CN113967198A - Steroid CYP17 inhibitor capsule and preparation method thereof - Google Patents

Steroid CYP17 inhibitor capsule and preparation method thereof Download PDF

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Publication number
CN113967198A
CN113967198A CN202010726010.9A CN202010726010A CN113967198A CN 113967198 A CN113967198 A CN 113967198A CN 202010726010 A CN202010726010 A CN 202010726010A CN 113967198 A CN113967198 A CN 113967198A
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abiraterone acetate
capsule
antioxidant
caprylic
polyethylene glycol
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郝贵周
王苗苗
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Lunan Pharmaceutical Group Corp
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Lunan Pharmaceutical Group Corp
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • 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
    • A61K9/4858—Organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

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  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
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  • General Chemical & Material Sciences (AREA)
  • Medicinal Preparation (AREA)
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Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a steroid CYP17 inhibitor capsule and a preparation method thereof. The capsule has high dissolution rate, good stability and process reproducibility, high bioavailability, and suitability for mass production.

Description

Steroid CYP17 inhibitor capsule and preparation method thereof
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a steroid CYP17 inhibitor capsule and a preparation method thereof.
Background
Abiraterone acetate, chemically known as 17- (3-pyridyl) -androst-5, 16-diene-3 β -acetate, is an oral steroidal CYP17 inhibitor, reduces androgen levels by inhibiting key enzymes in androgen synthesis (C17, C20-lyase and 17 α -hydroxylase), inhibits androgens in the testes and other parts of the body, is used in combination with prednisone to treat metastatic castration resistant prostate cancer (mCRPC) and newly diagnosed high risk metastatic endocrine therapy sensitive prostate cancer (mHSPC), and has the structural formula:
Figure BDA0002601697430000011
abiraterone two major circulating metabolites in human plasma are abiraterone sulfate (inactive) and abiraterone oxynitridosulfate (inactive), each accounting for about 43% of exposure; in addition, approximately 88% of the radioactive dose after oral administration of abiraterone acetate was recovered in the feces and approximately 5% in the urine, with the major compounds present in the feces being unchanged abiraterone acetate and abiraterone (approximately 55% and 22% of the administered dose, respectively); therefore, the bioavailability of the abiraterone acetate orally absorbed is extremely low, which is a key factor that the dosage of the abiraterone acetate needs to reach 1g per oral administration.
At present, researchers can solve the problem by adopting methods such as preparing solid dispersion by using polyethylene glycol 4000 or 6000 and the like, but the problems of poor stability and complex preparation process still exist; in addition, a large amount of surfactant is added in the prescription to dissolve the insoluble drug in the micelle, and the dissolution of the drug is improved by the solubilization of the surfactant, but the problem of safety is easily caused by the excessive use amount of the surfactant.
CN102743393A discloses a medicinal composition containing abiraterone acetate and a preparation process thereof, wherein abiraterone acetate and hydrophilic auxiliary materials are ground according to a proportion, the particle size of the raw material medicine is 10-30 μm, the medicinal composition is used for improving the dissolution rate and bioavailability of the medicament, although the particle size of the raw material medicine is controlled to be smaller, the improvement of the dissolution rate of the medicament is still limited, and the dissolution rate is only 60% in 15min in a medium with a surfactant added at pH 4.5.
CN102961358A discloses an abiraterone acetate liquid capsule, the content of the liquid capsule comprises abiraterone acetate, a solvent, an antioxidant and fatty acid monoglyceride, the prescription components and the preparation process are complex, the preparation process needs to be further heated, the stability of the medicine is reduced, the safety of the medicine is affected, and the problem of the bioavailability of the medicine cannot be solved.
CN103070828A discloses a solid dispersion and tablet containing abiraterone acetate and a preparation method thereof, wherein abiraterone acetate and povidone with the ratio of 1: 0.5-4 are dissolved in chloroform, the solid dispersion is obtained through drying under reduced pressure, the solid dispersion is dispersed in water and is subjected to micro-powder grinding, the particle size D (0.9) of the ground dispersion is less than 75 microns to obtain a solution, the solution is added into a filler and a disintegrating agent which are sieved by a 100-mesh sieve, the granulation and the drying are carried out, a lubricant is added, and the tablet is formed.
CN103446069 discloses an abiraterone acetate oral solid composition and a preparation method thereof, wherein abiraterone acetate raw material medicine is micronized, and the particle size is controlled within the range of 0-20 μm to improve the dissolution rate of tablets, but after research, the raw material medicine is micronized alone and the dissolution rate cannot be improved obviously, and special equipment is required for the pulverization within the particle size range.
CN106913539A discloses an abiraterone acetate sublingual tablet and a preparation method thereof, wherein abiraterone acetate and polyethylene glycol 1000 vitamin E succinate are dissolved in an organic solvent, the organic solvent is removed by drying under reduced pressure, the dried substance is mixed with a filler and a disintegrating agent, then a lubricant is added for mixing and tabletting, although complete dissolution can be realized in 15min, a large amount of organic solvent is still used, the labor protection is not facilitated, the impurity content is obviously increased in the long-term storage process, and the stability is poor.
CN106913537A discloses an abiraterone acetate sublingual tablet and a preparation method thereof, wherein abiraterone acetate and solid acid are heated and melted, and then mixed with a filler, a disintegrating agent and an adhesive to be granulated, dried and added with a lubricant to be tabletted, so that the dissolution rate of the drug is improved, but the process is complex, and the sublingual tablet has higher requirements on dissolution and is easily influenced by the environment in the storage and transportation processes.
CN109125276A discloses a medicinal composition of abiraterone acetate tablets and a preparation method thereof, wherein copovidone and abiraterone acetate are prepared into solid dispersion, and then the solid dispersion, diluent, adhesive, disintegrant and lubricant are prepared into a mixture to be tabletted. Although the stability is improved to a certain extent, the dissolution rate of the tablet obtained by the preparation method is too low, the dissolution rate in 20min is about 25% in hydrochloric acid solution with the pH value of 1.0, and the dissolution rate in 20min only reaches about 50% in pure water (0.5% SDS), and the dissolution rate needs to be improved.
Abiraterone acetate is a lipophilic compound, is easily soluble in organic solvents such as tetrahydrofuran and dichloromethane, especially alcohols, is almost insoluble in water at 20 ℃ under the condition of pH2-12, and is slightly soluble in 0.1N hydrochloric acid; BCS belongs to four categories, namely low solubility-low permeability drugs, so the bottleneck in pharmaceutical formulation research is how to improve dissolution and bioavailability.
In the existing oral preparation of abiraterone acetate, the problems of dissolution and bioavailability are solved by using a solid dispersion technology, but the existing oral preparation has the problems of complex process, raw material loss and coalescence caused by micronization, cost increase and solvent residue caused by adding an organic solvent, the risk of toxic and side effects caused by adding a surfactant and the like, and the problems of dissolution and bioavailability to be further improved, complex process, large difficulty in industrial production and the like exist in the preparation process of a liquid capsule, so that the abiraterone acetate preparation with simple preparation process, high dissolution and bioavailability and high stability is urgently needed to meet clinical requirements.
Disclosure of Invention
In view of the defects of the prior art, the inventor provides a steroid CYP17 inhibitor capsule, in particular to an abiraterone acetate capsule, an organic solvent is not used in the preparation process, and when water is used as a dissolving medium, the obtained capsule can be quickly dissolved without adding a surfactant in the dissolving medium.
The invention is realized by the following scheme:
the steroid CYP17 inhibitor capsule comprises abiraterone acetate, caprylic/capric polyethylene glycol glyceride and an antioxidant.
Preferably, in the steroid CYP17 inhibitor capsule, the weight ratio of abiraterone acetate to caprylic/capric polyethylene glycol glyceride is 1: 15-30.
Further preferably, in the steroid CYP17 inhibitor capsule, the weight ratio of abiraterone acetate to caprylic/capric polyethylene glycol glyceride is 1: 15-25.
More preferably, in the steroid CYP17 inhibitor capsule, the weight ratio of abiraterone acetate to caprylic capric polyethylene glycol glyceride is 1: 20.
Preferably, in the steroid CYP17 inhibitor capsule, the antioxidant is one or more of dibutyl hydroxy toluene, tert-butyl p-hydroxyanisole, gallic acid, ethyl gallate, propyl gallate, octyl gallate, isoamyl gallate, sodium ascorbate, and glutathione.
Further preferably, in the steroid CYP17 inhibitor capsule, the antioxidant is dibutylhydroxytoluene, tert-butyl p-hydroxyanisole or gallic acid.
Preferably, in the steroid CYP17 inhibitor capsule, the weight ratio of the abiraterone acetate to the antioxidant is 1: 0.002-0.2.
Further preferably, in the steroid CYP17 inhibitor capsule, the weight ratio of the abiraterone acetate to the antioxidant is 1: 0.01-0.1.
More preferably, in the steroid CYP17 inhibitor capsule, the weight ratio of the abiraterone acetate to the antioxidant is 1: 0.05.
The preparation method of the steroid CYP17 inhibitor-containing capsule comprises the specific steps of stirring and dissolving abiraterone acetate, an antioxidant and caprylic/capric polyethylene glycol glyceride, and then pressing the mixture into soft capsules on a soft capsule machine.
Compared with the prior art, the invention has the following advantages:
(1) the dissolution rate and the bioavailability of the product obtained by the invention are improved;
(2) the preparation method does not need complex micronization treatment, and has simple process and strong operability;
(3) the product prepared by the invention does not need to use a solvent, so that toxic and side effects and the like caused by solvent residue are avoided;
(4) when the product obtained by the invention takes water as a dissolving medium, the dissolving medium can be quickly dissolved without adding a surfactant;
(5) the product prepared by the invention has simple preparation process and stable and controllable quality, and is expected to realize industrial production.
Detailed Description
The advantages of the present invention are further illustrated by the following examples, it is to be properly understood that the examples are for illustrative purposes only and do not limit the scope of the present invention, and that variations and modifications obvious to those skilled in the art according to the present invention are included in the scope of the present invention.
Example 1
(I) prescription
Figure BDA0002601697430000041
(II) preparation process
The abiraterone acetate, the tert-butyl p-hydroxyanisole and the caprylic capric acid polyethylene glycol glyceride with the prescription amount are stirred and dissolved at 35 ℃, and then the soft capsule is pressed on a soft capsule machine by taking gelatin as a capsule wall material and glycerol as a plasticizer.
Example 2
(I) prescription
Figure BDA0002601697430000042
(II) preparation process
The abiraterone acetate, the gallic acid and the caprylic/capric polyethylene glycol glyceride with the prescription dose are stirred and dissolved at the temperature of 30 ℃, and then the soft capsule is pressed on a soft capsule machine by taking gelatin as a capsule wall material and glycerol as a plasticizer.
Example 3
(I) prescription
Figure BDA0002601697430000051
(II) preparation process
The abiraterone acetate, the dibutyl hydroxyl toluene and the caprylic capric acid polyethylene glycol glyceride with the prescription amount are stirred and dissolved at 30 ℃, and then the soft capsule is pressed on a soft capsule machine by taking gelatin as a capsule wall material and glycerol as a plasticizer.
Example 4
(I) prescription
Figure BDA0002601697430000052
(II) preparation process
The abiraterone acetate, the glutathione and the caprylic/capric polyethylene glycol glyceride with the prescription amount are stirred and dissolved at the temperature of 30 ℃, and then the soft capsule is pressed on a soft capsule machine by taking gelatin as a capsule wall material and glycerol as a plasticizer.
Example 5
(I) prescription
Figure BDA0002601697430000053
(II) preparation process
The abiraterone acetate, the ethyl gallate and the caprylic/capric polyethylene glycol glyceride with the prescription dose are stirred and dissolved at the temperature of 30 ℃, and then the soft capsule is pressed on a soft capsule machine by taking gelatin as a capsule wall material and glycerol as a plasticizer.
Example 6
(I) prescription
Figure BDA0002601697430000054
Figure BDA0002601697430000061
(II) preparation process
The abiraterone acetate, the propyl gallate, the octyl gallate and the caprylic capric polyethylene glycol glyceride with the prescription dose are stirred and dissolved at 30 ℃, and then the soft capsule is pressed on a soft capsule machine by taking gelatin as a capsule wall material and glycerol as a plasticizer.
Example 7
(I) prescription
Figure BDA0002601697430000062
(II) preparation process
The abiraterone acetate, the isoamyl gallate, the ascorbic acid and the caprylic capric acid polyethylene glycol glyceride with the prescription dose are stirred and dissolved at 30 ℃, and then the soft capsule is pressed on a soft capsule machine by taking gelatin as a capsule wall material and glycerol as a plasticizer.
Example 8
(I) prescription
Figure BDA0002601697430000063
(II) preparation process
The abiraterone acetate, the ethyl gallate and the caprylic/capric polyethylene glycol glyceride with the prescription dose are stirred and dissolved at the temperature of 30 ℃, and then the soft capsule is pressed on a soft capsule machine by taking gelatin as a capsule wall material and glycerol as a plasticizer.
Example 9
(I) prescription
Figure BDA0002601697430000064
Figure BDA0002601697430000071
(II) preparation process
The abiraterone acetate, the ethyl gallate and the caprylic/capric polyethylene glycol glyceride with the prescription dose are stirred and dissolved at the temperature of 30 ℃, and then the soft capsule is pressed on a soft capsule machine by taking gelatin as a capsule wall material and glycerol as a plasticizer.
Example 10
(I) prescription
Figure BDA0002601697430000072
(II) preparation process
The abiraterone acetate, cysteine hydrochloride and caprylic/capric polyethylene glycol glyceride with the prescription dose are stirred and dissolved at 30 ℃, and then the soft capsule is pressed on a soft capsule machine by taking gelatin as a capsule wall material and glycerol as a plasticizer.
Comparative example 1
(I) prescription
Figure BDA0002601697430000073
(II) preparation process
Weighing and dissolving the abiraterone acetate and BHT in the prescription amount in a mixed solution of glyceryl monocaprylate and PEG400 which is heated to 60 ℃, uniformly stirring, and encapsulating in a soft capsule to obtain the abiraterone acetate soft capsule.
Comparative example 2
(I) prescription
Figure BDA0002601697430000074
(II) preparation process
Weighing and dissolving the abiraterone acetate and BHT in the prescription amount in a mixed solution of glyceryl monocaprylate and PEG400 which is heated to 60 ℃, uniformly stirring, and encapsulating in a soft capsule to obtain the abiraterone acetate soft capsule.
Comparative example 3
(I) prescription
Component content g
Abiraterone acetate 10g
Oleic acid polyethylene glycol glyceride 150g
(II) preparation process
Weighing abiraterone acetate and polyethylene glycol oleate according to the prescription amount, stirring to dissolve into a uniform clear solution, and filling the solution into soft capsules.
Comparative example 4
(I) prescription
Component content g
Abiraterone acetate 1g
Caprylic capric acid polyethylene glycol glyceride 15g
(II) preparation process
The abiraterone acetate and the caprylic/capric polyethylene glycol glyceride with the prescription amount are stirred and dissolved at the temperature of 30 ℃, and then the soft capsule is pressed on a soft capsule machine by taking gelatin as a capsule wall material and glycerol as a plasticizer.
Comparative example 5
(I) prescription
Figure BDA0002601697430000081
(II) the preparation process comprises the following steps:
heating and melting the copovidone with the formula amount, adding the abiraterone acetate, uniformly stirring, and extruding particles by using an extruder; mixing the granules with microcrystalline cellulose, crospovidone and magnesium stearate according to the prescription amount, and tabletting.
Comparative example 6
(I) prescription
Figure BDA0002601697430000091
(II) the preparation process comprises the following steps:
the samples were vacuum dried in an oven at 50 ℃ after spray drying by mixing abiraterone acetate with copovidone in a mixture of solvents methanol: acetone (2:1) followed by spray drying the mixture to form a Spray Dried Dispersion (SDD) Drug Product Intermediate (DPI). After drying, the obtained granules are further mixed with other auxiliary materials for tabletting.
Comparative example 7
(I) prescription
Figure BDA0002601697430000092
(II) the preparation process comprises the following steps:
abiraterone acetate is combined with an intragranular excipient, after dry granulation, an extragranular excipient, namely croscarmellose sodium and sodium stearyl fumarate, is added and blended, and the mixture is pressed into tablets in a rotary tablet press.
Comparative example 8
(I) prescription
Figure BDA0002601697430000101
(II) the preparation process comprises the following steps:
weighing and mixing abiraterone acetate and sodium dodecyl sulfate according to the feeding amount, and grinding the mixture through a 200-mesh vortex oscillating screen; respectively sieving mannitol, microcrystalline cellulose, silicon dioxide, croscarmellose sodium and magnesium stearate with 80 mesh vortex oscillating screen; uniformly mixing abiraterone acetate, sodium dodecyl sulfate, mannitol, microcrystalline cellulose, croscarmellose sodium and silicon dioxide by using a mixer, sieving the mixture by using an 80-mesh sieve, and uniformly mixing again; adding the premixed raw and auxiliary materials into a high-speed stirring granulator, adding 8% of PVP k29/32 adhesive ethanol water solution, preparing granules, and sieving with a 24-mesh sieve; after granulation is finished, transferring the mixture to a fluidized bed, and drying the mixture until the moisture of the granules is less than or equal to 1.5 percent; sieving and granulating the dried particles by a stainless steel screen; adding adjuvants, mixing, and tabletting.
Comparative example 9
(I) prescription
Figure BDA0002601697430000102
(II) preparation process
The preparation method comprises the following steps of heating and melting abiraterone acetate and povidone according to the prescription amount by using a hot-melt extruder at 125 ℃, extruding, crushing an extruded product, mixing with starch and croscarmellose sodium, adding a lubricant zinc stearate, mixing, and tabletting.
Comparative example 10
(I) prescription
Figure BDA0002601697430000111
(II) preparation process
Uniformly mixing abiraterone acetate and copovidone to prepare a physical mixture; setting the extrusion temperature of a double-screw hot-melt extruder to be 100 ℃, starting a screw when the preset temperature is reached, adding the obtained physical mixture into the extruder, and extruding strips through the screw; crushing the strips, and sieving the crushed strips with a 40-mesh sieve to obtain a solid dispersion with uniform particle size distribution; uniformly mixing the obtained solid dispersion with a diluent, an adhesive, a disintegrating agent and a lubricant according to the weight percentage in the prescription; the mixture is compressed into tablets.
Verification examples
1. Dissolution test
The abiraterone acetate formulations obtained in examples 1-10 and comparative examples 1-10 were tested for dissolution as follows.
Taking the product, determining according to dissolution method, using 900mL of pure water as dissolution medium, rotating at 50 rpm, taking 10mL of solution after 10 minutes, filtering, and taking the subsequent filtrate as sample solution. Taking a proper amount of abiraterone acetate reference substance, placing the abiraterone acetate reference substance into a 10mL measuring flask, adding methanol to dissolve and dilute the abiraterone acetate reference substance to a scale, precisely measuring 1mL, placing the abiraterone acetate reference substance into the 10mL measuring flask, adding a dissolution medium to dilute the abiraterone acetate reference substance to the scale, and shaking up the abiraterone acetate reference substance to serve as a reference substance solution. According to the chromatographic conditions under the content determination item, 10 mu L of each of the test solution and the reference solution is taken, injected into a liquid chromatograph, the chromatogram is recorded, and the dissolution rate of each tablet is calculated by the peak area according to an external standard method. The limit is 80% of the indicated amount and should be met.
Table 1 dissolution test results
Figure BDA0002601697430000112
Figure BDA0002601697430000121
2. Stability test
To further prove the superiority of the present invention, the inventors conducted long-term stability experiments on the products obtained in the examples of the present invention and comparative examples.
The abiraterone acetate tablets prepared in examples 1 to 10 of the present invention were mixed with commercially available abiraterone acetate tablet (trade name: zeke;)@) The related substances of the retained samples are respectively measured at 0 month, 3 months and 6 months when the samples are examined under the conditions of 40 +/-2 ℃ and 75 +/-5% RH, and the specific data are shown in the following table:
TABLE 2 stability test results
Figure BDA0002601697430000122
Figure BDA0002601697430000131
3. Animal experiments
The inventive examples 1-10 were combined with zeke tablets to perform a pharmacokinetic experiment in dogs. 6 healthy Beagle dogs in each group, the body weight of the dogs is 12.5-15Kg, the dogs are fed once 12h before taking the medicines, the dosage of the abiraterone acetate is 250mg orally, 25mL of warm water is simultaneously given, 5min, 15min, 30min, 45min, 60min, 90min, 120min, 240min, 480min and 720min after the medicines are taken, the dogs are sampled by subcutaneous veins in forelimbs for about 3mL, the dogs are placed in heparinized test tubes, the blood concentration of the dogs is measured, the Cmax and the AUC are calculated, and the dogs are matched with commercial abiraterone acetate tablets (trade name: zeke)@) Contrast, further calculate for zeke@The ratio of Cmax to AUC of (c).
TABLE 3 results of pharmacokinetic experiments
Figure BDA0002601697430000132

Claims (10)

1. A steroid CYP17 inhibitor capsule is characterized in that the steroid CYP17 inhibitor capsule comprises abiraterone acetate, caprylic capric acid polyethylene glycol glyceride and an antioxidant.
2. The capsule according to claim 1, wherein the weight ratio of abiraterone acetate to caprylic/capric polyethylene glycol glyceride is 1: 15-30.
3. The capsule according to claim 1 or 2, wherein the weight ratio of abiraterone acetate to caprylic/capric polyethylene glycol glyceride is 1: 15-25.
4. The capsule according to claim 3, wherein the weight ratio of abiraterone acetate to caprylic/capric polyethylene glycol glyceride is 1: 20.
5. The capsule according to claim 1, wherein the antioxidant is one or more of dibutyl hydroxytoluene, tert-butyl p-hydroxyanisole, gallic acid, ethyl gallate, propyl gallate, octyl gallate, isoamyl gallate, sodium ascorbate, and glutathione.
6. The capsule according to claim 1 or 5, wherein the antioxidant is dibutylhydroxytoluene, tert-butyl p-hydroxyanisole or gallic acid.
7. The capsule according to claim 1 or 5, wherein the weight ratio of the abiraterone acetate to the antioxidant is 1: 0.002-0.2.
8. The capsule according to claim 7, wherein the weight ratio of the abiraterone acetate to the antioxidant is 1: 0.01-0.1.
9. The capsule according to claim 8, wherein the weight ratio of the abiraterone acetate to the antioxidant is 1: 0.05.
10. The method for preparing the capsule according to claim 1, wherein the method comprises the specific steps of dissolving abiraterone acetate, the antioxidant and caprylic/capric macrogol glyceride by stirring, and then pressing into the soft capsule on a soft capsule machine.
CN202010726010.9A 2020-07-24 2020-07-24 Steroid CYP17 inhibitor capsule and preparation method thereof Pending CN113967198A (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104857517A (en) * 2015-05-14 2015-08-26 南京海纳医药科技有限公司 Enzalutamide soft capsule and preparation method thereof
CN110831939A (en) * 2017-04-20 2020-02-21 大冢制药株式会社 6-pyrimidine-isoindole derivatives as ERK1/2 inhibitors

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104857517A (en) * 2015-05-14 2015-08-26 南京海纳医药科技有限公司 Enzalutamide soft capsule and preparation method thereof
CN110831939A (en) * 2017-04-20 2020-02-21 大冢制药株式会社 6-pyrimidine-isoindole derivatives as ERK1/2 inhibitors

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