CN115475172B - A pharmaceutical composition containing abiraterone or its pharmaceutically acceptable salt - Google Patents

A pharmaceutical composition containing abiraterone or its pharmaceutically acceptable salt Download PDF

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CN115475172B
CN115475172B CN202110658995.0A CN202110658995A CN115475172B CN 115475172 B CN115475172 B CN 115475172B CN 202110658995 A CN202110658995 A CN 202110658995A CN 115475172 B CN115475172 B CN 115475172B
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dry powder
composition
powder particles
particles
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CN115475172A (en
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郑翔玲
张志兵
卢迪
冯德月
李显
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Beijing Tide Pharmaceutical Co Ltd
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Abstract

The invention discloses a pharmaceutical composition containing abiraterone or medicinal salt thereof, which adopts a liquid phase precipitation method to obtain dry powder particles containing abiraterone or medicinal salt nanoparticles thereof and fat-soluble antioxidant nanoparticles, wherein the average particle diameter of the dry powder particles is smaller than 300nm, and the antioxidant nanoparticles and the drug nanocrystalline particles can be uniformly dispersed in the dry powder, so that the oxidation resistance is greatly improved, the stability of a preparation is effectively improved, and the preparation process of the liquid phase precipitation method is simple, the preparation period is short, and the preparation method is more beneficial to the industrial production of the nano preparation.

Description

A pharmaceutical composition containing abiraterone or its pharmaceutically acceptable salt
Technical Field
The invention belongs to the field of pharmaceutical preparations, and in particular relates to a pharmaceutical composition containing abiraterone or medicinal salt thereof and a preparation method thereof.
Background
Abiraterone acetate is a CYP17 inhibitor developed by the Qiangsheng pharmaceutical company in the United states and is used for treating metastatic castration of prostate tumor patients. Abiraterone acetate tablets were first marketed in the united states in 2011 under the trade name Zytiga. An oral dose of 1000mg, i.e. 4 tablets of 250mg gauge, is recommended. Because abiraterone acetate is a low-solubility and low-permeability drug, the abiraterone acetate has poor bioavailability (10%) and obvious food effect, and needs to be taken on an empty stomach, and cannot be eaten at least 2 hours before taking and at least 1 hour after taking.
To further increase the bioavailability of abiraterone acetate and reduce the food effect, indian sun pharmaceutical company employs dry grinding technology to pulverize the drug substance into nanocrystalline particles with average diameter less than 1 micron, which are then compressed into tablets, as reported in document CN 105246598A. This modified formulation was approved by the FDA in 5 2018 under the trade name Yonsa. The Yonsa specification was reduced to 125mg compared to the 250mg specification of Zytiga. Oral administration of 500mg Yonsa per day achieves therapeutic equivalence in reducing androgen levels in the serum of a patient as compared to oral administration of 1000mg Zytiga per day. The preparation adopts a dry grinding technology, and the ground dry powder has poor fluidity and serious static charge, so that the preparation and quality control of the tablet are difficult. In addition, abirater Long Yi oxidizes, and after nanocrystallization, the specific surface area increases, and the area in contact with air also increases, which accelerates oxidation of the drug. Because of the potential risk of genotoxicity of abiraterone oxidized impurities, antioxidants Butylated Hydroxyanisole (BHA) and Butylated Hydroxytoluene (BHT) are added to the formulation, and BHA has a certain carcinogenic effect. The use of other antioxidants is not effective, for example, when the use amount of the antioxidant is 0.4% by combining ascorbic acid and fumaric acid, the related substances are increased from 0.23% to 0.80% after heating at 80 ℃ for 4 hours, and the impurity is obviously increased.
Furthermore, patent document CN 111617258A discloses a process for preparing a pharmaceutical composition of abiraterone or derivatives thereof and its use, i.e. a nanosuspension (D90 less than 1000 nm) containing abiraterone or derivatives thereof is mixed with an absorption enhancer and optionally at least one excipient, granulated by a fluid bed and then prepared into a solid formulation. The obtained preparation has improved bioavailability, improved individual variability of administration patients, etc., compared with Zytiga. This technique also uses wet milling, but the recipe does not contain antioxidants nor gives any impurity content data. In addition, the prescription contains an oral absorption enhancer, and the oral absorption enhancer can promote the absorption of medicines and the permeation of all intestinal contents including toxins and pathogens, so that the toxins and pathogens can easily enter the blood circulation of a human body, and secondary infection can be caused.
Document CN111110646a also discloses a prescription of low specification abiraterone acetate oral preparation and a preparation method, the prescription comprises abiraterone acetate, a surfactant, a hydrophilic polymer, an antioxidant, a co-stabilizer, a diluent, a disintegrant and a lubricant; the preparation method comprises the steps of wet grinding, drying and dewatering, mixing and tabletting. The prepared abiraterone acetate tablet can promote drug dissolution and absorption. The technology also adopts wet grinding to prepare the Abiraterone Long Nami crystal, the grinding time is long, and the industrialization process difficulty is high. In addition, the intense collisions between the milling beads and the milling chamber can result in the incorporation of metal ions into the nanosuspension which can catalyze the drug to accelerate the self-oxidation reaction. Thus, antioxidants BHA and BHT are also added to the formulation.
Disclosure of Invention
In the research, it is found that fat-soluble antioxidant is added into the composition of the abiraterone or the medicinal salt thereof, and the liquid phase precipitation method is adopted, so that the prepared nano crystal particles of the abiraterone or the medicinal salt thereof are uniformly dispersed, and the oxidation resistance is obviously improved, thereby effectively improving the stability of the preparation containing the abiraterone or the medicinal salt thereof.
The invention provides a composition containing abiraterone or medicinal salt thereof, which contains dry powder particles, wherein the dry powder particles contain medicine abiraterone or medicinal salt thereof and fat-soluble antioxidants.
The active ingredients of the medicine are abiraterone, abiraterone acetate or other pharmaceutically acceptable abiraterone salts. The content of the pharmaceutically active ingredient in the dry powder particles can be more preferably 40-46%.
The lipid-soluble antioxidant is selected from one or more of phospholipids, tocopherols, ascorbyl palmitate, wherein the phospholipids may be selected from egg yolk lecithin, hydrogenated lecithin, soybean lecithin, etc., further preferably tocopherol or ascorbyl palmitate, in some embodiments, the lipid-soluble antioxidant is ascorbyl palmitate. Meanwhile, the content of the fat-soluble antioxidant in the dry powder particles is preferably 0.05-0.1%.
In some embodiments, the fat-soluble antioxidants described herein are present in the dry powder particles at 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, or 0.1%.
The average particle size of the dry powder particles is smaller than 300nm, wherein the particle size of the fat-soluble antioxidant is smaller than that of the active ingredient particles. In some embodiments, the average particle size of the fat-soluble antioxidant particles in the dry powder particles is less than 200nm, the average particle size of the pharmaceutically active ingredient particles is less than 300nm, and the total impurities of the dry powder particles produced are less than 0.3%.
The dry powder particles further comprise a pharmaceutical active ingredient, a fat-soluble antioxidant, a surfactant, a drying protective agent or other pharmaceutically acceptable excipients, wherein the content of the pharmaceutical active ingredient is 33-50%, the content of the fat-soluble antioxidant is 0.05-0.2%, the content of the surfactant is 1-10%, and the content of the drying protective agent is 40-70%, and the content is in mass percent.
The dry powder particles of the invention can be composed of particles containing single components formed by pharmaceutically active components, fat-soluble antioxidants, surfactants, dry protectants or other excipients, and also can be composed of composite component particles composed of multiple components.
The surfactant is selected from one or more of sodium dodecyl sulfate, span, poloxamer, polysorbate, sodium oleate, docusate sodium, cetyltrimethylammonium bromide, preferably polysorbate, sodium dodecyl sulfate, and in some embodiments the surfactant is polysorbate 80.
The content of the surfactant in the dry powder particles is preferably 5-10%.
The drying protective agent is selected from one or more of hydroxypropyl cellulose, polyethylene glycol, povidone, beta cyclodextrin and derivatives thereof, mannitol, lactose, sucrose and glucose, wherein the beta cyclodextrin and derivatives thereof are hydroxypropyl beta cyclodextrin, sodium sulfobutylbeta cyclodextrin, methyl beta cyclodextrin, carboxymethyl beta cyclodextrin and hydroxyethyl beta cyclodextrin, preferably mannitol, lactose and hydroxypropyl beta cyclodextrin.
In some embodiments the dryness protectant is mannitol, in some embodiments lactose, and in some embodiments hydroxypropyl beta cyclodextrin.
The content of the drying protective agent in the dry powder particles is preferably 50-60%.
The further dry powder particles are prepared by adopting a liquid phase precipitation method, namely, the fat-soluble antioxidant and Abiraterone are dissolved in an alcohol solution and then mixed with an aqueous solution, so that uniform nano suspension is formed, and the average particle size is smaller than 300nm. The preparation method specifically comprises the following steps: step (1), dissolving the active pharmaceutical ingredient and the fat-soluble antioxidant in an alcohol solvent to obtain a pharmaceutical solution; step (2) dissolving a surfactant and a drying protective agent in water to obtain an auxiliary material aqueous solution; and (3) mixing the drug solution and the auxiliary material aqueous solution to obtain a nano suspension, and drying the nano suspension to obtain the drug-loaded dry powder particles.
In the preparation method, the step (1) and the step (2) are not sequential, for example, the step (1) can be performed first, and the step (2) can be performed first.
Wherein the alcoholic solvent in step (1) is selected from ethanol, propanol, isopropanol, and the like, and in some embodiments the alcoholic solvent is ethanol.
The dry powder particles of the present invention can be used for preparing various forms of solid preparations, liquid preparations, for example, the solid preparations can be selected from tablets, capsules, solid granules, dispersing agents, pills, powder and the like, and the liquid preparations can be suspension agents, injection and the like.
Furthermore, the composition containing abiraterone or the medicinal salt thereof can further contain other pharmaceutically acceptable excipients such as diluents, disintegrants, lubricants or glidants besides the dry powder particles.
In the pharmaceutical composition, the content of dry powder particles is 30-70%, preferably 40-60%.
Wherein the diluent is one or more selected from microcrystalline cellulose, mannitol, starch, calcium hydrogen phosphate and calcium carbonate.
The disintegrating agent is one or more selected from pregelatinized starch, sodium carboxymethyl starch, crosslinked sodium carboxymethyl cellulose and crosslinked povidone.
The lubricant is one or more selected from magnesium stearate, calcium stearate and sodium fumarstearate.
The glidant is selected from one or more of talcum powder and micropowder silica gel.
The pharmaceutical composition of the unit dose of the present invention contains abiraterone or a pharmaceutically acceptable salt thereof in an amount of 15mg to 400mg, preferably 50mg to 250mg, and in some embodiments may be selected from 50mg, 55mg, 60mg, 65mg, 70mg, 75mg, 80mg, 85mg, 90mg, 95mg, 100mg, 105mg, 110mg, 115mg, 120mg, 125mg, 130mg, 135mg, 140mg, 145mg, 150mg, 155mg, 160mg, 165mg, 170mg, 175mg, 180mg, 185mg, 190mg, 195mg, 200mg, 205mg, 210mg, 215mg, 220mg, 225mg, 230mg, 235mg, 240mg, 245mg, 250mg.
The preparation method of the pharmaceutical composition further comprises the steps of uniformly mixing the dry powder particles with excipients such as diluents, lubricants, disintegrants, glidants and the like to obtain the pharmaceutical composition, and further comprises the following steps: (1) Dissolving the active pharmaceutical ingredient and the fat-soluble antioxidant in an alcohol solution to obtain a pharmaceutical solution; (2) Dissolving a surfactant and a drying protective agent in water to obtain an auxiliary material aqueous solution; (3) Mixing the medicine solution with the auxiliary material aqueous solution to obtain a nano suspension; (4) Spray drying the nanometer suspension to obtain medicine carrying dry powder particles; (5) The medicine-carrying dry powder particles are evenly mixed with the diluent, the lubricant, the disintegrating agent and the glidant to obtain the medicine-carrying dry powder.
In some embodiments of the present invention, the pharmaceutical composition of the present invention is a nanosuspension, and the method of preparation thereof is as follows: (1) Dissolving the active ingredients of the medicine and the fat-soluble antioxidant in ethanol to obtain a medicine solution; (2) Dissolving a surfactant and a drying protective agent in water to obtain an auxiliary material aqueous solution; (3) Mixing the medicinal solution with adjuvant water solution to obtain nanometer suspension.
In some embodiments of the present invention, the pharmaceutical composition of the present invention is a nanoparticle, and the preparation method thereof is as follows: (1) Dissolving the active ingredients of the medicine and the fat-soluble antioxidant in ethanol to obtain a medicine solution; (2) Dissolving a surfactant and a drying protective agent in water to obtain an auxiliary material aqueous solution; (3) Mixing the medicine solution with the auxiliary material aqueous solution to obtain a nano suspension; (4) Spray drying the nanometer suspension to obtain the medicine carrying dry powder particles.
In some embodiments of the present invention, the above dry powder particles are reconstituted to obtain a nanosuspension, wherein the reconstituted solvent is water, physiological saline or glucose solution.
In some embodiments of the present invention, the preparation method of the pharmaceutical composition of the present invention is as follows: (1) Dissolving the active ingredients of the medicine and the fat-soluble antioxidant in ethanol to obtain a medicine solution; (2) Dissolving a surfactant and a drying protective agent in water to obtain an auxiliary material aqueous solution; (3) Mixing the medicine solution with the auxiliary material aqueous solution to obtain a nano suspension; (4) Spray drying the nanometer suspension to obtain medicine carrying dry powder granule, granulating, mixing with diluent, lubricant, disintegrating agent and glidant, and tabletting.
The pharmaceutical compositions of the invention may be administered, for example, orally, rectally, pulmonary, intravaginally, topically, transdermally, parenterally, intravenously, intraperitoneally, intramuscularly, sublingually, or as an oral or nasal spray.
The pharmaceutical composition can be used for preparing solid preparations, liquid preparations, for example, the solid preparations can be selected from tablets, capsules, solid granules, dispersing agents and the like, further preferably tablets or capsules, and the liquid preparations can be suspension agents, injection agents and the like, and preferably suspension agents.
The composition of the invention can be used for other chemotherapy and/or preparation of cancer drugs, wherein the cancer can be selected from prostate cancer, breast cancer or ovarian cancer.
Furthermore, the pharmaceutical composition of the invention can be used for treating castration-resistant prostate cancer, metastatic breast cancer, epithelial ovarian cancer and the like.
According to the invention, the liquid phase precipitation method is adopted to prepare the nano particles, so that the active ingredients of the medicine and the fat-soluble antioxidant can be jointly and rapidly separated out, and nano-grade antioxidant particles and medicine particles are obtained, so that the antioxidant particles and the medicine particles are uniformly dispersed in the dry powder, the particle size of the antioxidant particles is smaller than that of the medicine particles, the contact area of the antioxidant and the medicine is further increased, the antioxidant property of the composition is greatly improved, the stability of the preparation is effectively improved, and the total impurities of the composition prepared by the invention can be kept below 0.3% in the preparation process and after the stability test.
Drawings
Figure 1 example 4 crystal SEM of abirater acetate Long Nami.
Figure 2 example 4 SEM images of ascorbyl palmitate nanoparticles.
Figure 3 example 4 nanocrystalline spray-dried drug-loaded particles.
Figure 4 example 5 XRD pattern of abiraterone acetate drug substance.
Figure 5 example 5 abirater acetate Long Nami crystalline XRD pattern.
FIG. 6 example 6 HPLC profile at 80℃for 0 h.
FIG. 7 example 7 HPLC profile at 80℃for 4 h.
FIG. 8 comparative example 1 HPLC profile at 80℃for 0 h.
FIG. 9 comparative example 1 HPLC plot at 80℃for 4 h.
Detailed Description
The following examples and experimental examples serve to further illustrate the invention but do not limit the effective scope of the invention in any way.
Example 1: comparison of antioxidant and drug particle mean particle size after devitrification
1) Dissolving the raw materials or the antioxidant in 15ml of ethanol;
2) Polysorbate 80 was dissolved in 150ml water;
3) And pouring the ethanol solution into the water solution under stirring to obtain the nano suspension.
The particle size test results of the nanosuspension are as follows:
。
from the results, the liquid phase precipitation method is adopted, the particle size of the precipitated drug particles and the particle size of the antioxidant are smaller than 300nm, the particle sizes of the tocopherols and the ascorbyl palmitate are smaller than 200nm, and the particle size of the precipitated ascorbyl palmitate is the smallest.
Example 2: comparison of antioxidant properties of different antioxidants
1) Dissolving the raw materials and an antioxidant in 15ml of ethanol;
2) Dissolving a surfactant and a drying protective agent in 150ml of water;
3) Pouring the ethanol solution into the water solution under stirring to obtain a nano suspension;
4) Spray drying the suspension at 120 ℃ to obtain the drug-loaded dry powder particles.
The drug-loaded dry powder is placed in an oven at 80 ℃ for 4 hours, taken out and analyzed for related substances, and the results are as follows:
。
from the results, the tocopherol and ascorbyl palmitate have the best oxidation resistance under the condition that the dosage of the antioxidant is 0.1 percent, can well inhibit the spray drying and the impurity generation at 80 ℃, and has the total impurities unchanged basically compared with the bulk drugs. And secondly, the total impurity growth of the egg yolk lecithin is obvious under the spray drying condition and the temperature of 80 ℃. Sodium metabisulfite has the worst antioxidant effect, and the total impurity growth is most obvious under the spray drying condition and at 80 ℃.
While patent document CN105246598A combines two antioxidants of ascorbic acid and fumaric acid, the antioxidants, the medicines and other auxiliary materials are ground together by a dry method, even if the dosage of the antioxidants is 0.4%, the antioxidant effect is still poor, and after heating for 4 hours at 80 ℃, the total impurity is increased from 0.23% to 0.80%.
Example 3: reducing the dosage of the antioxidant to 0.05 percent
1) Dissolving the raw materials and an antioxidant in 15ml of ethanol;
2) Dissolving a surfactant and a drying protective agent in 150ml of water;
3) Pouring the ethanol solution into the water solution under stirring to obtain a nano suspension;
4) Spray drying the suspension at 120 ℃ to obtain the drug-loaded dry powder particles.
The drug-loaded dry powder is placed in an oven at 80 ℃ for 4 hours, taken out and analyzed for related substances, and the results are as follows:
。
from the results, when the dosage of the antioxidant is reduced to 0.05%, the total impurity growth at 80 ℃ can be effectively inhibited by both the tocopherol and the ascorbyl palmitate, and the total impurity in the preparation process of the dry powder particles can be effectively inhibited by the ascorbyl palmitate, so that the antioxidation effect is better.
Example 4: particle characterization
In order to further determine the sizes of abiraterone acetate and antioxidant particles, the ethanol solution of the drug is mixed with the aqueous solution of polysorbate 80 to obtain only a suspension containing drug nanoparticles; the ascorbyl palmitate ethanol solution was mixed with the polysorbate 80 aqueous solution to give only a suspension containing antioxidant nanoparticles. And respectively taking a proper amount of the drug nano suspension and the ascorbic acid palmitic acid nano suspension, dripping the drug nano suspension and the ascorbic acid palmitic acid nano suspension on a glass sheet, airing at room temperature, and then performing Scanning Electron Microscope (SEM) analysis, wherein the results are shown in figures 1 and 2.
From the comparison of SEM images, the morphology of the abiraterone acetate Long Nami crystal particles is similar to a sphere, the particle size of the abiraterone acetate crystal particles is smaller than 300nm, the particle size of the abiraterone acetate crystal particles is far smaller than that of the abiraterone acetate crystal particles, and the particle size of the abiraterone acetate crystal particles is smaller than 150nm, which is in good agreement with the particle size test result.
After spray drying treatment of the nano suspension containing the drug and the antioxidant, the drug nano particles and the ascorbyl palmitate nano particles are uniformly dispersed in a drying protective agent to form a spherical or hollow spherical structure (see figure 3), and the structure ensures that the nano particles can be rapidly and uniformly dispersed after the nano suspension meets water.
EXAMPLE 5 Abiraterone acetate Crystal form study
To better analyze the effect of the liquid phase precipitation method on the drug crystal form, the drug nanosuspension of example 4 is filtered, washed, freeze-dried, then subjected to X-ray diffraction (XRD) analysis and compared with the crude drug, and the results are shown in fig. 4 and 5;
from XRD results, the peak position of the abirater Long Nami acetate crystal is consistent with that of the raw materials, which shows that the liquid phase precipitation method does not change the crystal form of the medicine, and the preparation method of the nano-crystal can effectively ensure the stability of the crystal form of the active substance of the medicine.
Example 6: preparation of nanocrystalline tablets
1) Abiraterone acetate and ascorbyl palmitate were dissolved in 150ml ethanol;
2) Polysorbate 80 and lactose are dissolved in 1200ml water;
3) Pouring the ethanol solution into the water solution under stirring to obtain a nano suspension;
4) Spray drying the suspension at 120 ℃ to obtain the drug-loaded dry powder particles.
5) And granulating the dry powder by a dry method, uniformly mixing with microcrystalline cellulose, crosslinked povidone, micro-powder silica gel and Fuma sodium stearate, and tabletting to obtain the finished product.
The average particle size of the nano suspension prepared in the embodiment is 227.7nm, after the nano suspension is dried, the obtained medicine-carrying dry powder particles are dispersed again by adding water, the average particle size is 230.6nm, the particle size is basically unchanged before and after spraying, and the average particle size of the ascorbyl palmitate particles is about 100nm.
Comparative example 1: preparation of tablets (Wet milling technique, recipe same as example 6)
1) Dissolving polysorbate 80 in 200ml of water, then adding abiraterone acetate and ascorbyl palmitate, stirring and suspending uniformly to obtain crude suspension;
2) Transferring the crude suspension to a nano grinder, wherein the grinding beads are made of zirconia, the diameter of the grinding beads is 0.2mm, the grinding rotation speed is controlled to 2500rpm, and the grinding is carried out for 120min to obtain nano suspension;
3) Lactose is dissolved in 100ml of water, then poured into the nano suspension, stirred uniformly and then spray-dried at 120 ℃ to obtain the medicine-carrying dry powder.
4) And granulating the dry powder by a dry method, uniformly mixing with microcrystalline cellulose, crosslinked povidone, micro-powder silica gel and Fuma sodium stearate, and tabletting to obtain the finished product.
The average diameter of the nano suspension prepared according to comparative example 1 is 235.5nm, and the average particle diameter of the drug-loaded dry powder after being redispersed in water is 242.2nm. In addition, the average particle diameter of ascorbyl palmitate was 249.4nm after grinding alone for 120 min.
Example 7 comparative substances
The starting materials, the tablets of example 5 and the tablets of comparative example 1 were placed in an oven at 80℃and taken out after 4 hours, and the relevant substances were analyzed, with the following results:
。
from the above results, it is understood that the total impurity content of the tablet of example 6 remains substantially unchanged at high temperature, not only the total impurity content of the prepared tablet remains substantially unchanged at less than 0.3% and the total impurity content thereof remains substantially unchanged at the stability test, but also the total impurity content of the tablet of comparative example 1 increases significantly, the total impurity content of the prepared tablet is 0.338%, and the total impurity content thereof is even higher than 0.746% after the stability test. The average particle size of the ascorbyl palmitate particles in example 6 is about 100nm, while the average particle size of the ascorbyl palmitate in comparative example 1 can be reduced to about 249.4nm after wet grinding, the specific surface area of the ascorbyl palmitate is greatly different, and the contact area of the ascorbyl palmitate and the drug nanocrystals is also different, so that the larger difference of the antioxidant effect is caused, and the particle size of the antioxidant agent is smaller, and the contact area of the antioxidant agent with the drug active ingredient is larger, so that the better antioxidant property is ensured. In general, the oxidation resistance of the nanoparticle formulations obtained according to the present invention is significantly better than that of the formulations prepared according to the prior art.

Claims (13)

1. The drug composition containing abiraterone acetate comprises dry powder particles, wherein the dry powder particles contain abiraterone acetate serving as a drug active ingredient, a fat-soluble antioxidant, a surfactant, a drying protective agent or other pharmaceutically acceptable excipients, the content of the abiraterone acetate is 33-50%, the content of the fat-soluble antioxidant is 0.05-0.2%, the content of the surfactant is 2-20%, and the content of the drying protective agent is 40-70%;
the dry powder particles are prepared by adopting a liquid phase precipitation method, and comprise the following steps: step (1), dissolving the active pharmaceutical ingredient and the fat-soluble antioxidant in an alcohol solvent to obtain a pharmaceutical solution; step (2) dissolving a surfactant and a drying protective agent in water to obtain an auxiliary material aqueous solution; step (3) mixing the drug solution and the auxiliary material aqueous solution to obtain a nano suspension, and drying the nano suspension to obtain drug-loaded dry powder particles;
wherein the fat-soluble antioxidant is selected from one or two of tocopherol and ascorbyl palmitate;
the average particle size of the fat-soluble antioxidant particles in the dry powder particles is smaller than that of the abiraterone acetate particles, the average particle size of the fat-soluble antioxidant particles in the dry powder particles is smaller than 200nm, and the average particle size of the abiraterone acetate particles is smaller than 300nm.
2. The composition according to claim 1, characterized in that the surfactant is selected from one or more of sodium dodecyl sulfate, span, poloxamer, polysorbate, sodium oleate, sodium docusate, cetyltrimethylammonium bromide; the drying protecting agent is one or more selected from hydroxypropyl cellulose, polyethylene glycol, povidone, beta cyclodextrin and its derivatives, mannitol, lactose, sucrose, and glucose.
3. The composition according to claim 1, wherein in step (1) the alcohol solvent is selected from ethanol, propanol or isopropanol.
4. The composition of claim 1, wherein the alcohol solvent in step (1) is ethanol.
5. The composition according to any one of claims 1 to 4, wherein the dry powder particles are used for preparing a solid preparation or a liquid preparation, the solid preparation is selected from a tablet, a capsule, a solid granule, a dispersing agent, a pill or a powder, and the liquid preparation is selected from a suspension or an injection.
6. Composition according to any one of claims 1 to 4, characterized in that the composition comprises, in addition to the dry powder particles, a diluent, a disintegrant, a lubricant or a glidant or other pharmaceutically acceptable excipients.
7. The composition of claim 6, wherein the dry powder particles comprise 30-70% of the pharmaceutical composition.
8. The composition of claim 6, wherein the dry powder particles comprise 40-60% of the pharmaceutical composition.
9. The composition of claim 6, wherein the diluent is selected from one or more of microcrystalline cellulose, mannitol, starch, dibasic calcium phosphate, and calcium carbonate; the disintegrating agent is one or more selected from pregelatinized starch, sodium carboxymethyl starch, crosslinked sodium carboxymethyl cellulose and crosslinked povidone; the lubricant is selected from one or more of magnesium stearate, calcium stearate and sodium fumarstearate; the glidant is selected from one or more of talcum powder and micropowder silica gel.
10. The composition of claim 6, wherein the unit dose of the pharmaceutical composition comprises between 15mg and 400mg abiraterone acetate.
11. The composition of claim 6, wherein the unit dose of the pharmaceutical composition comprises 50mg to 250mg abiraterone acetate.
12. The composition of claim 6, wherein the composition is useful in the preparation of a medicament for treating cancer selected from the group consisting of prostate cancer, breast cancer and ovarian cancer.
13. The composition of claim 6, wherein the composition is useful in the preparation of a medicament for treating a cancer selected from castration-resistant prostate cancer, metastatic breast cancer, or epithelial ovarian cancer.
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WO2015114314A1 (en) * 2014-01-28 2015-08-06 Cipla Limited Pharmaceutical composition comprising abiraterone
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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Publication number Priority date Publication date Assignee Title
CN1674871A (en) * 2002-08-06 2005-09-28 陶氏环球技术公司 Crystalline drug particles prepared using a controlled precipitation process
WO2015114314A1 (en) * 2014-01-28 2015-08-06 Cipla Limited Pharmaceutical composition comprising abiraterone
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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