CN112426412A - Dry suspension containing azithromycin and preparation method thereof - Google Patents
Dry suspension containing azithromycin and preparation method thereof Download PDFInfo
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- CN112426412A CN112426412A CN202011531320.1A CN202011531320A CN112426412A CN 112426412 A CN112426412 A CN 112426412A CN 202011531320 A CN202011531320 A CN 202011531320A CN 112426412 A CN112426412 A CN 112426412A
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- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 title claims abstract description 44
- 229960004099 azithromycin Drugs 0.000 title claims abstract description 44
- 239000000725 suspension Substances 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 239000000843 powder Substances 0.000 claims abstract description 28
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims abstract description 27
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims abstract description 27
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims abstract description 26
- 239000000230 xanthan gum Substances 0.000 claims abstract description 26
- 235000010493 xanthan gum Nutrition 0.000 claims abstract description 26
- 229920001285 xanthan gum Polymers 0.000 claims abstract description 26
- 229940082509 xanthan gum Drugs 0.000 claims abstract description 26
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims abstract description 25
- 229930006000 Sucrose Natural products 0.000 claims abstract description 25
- 229960004793 sucrose Drugs 0.000 claims abstract description 25
- 239000001488 sodium phosphate Substances 0.000 claims abstract description 16
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims abstract description 16
- 229910000406 trisodium phosphate Inorganic materials 0.000 claims abstract description 16
- 235000019801 trisodium phosphate Nutrition 0.000 claims abstract description 16
- 239000000463 material Substances 0.000 claims abstract description 10
- 241000167854 Bourreria succulenta Species 0.000 claims abstract description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 9
- 235000018290 Musa x paradisiaca Nutrition 0.000 claims abstract description 9
- 235000019693 cherries Nutrition 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 5
- 240000008790 Musa x paradisiaca Species 0.000 claims abstract 3
- 239000007788 liquid Substances 0.000 claims description 20
- 239000005720 sucrose Substances 0.000 claims description 20
- 238000005303 weighing Methods 0.000 claims description 20
- 239000008187 granular material Substances 0.000 claims description 17
- 238000005469 granulation Methods 0.000 claims description 17
- 230000003179 granulation Effects 0.000 claims description 17
- 238000002156 mixing Methods 0.000 claims description 14
- 238000000576 coating method Methods 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- 239000011248 coating agent Substances 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 238000005086 pumping Methods 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 238000000889 atomisation Methods 0.000 claims description 5
- 239000012530 fluid Substances 0.000 claims description 5
- 230000002572 peristaltic effect Effects 0.000 claims description 5
- 238000000227 grinding Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 235000019640 taste Nutrition 0.000 abstract description 16
- 230000000873 masking effect Effects 0.000 abstract description 14
- 230000000694 effects Effects 0.000 abstract description 10
- 239000003814 drug Substances 0.000 abstract description 9
- 235000019658 bitter taste Nutrition 0.000 abstract description 7
- 239000002245 particle Substances 0.000 description 24
- 239000000203 mixture Substances 0.000 description 23
- 238000009472 formulation Methods 0.000 description 15
- 239000006068 taste-masking agent Substances 0.000 description 12
- 238000004090 dissolution Methods 0.000 description 9
- 241000234295 Musa Species 0.000 description 6
- 239000000853 adhesive Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 229910019142 PO4 Inorganic materials 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 235000013339 cereals Nutrition 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
- 235000013355 food flavoring agent Nutrition 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 238000007873 sieving Methods 0.000 description 4
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- 241000894006 Bacteria Species 0.000 description 2
- 206010006451 bronchitis Diseases 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
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- 208000024891 symptom Diseases 0.000 description 2
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- 241000606153 Chlamydia trachomatis Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 241000202934 Mycoplasma pneumoniae Species 0.000 description 1
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
- 206010033078 Otitis media Diseases 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 241000193996 Streptococcus pyogenes Species 0.000 description 1
- 208000006374 Uterine Cervicitis Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000016150 acute pharyngitis Diseases 0.000 description 1
- 206010001093 acute tonsillitis Diseases 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 206010008323 cervicitis Diseases 0.000 description 1
- 229940038705 chlamydia trachomatis Drugs 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000007580 dry-mixing Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 238000009477 fluid bed granulation Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229940047650 haemophilus influenzae Drugs 0.000 description 1
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- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
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- 229940013390 mycoplasma pneumoniae Drugs 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 201000009890 sinusitis Diseases 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 235000019605 sweet taste sensations Nutrition 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 208000000143 urethritis Diseases 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
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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
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
-
- 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
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
- A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
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- Engineering & Computer Science (AREA)
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- Communicable Diseases (AREA)
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Abstract
The invention belongs to the field of medicine processing, and relates to a dry suspension containing azithromycin and a preparation method thereof. The dry suspension is prepared from the following raw materials and auxiliary materials in parts by weight: 100-110 parts of azithromycin, 1800-1900 parts of cane sugar, 9-9.5 parts of anhydrous trisodium phosphate, 33-33.5 parts of hydroxypropyl cellulose, 33-33.5 parts of xanthan gum, 12-13 parts of banana powder essence, 12-13 parts of cherry powder essence and 12-13 parts of vanilla powder essence. The dry suspension can achieve the effects of effectively masking taste and improving the bitter taste of azithromycin, and enhances the administration compliance of patients, particularly children patients.
Description
Technical Field
The invention belongs to the field of medicine processing, and relates to a preparation method of a dry suspension containing azithromycin.
Background
Azithromycin has the characteristics of wide antibacterial spectrum, small stimulation to gastrointestinal tracts, quick oral absorption and the like, and is widely applied to clinical infectious diseases in recent years.
The azithromycin is mainly used for acute pharyngitis and acute tonsillitis caused by streptococcus pyogenes; sinusitis, otitis media, acute bronchitis and acute attack of chronic bronchitis caused by sensitive bacteria; pneumonia caused by streptococcus pneumoniae, haemophilus influenzae, and mycoplasma pneumoniae; urethritis and cervicitis caused by chlamydia trachomatis and non-multiple drug-resistant neisseria gonorrhoeae; infection of skin soft tissue by sensitive bacteria. The characteristics are as follows: the product is granule or powder; the smell is fragrant.
The dry suspension has the characteristics of a solid preparation, convenient carrying, convenient transportation, good stability and the like, has the advantages of a liquid preparation, is convenient to take and is suitable for patients with swallowing difficulty. Azithromycin is one of the most bitter medicaments known at present, and the existing azithromycin dry suspension has obvious bitter and astringent feeling and poor taste, so that children with mild symptoms are unwilling to take the azithromycin dry suspension, and children with severe symptoms are easy to regurgitate when taking the azithromycin dry suspension, so that the children are difficult to take the azithromycin dry suspension, and the drug effect is influenced.
Disclosure of Invention
The invention provides a preparation method of a dry suspension containing azithromycin, which is used for binding and wrapping particles, thereby achieving the effects of effectively masking taste and improving the bitter taste of the azithromycin and enhancing the administration compliance of patients, particularly children patients.
The technical scheme provided by the invention is as follows:
a dry suspension containing azithromycin is prepared from the following raw materials in parts by weight: 100-110 parts of azithromycin, 1800-1900 parts of cane sugar, 9-9.5 parts of anhydrous trisodium phosphate, 33-33.5 parts of hydroxypropyl cellulose, 33-33.5 parts of xanthan gum, 12-13 parts of banana powder essence, 12-13 parts of cherry powder essence and 12-13 parts of vanilla powder essence.
Further, the feed is prepared from the following raw materials in parts by weight: 104.81 parts of azithromycin, 1882.03 parts of cane sugar, 9.00 parts of anhydrous trisodium phosphate, 33.33 parts of hydroxypropyl cellulose, 33.33 parts of xanthan gum, 12.50 parts of banana powder essence, 12.50 parts of cherry powder essence and 12.50 parts of vanilla powder essence.
The invention also provides a preparation method of the azithromycin-containing dry suspension, which comprises the following steps:
placing sucrose and azithromycin into a fluidized bed granulator, gradually pumping a granulating liquid through a peristaltic pump, carrying out fluidized bed granulation and granule coating, carrying out granule finishing on the granules to obtain dry granules, adding anhydrous trisodium phosphate and essence into the dry granules, and mixing in a three-dimensional mixer to obtain a dry suspension containing azithromycin; the adhesive is a mixed solution of hydroxypropyl cellulose and xanthan gum.
Further, in the granulating liquid, the concentration of hydroxypropyl cellulose is 0.15-15.0%; the concentration of the xanthan gum is 0.15-15.0%.
Further, the material temperature is controlled to be 35-45 ℃ in the production process.
Further, the sucrose is crushed by a powder grinding device and is sieved by a 80-mesh sieve.
Further, the parameters of the fluid bed granulator are as follows: air inlet temperature: 40-60 ℃; material temperature: 35-45 ℃; the rotating speed of the air exhaust fan is as follows: 800-1100 rpm; liquid inlet speed: 3-7 rpm; atomization pressure: 0.15 to 0.20 MPa.
Further, the preparation method of the granulating liquid comprises the following steps: precisely weighing 26.67 parts by mass of water, precisely weighing 3.33 parts by mass of hydroxypropyl cellulose and 3.33 parts by mass of xanthan gum, adding into a beaker, and continuously and magnetically stirring until the hydroxypropyl cellulose and the xanthan gum are completely dissolved to obtain a granulation liquid.
Furthermore, the mesh size of the whole grain is phi 0.8mm, and the frequency is 30 Hz.
Further, the mixing frequency of the three-dimensional mixer was 45Hz, and the mixing time was 15 min.
Advantageous effects
Xanthan gum is widely used as a suspending and stabilizing agent in oral and topical pharmaceutical preparations, cosmetics and foodstuffs, as well as a thickening and emulsifying agent. The product has no toxicity, can be combined with most of medicinal adjuvants, and has good stability and viscosity in wide pH and temperature range.
Hydroxypropyl cellulose is abbreviated as HPC, is white or light yellow powder, is tasteless and combustible, and is a nonionic cellulose derivative. Good thermoplasticity, film-forming property, cohesiveness, latex stability and dispersivity, and little ash content. It is mainly used as tablet binder, film coating, etc. in medicine, and also can be used as cosmetic, X-ray photographic developer, tackifier, dispersant, etc.
According to the invention, fluidized bed granulation and particle coating are completed, the temperature of the materials is controlled to be 35-45 ℃, so that the granulation liquid solution prepared from xanthan gum and hydroxypropyl cellulose can be bonded and coated with particles, thereby achieving the effects of effectively masking taste, improving the bitter taste of azithromycin and enhancing the administration compliance of patients, especially children patients.
Drawings
FIG. 1 is a dissolution profile of the reference formulation and the formulations prepared in example 1 and example 2 in phosphate at pH 6.4;
figure 2 is a dissolution profile of the reference formulation and the formulations prepared in examples 2, 3 and 4 in phosphate at ph 6.4.
Detailed Description
Example 1
| Prescription | Single dose formulation/ |
100 bags per gram | Function of |
| Azithromycin | 104.81 | 10.481 | Active ingredient of crude drug |
| Sucrose | 1882.03 | 188.203 | Flavouring agent |
| Anhydrous trisodium phosphate | 9.00 | 0.900 | pH regulator |
| Hydroxypropyl cellulose | 33.33 | 3.33 | Adhesive agent |
| Xanthan gum | 33.33 | 3.33 | Suspending aid |
| Banana powder essence | 12.50 | 1.250 | Taste masking agents |
| Cherry powder essence | 12.50 | 1.250 | Taste masking agents |
| Vanilla powder essence | 12.50 | 1.250 | Taste masking agents |
| Total up to | 2100 | 210.0 | —— |
The operation is as follows:
precisely weighing 26.67g of water in a 100ml beaker, precisely weighing 3.33g of hydroxypropyl cellulose and 3.33g of xanthan gum, adding the mixture into the beaker, and continuously and magnetically stirring until the mixture is completely dissolved to obtain a granulating solution;
crushing the sucrose particles by using crushing equipment, and sieving the crushed sucrose particles by using a 80-mesh sieve for later use;
precisely weighing the sucrose and the azithromycin in the formula, controlling the stirring speed to be 300rpm and the shearing speed to be 2000rpm, and carrying out dry mixing for 10 min;
adjusting the stirring speed to 200rpm and the shearing speed to 2000rpm, gradually pumping the granulating liquid in the step one, controlling the adding of all the granulating liquid for 1.5min, and continuously stirring and shearing for 8min to finish the soft material preparation;
fifthly, drying the soft material by a fluidized bed, wherein the control parameters are as follows:
air inlet temperature: at the temperature of 40-55 ℃,
material temperature: 35-45 ℃ of the temperature,
the rotating speed of the air exhaust fan is as follows: continuously drying at 800-1200 rpm for 10min to obtain dry particles;
sixthly, straightening the grains: controlling the mesh number phi of a whole grain screen to be 0.8mm and the frequency to be 30Hz, and carrying out whole grain;
and (seventhly), accurately weighing anhydrous trisodium phosphate and essence according to the prescribed formula amount, adding the anhydrous trisodium phosphate and the essence into the dry particles, controlling the mixing frequency to be 45Hz in a three-dimensional mixer, and fully mixing for 15min to obtain the finished product.
Example 2 (preferred):
| prescription | Single dose formulation/ |
100 bags per gram | Function of |
| Azithromycin | 104.81 | 10.481 | Active ingredient of crude drug |
| Sucrose | 1882.03 | 188.203 | Flavouring agent |
| Anhydrous trisodium phosphate | 9.00 | 0.900 | pH regulator |
| Hydroxypropyl cellulose | 33.33 | 3.33 | Adhesive agent |
| Xanthan gum | 33.33 | 3.33 | Suspending aid |
| Banana powder essence | 12.50 | 1.250 | Taste masking agents |
| Cherry powder essence | 12.50 | 1.250 | Taste masking agents |
| Vanilla powder essence | 12.50 | 1.250 | Taste masking agents |
| Total up to | 2100 | 210.0 | —— |
The operation is as follows:
precisely weighing 26.67g of water in a 100ml beaker, precisely weighing 3.33g of hydroxypropyl cellulose and 3.33g of xanthan gum, adding the mixture into the beaker, and continuously and magnetically stirring until the mixture is completely dissolved to obtain a granulating solution;
crushing the sucrose particles by using a powder crushing device, and sieving the crushed sucrose particles by using a 80-mesh sieve for later use;
thirdly, precisely weighing the sucrose and the azithromycin in the fluid bed granulator according to the prescription amount, and controlling the parameters as follows:
air inlet temperature: 40-60 ℃;
material temperature: 35-45 ℃;
the rotating speed of the air exhaust fan is as follows: 800-1100 rpm;
liquid inlet speed: 3-7 rpm;
atomization pressure: 0.15-0.20 Mpa;
gradually pumping the granulation liquid by a peristaltic pump, and performing fluidized bed granulation and particle coating;
fourthly, the particles are granulated, the grain size number phi of the granules is 0.8mm, and the frequency is 30 Hz;
accurately weighing anhydrous trisodium phosphate and essence according to the prescription amount, adding into the dry particles, controlling the mixing frequency to be 45Hz in a three-dimensional mixer, and fully mixing for 15min to obtain the finished product.
Evaluation:
comparison of powder Properties
Taste masking effect comparison:
dissolution profile and similarity comparison (ph6.4 phosphate medium):
in summary, the formulas prepared in example 1 and example 2 both had good flowability, and in terms of taste, blind tests showed that: example 2 has very weak bitter taste and obvious sweet taste, and can obviously achieve the taste masking effect, while the preparation prepared in example 1 has very bitter taste and poor taste masking effect.
Example 1 used a wet granulation process that differentiated the dissolution in a force medium from the factor f2 up to 72.47 similar to the reference formulation, example 2 used a fluid bed granulation and granule coating process that exhibited a dissolution from the factor f2 up to 79.11 similar to the reference formulation, and the formulations prepared in both examples were very similar to the reference formulation, but directly affected patient compliance due to taste masking effects. The taste masking effect is good, the clinical curative effect is positive, the taste masking effect is poor, and the influence on the clinical curative effect is negative. Therefore, we determined that the fluidized bed granulation and granule coating process of example 2 had good taste masking effect and the formulation technique was more successful.
Example 3:
| prescription | Single dose formulation/ |
100 bags per gram | Function of |
| Azithromycin | 104.81 | 10.481 | Active ingredient of crude drug |
| Sucrose | 1882.03 | 188.203 | Flavouring agent |
| Anhydrous trisodium phosphate | 9.00 | 0.900 | pH regulator |
| Hydroxypropyl cellulose | 33.33 | 3.33 | Adhesive agent |
| Xanthan gum | 33.33 | 3.33 | Suspending aid |
| Banana powder essence | 12.50 | 1.250 | Taste masking agents |
| Cherry powder essence | 12.50 | 1.250 | Taste masking agents |
| Vanilla powder essence | 12.50 | 1.250 | Taste masking agents |
| Total up to | 2100 | 210.0 | —— |
The operation is as follows:
precisely weighing 26.67g of water in a 100ml beaker, precisely weighing 4.9995g of hydroxypropyl cellulose and 1.6665g of xanthan gum, adding the mixture into the beaker, and continuously and magnetically stirring until the mixture is completely dissolved to obtain a granulating solution;
crushing the sucrose particles by using a powder crushing device, and sieving the crushed sucrose particles by using a 80-mesh sieve for later use;
thirdly, precisely weighing the sucrose and the azithromycin in the fluid bed granulator according to the prescription amount, and controlling the parameters as follows:
air inlet temperature: 40-60 ℃;
material temperature: 35-45 ℃;
the rotating speed of the air exhaust fan is as follows: 800-1100 rpm;
liquid inlet speed: 3-7 rpm;
atomization pressure: 0.15-0.20 Mpa;
gradually pumping the granulation liquid by a peristaltic pump, and performing fluidized bed granulation and particle coating;
fourthly, the particles are granulated, the grain size number phi of the granules is 0.8mm, and the frequency is 30 Hz;
accurately weighing anhydrous trisodium phosphate and essence according to the prescription amount, adding into the dry particles, controlling the mixing frequency to be 45Hz in a three-dimensional mixer, and fully mixing for 15min to obtain the finished product.
Example 4:
| prescription | Single dose formulation/ |
100 bags per gram | Function of |
| Azithromycin | 104.81 | 10.481 | Active ingredient of crude drug |
| Sucrose | 1882.03 | 188.203 | Flavouring agent |
| Anhydrous trisodium phosphate | 9.00 | 0.900 | pH regulator |
| Hydroxypropyl cellulose | 33.33 | 3.33 | Adhesive agent |
| Xanthan gum | 33.33 | 3.33 | Suspending aid |
| Banana powder essence | 12.50 | 1.250 | Taste masking agents |
| Cherry powder essence | 12.50 | 1.250 | Taste masking agents |
| Vanilla powder essence | 12.50 | 1.250 | Taste masking agents |
| Total up to | 2100 | 210.0 | —— |
The operation is as follows:
precisely weighing 26.67g of water in a 100ml beaker, precisely weighing 1.6665g of hydroxypropyl cellulose and 4.9995g of xanthan gum, adding the mixture into the beaker, and continuously and magnetically stirring until the mixture is completely dissolved to obtain a granulating solution;
crushing the sucrose particles by using a powder crushing device, and sieving the crushed sucrose particles by using a 80-mesh sieve for later use;
thirdly, precisely weighing the sucrose and the azithromycin in the fluid bed granulator according to the prescription amount, and controlling the parameters as follows:
air inlet temperature: 40-60 ℃;
material temperature: 35-45 ℃;
air exhaust fan: 800-1100 rpm;
liquid inlet speed: 3-7 rpm;
atomization pressure: 0.15-0.20 Mpa;
gradually pumping the granulation liquid by a peristaltic pump, and performing fluidized bed granulation and particle coating;
fourthly, the particles are granulated, the grain size number phi of the granules is 0.8mm, and the frequency is 30 Hz;
accurately weighing anhydrous trisodium phosphate and essence according to the prescription amount, adding into the dry particles, controlling the mixing frequency to be 45Hz in a three-dimensional mixer, and fully mixing for 15min to obtain the finished product.
Comparison of powder Properties
Taste masking effect comparison:
dissolution profile and similarity comparison (ph6.4 phosphate medium):
in summary, the formulas prepared in examples 3 and 4 respectively have better fluidity by adjusting the proportion of the hydroxypropyl cellulose to the xanthan gum, but the blind tests show that: example 3 has a significant bitterness, a high hydroxypropyl cellulose concentration, a low xanthan gum concentration, and a good granulation effect, but the granule coating effect is not significant and the taste masking effect is not good. Example 4 had a slightly bitter taste, low hydroxypropyl cellulose concentration, high xanthan gum concentration, poor granulation effect, more fine powder present, and no significant taste masking effect.
Meanwhile, the dissolution in example 3 was slow, and the dissolution in example 4 was fast, and it is highly probable that the granulation effect affects the particle size distribution, and the dissolution was slightly slow in example 3 in which the large particle content was large, and excessively fast in example 4 in which the fine powder content was large.
Therefore, we determined that example 2 is superior to examples 3 and 4, and that the formulation and formulation process was more successful in taste masking.
Claims (10)
1. The dry suspension containing azithromycin is characterized by being prepared from the following raw materials in parts by weight: 100-110 parts of azithromycin, 1800-1900 parts of cane sugar, 9-9.5 parts of anhydrous trisodium phosphate, 33-33.5 parts of hydroxypropyl cellulose, 33-33.5 parts of xanthan gum, 12-13 parts of banana powder essence, 12-13 parts of cherry powder essence and 12-13 parts of vanilla powder essence.
2. The azithromycin-containing dry suspension according to claim 1, which is prepared from the following raw materials in parts by weight: 104.81 parts of azithromycin, 1882.03 parts of cane sugar, 9.00 parts of anhydrous trisodium phosphate, 33.33 parts of hydroxypropyl cellulose, 33.33 parts of xanthan gum, 12.50 parts of banana powder essence, 12.50 parts of cherry powder essence and 12.50 parts of vanilla powder essence.
3. The method for preparing the azithromycin-containing dry suspension according to claim 1 or 2, which comprises the following steps:
placing sucrose and azithromycin into a fluidized bed granulator, gradually pumping a granulating liquid through a peristaltic pump, carrying out fluidized bed granulation and granule coating, carrying out granule finishing on the granules to obtain dry granules, adding anhydrous trisodium phosphate and essence into the dry granules, and mixing in a three-dimensional mixer to obtain a dry suspension containing azithromycin; the granulating liquid is a mixed solution of hydroxypropyl cellulose and xanthan gum.
4. The preparation method of the azithromycin-containing dry suspension according to claim 3, wherein the concentration of hydroxypropyl cellulose in the granulating liquid is 0.15-15.0%; the concentration of the xanthan gum is 0.15-15.0%.
5. The preparation method of the azithromycin-containing dry suspension according to claim 3, wherein the temperature of the materials is controlled to be 35-45 ℃ in the production process.
6. The method for preparing the azithromycin-containing dry suspension according to claim 3, wherein the sucrose is crushed by a powdering device and sieved by a 80-mesh sieve.
7. The method for preparing azithromycin-containing dry suspension according to claim 3, wherein the parameters of the fluid bed granulator are as follows: air inlet temperature: 40-60 ℃; material temperature: 35-45 ℃; the rotating speed of the air exhaust fan is as follows: 800-1100 rpm; liquid inlet speed: 3-7 rpm; atomization pressure: 0.15 to 0.20 MPa.
8. The preparation method of the azithromycin-containing dry suspension according to claim 3, wherein the preparation method of the granulation liquid is as follows: precisely weighing 26.67 parts by mass of water, precisely weighing 3.33 parts by mass of hydroxypropyl cellulose and 3.33 parts by mass of xanthan gum, adding into a beaker, and continuously and magnetically stirring until the hydroxypropyl cellulose and the xanthan gum are completely dissolved to obtain a granulation liquid.
9. The method for preparing the azithromycin-containing dry suspension according to claim 3, wherein the whole mesh size is phi 0.8mm, and the frequency is 30 Hz.
10. The method for preparing the azithromycin-containing dry suspension according to claim 3, wherein the mixing frequency of the three-dimensional mixer is 45Hz, and the mixing time is 15 min.
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| CN113332259A (en) * | 2021-04-21 | 2021-09-03 | 海南普利制药股份有限公司 | Azithromycin dry suspension |
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| US20040247580A1 (en) * | 2003-06-06 | 2004-12-09 | Myung-Jun Chung | Process for preparing double-coated lactic acid bacteria powder using protein and polysaccharide and product by the same |
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| US20040247580A1 (en) * | 2003-06-06 | 2004-12-09 | Myung-Jun Chung | Process for preparing double-coated lactic acid bacteria powder using protein and polysaccharide and product by the same |
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| CN113332259A (en) * | 2021-04-21 | 2021-09-03 | 海南普利制药股份有限公司 | Azithromycin dry suspension |
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