CN108524460B - Nitenpyram double-layer tablet - Google Patents
Nitenpyram double-layer tablet Download PDFInfo
- Publication number
- CN108524460B CN108524460B CN201810457467.7A CN201810457467A CN108524460B CN 108524460 B CN108524460 B CN 108524460B CN 201810457467 A CN201810457467 A CN 201810457467A CN 108524460 B CN108524460 B CN 108524460B
- Authority
- CN
- China
- Prior art keywords
- nitenpyram
- release layer
- quick
- controlled release
- tablet
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/14—Ectoparasiticides, e.g. scabicides
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Tropical Medicine & Parasitology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a nitenpyram double-layer tablet, which comprises a nitenpyram quick-release layer and a nitenpyram controlled-release layer; the nitenpyram quick-release layer comprises nitenpyram and a first excipient; the nitenpyram controlled release layer comprises nitenpyram and a second excipient. The quick release layer can quickly release the effective medicinal components, namely the nitenpyram, so that the effective components can quickly enter the body to quickly act to kill adult fleas on the body surfaces of dogs and cats; the controlled release layer adopts osmotic pump controlled release technology, enwraps the nitenpyram in a special structure insoluble in water, slowly releases the nitenpyram according to a certain speed, and is matched with the quick release layer to obtain a continuous and prolonged drug release time course, so that the effective content time of the nitenpyram in the blood of a medicine body is prolonged, the blood medicine curve is more ideal, and the probability of secondary recurrence of the flea disease is reduced.
Description
Technical Field
The invention relates to the technical field of antiparasitic drugs, in particular to a nitenpyram double-layer tablet.
Background
Nitenpyram, a novel nicotine pesticide with high efficiency, broad spectrum and the action mechanism of nitenpyram, mainly acts on insect nerves and has the nerve blocking effect on axon touch receptors of insects. Has the advantages of excellent systemic and osmotic action, less dosage, low toxicity, long lasting period, safety and no phytotoxicity to mammals and the like. Nitenpyram technical was developed and promoted by sumitomo corporation in 1995, and nitenpyram tablets were introduced in the united states in 2000 (Elanco US Inc.) for treating fleas on the body surfaces of dogs and cats, after which the tablets were registered in china in 2013 under the trade name noproxacin.
Nitenpyram is thought to act on the nervous system of fleas, interfering with the electrical signals conducted by the fleas's nerves, causing the fleas to remain excited for a long period of time and eventually die. Thanks to the excellent water solubility of the raw material medicines, the nitenpyram tablet is considered to start to act after being orally taken for 15 minutes, the blood concentration reaches the peak value within 0.5-2 hours and is rapidly metabolized, 90 percent of the nitenpyram tablet is discharged in the form of raw material medicine through urine, the half-life period of a dog is only 4 hours, and the half-life period of a cat is 8 hours.
The nitenpyram tablets can be used for killing flea imagoes on the surfaces of dogs and cats, but because the nitenpyram tablets are rapidly ineffective and difficult to isolate secondary infection of flea diseases caused by environmental fleas, the nitenpyram tablets need to be repeatedly used in a short time for dogs and cats exposed to flea environments.
Disclosure of Invention
Based on the above, the invention provides the nitenpyram double-layer tablet which has the characteristics of quick response and long drug effect time.
A nitenpyram double-layer tablet comprises a nitenpyram quick release layer and a nitenpyram controlled release layer; the nitenpyram quick-release layer comprises nitenpyram and a first excipient; the nitenpyram controlled release layer comprises nitenpyram and a second excipient.
The quick release layer of the nitenpyram double-layer tablet can quickly release effective medicinal components, and the nitenpyram can ensure that the effective components can quickly enter the body to quickly act so as to kill adult fleas on the body surfaces of dogs and cats; the controlled release layer adopts a controlled release technology, the nitenpyram is wrapped in the controlled release material, is slowly released according to a certain speed, and is matched with the quick release layer to obtain a continuous and prolonged drug release time course, so that the effective content time of the nitenpyram in the blood of a medicine body is prolonged, the blood medicine curve is more ideal, and the probability of secondary recurrence of the flea disease is reduced.
In one embodiment, the mass ratio of the nitenpyram in the nitenpyram quick-release layer and the nitenpyram controlled-release layer is 1:1-1: 30.
in one embodiment, the mass ratio of the nitenpyram in the nitenpyram quick-release layer and the nitenpyram controlled-release layer is 1:2-1: 10.
In one embodiment, the mass percentage of the nitenpyram in the nitenpyram quick-release layer is 1-40%, and the mass percentage of the nitenpyram in the nitenpyram controlled-release layer is 1-40%.
In one embodiment, the nitenpyram double-layer tablet is of an upper-lower laminated structure or an inner-outer layer structure, the nitenpyram controlled-release layer serves as a tablet core, and the nitenpyram quick-release layer serves as an outer cladding.
In one embodiment, the first excipient comprises a binder, a lubricant, a disintegrant, and a diluent.
In one embodiment, the first excipient further comprises a glidant and/or an insect repellent bactericidal aid.
In one embodiment, the second excipient comprises a binder, a lubricant, a release controlling agent, and a diluent.
In one embodiment, the second excipient further comprises a glidant and/or a film-forming agent.
In one embodiment, the nitenpyram bilayer tablet further comprises a gastric-soluble coating material, and the gastric-soluble coating material is coated on the periphery of the nitenpyram quick-release layer and the nitenpyram controlled-release layer.
Detailed Description
In order that the invention may be more fully understood, reference will now be made to the following description. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.
Test methods not specifically identified in the following examples were selected according to conventional methods and conditions, or according to adjustments suggested in the commercial specifications. The reagents or instruments used are not indicated by the manufacturer, and are conventional products available commercially.
The invention provides a nitenpyram double-layer tablet which takes nitenpyram as a main effective component and is mainly used for killing fleas on the body surfaces of dogs and cats.
The nitenpyram double-layer tablet is of a double-layer tablet structure, and comprises a nitenpyram quick-release layer and a nitenpyram controlled-release layer; the nitenpyram quick-release layer comprises nitenpyram and a first excipient; the nitenpyram controlled release layer comprises nitenpyram and a second excipient.
In one embodiment, the mass ratio of the nitenpyram in the nitenpyram quick release layer and the nitenpyram controlled release layer is 1:1-1:30, and may be, for example, but not limited to, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:15, 1:20, 1:25, or 1:30, etc. Optionally, the mass ratio of the nitenpyram in the nitenpyram quick-release layer and the nitenpyram controlled-release layer is 1:2-1: 10.
In one embodiment, the mass percentage of the nitenpyram in the nitenpyram quick-release layer is 1% -40%, and for example, but not limited to, 1%, 2%, 3%, 4%, 5%, 10%, 12%, 15%, 18%, 20%, 22%, 25%, 28%, 30%, 35%, 40%, or the like; the content of the nitenpyram in the nitenpyram controlled release layer is 1-40% by mass, and for example, but not limited to, 1%, 2%, 5%, 7%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 30%, 32%, 35%, 36%, or 40% by mass.
By controlling the mass content and the mass ratio of the nitenpyram in the nitenpyram quick-release layer and the nitenpyram controlled-release layer, the nitenpyram can take effect quickly, the drug effect can be kept in the release process of the nitenpyram controlled-release layer, the killing effect brought by the nitenpyram quick-release layer is consolidated, a continuous and prolonged drug release time course is obtained, the effective content time of the nitenpyram in the blood of a medicine receiver is prolonged, the blood medicine curve is more ideal, and the probability of secondary recurrence of flea diseases is reduced.
In one embodiment, the nitenpyram double-layer tablet is of an upper-lower laminated structure, and the nitenpyram quick release layer is laminated with the nitenpyram controlled release layer.
In one embodiment, the nitenpyram double-layer tablet is of an inner-layer structure and an outer-layer structure, the nitenpyram controlled-release layer serves as a tablet core, the nitenpyram quick-release layer serves as an outer cladding layer, and the quick-release layer is released firstly and then reaches the controlled-release layer.
In one embodiment, the first excipient includes a binder, a lubricant, a disintegrant, and a diluent.
In one embodiment, the mass percentage content of each component of the first excipient in the nitenpyram quick-release layer is respectively as follows: 1% -10% of binder, for example, but not limited to, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10%, etc.; lubricants 1% to 3%, for example, but not limited to, 1%, 1.2%, 1.3%, 1.5%, 1.8%, 2%, 2.2%, 2.4%, 2.5%, 2.7%, 2.8%, or 3%, etc.; 1% to 10% of disintegrant, for example, but not limited to, 1%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, or 10% and the like; the balance of the diluent, also known as the filler, which is generally inert, does not react with most drugs and serves primarily to fill the weight or volume of the tablet to facilitate formulation and dosage, and thus tableting, depending primarily on the weight or volume of the dosage form being prepared.
The binder is mainly used for wetting and binding fine medicine powder to prepare granules so as to facilitate tabletting. The adhesive is selected from one or more of polyvinylpyrrolidone, polyvinylpyrrolidone-vinyl acetate polymer, starch, pregelatinized starch, dextrin, carboxymethyl cellulose, ethanol-water mixed solution, methylcellulose, carboxymethyl starch sodium, hydroxypropyl methyl cellulose and sodium alginate. For example, the adhesive can be polyvinylpyrrolidone, or a polyvinylpyrrolidone-vinyl acetate polymer, or starch, or pregelatinized starch, or dextrin, or an ethanol-water mixed solution, or sodium carboxymethyl starch, or starch and pregelatinized starch, or hydroxypropyl methyl cellulose and sodium alginate, etc.
The lubricant is used as flow promoter of medicine, and can improve granule fluidity, increase bulk density, increase hardness of the obtained tablet, and shorten disintegration time, thereby increasing drug dissolution rate. The lubricant is selected from one or more of talc, stearic acid, silicon dioxide, calcium stearate, magnesium stearate and liquid paraffin. For example, the lubricant may be talc, or stearic acid, or silica, or calcium stearate, or magnesium stearate, or liquid paraffin, or a mixture of talc and stearic acid, or a mixture of talc and magnesium stearate, or a mixture of stearic acid and silica, and the like.
The disintegrant is a substance which can rapidly break the tablet into fine particles in gastrointestinal fluid, so that the active ingredient is rapidly dissolved and absorbed to play a role. The disintegrating agent is selected from one or more of starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone and cross-linked sodium carboxymethyl cellulose. For example, the disintegrant can be starch, or sodium carboxymethyl starch, or low-substituted hydroxypropyl cellulose, or crosslinked polyvinylpyrrolidone, or crosslinked sodium carboxymethyl cellulose, or starch and sodium carboxymethyl starch, or low-substituted hydroxypropyl cellulose and crosslinked polyvinylpyrrolidone, or crosslinked polyvinylpyrrolidone and crosslinked sodium carboxymethyl cellulose, etc.
The diluent is selected from one or more of starch, pregelatinized starch, calcium hydrogen phosphate, dextrin, microcrystalline cellulose, lactose, mannitol, xylitol and sorbitol. For example, the diluent may be starch, or pregelatinized starch, or calcium hydrogen phosphate, or dextrin, or microcrystalline cellulose, or lactose, or microcrystalline cellulose and lactose, or mannitol, xylitol, sorbitol, etc.
In one embodiment, the first excipient further comprises a glidant and/or an insect repellent bactericidal aid. The mass percentages of the glidant and the insect-repellent bactericidal auxiliary agent in the nitenpyram quick-release layer are respectively as follows: glidants 0-3%, for example, can be, but are not limited to, 0, 1%, 1.3%, 1.5%, 1.7%, 1.9%, 2%, 2.2%, 2.5%, 2.7%, 2.9%, or 3%, etc.; the insect-repellent bactericidal agent may be, for example, but not limited to, 0.5% to 2%, 0.8%, 0.9%, 1%, 1.1%, 1.3%, 1.5%, 1.7%, 1.9%, or 2%.
When the excipient contains both the lubricant and the glidant, the total mass content of the lubricant and the glidant in the nitenpyram quick-release layer is 1-3%.
The insect-repellent bactericidal auxiliary promotes the bactericidal effect of the preparation, has a certain flavoring effect on the preparation, brings a relatively pleasant smell to the preparation, and optimizes the user experience. The insect-repellent bactericidal auxiliary agent can be one or more of thymol, carvacrol, eugenol, carvacrol, linalool, para-cymene and the like. For example, the insect-repellent bactericidal auxiliary agent can be thymol, carvacrol, eugenol, carvacrol, linalool, para-cymene, thymol and carvacrol, eugenol, carvacrol and linalool, etc.
In one embodiment, the second excipient includes a binder, a lubricant, a release controlling agent, and a diluent.
The mass percentage of each component of the second excipient in the nitenpyram controlled release layer is respectively as follows: 1% -10% of binder, for example, but not limited to, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10%, etc.; lubricants 1% -3%, for example, but not limited to, 1%, 1.3%, 1.5%, 1.7%, 2%, 2.2%, 2.5%, 2.8%, or 3%, etc.; 20% to 65% of a controlled release agent, for example, but not limited to, 20%, 23%, 25%, 30%, 35%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 50%, 55%, 58%, 60%, 65%, etc.; the amount of diluent remaining depends primarily on the weight or volume of the dosage form being prepared, as well as the needs of the tableting process.
The binder is mainly used for wetting and binding fine medicine powder to prepare granules so as to facilitate tabletting. The adhesive is selected from one or more of polyvinylpyrrolidone, polyvinylpyrrolidone-vinyl acetate polymer, starch, pregelatinized starch, dextrin, carboxymethyl cellulose, ethanol-water mixed solution, methylcellulose, carboxymethyl starch sodium, hydroxypropyl methyl cellulose and sodium alginate. For example, the adhesive can be polyvinylpyrrolidone, or a polyvinylpyrrolidone-vinyl acetate polymer, or starch, or pregelatinized starch, or dextrin, or an ethanol-water mixed solution, or sodium carboxymethyl starch, or starch and pregelatinized starch, or hydroxypropyl methyl cellulose and sodium alginate, etc.
The lubricant is used as flow promoter of medicine, and can improve granule fluidity, increase bulk density, increase hardness of the obtained tablet, and shorten disintegration time, thereby increasing drug dissolution rate. The lubricant is selected from one or more of talc, stearic acid, silicon dioxide, calcium stearate, magnesium stearate and liquid paraffin. For example, the lubricant may be talc, or stearic acid, or silica, or calcium stearate, or magnesium stearate, or liquid paraffin, or a mixture of talc and stearic acid, or a mixture of talc and magnesium stearate, or a mixture of stearic acid and silica, and the like.
The controlled release agent can swell after contacting with a liquid with gastrointestinal fluid property to form a controlled release framework, and the nitenpyram is wrapped in the controlled release framework. The skeleton is constructed by insoluble water substances, and a drug concentration gradient exists between the skeleton and gastrointestinal fluid to attract nitenpyram in the skeleton to gradually diffuse to the outside; the matrix may optionally have slow erosion properties, releasing the drug by slow erosion; the skeleton can have hydrophilic gel property, and can form gel when meeting water, the release speed of the water-soluble drug depends on the diffusion speed of the drug passing through the gel layer, and the release speed of the drug with low solubility in water is determined by the gradual erosion speed of the gel layer; the skeleton may have one or more of the above properties.
The controlled release agent may be, but is not limited to, one or more of ethyl cellulose, methacrylate, cellulose polymers, acrylics, polyvinyl pyrrolidone, guar gum, starch-based polymers, methacrylic acid copolymers, high molecular weight polyvinyl alcohol. For example, the controlled release agent may be methacrylate, or a cellulose polymer, or an acrylic resin, or polyvinylpyrrolidone, or guar gum, or starch, or a starch-based polymer and a methacrylic acid copolymer, or a cellulose polymer and a high molecular weight polyvinyl alcohol, and the like.
The diluent is selected from one or more of starch, pregelatinized starch, calcium hydrogen phosphate, dextrin, microcrystalline cellulose, lactose, mannitol, xylitol and sorbitol. For example, the diluent may be starch, or pregelatinized starch, or calcium hydrogen phosphate, or dextrin, or microcrystalline cellulose, or lactose, or microcrystalline cellulose and lactose, or mannitol, xylitol, sorbitol, etc.
In one embodiment, the second excipient further comprises a glidant and/or a film-forming agent.
The mass contents of the glidant and the film forming agent in the nitenpyram controlled release layer are respectively as follows: glidants 0-3%, for example, can be, but are not limited to, 0, 0.5%, 1%, 1.3%, 1.5%, 1.7%, 2%, 2.2%, 2.5%, 2.8%, or 3%, etc.; the film former may be, for example, but not limited to, 0.05%, 0.1%, 0.5%, 0.7%, 1%, 1.3%, 1.5%, 1.7%, 1.9%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, or 5%, etc. the film former may be present in an amount of 0.05% to 5%.
The film forming agent may be, but is not limited to, one or more of ethyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, styrene-vinylpyridine copolymer, polyvinylpyrrolidone, polyvinyl alcohol, ethylene glycol, acrylic resin, and the like. For example, the film forming agent is hydroxypropyl methyl cellulose, or hydroxypropyl cellulose, or styrene-vinylpyridine copolymer, or polyvinylpyrrolidone, or polyvinyl alcohol, or ethylene glycol and acrylic resin, etc.
In some embodiments, the film forming agent is composed of a plurality of components, wherein the film forming agent comprises a pore-forming material, the pore-forming material is a soluble substance, the pore-forming material occupies a certain space when the preparation is formed, and the pore-forming material is matched with a water-insoluble coating material or the film forming agent for use, so that holes are formed on the surface of the film, and the release speed of the medicament is regulated. The pore-forming material may be, but is not limited to, polyol and derivatives thereof or water-soluble polymer material, for example, the pore-forming material may be one or more of PEG400, PEG600, PEG1000, PEG1500, hydroxypropyl methylcellulose, polyvinyl alcohol, urea, and the like.
The mass ratio of the pore-forming material in the film forming agent is 5% to 50%, and may be, for example, but not limited to, 5%, 5.5%, 10%, 15%, 20%, 22%, 25%, 28%, 30%, 34%, 35%, 36%, 38%, 40%, 45%, 46%, or 50%.
In one embodiment, the nitenpyram bilayer tablet further comprises a gastric-soluble coating material, and the gastric-soluble coating material is coated on the periphery of the nitenpyram quick-release layer and the nitenpyram controlled-release layer. The content of the gastric-soluble coating material in the nitenpyram bilayer tablet is 1-3% by mass, and for example, but not limited to, 1%, 1.3%, 1.5%, 1.7%, 2%, 2.2%, 2.5%, 2.8%, or 3% and the like.
The gastric-soluble coating material may be, but is not limited to, one or more of hydroxypropylmethyl cellulose, hydroxypropyl cellulose, styrene-vinylpyridine copolymer, polyvinylpyrrolidone, polyvinyl alcohol, ethylene glycol, acrylic resin, and the like. For example, the stomach soluble coating material is hydroxypropyl methylcellulose, or hydroxypropyl cellulose, or styrene-vinyl pyridine copolymer, or polyvinylpyrrolidone, or polyvinyl alcohol, or ethylene glycol, or acrylic resin, or hydroxypropyl methylcellulose and hydroxypropyl cellulose, or polyvinylpyrrolidone and polyvinyl alcohol, etc.
The nitenpyram double-layer tablet has the advantages that the quick release layer can quickly release effective medicinal components, and the nitenpyram can ensure that the effective components can quickly enter the body to quickly act so as to kill adult fleas on the surfaces of dogs and cats; the controlled release layer adopts osmotic pump controlled release technology, wraps the nitenpyram in a special structure insoluble in water, slowly releases the nitenpyram at a certain speed, and is matched with the quick release layer, so that the drug effect of the nitenpyram is effectively prolonged, and the effects of quick response and long drug effect are obtained.
The following are specific examples:
example 1
The nitenpyram double-layer tablet of the embodiment has an up-and-down laminated structure, and the total tablet weight is 0.35g, wherein the nitenpyram quick-release layer is 150mg, and the nitenpyram controlled-release layer is 200 mg.
The mass contents of the components in the nitenpyram quick-release layer are respectively as follows: 6.7 percent of nitenpyram serving as a main drug, 5 percent of carboxymethyl cellulose sodium serving as an adhesive, 3 percent of croscarmellose sodium serving as a disintegrating agent, 2 percent of silicon dioxide serving as a glidant, 1 percent of magnesium stearate serving as a lubricant, and 82.3 percent of microcrystalline cellulose serving as a filler in balance.
The mass contents of the components in the nitenpyram controlled release layer are respectively as follows: the main drug nitenpyram is 12.5 percent, the controlled release agent hydroxypropyl methylcellulose is 40 percent, the adhesive sodium carboxymethyl cellulose is 3 percent, the glidant silicon dioxide is 2 percent, the lubricant magnesium stearate is 1 percent, and the rest is the filler microcrystalline cellulose.
The preparation method comprises the following steps:
nitenpyram quick-release layer: in a rapid mixer, nitenpyram and microcrystalline cellulose are uniformly mixed, granulated by using sodium carboxymethyl cellulose solution with proper concentration, dried, screened, uniformly mixed with silicon dioxide, magnesium stearate and croscarmellose sodium, and prepared into granules 1.
Nitenpyram controlled release layer: mixing nitenpyram, microcrystalline cellulose and hydroxypropyl methyl cellulose in a quick mixer, granulating with appropriate concentration of sodium carboxymethyl cellulose solution, oven drying, sieving, mixing with silicon dioxide and magnesium stearate, and making into granule 2.
Granules 1 and 2 were compressed into bilayer tablets using a bilayer tablet press with separate feeds.
Example 2
The nitenpyram double-layer tablet of the embodiment has a vertically laminated structure, and the total tablet weight is 0.5g, wherein the nitenpyram quick-release layer weighs 200mg, and the nitenpyram controlled-release layer weighs 300 mg.
The mass contents of the components in the nitenpyram quick-release layer are respectively as follows: the main drug nitenpyram 15%, the adhesive starch 5%, the disintegrant sodium carboxymethyl starch 2.25%, the glidant silicon dioxide 2%, the lubricant magnesium stearate 1%, and the rest is the filler lactose 74.75%.
The mass contents of the components in the nitenpyram controlled release layer are respectively as follows: the main drug nitenpyram is 25 percent, the controlled release agent ethyl cellulose is 45 percent, the adhesive starch is 5 percent, the glidant talc powder is 2 percent, the lubricant magnesium stearate is 1 percent, and the rest is the filler lactose is 22 percent.
The preparation method comprises the following steps:
nitenpyram quick-release layer: mixing nitenpyram, lactose and carboxymethyl starch sodium uniformly in a rapid mixer, granulating with starch solution with proper concentration, oven drying, sieving, mixing with silicon dioxide and magnesium stearate uniformly, and making into granule 1.
Nitenpyram controlled release layer: mixing nitenpyram, lactose and ethyl cellulose in a rapid mixer, granulating with starch solution with proper concentration, oven drying, sieving, mixing with pulvis Talci and magnesium stearate, and making into granule 2.
Granules 1 and 2 were compressed into bilayer tablets using a bilayer tablet press with separate feeds.
Example 3
The nitenpyram double-layer tablet of the embodiment has an inner-layer structure and an outer-layer structure, and the total weight of the tablet is 0.66g, wherein the weight of the nitenpyram quick-release layer is 200mg, the weight of the nitenpyram controlled-release layer is 439.6mg, and the weight of the gastric-soluble coating material is 20.4 mg.
The mass contents of the components in the nitenpyram quick-release layer are respectively as follows: the desinsection composition comprises a main drug of nitenpyram 25%, a binder of sodium carboxymethylcellulose 5%, a disintegrant of croscarmellose sodium 3%, a glidant of talcum powder 2%, a lubricant of magnesium stearate 1%, a desinsectization auxiliary of thymol 1%, and the balance of fillers of lactose and microcrystalline cellulose, wherein the total content is 63%.
The mass contents of the components in the nitenpyram controlled release layer are respectively as follows: 27.17 percent of nitenpyram serving as a main drug, 5 percent of carboxymethyl cellulose sodium serving as an adhesive, 40 percent of hydroxypropyl methyl cellulose serving as a controlled release agent, 2 percent of glidant silicon dioxide, 1 percent of magnesium stearate serving as a lubricant, and the balance of lactose serving as a filler.
The gastric coating material acrylic resin accounts for about 3% of the total.
The preparation method comprises the following steps:
nitenpyram quick-release layer: mixing nitenpyram with lactose, microcrystalline cellulose and croscarmellose sodium uniformly in a rapid mixer, granulating with appropriate concentration carboxymethylcellulose sodium solution, oven drying, sieving, mixing with pulvis Talci and magnesium stearate uniformly, and making into granule 1.
Nitenpyram controlled release layer: mixing nitenpyram, lactose and hydroxypropyl methyl cellulose in a rapid mixer, granulating with sodium carboxymethyl cellulose solution with proper concentration, oven drying, sieving, mixing with silicon dioxide and magnesium stearate, and making into granule 2.
Granules 1 and 2 were compressed into bilayer tablets using separate feeds using a bilayer tablet press and coated with an acrylic resin solution of the appropriate concentration.
Example 4
The nitenpyram double-layer tablet of the embodiment has an inner-layer structure and an outer-layer structure, and the total weight of the tablet is 0.5g, wherein the nitenpyram quick-release layer is 150mg, the nitenpyram controlled-release layer is 340mg, and the gastric-soluble coating material is 10 mg.
The mass contents of the components in the nitenpyram quick-release layer are respectively as follows: the desinsectization drug comprises main drug nitenpyram 20%, adhesive pregelatinized starch 3%, disintegrant croscarmellose sodium 5%, lubricant magnesium stearate 2.5%, desinsectization auxiliary agent carvacrol 0.5%, and the balance of filler mannitol and microcrystalline cellulose.
The mass contents of the components in the nitenpyram controlled release layer are respectively as follows: 16 percent of nitenpyram serving as a main drug, 7 percent of adhesive pregelatinized starch, 35 percent of controlled release agent guar gum, 1 percent of glidant silicon dioxide, 2 percent of lubricant magnesium stearate and the balance of filler lactose.
The gastric coating material acrylic resin accounts for about 2% of the total.
The preparation method comprises the following steps:
nitenpyram quick-release layer: mixing nitenpyram, mannitol, microcrystalline cellulose and carvacrol uniformly in a rapid mixer, granulating with pregelatinized starch solution with proper concentration, oven drying, sieving, mixing with magnesium stearate and croscarmellose sodium uniformly, and making into granule 1.
Nitenpyram controlled release layer: mixing nitenpyram, lactose and guar gum in a rapid mixer, granulating with pregelatinized starch solution with proper concentration, oven drying, sieving, mixing with silicon dioxide and magnesium stearate, and making into granule 2.
Granules 1 and 2 were compressed into bilayer tablets using separate feeds using a bilayer tablet press and coated with an acrylic resin solution of the appropriate concentration.
Example 5
The nitenpyram double-layer tablet of the embodiment has an up-and-down laminated structure, and the total tablet weight is 0.6g, wherein the nitenpyram quick-release layer weighs 180mg, and the nitenpyram controlled-release layer weighs 420 mg.
The mass contents of the components in the nitenpyram quick-release layer are respectively as follows: the main drug nitenpyram is 20 percent, the adhesive dextrin is 10 percent, the disintegrant is 7 percent, the glidant is 1 percent, the lubricant is 2 percent, and the rest is the filler starch and the xylitol.
The mass contents of the components in the nitenpyram controlled release layer are respectively as follows: main drug nitenpyram 20%, controlled release agent cellulose polymer 30%, adhesive dextrin 10%, lubricant stearic acid 3%, film forming agent 2%, and the balance filler starch and xylitol; the film forming agent is a mixture of ethyl cellulose and polyvinyl alcohol, and the polyvinyl alcohol is a pore-forming material and accounts for 12% of the film forming agent by mass.
The preparation method comprises the following steps:
nitenpyram quick-release layer: mixing nitenpyram with starch, xylitol and starch uniformly in a rapid mixer, granulating with dextrin solution with proper concentration, oven drying, sieving, mixing with stearic acid uniformly, and making into granule 1.
Nitenpyram controlled release layer: mixing nitenpyram with starch, xylitol and cellulose polymer in a rapid mixer, granulating with dextrin solution with proper concentration, oven drying, sieving, mixing with magnesium stearate, making into granule 2, tabletting, and coating with mixed solution of ethyl cellulose and polyvinyl alcohol with proper concentration.
Granule 1 and the coated controlled release layer were laminated into a bilayer tablet using a bilayer tablet press.
Example 6
The nitenpyram double-layer tablet of the embodiment has an up-and-down laminated structure, and the total tablet weight is 0.68g, wherein the nitenpyram quick-release layer weighs 300mg, and the nitenpyram controlled-release layer weighs 380 mg.
The mass contents of the components in the nitenpyram quick-release layer are respectively as follows: the main drug nitenpyram is 2 percent, the adhesive is polyvinylpyrrolidone-vinyl acetate polymer 6 percent, the disintegrant is low-substituted hydroxypropyl cellulose 8 percent, the lubricant is talcum powder 3 percent, the insect-expelling and sterilizing auxiliary agent is eugenol 0.5 percent, and the rest is filler starch and sorbitol.
The mass contents of the components in the nitenpyram controlled release layer are respectively as follows: the main drug nitenpyram is 10 percent, the controlled release agent cellulose polymer is 20 percent, the adhesive is polyvinylpyrrolidone-vinyl acetate polymer 4 percent, the lubricant talcum powder is 3 percent, the film forming agent is polyvinyl alcohol 4 percent, and the rest is filler starch and sorbitol.
The preparation method comprises the following steps:
nitenpyram quick-release layer: mixing nitenpyram, starch, sorbitol and eugenol uniformly in a quick mixer, granulating with polyvinylpyrrolidone-vinyl acetate polymer solution with proper concentration, oven drying, sieving, mixing with pulvis Talci and low-substituted hydroxypropyl cellulose uniformly, and making into granule 1.
Nitenpyram controlled release layer: mixing nitenpyram with starch, sorbitol and cellulose polymer in a rapid mixer, granulating with polyvinylpyrrolidone-vinyl acetate polymer solution with proper concentration, oven drying, sieving, mixing with pulvis Talci, making into granule 2, tabletting, and coating with polyvinyl alcohol solution with proper concentration.
The granules 1 and the coated controlled release layer were laminated into a bilayer tablet by feeding separately using a bilayer tablet press.
Example 7
The nitenpyram double-layer tablet of the embodiment has an inner-layer structure and an outer-layer structure, and the total weight of the tablet is 0.4g, wherein the nitenpyram quick-release layer is 150mg, the nitenpyram controlled-release layer is 246mg, and the gastric-soluble coating material is 4 mg.
The mass content of each component in the nitenpyram quick-release layer is as follows: the desinsectization auxiliary agent comprises main drug nitenpyram 10%, adhesive dextrin 7%, disintegrant croscarmellose sodium 4%, lubricant liquid paraffin 2%, desinsectization auxiliary agent thymol 2%, and the balance of filler starch and microcrystalline cellulose.
The nitenpyram controlled release layer comprises the following components in percentage by mass: main drug nitenpyram 18.2%, adhesive dextrin 3.5%, controlled release agent guar gum 27%, film forming agent 3%, lubricant liquid paraffin 2.5%, and the balance filler starch and microcrystalline cellulose; the film forming agent is a mixture of hydroxypropyl cellulose and PEG400, and the PEG400 is used as a pore-forming material and accounts for 8% of the film forming agent by mass.
The stomach-soluble coating material hydroxypropyl cellulose accounts for about 1% of the total.
The preparation method comprises the following steps:
nitenpyram quick-release layer: mixing nitenpyram, starch, microcrystalline cellulose and croscarmellose sodium uniformly in a rapid mixer, granulating with dextrin ethanol solution with proper concentration, oven drying, sieving, and mixing with liquid paraffin uniformly to obtain granule 1.
Nitenpyram controlled release layer: mixing nitenpyram with starch, microcrystalline cellulose and guar gum in a rapid mixer, granulating with dextrin solution with proper concentration, oven drying, sieving, mixing with liquid paraffin uniformly, making into granule 2, tabletting, and coating with hydroxypropyl cellulose and PEG400 mixed solution with proper concentration.
The granules 1 and the coated controlled release layer were laminated into a bilayer tablet using a bilayer tablet press with separate feeds and coated with a solution of the appropriate concentration of hydroxypropyl cellulose.
Example 8
The nitenpyram double-layer tablet of the embodiment has an inner-layer structure and an outer-layer structure, and the total tablet weight is 0.55g, wherein the nitenpyram quick-release layer is 220mg, the nitenpyram controlled-release layer is 314mg, and the gastric-soluble coating material is 16 mg.
The mass contents of the components in the nitenpyram quick-release layer are respectively as follows: main drug nitenpyram 17.8%, adhesive pregelatinized starch 8%, disintegrant croscarmellose sodium 10%, glidant corn starch 1%, lubricant magnesium stearate 2%, insect repellent auxiliary carvacrol 0.5%, and the balance of filler lactose and microcrystalline cellulose.
The mass contents of the components in the nitenpyram controlled release layer are respectively as follows: 23 percent of nitenpyram serving as a main medicine, 3 percent of adhesive pregelatinized starch, 42 percent of controlled release agent starch-based polymer, 1 percent of glidant corn starch, 2 percent of lubricant magnesium stearate and the balance of filler lactose.
The gastric soluble coating material sodium alginate accounts for about 3 percent of the total mass.
The preparation method comprises the following steps:
nitenpyram quick-release layer: mixing nitenpyram with lactose and microcrystalline cellulose in a rapid mixer, granulating with pregelatinized starch solution with proper concentration, oven drying, sieving, mixing with corn starch, croscarmellose sodium and magnesium stearate, and making into granule 1.
Nitenpyram controlled release layer: mixing nitenpyram, lactose and starch-based polymer in a rapid mixer, granulating with pregelatinized starch solution with proper concentration, oven drying, sieving, mixing with corn starch and magnesium stearate, and making into granule 2.
Granules 1 and 2 were compressed into bilayer tablets using separate feeds with a bilayer tablet press and coated with a sodium alginate solution of the appropriate concentration.
Release test
The nitenpyram bilayer tablets of examples 1 to 8 were measured for release using a pharmaceutical intelligent dissolution apparatus with reference to the relevant regulations of the veterinary dictionary, and the results are shown in table 1 below.
TABLE 1
From the above release test results, it can be seen that the active ingredients of the nitenpyram bilayer tablets of examples 1 to 8 can be released for more than 24 hours, i.e. the duration of the drug effect is longer than 24 hours, and the effect can be obtained within 1 hour.
Effect test
According to the breeding base of a certain Guangdong pet dog, the flea imagoes are screened out according to the pruritus condition and the body surface, 10 naturally occurring flea dogs are selected, are male with the same weight and are averagely divided into two groups, and the dogs are respectively raised in two separated natural environments. Group 1 was fed with regular nitenpyram tablets on the first day of the experiment, and then the flea count on the back of the abdomen was calculated at 4 hours, 12 hours and 24 hours; group 2 was fed the nitenpyram bilayer controlled release tablet of example 2 on the first day of the experiment, and thereafter the flea count on the back of the abdomen was calculated at 4 hours, 12 hours and 24 hours, and the results are shown in table 2.
TABLE 2
| Group of | Average flea count (4h) | Average flea count (12h) | Average flea count (24h) |
| Group 1 | 0 | 0.3 | 1.1 |
| Group 2 | 0 | 0 | 0.2 |
The common nitenpyram tablets can kill fleas on the body surface in a short time, but have rapid failure and can not defend secondary infection from the environment, and more newly infected fleas can be found on the body surface of a dog after 12 hours. The nitenpyram double-layer tablet in the embodiment 2 has the characteristics of quick killing and controlled release, overcomes the defects of nitenpyram, ensures that the nitenpyram double-layer tablet has quick and lasting effect, is protected for 24 hours or more, is safe for target animals, and has no adverse reaction for experimental animals.
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (10)
1. The nitenpyram double-layer tablet is characterized by comprising a nitenpyram quick-release layer and a nitenpyram controlled-release layer; the nitenpyram quick-release layer comprises nitenpyram and a first excipient, the nitenpyram in the nitenpyram quick-release layer accounts for 1-18% by mass, the first excipient comprises an adhesive, a lubricant, a disintegrant and a diluent, and the nitenpyram quick-release layer comprises the following components in percentage by mass: 1-10% of adhesive, 1-3% of lubricant, 1-10% of disintegrating agent and the balance of diluent; the nitenpyram controlled release layer comprises nitenpyram and a second excipient, the nitenpyram in the nitenpyram controlled release layer accounts for 1-19% by mass, the second excipient comprises an adhesive, a lubricant, a controlled release agent and a diluent, and the nitenpyram controlled release layer comprises the following components in percentage by mass: 1-10% of adhesive, 1-3% of lubricant, 20-65% of controlled release agent and the balance of diluent;
the nitenpyram double-layer tablet is of an upper-lower laminated structure or an inner-outer layer structure, the nitenpyram controlled release layer serves as a tablet core, and the nitenpyram quick release layer serves as an outer cladding layer.
2. The nitenpyram bilayer tablet of claim 1, wherein the weight ratio of nitenpyram in the nitenpyram quick release layer and the nitenpyram controlled release layer is 1:1-1: 30.
3. the nitenpyram bilayer tablet of claim 2, wherein the weight ratio of nitenpyram in the nitenpyram quick release layer and the nitenpyram controlled release layer is 1:2-1: 10.
4. The nitenpyram bilayer tablet of claim 3, wherein the weight ratio of nitenpyram in the nitenpyram quick release layer and the nitenpyram controlled release layer is 1:2-1: 5.
5. The nitenpyram bilayer tablet of claim 1, wherein the first excipient further comprises a glidant and/or an insect-repellent bactericidal aid.
6. The nitenpyram bilayer tablet of claim 5, wherein the glidant and the insect-repellent bactericidal auxiliary are respectively contained in the nitenpyram quick-release layer in the following weight percentages: 0 to 3 percent of flow aid and 0.5 to 2 percent of insect-expelling and sterilizing auxiliary agent.
7. The nitenpyram bilayer tablet of claim 1, wherein the second excipient further comprises a glidant and/or a film-forming agent.
8. The nitenpyram bilayer tablet of claim 7, wherein the mass contents of the glidant and the film forming agent in the nitenpyram controlled release layer are respectively as follows: 0-3% of glidant and 0.05-5% of film forming agent.
9. The nitenpyram bilayer tablet of claim 7 or 8, wherein the film forming agent comprises a pore-forming material, and the pore-forming material is a soluble substance; the pore-forming material accounts for 5-50% of the film-forming agent by mass.
10. The nitenpyram bilayer tablet of claim 1, further comprising a gastric-soluble coating material, wherein the gastric-soluble coating material coats the periphery of the nitenpyram quick-release layer and the nitenpyram controlled-release layer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810457467.7A CN108524460B (en) | 2018-05-14 | 2018-05-14 | Nitenpyram double-layer tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810457467.7A CN108524460B (en) | 2018-05-14 | 2018-05-14 | Nitenpyram double-layer tablet |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108524460A CN108524460A (en) | 2018-09-14 |
| CN108524460B true CN108524460B (en) | 2021-01-01 |
Family
ID=63477087
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810457467.7A Active CN108524460B (en) | 2018-05-14 | 2018-05-14 | Nitenpyram double-layer tablet |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108524460B (en) |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006048699A1 (en) * | 2004-11-04 | 2006-05-11 | Wockhardt Limited | Pharmaceutical compositions of antihistamine and decongestant |
| CN101015519A (en) * | 2007-02-27 | 2007-08-15 | 重庆医药工业研究院有限责任公司 | Loratadine oral compound medication composition |
| WO2007138466A3 (en) * | 2006-06-01 | 2009-04-23 | Wockhardt Ltd | Pharmaceutical compositions comprising meloxicam and tramadol combination |
| CN102395276A (en) * | 2009-02-13 | 2012-03-28 | 罗马克实验室有限公司 | Controlled release pharmaceutical formulations of nitazoxanide |
| CN102883711A (en) * | 2010-05-05 | 2013-01-16 | 贝林格尔.英格海姆国际有限公司 | Pharmaceutical formulations comprising pioglitazone and linagliptin |
| CN103402499A (en) * | 2010-12-21 | 2013-11-20 | 马林克罗特有限公司 | Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans |
| WO2015066784A1 (en) * | 2013-11-08 | 2015-05-14 | Hypermarcas S.A. | Pharmaceutical composition, oral pharmaceutical form, capsule, bilayer tablet, uses, method of treating hypercholesterolemia, hypertriglyceridemia and/or mixed dyslipidemia, and method of preventing atherosclerosis, diabetes or secondary prevention of other cardiovascular diseases |
| EP3238714A1 (en) * | 2016-04-28 | 2017-11-01 | Sanovel Ilac Sanayi ve Ticaret A.S. | Extended release formulations of flurbiprofen and tramadol |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006070406A1 (en) * | 2004-12-29 | 2006-07-06 | J.B. Chemicals & Pharmaceuticals Ltd | Bilayer tablets of oxcarbazepine for controlled delivery and a process of preparation thereof |
| US8637078B2 (en) * | 2005-11-24 | 2014-01-28 | Boehringer Ingelheim International Gmbh | Bilayer tablet comprising telmisartan and diuretic |
| US20140037725A1 (en) * | 2012-08-01 | 2014-02-06 | Cadila Healthcare Limited | Bilayer pharmaceutical compositions of naproxen |
-
2018
- 2018-05-14 CN CN201810457467.7A patent/CN108524460B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006048699A1 (en) * | 2004-11-04 | 2006-05-11 | Wockhardt Limited | Pharmaceutical compositions of antihistamine and decongestant |
| WO2007138466A3 (en) * | 2006-06-01 | 2009-04-23 | Wockhardt Ltd | Pharmaceutical compositions comprising meloxicam and tramadol combination |
| CN101015519A (en) * | 2007-02-27 | 2007-08-15 | 重庆医药工业研究院有限责任公司 | Loratadine oral compound medication composition |
| CN102395276A (en) * | 2009-02-13 | 2012-03-28 | 罗马克实验室有限公司 | Controlled release pharmaceutical formulations of nitazoxanide |
| CN102883711A (en) * | 2010-05-05 | 2013-01-16 | 贝林格尔.英格海姆国际有限公司 | Pharmaceutical formulations comprising pioglitazone and linagliptin |
| CN103402499A (en) * | 2010-12-21 | 2013-11-20 | 马林克罗特有限公司 | Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans |
| WO2015066784A1 (en) * | 2013-11-08 | 2015-05-14 | Hypermarcas S.A. | Pharmaceutical composition, oral pharmaceutical form, capsule, bilayer tablet, uses, method of treating hypercholesterolemia, hypertriglyceridemia and/or mixed dyslipidemia, and method of preventing atherosclerosis, diabetes or secondary prevention of other cardiovascular diseases |
| EP3238714A1 (en) * | 2016-04-28 | 2017-11-01 | Sanovel Ilac Sanayi ve Ticaret A.S. | Extended release formulations of flurbiprofen and tramadol |
Non-Patent Citations (1)
| Title |
|---|
| 烯啶虫胺片(诺普星)说明书;827283838qq;《https://wenku.baidu.com/view/dba1c8bb77232f60dccca1b6.html，百度文库》;20160325;第1页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108524460A (en) | 2018-09-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU642704B2 (en) | Long-term delivery device including loading dose | |
| DK175899B1 (en) | Matrix device for controlled release of at least one active agent into a surrounding environment and methods of preparation and use thereof | |
| US20110071137A1 (en) | Process for preparing sustained release tablets | |
| CZ189597A3 (en) | Feeding preparation for controlled release of a medicament suspension | |
| SK284388B6 (en) | Tablet with controlled release of alfuzosine chlorhydrate | |
| EP1138320A2 (en) | Floating forms containing drug, polyvinyl acetate and polyvinyl pyrrolidone, their use and preparation | |
| MX2013003556A (en) | Gastric retentive dosage forms for extended release of acamprosate into the upper gastrointestinal tract. | |
| Majeed et al. | Formulation and evaluation of bilayer matrix tablets of amoxicillin and esomeprazole as an oral modified release dosage form for treatment of peptic ulcer | |
| US4066754A (en) | Slow release bolus | |
| CN102935084A (en) | Compound ivermectin sustained release tablet and preparation method thereof | |
| CN111700874A (en) | Enteric fast-release taste-masking granules of enrofloxacin and preparation method thereof | |
| JP2004143175A (en) | Sustained release composition for oral administration of medicine | |
| WO2006123213A1 (en) | Modified release formulations of gliclazide | |
| CA2165190C (en) | Dispenser containing hydrophobic agent | |
| CN108524460B (en) | Nitenpyram double-layer tablet | |
| WO2014138881A1 (en) | Drug delivery system | |
| CN100488514C (en) | Slowly released solid ivermectin microballoon preparation | |
| EP2704698B1 (en) | Dosage form for the controlled release of active ingredients | |
| JP2023517906A (en) | Molded soft chewing agent for administration to animals | |
| CN111346066A (en) | Sustained release preparation containing piracetam | |
| Sarangi et al. | Formulation Development and evaluation of Bilayer tablets containing Paracetamol SR and Tizanidine | |
| Ramesh et al. | Design and evaluation of sustained release matrix tablets of Levofloxacin employing almond gum | |
| DE102011051308A1 (en) | Manufacturing process and dosage form | |
| CN106466302A (en) | Oral potassium chloride slow releasing tablet and preparation method thereof | |
| Singh et al. | Design development and evaluation of matrix tablets of Ambroxol Hydrochloride: In Vitro–In Vivo Study |
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 |