CN112076163B - Pharmaceutical composition of bazedoxifene acetate tablet and preparation method thereof - Google Patents
Pharmaceutical composition of bazedoxifene acetate tablet and preparation method thereof Download PDFInfo
- Publication number
- CN112076163B CN112076163B CN201910514050.4A CN201910514050A CN112076163B CN 112076163 B CN112076163 B CN 112076163B CN 201910514050 A CN201910514050 A CN 201910514050A CN 112076163 B CN112076163 B CN 112076163B
- Authority
- CN
- China
- Prior art keywords
- parts
- weight
- bazedoxifene acetate
- pharmaceutical composition
- sodium dodecyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Biophysics (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Molecular Biology (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The application relates to a pharmaceutical composition containing bazedoxifene acetate as an active ingredient and a preparation method thereof. The composition comprises: bazedoxifene acetate; lactose; microcrystalline cellulose; pregelatinized starch; low substituted hydroxypropyl cellulose; colloidal silica; sodium dodecyl sulfate; vitamin C; and glyceryl behenate. The application also relates to a method for preparing said composition. The medicine composition disclosed by the invention has the advantages of improving the difference between medicine batches, ensuring the content uniformity of medicines, keeping the dissolution of medicines in different batches consistent all the time, and having medicinal safety and effectiveness.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and in particular relates to a pharmaceutical composition of bazedoxifene acetate tablets and a preparation method thereof.
Background
Bazedoxifene acetate, english name: bazedoxifene Acetate, also known as bazedoxifene acetate, having the chemical name 1- {4-2- (cyclohexylimino-1-) ethoxy ] benzyl } -2- (4-hydroxyphenyl) -3-methyl-1H-indol-5-ol acetate, has the following structural formula:
bazedoxifene acetate, a Selective Estrogen Receptor Modulator (SERM) developed by the european Ligand company partner Wyeth 1997, approved for sale by the company pyroxene in the european union (EMA) at month 4 of 2009 under the trade name
The company fei, 7, 23, of fei corporation is approved for sale in japan under the trade name Viviant. Bazedoxifene acetate can competitively inhibit the combination of 17 beta-estradiol with ER alpha and ER beta, and the bazedoxifene acetate has no agonist activity on a human breast cancer cell line when used alone, and is mainly used for treating osteoporosis of postmenopausal women.
The bazedoxifene acetate pharmaceutical composition disclosed in the prior art consists of an active ingredient, a filler, an antioxidant, a disintegrating agent, a glidant, a lubricant and a binder, and is prepared into an orally-taken tablet through a wet granulation process. Wet granulation is a process in which a binder is added to a drug powder and the powder is agglomerated together by the bridge or bonding action of the binder to produce granules. It comprises extrusion granulation, rotary granulation, fluidization granulation, stirring granulation and the like.
Through in vitro dissolution deep comparison research on a plurality of batches of samples of the existing commercial products, the problems of large batch-to-batch difference and poor reproducibility of the commercial products are found, so that certain hidden hazards exist in clinical treatment effect and safety.
Disclosure of Invention
In view of the above, the present invention is mainly aimed at providing a pharmaceutical composition of bazedoxifene acetate tablet with excellent dissolution performance, stable quality between batches and excellent bioavailability, and a preparation method thereof.
In order to achieve the above purpose, the invention is realized according to the following technical scheme:
the first aspect of the present invention provides a pharmaceutical composition of bazedoxifene acetate tablet, comprising:
bazedoxifene acetate;
lactose;
microcrystalline cellulose;
pregelatinized starch;
low substituted hydroxypropyl cellulose;
colloidal silica;
sodium dodecyl sulfate;
vitamin C; and
glyceryl behenate.
Wherein bazedoxifene acetate is an active ingredient.
Unless otherwise indicated, the term "low substituted hydroxypropyl cellulose" as used herein refers to low substituted hydroxypropyl ethers of cellulose, low substituted hydroxypropyl cellulose having a hydroxypropyl content of 5% to 16%, and is generally commercially available.
In some embodiments, the invention provides a pharmaceutical composition comprising the following ingredients:
21-24 parts by weight of bazedoxifene acetate;
118-145 parts by weight of lactose;
40-65 parts by weight of microcrystalline cellulose;
14-33 parts by weight of pregelatinized starch;
45-56 parts by weight of low-substituted hydroxypropyl cellulose;
1 to 6 parts by weight of colloidal silica;
3-8 parts by weight of sodium dodecyl sulfate;
4-8 parts by weight of vitamin C; and
2 to 8 parts by weight of glyceryl behenate.
In some embodiments, the invention provides a pharmaceutical composition comprising the following ingredients:
22.60 parts by weight of bazedoxifene acetate;
120.60 to 141.30 parts by weight of lactose;
42.50 to 62.00 parts by weight of microcrystalline cellulose;
15.50 to 31.00 parts by weight of pregelatinized starch;
46.50 to 54.25 parts by weight of low-substituted hydroxypropyl cellulose;
1.55 to 4.65 parts by weight of colloidal silica;
4.65 to 6.00 weight portions of sodium dodecyl sulfate;
5.00 to 6.00 weight portions of vitamin C; and
3.10 to 6.20 parts by weight of glyceryl behenate.
In some embodiments, the invention provides a pharmaceutical composition comprising the following ingredients: 22.60 parts of bazedoxifene acetate, 127.94 parts of lactose, 6.00 parts of vitamin C, 15.50 parts of pregelatinized starch, 54.25 parts of low-substituted hydroxypropyl cellulose, 4.65 parts of colloidal silicon dioxide, 62.00 parts of microcrystalline cellulose, 4.65 parts of sodium dodecyl sulfate and 6.20 parts of glyceryl behenate.
In some embodiments, the invention provides a pharmaceutical composition comprising the following ingredients: 22.60 parts of bazedoxifene acetate, 130.94 parts of lactose, 6.00 parts of vitamin C, 15.50 parts of pregelatinized starch, 54.25 parts of low-substituted hydroxypropyl cellulose, 4.65 parts of colloidal silicon dioxide, 62.00 parts of microcrystalline cellulose, 4.65 parts of sodium dodecyl sulfate and 6.20 parts of glyceryl behenate.
In some embodiments, the invention provides a pharmaceutical composition comprising the following ingredients: 22.60 parts of bazedoxifene acetate, 123.29 parts of lactose, 6.00 parts of vitamin C, 31.00 parts of pregelatinized starch, 46.50 parts of low-substituted hydroxypropyl cellulose, 1.55 parts of colloidal silicon dioxide, 42.50 parts of microcrystalline cellulose, 4.65 parts of sodium dodecyl sulfate and 6.20 parts of glyceryl behenate.
In some embodiments, the pharmaceutical composition provided by the invention, the particle size Dv (90) of bazedoxifene acetate is 3.5 μm to 14.1 μm, i.e., at least 90% of the volume fraction of bazedoxifene acetate has a particle size of 3.5 μm to 14.1 μm.
In some embodiments, the invention provides a pharmaceutical composition, the tablet having a coating.
In a second aspect, the present invention provides a method of preparing a pharmaceutical composition according to the first aspect of the invention:
the method comprises the following steps:
a) Mixing bazedoxifene acetate, vitamin C, colloidal silicon dioxide and 1/2 of the prescription amount of lactose, and then adding the rest amount of lactose and microcrystalline cellulose to mix to obtain a first mixture;
b) Mixing the first mixture with pregelatinized starch and low-substituted hydroxypropyl cellulose to obtain a second mixture;
c) Wet granulating and drying the second mixture;
d) Mixing the granules obtained in step c) with glyceryl behenate to obtain total mixed granules;
e) Tabletting the total mixed particles obtained in the step d).
In some embodiments, the particle size Dv (90) of bazedoxifene acetate in step a) is 3.5 μm to 14.1 μm.
In some embodiments, the present invention provides the preparation method wherein in said step c), wet granulation is performed with an aqueous solution of sodium dodecyl sulfate.
Preferably, the wet granulation in step c) is performed by adding an aqueous solution of sodium dodecyl sulfate with stirring.
In some embodiments, the preparation method provided by the invention, the aqueous solution of sodium dodecyl sulfate is added into a granulator in a spray mode for wet granulation.
In some embodiments, the present invention provides a method of preparing, wherein the time for adding the aqueous solution of sodium dodecyl sulfate to the wet granulator is controlled to be 90s to 120s, preferably the addition is completed in a period of 100s to 120 s.
In some embodiments, the preparation method provided by the invention controls the time of adding the sodium dodecyl sulfate aqueous solution and the granulating time to be 2-6 min, preferably 2-3 min.
In some embodiments, in the preparation method provided by the present invention, the drying mode in the step c) is fluidized bed boiling drying; the drying temperature is 50-70 ℃; preferably, the drying temperature is 60 ℃.
In some embodiments, the present invention provides the method wherein in step c), the moisture of the produced particles is controlled to be not higher than 2.0%.
In some embodiments, the present invention provides the method wherein the tablet hardness in step e) is controlled to be 130 to 150N/mm 2 。
In some embodiments, the present invention provides the preparation method, further optionally comprising a step of film coating and/or packaging after step e).
The invention has the following beneficial effects:
compared with the prior art, the pharmaceutical composition of the bazedoxifene acetate tablet provided by the invention can better improve the quality difference among medicine batches, ensure the content uniformity of medicines, keep the quality of medicines among different batches consistent all the time, and has medicinal safety, effectiveness and controllability.
Drawings
FIG. 1 shows the dissolution profiles of three example samples from example 11 at pH4.5 and 0.25% SDS medium;
FIG. 2 shows the dissolution profiles of three samples of the reference formulation of example 11 at pH4.5 and 0.25% SDS medium.
FIG. 3 shows a graph of the in vivo drug delivery of the sample of example 6-1 of example 12.
Detailed Description
The present invention will be further described in detail below with reference to examples, which are provided to illustrate the objects, technical solutions and advantages of the present invention. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
The dissolution rate or dissolution profile was used in the following examples to compare and examine samples of the examples and reference formulations of the present application, and the dissolution profile was determined as follows:
dissolution profile determination method:
taking a sample to be tested, taking a dissolution rate measurement method (second method of the 2015 general rule 0931 of Chinese pharmacopoeia), taking 900ml buffer solution as a dissolution medium, respectively, taking a proper amount of solution at different time points to measure the content of bazedoxifene acetate at the rotation speed of 50rpm, and calculating the dissolution rate in each unit preparation.
Wherein, the preparation of the pH4.5 and 0.25% SDS buffer solution is as follows: 2.99g of sodium acetate (trihydrate) and 2.5g of sodium dodecyl sulfate were weighed out and dissolved in 1000ml of pure water, and glacial acetic acid was used to adjust the pH to 4.5.
Examples
Example 1 bazedoxifene acetate particle size study test
Bazedoxifene acetate raw material medicines with different particle sizes are taken, bazedoxifene acetate tablets are prepared according to the following prescription and preparation process, dissolution rate of the obtained tablets is measured under the conditions of pH4.5 and 0.25% SDS, so that influence of the particle sizes of the raw material medicines on the dissolution of the tablets is examined, and the results are shown in Table 1.
Prescription:
| material name | Prescription dose (mg) |
| Bazedoxifene acetate | 22.60 |
| Lactose and lactose | 127.94 |
| Vitamin C | 6.00 |
| Pre-cross-linked starch | 15.50 |
| Low substituted hydroxypropyl cellulose | 54.25 |
| Colloidal silica | 4.65 |
| Microcrystalline cellulose | 62.00 |
| Sodium dodecyl sulfate | 4.65 |
| Glyceryl behenate | 6.20 |
The preparation process comprises the following steps:
mixing bazedoxifene acetate, vitamin C, colloidal silicon dioxide and lactose with 1/2 prescription amount in a three-dimensional mixer, finishing the granules twice, and obtaining mixed medicinal powder with the sieve aperture of 0.8 mm. The remaining prescribed amounts of lactose and microcrystalline cellulose were added to the wet granulator and mixed. Sequentially adding the mixed powder, pregelatinized starch and low-substituted hydroxypropyl cellulose, and starting a wet granulator to stir and mix for 20min. Sodium dodecyl sulfate was added to the purified water with stirring, and stirring was continued until complete dissolution. Adding the aqueous solution of sodium dodecyl sulfate into a wet granulator in a spraying mode, starting the wet granulator (a cutter is started together) and a peristaltic pump, controlling the liquid adding time to be 100-120 s, continuously preparing the soft material after the liquid adding is finished, and controlling the total time of the liquid adding time and the subsequent soft material preparing time to be 3.5-5 min. And (3) finishing, namely obtaining wet particles, wherein the pore diameter of the screen is 2.0 mm. And (3) boiling and drying the wet particles by using a fluidized bed, wherein the drying temperature is 60 ℃, and the moisture of the particles is controlled to be not higher than 2.0%. DryingThe granules are granulated by a movable granulator, and the aperture of a screen is 2.0mm, thus obtaining the dry granules. And (3) putting the dry granules and the glyceryl behenate into a three-dimensional mixer, and mixing for 5min to obtain the total mixed granules. Controlling the hardness of the pressed tablet to be 130-150N/mm 2 Tabletting and film coating are carried out.
TABLE 1 test results of dissolution profile of API particle size Range study trial samples
As can be seen from the above table, when the particle size of bazedoxifene acetate bulk drug is in the range of 3.5 μm to 14.1. Mu.m, the dissolution rate of the samples of examples 1-1 to 1-5 in 60 minutes can be substantially 80%, whereas when the particle size is 19.2. Mu.m, the cumulative dissolution in 60 minutes is slowed down, so that the API particle size range of the present invention is preferably 3.5 μm to 14.1. Mu.m.
EXAMPLE 2 wet granulation time study
Bazedoxifene acetate tablets were prepared according to the formulation of example 1 using different wet granulation times, respectively, with the remainder of the preparation process being the same as in example 1. The prepared tablets were subjected to dissolution measurement at pH4.5 and 0.25% SDS to examine the effect of different granulation times on tablet dissolution, and the results are shown in Table 2.
Table 2 wet granulation time investigation test sample dissolution curve detection results
From the above table, it can be seen that the dissolution rates of the samples of examples 2-1 to 2-7 in 60 minutes are all above 80% when the granulating time is within the range of 2min to 6min, and especially when the granulating time is within the range of 2min to 3min, the dissolution rates can be above 90%, which indicates that the granulating time can meet the pharmaceutical requirements within the range of 2min to 6 min.
EXAMPLE 3 time of addition of wetting agent solution
Bazedoxifene acetate tablets were prepared according to the recipe of example 1, using different wetting agent solution addition times, respectively, with the remainder of the preparation process being the same as that of example 1. The prepared tablets were subjected to dissolution measurement at pH4.5 and 0.25% SDS to examine the effect of different wetting agent solution addition times on tablet dissolution, and the results are shown in Table 3.
TABLE 3 detection results of dissolution curves of test samples for examination of the time of addition of the wetting agent solution
From the above table, it can be seen that when the wetting agent is added for 90s to 120s, the dissolution rate of the samples of examples 3-1 to 3-4 in 60min is above 75%, especially when the wetting agent solution is added for 100s to 120s, the dissolution rate can reach above 85%, the dissolution behavior is excellent, and the test shows that in the wet granulation process, the pharmaceutical requirements can be better satisfied by controlling the addition time of the wetting agent solution in the range of 100s to 120 s.
EXAMPLES 4-9 preparation of bazedoxifene acetate tablets
Bazedoxifene acetate tablets were prepared according to the formulation in table 4 below using the preparation method of example 1.
Table 4 prescription compositions of examples 4 to 9
EXAMPLE 10 content uniformity investigation
3 batches of samples were prepared by repeating the recipe and preparation process of example 6, and recorded as examples 6-1, 6-2 and 6-3, respectively, and content uniformity of the 3 batches of samples was measured. In addition, 3 commercial bazedoxifene acetate tablets were purchased as reference formulations (from the pyroxene pharmaceutical, 20mg format) for comparative investigation. The content uniformity inspection results are shown in Table 5.
The content uniformity investigation method comprises the following steps: according to the content uniformity inspection method of the 2015 edition of Chinese pharmacopoeia, namely comparing the relative standard deviation RSD and A+2.2 of the sample and the reference preparation of the example, wherein A is the absolute value of the difference between the marked quantity and the mean value, and S is the standard deviation.
Table 5 results of examination of content uniformity of samples and reference formulations of examples
As can be seen from the above table data, the amounts RSD and A+2.2S of the 3 batches of samples of examples 6-1, 6-2 and 6-3 are significantly less than those of the reference formulation, indicating that the samples of the examples of the present application have significantly better content uniformity from batch to batch than those of the reference formulation.
EXAMPLE 11 batch-to-batch dissolution differential investigation
The samples of examples 6-1, 6-2 and 6-3 prepared in example 10 and 3 commercial reference preparation samples were subjected to dissolution measurement at pH4.5+0.25% SDS, respectively, and the RSD values of the dissolution amounts of the samples at the respective sampling time points were calculated to examine the differences in dissolution rates between the different batches. The results of the examination of the samples of examples 6-1, 6-2 and 6-3 and the reference preparation are shown in Table 6 and Table 7, respectively, and the spectra are shown in FIGS. 1 and 2.
TABLE 6 statistical results of the batch-to-batch variation of samples of the examples of the invention (pH4.5+0.25% SDS)
| Time point (min)) | Example 6-1 | Example 6-2 | Examples 6 to 3 | RSD |
| 5 | 15.3％ | 12.8％ | 13.1％ | 9.9％ |
| 10 | 30.2％ | 24.2％ | 27.1％ | 11.0％ |
| 15 | 42.8％ | 38.3％ | 39.0％ | 6.0％ |
| 30 | 67.0％ | 65.0％ | 65.2％ | 1.7％ |
| 45 | 80.3％ | 80.6％ | 82.0％ | 1.1％ |
| 60 | 87.9％ | 89.7％ | 90.2％ | 1.4％ |
Table 7 statistics of the batch-to-batch variation of the reference preparation samples (pH4.5+0.25% SDS)
| Time point (min) | Reference formulation 1 | Reference formulation 2 | |
RSD |
| 5 | 29.1％ | 18.0％ | 15.0％ | 35.9％ |
| 10 | 42.6％ | 32.6％ | 28.1％ | 21.6％ |
| 15 | 53.3％ | 44.4％ | 38.2％ | 16.8％ |
| 30 | 74.8％ | 67.9％ | 61.7％ | 9.6％ |
| 45 | 85.1％ | 79.7％ | 76.0％ | 5.7％ |
| 60 | 91.4％ | 86.8％ | 84.1％ | 4.2％ |
As can be seen from tables 6 and 7, the RSD between the time-point batches of the three example samples was significantly smaller than the RSD between the time-point batches of the three reference formulations, indicating that the dissolution rate of the example samples was significantly less than the reference formulations.
EXAMPLE 12 in vivo pharmacokinetic investigation
The in vivo pharmacokinetic study was performed on the samples of example 6-1, and the results of the parameters are shown in Table 8.
TABLE 8 in vivo pharmacokinetic analysis results statistics
| t 1/2 (h) | 24.62±13.02 |
| T max (h) | 2.13±1.82 |
| C max (ng/mL) | 7.34±2.60 |
| AUC all (h*ng/mL) | 127.07±45.92 |
| AUC INF_obs (h*ng/mL) | 133.49±49.45 |
Example 13 in vitro dissolution profile investigation
The samples of inventive example 6-1 were examined for elution in different elution media (pH 1.0+0.2% SDS, pH4.5+0.25% SDS, pH6.8+0.25% SDS and water+0.5% SDS) and the results are shown in Table 9.
TABLE 9 investigation of dissolution behavior of samples according to the example of the invention
As can be seen from the examination results of the table, under the condition of each dissolution medium, the dissolution rate of the sample in the embodiment of the invention can reach more than 85% within 60min, and the RSD value at each time point is smaller, which indicates that the medicine of the invention has excellent dissolution behavior and is beneficial to quick release and effect of the medicine in vivo.
Claims (6)
1. A method of preparing a pharmaceutical composition of bazedoxifene acetate tablet, the method comprising the steps of:
a) Mixing bazedoxifene acetate, vitamin C, colloidal silicon dioxide and lactose with a 1/2 prescription amount, and adding the rest lactose and microcrystalline cellulose to mix to obtain a first mixture;
b) Mixing the first mixture obtained in step a) with pregelatinized starch and low-substituted hydroxypropyl cellulose to obtain a second mixture;
c) Carrying out wet granulation on the second mixture prepared in the step b) by using a sodium dodecyl sulfate aqueous solution, and drying, wherein the time for adding the sodium dodecyl sulfate aqueous solution into the wet granulator is 100 s-120 s, and the time for carrying out wet granulation is 2 min-3 min;
d) Mixing the granules obtained in step c) with glyceryl behenate to obtain total mixed granules;
e) Tabletting the total mixed particles prepared in the step d);
wherein, the pharmaceutical composition comprises the following components:
21-24 parts by weight of bazedoxifene acetate;
118-145 parts by weight of lactose;
40-65 parts by weight of microcrystalline cellulose;
14-33 parts by weight of pregelatinized starch;
45-56 parts by weight of low-substituted hydroxypropyl cellulose;
1-6 parts by weight of colloidal silica;
3-8 parts by weight of sodium dodecyl sulfate;
4-8 parts by weight of vitamin C; and
2-8 parts by weight of glyceryl behenate;
the particle size Dv (90) of the bazedoxifene acetate is 3.5-14.1 mu m.
2. The method of claim 1, wherein the pharmaceutical composition comprises the following ingredients:
22.60 parts by weight of bazedoxifene acetate;
120.60-141.30 parts by weight of lactose;
42.50 to 62.00 parts by weight of microcrystalline cellulose;
15.50 to 31.00 parts by weight of pregelatinized starch;
46.50 to 54.25 parts by weight of low-substituted hydroxypropyl cellulose;
1.55 to 4.65 parts by weight of colloidal silica;
4.65 to 6.00 weight portions of sodium dodecyl sulfate;
5.00 to 6.00 weight portions of vitamin C; and
3.10 to 6.20 parts by weight of glyceryl behenate.
3. The method of claim 1, wherein the aqueous solution of sodium dodecyl sulfate is added to the granulator in a spray manner for wet granulation.
4. The method according to claim 1, wherein the drying in step c) is fluidized bed ebullated drying; the drying temperature was 60 ℃.
5. The method according to claim 1, wherein the method further comprises a step of film coating and/or packaging after step e).
6. A pharmaceutical composition of bazedoxifene acetate tablets prepared according to the method of any one of claims 1-5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910514050.4A CN112076163B (en) | 2019-06-14 | 2019-06-14 | Pharmaceutical composition of bazedoxifene acetate tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910514050.4A CN112076163B (en) | 2019-06-14 | 2019-06-14 | Pharmaceutical composition of bazedoxifene acetate tablet and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112076163A CN112076163A (en) | 2020-12-15 |
| CN112076163B true CN112076163B (en) | 2023-06-20 |
Family
ID=73733807
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910514050.4A Active CN112076163B (en) | 2019-06-14 | 2019-06-14 | Pharmaceutical composition of bazedoxifene acetate tablet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112076163B (en) |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005531613A (en) * | 2002-06-13 | 2005-10-20 | ワイス | Bazedoxifene treatment rules |
| US7771744B2 (en) * | 2005-08-24 | 2010-08-10 | Wyeth Llc | Bazedoxifene acetate formulations |
| CN103860496A (en) * | 2014-03-14 | 2014-06-18 | 王志刚 | Bazedoxifene acetate dispersing tablet and preparation method thereof |
| CN103845336B (en) * | 2014-03-24 | 2016-03-09 | 江苏知原药业有限公司 | A kind of acetic acid Bazedoxifene compositions of excellent performance |
| CN104546794A (en) * | 2015-01-05 | 2015-04-29 | 万特制药(海南)有限公司 | Bazedoxifene acetate capsule and preparation method thereof |
-
2019
- 2019-06-14 CN CN201910514050.4A patent/CN112076163B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN112076163A (en) | 2020-12-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10537524B2 (en) | Apixaban solid composition and preparation method thereof | |
| CN112220770B (en) | Pharmaceutical composition of selepag and preparation method thereof | |
| CN109674754B (en) | Flupentixol and melitracen pharmaceutical composition and preparation thereof | |
| CN104586804A (en) | Preparation method for letrozole tablets with good stability | |
| CN106943367B (en) | Afatinib maleate tablet and preparation method thereof | |
| CN106551946B (en) | Pharmaceutical composition containing trifluorothymidine and tipyrimidine hydrochloride and preparation method thereof | |
| Sun et al. | A microcrystalline cellulose based drug-composite formulation strategy for developing low dose drug tablets | |
| CN112076163B (en) | Pharmaceutical composition of bazedoxifene acetate tablet and preparation method thereof | |
| CN108066312A (en) | A kind of Pa Boxini pharmaceutical compositions and preparation method thereof | |
| CN115154431B (en) | Nitroglycerin tablet and preparation method thereof | |
| CN114557975B (en) | Sustained release tablet containing exemestane, process and use thereof | |
| CN114146059B (en) | Levothyroxine sodium microchip and preparation method and preparation thereof | |
| CN112245402A (en) | Indapamide tablet and preparation method thereof | |
| CN109700773B (en) | Ticagrelor preparation composition and preparation method thereof | |
| CN103919780B (en) | Calming soporific preparation, its compound preparation, preparation method and pharmaceutical composition | |
| CN110721171A (en) | Improved vibration source sheet and preparation method thereof | |
| CN104865215A (en) | Ulipristal acetate tablet and method for determining dissolution of ulipristal acetate tablet | |
| CN112535674B (en) | Letrozole tablet and preparation method thereof | |
| CN114831943B (en) | Preparation method of pharmaceutical composition | |
| CN113133977B (en) | Afatinib maleate tablet and preparation method thereof | |
| US11801252B2 (en) | Pharmaceutical composition | |
| CN111821307B (en) | 17- (3-pyridyl) androstane-5, 16-diene-3 beta-alcohol acetate solid preparation and preparation method thereof | |
| CN114209668B (en) | Alfuzosin hydrochloride sustained release preparation and preparation method thereof | |
| CN115487157A (en) | Cabotinib malate tablet and preparation method thereof | |
| Zhao et al. | Transdermal drug delivery system of domperidone sustained-release coated microsphere gels: In vitro characterization and in vivo evaluation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |