CN116687877B - Taqniamycin tartrate dry suspension and preparation method thereof - Google Patents
Taqniamycin tartrate dry suspension and preparation method thereof Download PDFInfo
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- CN116687877B CN116687877B CN202310980964.6A CN202310980964A CN116687877B CN 116687877 B CN116687877 B CN 116687877B CN 202310980964 A CN202310980964 A CN 202310980964A CN 116687877 B CN116687877 B CN 116687877B
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- coating
- tartrate
- enteric
- suspending agent
- agent layer
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- 239000000725 suspension Substances 0.000 title claims abstract description 68
- 238000002360 preparation method Methods 0.000 title claims abstract description 40
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 title claims description 53
- 229940095064 tartrate Drugs 0.000 title claims description 53
- 238000000576 coating method Methods 0.000 claims abstract description 80
- 239000011248 coating agent Substances 0.000 claims abstract description 74
- ICVKYYINQHWDLM-KBEWXLTPSA-N (2r,3r)-2,3-dihydroxybutanedioic acid;2-[(4r,5s,6s,7r,9r,11e,13e,15r,16r)-6-[(2r,3r,4r,5s,6r)-5-[(2s,4r,5s,6s)-4,5-dihydroxy-4,6-dimethyloxan-2-yl]oxy-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-16-ethyl-4-hydroxy-15-[[(2r,3r,4r,5r,6r)-5-hydroxy-3,4 Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.O([C@@H]1[C@@H](C)O[C@H]([C@@H]([C@H]1N(C)C)O)O[C@@H]1[C@@H](C)[C@H](O)CC(=O)O[C@@H]([C@H](/C=C(\C)/C=C/C(=O)[C@H](C)C[C@@H]1CC=O)CO[C@H]1[C@@H]([C@H](OC)[C@H](O)[C@@H](C)O1)OC)CC)[C@H]1C[C@@](C)(O)[C@@H](O)[C@H](C)O1 ICVKYYINQHWDLM-KBEWXLTPSA-N 0.000 claims abstract description 57
- 229960001717 tylosin tartrate Drugs 0.000 claims abstract description 57
- 239000010410 layer Substances 0.000 claims abstract description 53
- 239000007788 liquid Substances 0.000 claims abstract description 50
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 49
- 239000008188 pellet Substances 0.000 claims abstract description 48
- 239000000375 suspending agent Substances 0.000 claims abstract description 46
- 239000002702 enteric coating Substances 0.000 claims abstract description 44
- 238000001035 drying Methods 0.000 claims abstract description 30
- 239000008213 purified water Substances 0.000 claims abstract description 27
- 238000002156 mixing Methods 0.000 claims abstract description 15
- 239000012055 enteric layer Substances 0.000 claims abstract description 14
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 14
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 14
- 229920001285 xanthan gum Polymers 0.000 claims abstract description 14
- 239000000230 xanthan gum Substances 0.000 claims abstract description 14
- 235000010493 xanthan gum Nutrition 0.000 claims abstract description 14
- 229940082509 xanthan gum Drugs 0.000 claims abstract description 14
- 229960005240 telavancin Drugs 0.000 claims description 43
- 108010089019 telavancin Proteins 0.000 claims description 43
- ONUMZHGUFYIKPM-MXNFEBESSA-N telavancin Chemical compound O1[C@@H](C)[C@@H](O)[C@](NCCNCCCCCCCCCC)(C)C[C@@H]1O[C@H]1[C@H](OC=2C3=CC=4[C@H](C(N[C@H]5C(=O)N[C@H](C(N[C@@H](C6=CC(O)=C(CNCP(O)(O)=O)C(O)=C6C=6C(O)=CC=C5C=6)C(O)=O)=O)[C@H](O)C5=CC=C(C(=C5)Cl)O3)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](NC(=O)[C@@H](CC(C)C)NC)[C@H](O)C3=CC=C(C(=C3)Cl)OC=2C=4)O[C@H](CO)[C@@H](O)[C@@H]1O ONUMZHGUFYIKPM-MXNFEBESSA-N 0.000 claims description 43
- 238000009505 enteric coating Methods 0.000 claims description 41
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 24
- 239000000853 adhesive Substances 0.000 claims description 22
- 230000001070 adhesive effect Effects 0.000 claims description 22
- 239000011812 mixed powder Substances 0.000 claims description 20
- 239000000843 powder Substances 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 15
- 229920003082 Povidone K 90 Polymers 0.000 claims description 14
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 claims description 14
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 claims description 14
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 12
- 229920002472 Starch Polymers 0.000 claims description 12
- 239000008101 lactose Substances 0.000 claims description 12
- 239000011734 sodium Substances 0.000 claims description 12
- 229910052708 sodium Inorganic materials 0.000 claims description 12
- 239000008107 starch Substances 0.000 claims description 12
- 235000019698 starch Nutrition 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 11
- 230000002572 peristaltic effect Effects 0.000 claims description 6
- 239000006187 pill Substances 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 4
- 238000005469 granulation Methods 0.000 claims description 3
- 230000003179 granulation Effects 0.000 claims description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
- 210000002784 stomach Anatomy 0.000 abstract description 10
- 239000000428 dust Substances 0.000 abstract description 6
- 230000007794 irritation Effects 0.000 abstract description 5
- 210000004211 gastric acid Anatomy 0.000 abstract description 4
- 230000007062 hydrolysis Effects 0.000 abstract description 4
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 4
- 235000019629 palatability Nutrition 0.000 abstract description 4
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
- 230000000052 comparative effect Effects 0.000 description 22
- 230000004584 weight gain Effects 0.000 description 22
- 235000019786 weight gain Nutrition 0.000 description 22
- 238000007599 discharging Methods 0.000 description 15
- 238000005303 weighing Methods 0.000 description 15
- 229940079593 drug Drugs 0.000 description 14
- 239000000243 solution Substances 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 238000004062 sedimentation Methods 0.000 description 8
- 238000005507 spraying Methods 0.000 description 8
- WBPYTXDJUQJLPQ-VMXQISHHSA-N tylosin Chemical compound O([C@@H]1[C@@H](C)O[C@H]([C@@H]([C@H]1N(C)C)O)O[C@@H]1[C@@H](C)[C@H](O)CC(=O)O[C@@H]([C@H](/C=C(\C)/C=C/C(=O)[C@H](C)C[C@@H]1CC=O)CO[C@H]1[C@@H]([C@H](OC)[C@H](O)[C@@H](C)O1)OC)CC)[C@H]1C[C@@](C)(O)[C@@H](O)[C@H](C)O1 WBPYTXDJUQJLPQ-VMXQISHHSA-N 0.000 description 8
- 241000204031 Mycoplasma Species 0.000 description 6
- 230000002378 acidificating effect Effects 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 238000013112 stability test Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 230000007547 defect Effects 0.000 description 3
- 239000003651 drinking water Substances 0.000 description 3
- 235000020188 drinking water Nutrition 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 244000144972 livestock Species 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 241000192125 Firmicutes Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229930194936 Tylosin Natural products 0.000 description 2
- 239000004182 Tylosin Substances 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 235000019658 bitter taste Nutrition 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 230000001055 chewing effect Effects 0.000 description 2
- 230000035622 drinking Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 229960004059 tylosin Drugs 0.000 description 2
- 235000019375 tylosin Nutrition 0.000 description 2
- 241000606750 Actinobacillus Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000014085 Chronic respiratory disease Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- IKMDFBPHZNJCSN-UHFFFAOYSA-N Myricetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC(O)=C(O)C(O)=C1 IKMDFBPHZNJCSN-UHFFFAOYSA-N 0.000 description 1
- 241000589970 Spirochaetales Species 0.000 description 1
- 108010053950 Teicoplanin Proteins 0.000 description 1
- OLLSDNUHBJHKJS-XKORHJEPSA-N [(2s,3s,4r,6s)-6-[(2r,3s,4r,5r,6r)-6-[[(4r,5s,6s,7r,9r,11e,13e,15r,16r)-4-acetyloxy-16-ethyl-15-[[(2r,3r,4r,5r,6r)-5-hydroxy-3,4-dimethoxy-6-methyloxan-2-yl]oxymethyl]-5,9,13-trimethyl-2,10-dioxo-7-(2-oxoethyl)-1-oxacyclohexadeca-11,13-dien-6-yl]oxy]-4-(d Chemical group OC(=O)[C@H](O)[C@@H](O)C(O)=O.O([C@@H]1[C@@H](C)O[C@H]([C@@H]([C@H]1N(C)C)O)O[C@@H]1[C@@H](C)[C@H](OC(C)=O)CC(=O)O[C@@H]([C@H](/C=C(\C)/C=C/C(=O)[C@H](C)C[C@@H]1CC=O)CO[C@H]1[C@@H]([C@H](OC)[C@H](O)[C@@H](C)O1)OC)CC)[C@H]1C[C@@](C)(O)[C@@H](OC(=O)CC(C)C)[C@H](C)O1 OLLSDNUHBJHKJS-XKORHJEPSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 210000004712 air sac Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- DDTDNCYHLGRFBM-YZEKDTGTSA-N chembl2367892 Chemical compound CC(=O)N[C@H]1[C@@H](O)[C@H](O)[C@H](CO)O[C@H]1O[C@@H]([C@H]1C(N[C@@H](C2=CC(O)=CC(O[C@@H]3[C@H]([C@H](O)[C@H](O)[C@@H](CO)O3)O)=C2C=2C(O)=CC=C(C=2)[C@@H](NC(=O)[C@@H]2NC(=O)[C@@H]3C=4C=C(O)C=C(C=4)OC=4C(O)=CC=C(C=4)[C@@H](N)C(=O)N[C@H](CC=4C=C(Cl)C(O5)=CC=4)C(=O)N3)C(=O)N1)C(O)=O)=O)C(C=C1Cl)=CC=C1OC1=C(O[C@H]3[C@H]([C@@H](O)[C@H](O)[C@H](CO)O3)NC(C)=O)C5=CC2=C1 DDTDNCYHLGRFBM-YZEKDTGTSA-N 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000011247 coating layer Substances 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000009477 fluid bed granulation Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229940116852 myricetin Drugs 0.000 description 1
- PCOBUQBNVYZTBU-UHFFFAOYSA-N myricetin Natural products OC1=C(O)C(O)=CC(C=2OC3=CC(O)=C(O)C(O)=C3C(=O)C=2)=C1 PCOBUQBNVYZTBU-UHFFFAOYSA-N 0.000 description 1
- 235000007743 myricetin Nutrition 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229960001608 teicoplanin Drugs 0.000 description 1
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
- A61K9/48—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
- 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
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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
- A61K9/501—Inorganic compounds
-
- 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
- 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
- A61K9/5073—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 having two or more different coatings optionally including drug-containing subcoatings
-
- 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
- A61K9/5089—Processes
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (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 invention discloses a tylosin tartrate dry suspension and a preparation method thereof, belonging to the technical field of pharmaceutical preparations, wherein the preparation method comprises the following steps: preparing a pill-carrying core, coating an enteric layer and coating a suspending agent layer; the suspending agent layer is coated, HPMC and xanthan gum are dispersed in purified water to prepare suspending agent layer coating liquid; coating the tylosin tartrate enteric pellets with a coating solution of a suspending agent layer in a fluidized bed, and drying after the coating is finished to obtain a tylosin tartrate dry suspension; the invention can solve the problems of poor stability, poor uniformity in mixing, easy hydrolysis by gastric acid in stomach, low bioavailability, large dust irritation and poor palatability of the tylosin tartrate.
Description
Technical Field
The invention relates to the technical field of pharmaceutical preparations, in particular to a telavancin tartrate dry suspension and a preparation method thereof.
Background
The chemical name of the tylosin tartrate is acetyl isovaleryl tylosin tartrate, which is a derivative generated by chemical modification of tylosin A, so that the defect that the tylosin has poor effect on actinobacillus pleuralis is overcome. The antibacterial spectrum is similar to tylosin, has stronger antibacterial activity on mycoplasma, spirochete, most gram-positive bacteria and partial gram-negative bacteria, especially has strong antibacterial activity on mycoplasma, and has stronger antibacterial activity on mycoplasma septicum and synovial mycoplasma. Can be used for treating infectious diseases caused by mycoplasma and sensitive gram positive bacteria, such as chicken chronic respiratory disease, infectious rhinitis, air sac inflammation, and streptococcosis.
The tylosin tartrate preparation in the market is generally divided into soluble powder and a premix, wherein the soluble powder is easy to raise dust and is easy to generate dust irritation to influence the health of operators, and the premix is generally used for mixing materials, but the uniformity cannot be ensured. The original powder of the tavancomycin tartrate has extremely heavy bitter taste and poor palatability, is unstable under acidic conditions and is easy to hydrolyze, and the hydrolysis of the tavancomycin tartrate can be caused in the stomach of livestock due to the action of gastric acid, so that the bioavailability is poor.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides the tylosin tartrate dry suspension and the preparation method thereof, which can solve the problems of poor stability, poor uniformity, easy hydrolysis by gastric acid in the stomach, reduced bioavailability, large dust irritation and poor palatability of the tylosin tartrate.
In order to solve the technical problems, the technical scheme adopted by the invention is as follows:
the preparation method of the telavancin tartrate dry suspension comprises the following steps: preparing a pill-carrying core, coating an enteric layer and coating a suspending agent layer;
the preparation of the pill carrying core comprises the steps of respectively crushing and uniformly mixing the tylosin tartrate raw powder, sodium carboxymethyl starch, talcum powder and lactose to obtain mixed powder; PVP K90 is dissolved in water and stirred uniformly to be used as an adhesive; granulating the mixed powder and the adhesive by a fluidized bed, and drying to obtain a pill carrying core;
in the step of preparing the pill carrying core, the weight ratio of Dan Suantai myricetin raw powder to carboxymethyl starch sodium to talcum powder to lactose to PVP K90 is 50:5-15:5-8:22-29:5-10;
the mass volume ratio of PVP K90 to water in the adhesive is 5-10 g/100 mL;
peristaltic pump frequency in the fluidized bed granulation process is 10%, and air inlet speed is 30m 3 And/h, wherein the air inlet temperature is 55 ℃;
the enteric coating is prepared by dispersing hydroxypropyl methylcellulose phthalate and talcum powder in purified water to prepare enteric coating liquid; coating the pill-carrying cores by using enteric coating liquid in a fluidized bed, and drying after coating to obtain the telavancin tartrate enteric pellets;
in the enteric coating step, the mass ratio of hydroxypropyl methylcellulose phthalate, talcum powder and purified water in the enteric coating liquid is 12-32:8-12:100;
the mass ratio of the telavancin tartrate enteric-coated pellets to the pill-carrying cores is 1.2-1.4:1;
the suspending agent layer is coated, HPMC and xanthan gum are dispersed in purified water to prepare suspending agent layer coating liquid; coating the tylosin tartrate enteric pellets with a coating solution of a suspending agent layer in a fluidized bed, and drying after the coating is finished to obtain a tylosin tartrate dry suspension;
in the step of coating the suspending agent layer, the mass ratio of HPMC, xanthan gum and purified water in the suspending agent layer coating liquid is 7-13:7-13:100;
the mass ratio of the telavancin tartrate dry suspension to the telavancin tartrate enteric pellets is 1.1-1.2:1;
peristaltic pump frequency in the fluidized bed coating process in the enteric coating layer coating and the suspending agent layer coating is 15%, and air inlet quantity is 50m 3 And/h, wherein the air inlet temperature is 45 ℃.
The tylosin tartrate dry suspension is prepared by the method.
Compared with the prior art, the invention has the beneficial effects that:
(1) Compared with the prior art, the preparation method of the tylosin tartrate dry suspension has the advantages that the fluidized bed granulation and coating technology is utilized, the prepared sample has good fluidity and less fine powder, the problem of large irritation of the tylosin tartrate soluble powder dust is solved, and meanwhile, the enteric coating layer is additionally arranged on the drug-carrying particles, so that the problem of poor stability of the tylosin tartrate is solved, and the bitter taste of the tylosin tartrate can be covered; the suspending agent layer is added on the outer layer of the enteric coating, and the xanthan gum and HPMC are used as suspending agents, so that the tylosin tartrate can be uniformly dispersed in water, the enteric coating layer can not be damaged in drinking water use, and the tylosin tartrate is prevented from being decomposed in the stomach;
(2) Because the tylosin tartrate is unstable under the acidic condition and is easy to hydrolyze by gastric acid, the product takes hydroxypropyl methyl cellulose phthalate as an enteric layer outside drug-carrying particles, and the hydroxypropyl methyl cellulose phthalate is stable and has plasticity, so that the stability of the tylosin tartrate can be improved, and meanwhile, the use of plasticizers is avoided; in addition, the suspending agent coating layer is added outside the enteric layer, so that the product is in a suspension state in water, the problem of dust irritation is avoided, and the palatability is good, therefore, the enteric preparation can be used for drinking water administration, and the defect that the conventional enteric preparation can only be used for mixing materials, and the enteric layer is damaged by livestock chewing, so that the bioavailability of the product is reduced is avoided;
(3) According to the preparation method of the tylosin tartrate dry suspension, the prepared tylosin tartrate dry suspension is stable after being dissolved in water, 5g of the tylosin tartrate dry suspension prepared by the preparation method is dissolved in 50mL of purified water, and after standing for 3 hours, the tylosin tartrate dry suspension is still in a white viscous state, and the sedimentation volume ratio is 0.96-1.00;
(4) According to the preparation method of the tylosin tartrate dry suspension, the prepared tylosin tartrate dry suspension has good component stability, the prepared tylosin tartrate dry suspension is packaged and then placed in a stability test box with the temperature of 40 ℃ and the humidity of 75% for component stability test, the content of tylosin A before the test is 88.52-88.87%, the content of tylosin A after the test is 88.26-88.65%, the content of tylosin A after the test is 2 months is 88.04-88.42%, the content of tylosin A after the test is 3 months is 87.57-87.96%, and the content of tylosin A after the test is 6 months is 87.14-87.56%;
(5) According to the preparation method of the tylosin tartrate dry suspension, the prepared tylosin tartrate dry suspension is high in stability in the stomach and high in release rate in an intestinal solution environment, the prepared tylosin tartrate dry suspension is 2.04-2.23% in pH (potential of hydrogen) 1.0 in an environment of 5min, 2.99-3.38% in 30min, 4.36-4.59% in 60min, 4.95-5.13% in 90min and 6.56-6.95% in 120 min; the dissolution rate of the prepared tylosin tartrate dry suspension is 20.20-20.63% in 5min, 48.22-48.66% in 15min, 77.96-78.33% in 30min and 98.68-99.12% in 45min in the environment with the pH of 6.8;
(6) According to the preparation method of the tylosin tartrate dry suspension, the prepared tylosin tartrate dry suspension can be uniformly dispersed in water so as to be used by drinking water, so that the damage of an enteric layer is avoided, the treatment effect of the tylosin tartrate is ensured, the tylosin tartrate dry suspension is used for treating piglets, and the cure rate is 100% after being continuously taken for three days in a mixed drinking mode.
Detailed Description
Specific embodiments of the present invention will now be described in order to provide a clearer understanding of the technical features, objects and effects of the present invention.
Example 1
A preparation method of a tylosin tartrate dry suspension comprises the following steps:
1. respectively crushing 50g of tavancomycin tartrate raw powder, 10g of sodium carboxymethyl starch, 5g of talcum powder and 27g of lactose, and uniformly mixing to obtain mixed powder; 8g PVP K90 is dissolved in 100mL water and stirred uniformly to be used as an adhesive; opening the fluidized bed, adding the mixed powder into the fluidized bed, spraying the adhesive into the fluidized bed for granulating, and drying after granulating to obtain the pill-carrying core.
2. Dispersing 12g of hydroxypropyl methyl cellulose phthalate and 8g of talcum powder in 100g of purified water to prepare enteric coating liquid, putting the pill-carrying core into a fluidized bed, coating the enteric coating liquid with the enteric coating liquid, drying after coating, discharging, weighing, and obtaining the telavancin tartrate enteric pellets with the weight gain of 20% of the pill-carrying core.
3. Dispersing 12g HPMC and 12g xanthan gum in 100g purified water to prepare a suspending agent layer coating liquid, putting the enteric pellets into a fluidized bed, coating the suspending agent layer by using the suspending agent layer coating liquid, drying after coating, discharging, and weighing to prepare the telavancin tartrate dry suspension with the weight gain of 20% of the enteric pellets.
Example 2
A preparation method of a tylosin tartrate dry suspension comprises the following steps:
1. respectively crushing 50g of tavancomycin tartrate raw powder, 5g of sodium carboxymethyl starch, 6g of talcum powder and 29g of lactose, and uniformly mixing to obtain mixed powder; 10g PVP K90 is dissolved in 100mL water and stirred uniformly to be used as an adhesive; opening the fluidized bed, adding the mixed powder into the fluidized bed, spraying the adhesive into the fluidized bed for granulating, and drying after granulating to obtain the pill-carrying core.
2. Dispersing 21g of hydroxypropyl methyl cellulose phthalate and 9g of talcum powder in 100g of purified water to prepare enteric coating liquid, putting the drug-loaded pellet core into a fluidized bed, coating the enteric coating liquid with the enteric coating liquid, drying after coating, discharging, and weighing to prepare the telavancin tartrate enteric pellets with the weight gain of 30% of the drug-loaded pellet core.
3. Dispersing 8g HPMC and 12g xanthan gum in 100g purified water to prepare a suspending agent layer coating liquid, putting the obtained enteric pellets into a fluidized bed, coating the suspending agent layer with the suspending agent layer coating liquid, drying after coating, discharging, and weighing to prepare the telavancin dry suspension with the weight gain of 15% of the enteric pellets.
Example 3
A preparation method of a tylosin tartrate dry suspension comprises the following steps:
1. respectively crushing 50g of tavancomycin tartrate raw powder, 12g of sodium carboxymethyl starch, 8g of talcum powder and 25g of lactose, and uniformly mixing to obtain mixed powder; 5g PVP K90 is dissolved in 100mL water and stirred uniformly to be used as an adhesive; opening the fluidized bed, adding the mixed powder into the fluidized bed, spraying the obtained adhesive into the fluidized bed for granulating, and drying after granulating to obtain the pill-carrying core.
2. Dispersing 32g of hydroxypropyl methyl cellulose phthalate and 8g of talcum powder in 100g of purified water to prepare enteric coating liquid, putting the drug-loaded pellet core into a fluidized bed, coating the enteric coating liquid with the enteric coating liquid, drying after coating, discharging, weighing, and obtaining the telavancin tartrate enteric pellets with weight gain of 40% of the drug-loaded pellet core.
3. Dispersing 7g HPMC and 7g xanthan gum in 100g purified water to prepare a suspending agent layer coating liquid, putting the enteric pellets into a fluidized bed, coating the suspending agent layer by using the suspending agent layer coating liquid, drying after coating, discharging, and weighing to prepare the telavancin tartrate dry suspension with weight gain of 10% of the enteric pellets.
Example 4
A preparation method of a tylosin tartrate dry suspension comprises the following steps:
1. respectively crushing 50g of tavancomycin tartrate raw powder, 15g of sodium carboxymethyl starch, 7g of talcum powder and 22g of lactose, and uniformly mixing to obtain mixed powder; 6g PVP K90 is dissolved in 100mL water and stirred uniformly to be used as an adhesive; opening the fluidized bed, adding the mixed powder into the fluidized bed, spraying the adhesive into the fluidized bed for granulating, and drying after granulating to obtain the pill-carrying core.
2. Dispersing 18g of hydroxypropyl methyl cellulose phthalate and 12g of talcum powder in 100g of purified water to prepare enteric coating liquid, putting the drug-loaded pellet core into a fluidized bed, coating the enteric coating liquid with the enteric coating liquid, drying after coating, discharging, and weighing to prepare the telavancin tartrate enteric pellets with the weight gain of 30% of the drug-loaded pellet core.
3. Dispersing 13g HPMC and 13g xanthan gum in 100g purified water to prepare a suspending agent layer coating liquid, putting the enteric pellets into a fluidized bed, coating the suspending agent layer by using the suspending agent layer coating liquid, drying after coating, discharging, and weighing to prepare the telavancin tartrate dry suspension with the weight gain of 20% of the enteric pellets.
Comparative example 1 reduction of enteric layer weight gain
A preparation method of a tylosin tartrate dry suspension comprises the following steps:
1. respectively crushing 50g of tavancomycin tartrate raw powder, 15g of sodium carboxymethyl starch, 7g of talcum powder and 22g of lactose, and uniformly mixing to obtain mixed powder; 6g PVP K90 is dissolved in 100mL water and stirred uniformly to be used as an adhesive; opening the fluidized bed, adding the mixed powder into the fluidized bed, spraying the adhesive into the fluidized bed for granulating, and drying after granulating to obtain the pill-carrying core.
2. And dispersing 6g of hydroxypropyl methyl cellulose phthalate and 4g of talcum powder in 100g of purified water to prepare enteric coating liquid, putting the obtained drug-loaded pellet core into a fluidized bed, coating the enteric coating liquid with the enteric coating liquid, drying after coating, discharging, and weighing to prepare the telavancin tartrate enteric pellets with weight gain of 10% of the drug-loaded pellet core.
3. Dispersing 11g HPMC and 11g xanthan gum in 100g purified water to prepare a suspending agent layer coating liquid, putting the enteric pellets into a fluidized bed, coating the suspending agent layer by using the suspending agent layer coating liquid, drying after coating, discharging, and weighing to prepare the telavancin tartrate dry suspension with the weight gain of 20% of the enteric pellets.
Comparative example 2 increasing the weight gain of the enteric layer
A preparation method of a tylosin tartrate dry suspension comprises the following steps:
1. respectively crushing 50g of tavancomycin tartrate raw powder, 15g of sodium carboxymethyl starch, 7g of talcum powder and 22g of lactose, and uniformly mixing to obtain mixed powder; 6g PVP K90 is dissolved in 100mL water and stirred uniformly to be used as an adhesive; opening the fluidized bed, adding the mixed powder into the fluidized bed, spraying the obtained adhesive into the fluidized bed for granulating, and drying after granulating to obtain the pill-carrying core.
2. 30g of hydroxypropyl methyl cellulose phthalate and 20g of talcum powder are dispersed in 100g of purified water to prepare enteric coating liquid, the drug-loaded pellet cores are put into a fluidized bed to be subjected to enteric coating by using the enteric coating liquid, and after coating, the materials are dried, discharged and weighed, so that the telavancin tartrate enteric pellets with weight gain of 50% of the drug-loaded pellet cores are prepared.
3. Dispersing 15g HPMC and 15g xanthan gum in 100g purified water to prepare a suspending agent layer coating liquid, putting the enteric pellets into a fluidized bed, coating the suspending agent layer by using the suspending agent layer coating liquid, drying after coating, discharging, and weighing to prepare the telavancin tartrate dry suspension with the weight gain of 20% of the enteric pellets.
Comparative example 3 reduction of weight gain of a suspension layer
A preparation method of a tylosin tartrate dry suspension comprises the following steps:
1. respectively crushing 50g of tavancomycin tartrate raw powder, 15g of sodium carboxymethyl starch, 7g of talcum powder and 22g of lactose, and uniformly mixing to obtain mixed powder; 6g PVP K90 is dissolved in 100mL water and stirred uniformly to be used as an adhesive; opening the fluidized bed, adding the mixed powder into the fluidized bed, spraying the adhesive into the fluidized bed for granulating, and drying after granulating to obtain the pill-carrying core.
2. Dispersing 18g of hydroxypropyl methyl cellulose phthalate and 12g of talcum powder in 100g of purified water to prepare enteric coating liquid, putting the obtained drug-loaded pellet core into a fluidized bed, coating the enteric coating liquid with the enteric coating liquid, drying after coating, discharging, weighing, and obtaining the telavancin tartrate enteric pellets with weight gain of 30% of the drug-loaded pellet core.
3.3 g HPMC and 3.5g xanthan gum are dispersed in 100g purified water to prepare a suspending agent layer coating liquid, enteric pellets are put into a fluidized bed to be coated with the suspending agent layer coating liquid, and after coating, drying, discharging and weighing are carried out to prepare the telavancin dry suspension with weight gain of 5% of the enteric pellets.
Comparative example 4 increasing the weight gain of the suspension layer
A preparation method of a tylosin tartrate dry suspension comprises the following steps:
1. respectively crushing 50g of tavancomycin tartrate raw powder, 15g of sodium carboxymethyl starch, 7g of talcum powder and 22g of lactose, and uniformly mixing to obtain mixed powder; 6g PVP K90 is dissolved in 100mL water and stirred uniformly to be used as an adhesive; opening the fluidized bed, adding the mixed powder into the fluidized bed, spraying the obtained adhesive into the fluidized bed for granulating, and drying after granulating to obtain the pill-carrying core.
2. Dispersing 18g of hydroxypropyl methyl cellulose phthalate and 12g of talcum powder in 100g of purified water to prepare enteric coating liquid, putting the obtained drug-loaded pellet core into a fluidized bed, coating the enteric coating liquid with the enteric coating liquid, drying after coating, discharging, weighing, and obtaining the telavancin tartrate enteric pellets with weight gain of 30% of the drug-loaded pellet core.
3. Dispersing 19g HPMC and 20g xanthan gum in 100g purified water to prepare a suspending agent layer coating liquid, putting the obtained enteric pellets into a fluidized bed, coating the suspending agent layer with the suspending agent layer coating liquid, drying after coating, discharging, and weighing to prepare the telavancin dry suspension with the weight gain of 30% of the enteric pellets.
Comparative example 5
The content of the telavancin tartrate in the commercial telavancin tartrate premix 1 is 50 percent.
Comparative example 6
The content of the tylwanin tartrate in the commercial tylwanin tartrate premix 2 is 50 percent.
In examples 1-4 and comparative examples 1-4 above, the process parameters of the fluid bed granulation process were: peristaltic pump frequency is 10%, air inlet speed is 30m 3 And/h, the air inlet temperature is 55 ℃ until the sample is granulated; the coating process comprises the following technological parameters: peristaltic pump frequency is 15%, air inlet quantity is 50m 3 And/h, wherein the air inlet temperature is 45 ℃.
Test example 1 determination of the State in Water and the sedimentation volume ratio of the Dry suspension
According to the 2020 edition of the animal pharmacopoeia of the people's republic of China, 5g of the dry suspension or the commercial preparation prepared in the examples 1-4 and the comparative examples 1-6 are respectively put into different beakers, 50mL of purified water is respectively added, the solution is obtained after the solution is stirred and uniformly dispersed, the solution is transferred into a 50mL measuring cylinder with a plug, the initial height H0 of the suspension is recorded, the standing is carried out for 3 hours, the height H of the suspension is recorded again, the sedimentation volume ratio F value of the suspension is calculated, the sedimentation volume ratio F value = the height H of the suspension/the initial height H0 of the suspension, the F value is between 0 and 1, and the larger the F value is, the more stable the suspension is represented; simultaneously observing the state of each solution after 3 hours, and calculating and observing the F value as follows:
from the above results, it can be seen that the dry suspensions prepared in examples 1 to 4 all have excellent stability and do not substantially generate sedimentation; the dry suspension prepared in the comparative example 3 has obviously smaller sedimentation volume ratio and unstable sedimentation, and the generated sedimentation is more, mainly because the suspension agent is reduced, the complete suspension of the enteric pellets cannot be ensured; the dry suspension prepared in comparative example 4 was agglomerated in water mainly because the suspension had too much viscosity, and thus agglomerated.
Test example 2 stability test
100g of the dry suspension or the commercially available preparation prepared in examples 1 to 4 and comparative examples 1 to 6 were taken, and the dry suspension or the commercially available preparation was subjected to simulation to be packaged on the market, and simultaneously placed in a stability test box at a temperature of 40 ℃ and a humidity of 75%, and sampled after 1, 2, 3 and 6 months respectively according to pharmacopoeia specifications, and the content of telavancin A was detected, and the results were as follows:
from the above results, it can be seen that the stability of the active ingredient telavancin a in the telavancin tartrate formulations of examples 1-4 is far superior to that of comparative examples 5 and 6, and it can be found by comparison of examples 1-4 and comparative example 1 that the stability of the products of examples 1-4 is higher than that of comparative example 1, so that the addition of an enteric coating layer with an increase of 20% -40% by weight can play a role in protecting telavancin tartrate and increasing the stability of the granules.
Test example 3 Release Rate of Dry suspension under different conditions
The dry suspensions or commercially available preparations prepared in examples 1 to 4 and comparative examples 1 to 6 were tested according to method 1 for enteric preparation of the method for measuring dissolution and release of an annex in the "animal pharmacopoeia of the people's republic of China" 2020 edition, and gastric solution was simulated with 0.1mol/L hydrochloric acid solution to test the release rate in acid for 2 hours; adding phosphate buffer solution, adjusting pH to 6.8, simulating intestinal solution, and detecting leaching amount in the buffer solution for 45 min; according to pharmacopoeia requirements, the dissolution rate of the preparation in acid for 2 hours should not exceed 10%, the dissolution rate in buffer solution for 45min should not be lower than 70%, and the measurement results are shown as follows:
from the above results, it can be seen that comparative example 5 and comparative example 6 have high release rates at ph1.0, indicating that the formulation is unstable under acidic conditions of the stomach, easily resulting in failure of telavancin tartrate; the tylosin tartrate preparation prepared in the examples 1-4 has low release rate at the pH of 1.0, which shows that the stability in the stomach is higher, the release rate at the pH of 6.8 is high, and the release rate can reach more than 90% at 45min, so that the tylosin tartrate preparation prepared in the examples 1-4 has higher release rate in the intestinal solution environment and meets the pharmacopoeia requirements. The tylosin tartrate preparation prepared in the comparative example 1 has higher release rate under the condition of pH1.0 after the weight gain of the enteric layer is reduced, the stability is obviously reduced, and the tylosin tartrate preparation prepared in the comparative example 2 has slow release under the condition of pH 6.8 after the weight gain of the enteric layer is improved, so that the weight of the enteric coating layer has a critical influence on the stability of the product in the stomach environment and the release rate in the duodenum environment.
Test example 4 determination of therapeutic effect of teicoplanin tartrate
The piglets 200 suffering from mycoplasma respiratory disease are equally divided into 10 groups, 20 groups are treated by using the tylosin tartrate preparations of the examples 1-4 and the comparative examples 1-4 respectively, and the tylosin tartrate preparations of the examples 1-4 and the comparative examples 1-4 are directly added into water for mixing and drinking, wherein the tylosin tartrate content in each 1L of water is 50mg; the commercial tylosin tartrate premix of comparative examples 5-6 adopts a mixed feeding method, and the tylosin tartrate content in each 1000kg is 50g; three days after continuous administration, the curing conditions of each group of piglets are counted, and the curing results are shown as follows:
from the above results, it can be seen that the therapeutic effect of the telavancin tartrate dry suspension prepared in examples 1-4 is significantly higher than that of the commercial telavancin tartrate premix, mainly because the telavancin tartrate is unstable under the acidic condition in the stomach, while the commercial telavancin tartrate premix is insoluble in water and can only be used for mixing, and the chewing effect of livestock during eating can cause the enteric layer to be destroyed, thereby leading to the hydrolysis of the telavancin tartrate in the stomach and the therapeutic effect to be reduced; in the embodiments 1-4, the suspending agent layer is further coated on the outer layer of the enteric layer, so that the telavancin tartrate preparation can be uniformly dispersed in water, and further can be drunk, the damage of the enteric layer is avoided, and the therapeutic effect of the telavancin tartrate is ensured.
The percentages used in the present invention are mass percentages unless otherwise indicated.
Finally, it should be noted that: the foregoing description is only a preferred embodiment of the present invention, and the present invention is not limited thereto, but it is to be understood that modifications and equivalents of some of the technical features described in the foregoing embodiments may be made by those skilled in the art, although the present invention has been described in detail with reference to the foregoing embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (4)
1. The preparation method of the telavancin tartrate dry suspension is characterized by comprising the following steps of: preparing a pill-carrying core, coating an enteric layer and coating a suspending agent layer;
the preparation of the pill carrying core comprises the steps of respectively crushing and uniformly mixing the tylosin tartrate raw powder, sodium carboxymethyl starch, talcum powder and lactose to obtain mixed powder; PVP K90 is dissolved in water and stirred uniformly to be used as an adhesive; granulating the mixed powder and the adhesive by a fluidized bed, and drying to obtain a pill carrying core;
in the step of preparing the medicine carrying pill core, the weight ratio of the tylosin tartrate raw powder to the carboxymethyl starch sodium to the talcum powder to the lactose to the PVP K90 is 50:5-15:5-8:22-29:5-10;
the mass volume ratio of PVP K90 to water in the adhesive is 5-10 g/100 mL;
the enteric coating is prepared by dispersing hydroxypropyl methylcellulose phthalate and talcum powder in purified water to prepare enteric coating liquid; coating the pill-carrying cores by using enteric coating liquid in a fluidized bed, and drying after coating to obtain the telavancin tartrate enteric pellets;
in the enteric coating step, the mass ratio of hydroxypropyl methylcellulose phthalate, talcum powder and purified water in the enteric coating liquid is 12-32:8-12:100;
the mass ratio of the telavancin tartrate enteric-coated pellets to the pill-carrying cores is 1.2-1.4:1;
the suspending agent layer is coated, HPMC and xanthan gum are dispersed in purified water to prepare suspending agent layer coating liquid; coating the tylosin tartrate enteric pellets with a coating solution of a suspending agent layer in a fluidized bed, and drying after the coating is finished to obtain a tylosin tartrate dry suspension;
in the step of coating the suspending agent layer, the mass ratio of HPMC, xanthan gum and purified water in the suspending agent layer coating liquid is 7-13:7-13:100;
the mass ratio of the telavancin tartrate dry suspension to the telavancin tartrate enteric-coated pellets is 1.1-1.2:1.
2. The method for preparing a dry suspension of telavancin tartrate according to claim 1, wherein in the step of preparing the pill-carrying cores, peristaltic pump frequency in the fluidized bed granulation process is 10%, and air inlet speed is 30m 3 And/h, wherein the inlet air temperature is 55 ℃.
3. The method for preparing the tylosin tartrate dry suspension according to claim 1, wherein peristaltic pump frequency in the fluidized bed coating process in the enteric coating layer coating and the suspending agent layer coating is 15%, and air inlet quantity is 50m 3 And/h, wherein the air inlet temperature is 45 ℃.
4. A telavancin tartrate dry suspension prepared by the method of any one of claims 1-3.
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