characterized in that, described surfactant is sodium lauryl sulphate, and consumption is 4%.
7. Abiraterone acetate oral tablet as claimed in claim 1, it is characterized in that, described binding agent is selected from polyvidone, starch, HPMC, HPC or their mixture;
Described disintegrating agent is selected from cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, crosslinked carboxymethyl fecula sodium or their mixture;
Described lubricant is for being selected from magnesium stearate, stearic acid, sodium stearyl fumarate;
Described fluidizer is micropowder silica gel.
8. Abiraterone acetate oral tablet as claimed in claim 1, is characterized in that, comprise the component of following weight proportion:
。
9. Abiraterone acetate oral tablet as claimed in claim 1, its preparation method comprises the following steps:
(1) Abiraterone acetate being crushed to particle diameter is 5<D
90<60 μm and 3<D
50<15 μm, obtains Abiraterone acetate powder compounds;
(2) disintegrating agent of the filler of Abiraterone acetate powder compounds and formula ratio, surfactant, binding agent and 1%-3% is mixed;
(3) wet granulation;
(4) disintegrating agent of dried granule and fluidizer, lubricant and 4%-6% is mixed to form mixture;
(5) mixture that obtains of pressing step (4) is to form tablet.
10. Abiraterone acetate oral tablet as claimed in claim 9, it is characterized in that, the method obtaining the Abiraterone acetate powder compounds of described particle diameter is comminution by gas stream.
11. Abiraterone acetate oral tablet as claimed in claim 10, it is characterized in that, the pulverizing stream pressure of described comminution by gas stream is 0.3-0.6MPa.
12. Abiraterone acetate oral tablets as described in claim 1 or 9, is characterized in that, the compacting shape of tablet is preferably oval.
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| CN110636837A (en) * | 2017-08-28 | 2019-12-31 | 江苏恒瑞医药股份有限公司 | Pharmaceutical composition of CYP17 inhibitor and preparation method thereof |
| CN110636837B (en) * | 2017-08-28 | 2022-05-24 | 江苏恒瑞医药股份有限公司 | Pharmaceutical composition of CYP17 inhibitor and preparation method thereof |
| WO2020126017A1 (en) * | 2018-12-20 | 2020-06-25 | Pharmaceutical Oriented Services Ltd | Dosage form containing abiraterone acetate |
| CN111110646A (en) * | 2020-02-19 | 2020-05-08 | 纳兰迦(上海)生物医药科技有限公司 | Prescription and preparation method of low-specification abiraterone acetate oral preparation |
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