CN113318079A - Method for improving dissolution rate of triclabendazole particles and dissolution rate detection method thereof - Google Patents
Method for improving dissolution rate of triclabendazole particles and dissolution rate detection method thereof Download PDFInfo
- Publication number
- CN113318079A CN113318079A CN202110523161.9A CN202110523161A CN113318079A CN 113318079 A CN113318079 A CN 113318079A CN 202110523161 A CN202110523161 A CN 202110523161A CN 113318079 A CN113318079 A CN 113318079A
- Authority
- CN
- China
- Prior art keywords
- triclabendazole
- dissolution rate
- dissolution
- mixing
- granules
- 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.)
- Granted
Links
- 238000004090 dissolution Methods 0.000 title claims abstract description 82
- NQPDXQQQCQDHHW-UHFFFAOYSA-N 6-chloro-5-(2,3-dichlorophenoxy)-2-(methylthio)-1H-benzimidazole Chemical compound ClC=1C=C2NC(SC)=NC2=CC=1OC1=CC=CC(Cl)=C1Cl NQPDXQQQCQDHHW-UHFFFAOYSA-N 0.000 title claims abstract description 48
- 229960000323 triclabendazole Drugs 0.000 title claims abstract description 48
- 238000000034 method Methods 0.000 title claims abstract description 29
- 239000002245 particle Substances 0.000 title claims abstract description 15
- 238000001514 detection method Methods 0.000 title abstract description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 32
- 238000002156 mixing Methods 0.000 claims abstract description 32
- 239000008187 granular material Substances 0.000 claims abstract description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229920002472 Starch Polymers 0.000 claims abstract description 18
- 239000008107 starch Substances 0.000 claims abstract description 18
- 235000019698 starch Nutrition 0.000 claims abstract description 18
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 claims abstract description 16
- 235000019441 ethanol Nutrition 0.000 claims abstract description 16
- 229920006316 polyvinylpyrrolidine Polymers 0.000 claims abstract description 16
- 239000001593 sorbitan monooleate Substances 0.000 claims abstract description 16
- 235000011069 sorbitan monooleate Nutrition 0.000 claims abstract description 16
- 229940035049 sorbitan monooleate Drugs 0.000 claims abstract description 16
- 239000002131 composite material Substances 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 13
- 239000007779 soft material Substances 0.000 claims abstract description 12
- 238000003756 stirring Methods 0.000 claims abstract description 11
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims abstract description 9
- 239000008103 glucose Substances 0.000 claims abstract description 9
- 238000001035 drying Methods 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims abstract description 4
- 239000000853 adhesive Substances 0.000 claims description 15
- 230000001070 adhesive effect Effects 0.000 claims description 15
- 239000000080 wetting agent Substances 0.000 claims description 15
- 239000012738 dissolution medium Substances 0.000 claims description 10
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 7
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 7
- 239000002002 slurry Substances 0.000 claims description 7
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 7
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 238000000338 in vitro Methods 0.000 claims description 6
- 239000004094 surface-active agent Substances 0.000 claims description 5
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 3
- 239000000945 filler Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 abstract description 7
- 238000002360 preparation method Methods 0.000 abstract description 4
- 239000000243 solution Substances 0.000 description 23
- 241001494479 Pecora Species 0.000 description 8
- 241000242711 Fasciola hepatica Species 0.000 description 7
- 241000283690 Bos taurus Species 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 210000000013 bile duct Anatomy 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 241000283707 Capra Species 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- PBETVWPFDZWCGN-UHFFFAOYSA-N N1C=CC=C1.ClC=1C(=C(C=CC1)Cl)Cl Chemical compound N1C=CC=C1.ClC=1C(=C(C=CC1)Cl)Cl PBETVWPFDZWCGN-UHFFFAOYSA-N 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000012322 Raynaud phenomenon Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000000507 anthelmentic effect Effects 0.000 description 1
- 229940124339 anthelmintic agent Drugs 0.000 description 1
- 239000000921 anthelmintic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 150000001556 benzimidazoles Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 239000000273 veterinary drug Substances 0.000 description 1
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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/10—Anthelmintics
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/15—Medicinal preparations ; Physical properties thereof, e.g. dissolubility
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Tropical Medicine & Parasitology (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a method for improving the dissolution rate of triclabendazole particles and a dissolution rate detection method thereof, comprising the following steps: firstly, mixing water, 95% ethanol, sorbitan monooleate and polyvinylpyrrolidone K30 according to the weight ratio of 3: 6: 0.4: 0.6, stirring and dissolving to obtain a clear and uniform composite solution for later use; then mixing triclabendazole, starch and glucose according to the ratio of 1: 1: 8, mixing in a high-speed mixing pot for 5 minutes, slowly adding the mixture into the composite solution obtained in the step S1 according to the proportion of 5 percent by adopting a method of adding and stirring at the same time, and mixing for 5-10 minutes to prepare a soft material; and finally, putting the soft material into a granulator, granulating by using a 18-mesh screen, collecting and putting into an oven for drying. Compared with the prior art, the invention uses the composite solution as the preparation method of the triclabendazole granules, improves the drug dissolution rate, and adopts water, 95% ethanol, sorbitan monooleate and polyvinylpyrrolidone K30 according to the weight ratio of 3: 6: 0.4: the triclabendazole granule prepared at 0.6 has the best dissolution rate.
Description
Technical Field
The invention relates to the technical field of chemical pharmaceutical preparations, in particular to a method for improving the dissolution rate of triclabendazole particles and a dissolution rate detection method thereof.
Background
Triclabendazole (TCBZ) is a class of benzimidazole derivatives developed and produced by Raynaud-Jiaji (Ciba-Geigy) pharmaceutical factories in the 80 th century, is mainly used for controlling the infection of fasciola hepatica in sheep and cattle in veterinary practice since 1983, is white to white crystalline powder, is odorless, has slight aromatic flavor, is insoluble in water, belongs to a hydrophobic medicament, is not easy to disperse in water, and needs to be improved in bioavailability by some technological means.
Fasciola hepatica is a common parasite parasitizing in bile ducts of cattle, sheep and dozens of mammals, is sporadically popular all over the world, adults parasitize in the bile ducts of cattle, sheep and other mammals, the infection rate is more than 20-60%, triclabendazole has obvious killing effect on fasciola hepatica of various animals of different ages of days, and the fasciola hepatica not only aims at adults existing in bile ducts, but also aims at immature larvae of fasciola hepatica migrating through parenchyma of livers.
The research shows that: the triclabendazole is easy to absorb from gastrointestinal tracts after oral administration, is not easy to be damaged by acid and alkali, has high bioavailability, reaches the peak value in blood 24 to 36 hours after the oral administration of the triclabendazole in goats and sheep, and has the peak value in blood of prototypes and metabolites thereof 5 to 20 times that of other benzimidazole anthelmintics. Most of the oxidation occurs in cattle, sheep, dogs and rabbits as sulfoxide, sulfone and 4-hydroxy derivatives, which bind to albumin and persist in plasma for more than 7 days. After 10 days of administration, about 95% of the medicine is discharged from the feces, 2% is discharged from the urine, less than 1% is discharged from the milk, the metabolism is slowly discharged, and the half-life period T1/2 of the goat and sheep is about 22 days. Relevant reports indicate that the drug is selected to universally expel insects for sheep at 12 months per year, the best effect that no fasciola hepatica exists in sheep bodies in spring can be achieved, fasciola hepatica diseases can be thoroughly controlled, death in spring is reduced, production performance and economic benefit are improved, and the drug is a simple, convenient, practical and efficient insect expelling technology and should be popularized and applied in a large area.
The trichlorobenzene azole is used as a high-efficiency anti-liver-tablet medicament, the high-efficiency anti-insect effect of the trichlorobenzene azole is clinically determined in veterinarians, the types of foreign medicaments mainly comprise two dosage forms of suspension and pills, the dosage form of granules is in China, and the preparation is currently included in the 2015 edition of the veterinary drug dictionary of the people's republic of China, but a specific dissolution operation method is lacked.
The ethanol, sorbitan monooleate and polyvinylpyrrolidone K30 composite aqueous solution has the advantages of small dosage, low price and safety, and is widely applied to oral solid preparations, particularly to insoluble pharmaceutical preparations as a wetting agent, a surfactant and an adhesive, but is less applied to the research of changing the dissolution rate of the granules.
Disclosure of Invention
The invention aims to overcome the defects in the prior art, provides a composite solution as a wetting agent, a surfactant and an adhesive to change the dispersity of triclabendazole, improve the drug dissolution rate of the triclabendazole, solve the problem of low dissolution rate of triclabendazole, and obtain the triclabendazole by dissolution rate analysis, wherein the ratio of water to 95% ethanol to sorbitan monooleate to polyvinylpyrrolidone K30 is 3: 6: 0.4: 0.6, the best dissolution rate is the method for improving the dissolution rate of the triclabendazole particles and the dissolution rate detection method thereof.
In order to achieve the purpose, the technical scheme of the invention is as follows:
a method for improving the dissolution rate of triclabendazole particles comprises the following steps:
step S1, mixing water, 95% ethanol, sorbitan monooleate and polyvinylpyrrolidone K30 according to the weight ratio of 3: 6: 0.4: 0.6, stirring and dissolving to obtain a clear and uniform composite solution for later use;
step S2, mixing triclabendazole, starch and glucose according to the ratio of 1: 1: 8, mixing in a high-speed mixing pot for 5 minutes, slowly adding the mixture into the composite solution obtained in the step S1 according to the proportion of 5 percent by adopting a method of adding and stirring at the same time, and mixing for 5-10 minutes to prepare a soft material;
and step S3, putting the soft material on a granulator, granulating by using an 18-mesh screen, collecting, and putting into an oven for drying, wherein the temperature of the oven is set to be 80 ℃, and the time is 120 minutes.
Preferably, the sorbitan monooleate is a surfactant, the polyvinylpyrrolidone K30 is an adhesive, the water and the ethanol are wetting agents, and the starch and the glucose are carrier fillers.
Preferably, in the step S2, when the 10% starch slurry is the wetting agent or/and the adhesive, the dissolution rate of the triclabendazole granules is 65.14%; when 0.5% sodium carboxymethylcellulose solution is used as a wetting agent or/and an adhesive, the dissolution rate of the triclabendazole granules is 72.25%; when mixing water, 95% ethanol, sorbitan monooleate and polyvinylpyrrolidone K30 in the ratio of 3: 6: 0.4: 0.6 is wetting agent or/and adhesive, the dissolution rate of the triclabendazole particles is 100.00%.
Preferably, the ratio of water, 95% ethanol, sorbitan monooleate and polyvinylpyrrolidone K30 is 3: 6: 0.4: 0.6 is wetting agent or/and adhesive, the dissolution rate is improved by 30%.
A dissolution rate detection method of triclabendazole particles uses an intelligent dissolution instrument to examine the in-vitro dissolution condition.
Preferably, the set parameters of the intelligent dissolution instrument are as follows: the temperature is 37 ℃, the second method is carried out, and the rotating speed is 75 rpm/min; the dissolution medium is 900mL of 0.1mol/L hydrochloric acid solution and solution containing 0.5% Tween 20.
Preferably, 200mg of triclabendazole particles are added into a dissolution cup of the intelligent dissolution apparatus, 5mL of samples are sucked at 5 min, 15 min, 30min, 60 min, 90 min and 120min respectively after the medicine just contacts with the dissolution medium, and 5mL of fresh dissolution medium is immediately supplemented to calculate the dissolution rate change of the triclabendazole particles.
The invention uses a compound solution as a wetting agent, a surfactant and an adhesive to change the dispersion degree of triclabendazole, improve the drug dissolution rate, solve the problem of low dissolution rate of triclabendazole, and obtain the compound solution by dissolution rate analysis, wherein the ratio of water, 95% ethanol, sorbitan monooleate and polyvinylpyrrolidone K30 is 3: 6: 0.4: the dissolution rate is most preferable at 0.6.
Drawings
FIG. 1 is a reference graph of the dissolution profile of pellets prepared from a 10% starch slurry according to the present invention;
FIG. 2 is a reference graph of the dissolution profile of granules prepared from 0.5% sodium carboxymethyl cellulose solution in accordance with the present invention;
FIG. 3 is a reference graph of dissolution curves for particles prepared from the composite solution according to the present invention;
FIG. 4 is a graph showing the dissolution rate of triclabendazole granules prepared by different methods;
wherein, in the graph of fig. 4, the curve 1 is the dissolution curve of the granules prepared from 10% starch slurry, the curve 2 is the dissolution curve of the granules prepared from 0.5% sodium carboxymethyl cellulose solution, and the curve 3 is the dissolution curve of the granules prepared from composite solution.
Detailed Description
So that the manner in which the above recited features of the present invention can be understood and readily understood, a more particular description of the invention, briefly summarized above, may be had by reference to embodiments, some of which are illustrated in the appended drawings, wherein:
a method for improving the dissolution rate of triclabendazole particles comprises the following specific steps:
(1) through screening experiments, the invention uses triclabendazole, starch and glucose according to the weight ratio of 1: 1: 8 is the prescription subject;
(2) adding 1 part of starch into 9 parts of water, flushing the starch into uniform starch slurry by using steam, and cooling the starch slurry for later use;
(3) adding 0.5 part of sodium carboxymethylcellulose into 99.5 parts of water, and stirring to dissolve the sodium carboxymethylcellulose into a clear solution for later use;
(4) mixing water, 95% ethanol, sorbitan monooleate and polyvinylpyrrolidone K30 according to the weight ratio of 3: 6: 0.4: 0.6, stirring and dissolving to obtain a clear and uniform solution for later use;
(5) mixing triclabendazole, starch and glucose according to the weight ratio of 1: 1: 8, mixing in a high-speed mixing pot for 5 minutes, slowly adding the solution prepared in the step (2) according to the proportion of 15 percent by adopting a method of adding and stirring at the same time, and mixing for 5-10 minutes to prepare a soft material A;
(6) mixing triclabendazole, starch and glucose according to the weight ratio of 1: 1: 8, mixing in a high-speed mixing pot for 5 minutes, slowly adding the solution prepared in the step (3) according to the proportion of 20% by adopting a method of adding and stirring at the same time, and mixing for 5-10 minutes to prepare a soft material B;
(7) mixing triclabendazole, starch and glucose according to the weight ratio of 1: 1: 8, mixing in a high-speed mixing pot for 5 minutes, slowly adding the solution prepared in the step (4) according to the proportion of 5% by adopting a method of adding and stirring at the same time, and mixing for 5-10 minutes to prepare a soft material C;
(8) respectively putting the soft material A, the soft material B and the soft material C on a granulator, granulating by using a 18-mesh screen, collecting, putting in an oven at 80 ℃ for 120 minutes, and drying;
(9) taking out the dried sample in the step (8), and placing the sample (A), the sample (B) and the sample (C) into a dryer for cooling;
(10) an intelligent dissolution instrument is used for inspecting the in-vitro dissolution condition, and parameters are set as follows: the temperature is 37 ℃, the second method is carried out, and the rotating speed is 75 rpm/min; the dissolution medium is 900mL of 0.1mol/L hydrochloric acid solution and solution containing 0.5% Tween 20. An appropriate amount of granules (equivalent to 20mg of triclabendazole) was added to the dissolution cup, 5mL of sample was aspirated at 5, 10, 15, 30, 60, 90, 120min, respectively, beginning with the time when the drug just contacted the dissolution medium, and 5mL of fresh dissolution medium was immediately replenished.
(11) Observing the dissolution condition in vitro by using an intelligent dissolution instrument, wherein the dissolution result of the sample (A) is shown in figure 1;
(12) observing the in-vitro dissolution condition by using an intelligent dissolution instrument, wherein the dissolution result of the sample (B) is shown in figure 2;
(13) observing the dissolution condition in vitro by using an intelligent dissolution instrument, and obtaining the dissolution result of the sample (C) (shown in figure 3);
in one embodiment of the invention, the mixture of water, 95% ethanol, sorbitan monooleate and polyvinylpyrrolidone K30 was mixed in a ratio of 3: 6: 0.4: 0.6 is wetting agent or/and adhesive, the dissolution rate reaches 100%, and is improved by more than 30%.
In one embodiment of the present invention, it can be seen from fig. 1 that the release rate of triclabendazole granules prepared from 10% starch slurry is relatively slow, the dissolution rate in 2 hours is 65.14%, the second time the dissolution rate of 0.5% sodium carboxymethylcellulose (fig. 2) is 72.25%, and the dissolution rate of the sample prepared from the composite solution is much greater than the above two methods, reaching 100.00% (fig. 3). During the dissolution process, significant dissolution rate differences were observed in the first 30min of each method, especially for the composite solution (fig. 4).
In conclusion, the invention uses the composite solution as a preparation method of triclabendazole granules, improves the drug dissolution rate, solves the problems of lower dissolution rate and slow dissolution rate, and is obtained by dissolution rate analysis, wherein the compound solution is prepared by mixing water, 95% ethanol, sorbitan monooleate and polyvinylpyrrolidone K30 according to the weight ratio of 3: 6: 0.4: 0.6 is wetting agent or/and adhesive, and the dissolution rate is the best.
The foregoing shows and describes the general principles, essential features, and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are merely illustrative of the principles of the invention, but that various changes and modifications may be made without departing from the spirit and scope of the invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (7)
1. A method for improving the dissolution rate of triclabendazole particles is characterized by comprising the following steps: the method comprises the following steps:
step S1, mixing water, 95% ethanol, sorbitan monooleate and polyvinylpyrrolidone K30 according to the weight ratio of 3: 6: 0.4: 0.6, stirring and dissolving to obtain a clear and uniform composite solution for later use;
step S2, mixing triclabendazole, starch and glucose according to the ratio of 1: 1: 8, mixing in a high-speed mixing pot for 5 minutes, slowly adding the mixture into the composite solution obtained in the step S1 according to the proportion of 5 percent by adopting a method of adding and stirring at the same time, and mixing for 5-10 minutes to prepare a soft material;
and step S3, putting the soft material on a granulator, granulating by using an 18-mesh screen, collecting, and putting into an oven for drying, wherein the temperature of the oven is set to be 80 ℃, and the time is 120 minutes.
2. The method for improving the dissolution rate of triclabendazole granules according to claim 1, wherein: the sorbitan monooleate is a surfactant, the polyvinylpyrrolidone K30 is an adhesive, the water and the ethanol are wetting agents, and the starch and the glucose are carrier fillers.
3. The method for improving the dissolution rate of triclabendazole granules according to claim 1, wherein: in the step S2, when the 10% starch slurry is the wetting agent or/and the adhesive, the dissolution rate of the triclabendazole granules is 65.14%; when 0.5% sodium carboxymethylcellulose solution is used as a wetting agent or/and an adhesive, the dissolution rate of the triclabendazole granules is 72.25%; when mixing water, 95% ethanol, sorbitan monooleate and polyvinylpyrrolidone K30 in the ratio of 3: 6: 0.4: 0.6 is wetting agent or/and adhesive, the dissolution rate of the triclabendazole particles is 100.00%.
4. The method for improving the dissolution rate of triclabendazole granules according to claim 1, wherein: mixing water, 95% ethanol, sorbitan monooleate and polyvinylpyrrolidone K30 according to the weight ratio of 3: 6: 0.4: 0.6 is wetting agent or/and adhesive, the dissolution rate is improved by 30%.
5. A method for detecting the dissolution rate of triclabendazole granules prepared according to any one of claims 1 to 4, wherein: the in vitro dissolution was examined using an intelligent dissolution apparatus.
6. The method for detecting the dissolution rate of triclabendazole granules according to claim 5, wherein: the set parameters of the intelligent dissolution instrument are as follows: the temperature is 37 ℃, the second method is carried out, and the rotating speed is 75 rpm/min; the dissolution medium is 900mL of 0.1mol/L hydrochloric acid solution and solution containing 0.5% Tween 20.
7. The method for detecting the dissolution rate of triclabendazole granules according to claim 5, wherein: 200mg of triclabendazole particles are added into a dissolution cup of an intelligent dissolution instrument, timing is started when the medicine just contacts a dissolution medium, 5mL of samples are sucked at 5 min, 15 min, 30min, 60 min, 90 min and 120min respectively, and 5mL of fresh dissolution medium is immediately supplemented to calculate the dissolution rate change of the dissolution medium.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110523161.9A CN113318079B (en) | 2021-05-13 | 2021-05-13 | Method for improving dissolution rate of triclabendazole particles and dissolution rate detection method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110523161.9A CN113318079B (en) | 2021-05-13 | 2021-05-13 | Method for improving dissolution rate of triclabendazole particles and dissolution rate detection method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113318079A true CN113318079A (en) | 2021-08-31 |
| CN113318079B CN113318079B (en) | 2024-01-09 |
Family
ID=77415536
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110523161.9A Active CN113318079B (en) | 2021-05-13 | 2021-05-13 | Method for improving dissolution rate of triclabendazole particles and dissolution rate detection method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113318079B (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0315617D0 (en) * | 2003-07-03 | 2003-08-13 | Burke Michael H | Process for preparing a stable anthelmintic suspension formulation |
| WO2006105798A2 (en) * | 2005-07-11 | 2006-10-12 | Nycomed Danmark Aps | Benzimidazole formulation |
| CN102872013A (en) * | 2012-10-26 | 2013-01-16 | 天津必佳药业集团有限公司 | Anti-parasitic disease compound Triclabendazole granule for flocks and herds and preparation method for anti-parasitic disease compound Triclabendazole granule |
| US20140255498A1 (en) * | 2011-10-19 | 2014-09-11 | Universteit Gent | Pharmaceutical nanosuspension |
| CN106821995A (en) * | 2017-02-22 | 2017-06-13 | 佛山市南海东方澳龙制药有限公司 | Triclabendazole preparation and its preparation method and application |
| RU2016115779A (en) * | 2016-04-22 | 2017-10-26 | ФАНО России Федеральное государственное бюджетное научное учреждение Всероссийский научно-исследовательский институт фундаментальной и прикладной паразитологии животных и растений им. К.И. Скрябина (ФГБНУ "ВНИИП им. К.И. Скрябина") | Triclabendazole supramolecular complex for the treatment of animals with fascioliasis |
-
2021
- 2021-05-13 CN CN202110523161.9A patent/CN113318079B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0315617D0 (en) * | 2003-07-03 | 2003-08-13 | Burke Michael H | Process for preparing a stable anthelmintic suspension formulation |
| WO2006105798A2 (en) * | 2005-07-11 | 2006-10-12 | Nycomed Danmark Aps | Benzimidazole formulation |
| US20140255498A1 (en) * | 2011-10-19 | 2014-09-11 | Universteit Gent | Pharmaceutical nanosuspension |
| CN102872013A (en) * | 2012-10-26 | 2013-01-16 | 天津必佳药业集团有限公司 | Anti-parasitic disease compound Triclabendazole granule for flocks and herds and preparation method for anti-parasitic disease compound Triclabendazole granule |
| RU2016115779A (en) * | 2016-04-22 | 2017-10-26 | ФАНО России Федеральное государственное бюджетное научное учреждение Всероссийский научно-исследовательский институт фундаментальной и прикладной паразитологии животных и растений им. К.И. Скрябина (ФГБНУ "ВНИИП им. К.И. Скрябина") | Triclabendazole supramolecular complex for the treatment of animals with fascioliasis |
| CN106821995A (en) * | 2017-02-22 | 2017-06-13 | 佛山市南海东方澳龙制药有限公司 | Triclabendazole preparation and its preparation method and application |
Non-Patent Citations (1)
| Title |
|---|
| 中国兽药典委员会: "中国兽药典委员会办公室关于公示2019年第十四批兽药国家标准制修订草案的通知", pages 1 - 3 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113318079B (en) | 2024-01-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI478735B (en) | Solid dosage form comprising proton pump inhibitor and suspension made thereof | |
| EP0850059B1 (en) | Pharmaceutical formulations containing darifenacin | |
| JP6034377B2 (en) | Aripiprazole pharmaceutical preparation and preparation method thereof | |
| NO333301B1 (en) | Pharmaceutical composition containing fenofibrate and process for its preparation | |
| EP3981399A1 (en) | Oral solid tablet comprising bruton's tyrosine kinase inhibitor and preparation method therefor | |
| US20230381173A1 (en) | Methods and pharmaceutical composition for treating diseases | |
| CN111514142B (en) | Pharmaceutical composition containing nitroxoline prodrug and preparation method and application thereof | |
| KR20150110825A (en) | Improved taste-masking extrudates | |
| CN103181923B (en) | Pharmaceutical preparation comprising Repaglinide and preparation method thereof | |
| CN108853042B (en) | Mirtazapine freeze-dried orally disintegrating tablet and preparation method and application thereof | |
| CN106822034A (en) | The capsule core material or micro-capsule of drug containing are prepared as capsule core material with maize cob meal | |
| CN113318079A (en) | Method for improving dissolution rate of triclabendazole particles and dissolution rate detection method thereof | |
| AU2020327255A1 (en) | Pharmaceutical composition containing nitroxoline, nitroxoline oral solid tablet, preparation method therefor and use thereof | |
| CN106420600A (en) | In situ gel for tilmicosin injection and preparation method thereof | |
| CN105232450A (en) | Rifaximin-containing in-situ gel for breast injection and preparation method of rifaximin-containing in-situ gel | |
| CN108210452B (en) | Veterinary cyadox nano suspension and preparation method thereof | |
| CN113350297A (en) | Tilmicosin dry suspension and preparation method thereof | |
| CN107744509B (en) | Mosapride citrate tablet and preparation method thereof | |
| CN107569504A (en) | A kind of ambroxol hydrochloride dispersible tablet and preparation method | |
| US20040092480A1 (en) | Medicinal composition | |
| CN102151252B (en) | Glipizide osmotic pump type controlled release tablet | |
| CN110772509A (en) | Imidacloprid and moxidectin diatomic alcohol plastid and preparation method and application thereof | |
| CN105748438A (en) | Method for preparing microcapsules by combining acetamido abamectin and attapulgite | |
| WO2024066765A1 (en) | Antiviral pharmaceutical composition, preparation process therefor, and use thereof | |
| CN103169654B (en) | Aqueous suspension injection contain Cefquinome sulfate and preparation method |
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 |