CN109966259B - Clonidine hydrochloride microporous membrane osmotic pump sustained release tablet and preparation method thereof - Google Patents
Clonidine hydrochloride microporous membrane osmotic pump sustained release tablet and preparation method thereof Download PDFInfo
- Publication number
- CN109966259B CN109966259B CN201910227249.9A CN201910227249A CN109966259B CN 109966259 B CN109966259 B CN 109966259B CN 201910227249 A CN201910227249 A CN 201910227249A CN 109966259 B CN109966259 B CN 109966259B
- Authority
- CN
- China
- Prior art keywords
- clonidine hydrochloride
- coating
- ethyl cellulose
- sustained release
- osmotic pump
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/4168—1,3-Diazoles having a nitrogen attached in position 2, e.g. clonidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/2853—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
-
- 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
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Molecular Biology (AREA)
- Reproductive Health (AREA)
- Biophysics (AREA)
- Endocrinology (AREA)
- Rheumatology (AREA)
- Inorganic Chemistry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a clonidine hydrochloride microporous membrane osmotic pump sustained release tablet and a preparation method thereof, belonging to the technical field of pharmaceutical preparations. The clonidine hydrochloride microporous membrane osmotic pump sustained release tablet is prepared from a drug-containing layer tablet core and a semipermeable membrane coating. The clonidine hydrochloride microporous membrane osmotic pump sustained release tablet prepared by the invention has the advantages that the release speed is not influenced by gastrointestinal tract variable factors such as peristalsis, pH, gastric emptying time and the like, and the sustained release tablet has good controlled release effect; and the preparation process is simple, the industrial production is easy, the defects of the existing clonidine hydrochloride controlled release tablet are effectively overcome, the cost is reduced, and therefore, the clonidine hydrochloride controlled release tablet has good practical application value.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a clonidine hydrochloride microporous membrane osmotic pump sustained release tablet and a preparation method thereof.
Background
The information in this background section is only for enhancement of understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art that is already known to a person of ordinary skill in the art.
Clonidine hydrochloride, chemically named 2- [ (2, 6-dichloroaniline) -2 imino ] -imidazolidine hydrochloride, is a central alpha-adrenergic receptor agonist, mainly inhibits the efferent impulse of sympathetic nerve center by exciting the alpha 2 receptor of postsynaptic membranes of dorsal ramus medullaris nucleus to expand peripheral blood vessels, and also acts on imidazoline receptors (I1 receptors) in the ventral region of medullary oblongata end to reduce sympathetic tone and peripheral vascular resistance to generate a blood pressure reducing effect. On the other hand, clonidine hydrochloride can promote the recovery of the prefrontal cortex to inhibit the control function by regulating the noradrenaline function, so that the effect of improving attention and learning capacity is achieved, and the indications are approved and increased by the FDA in the United states in 2010 and are used for treating Attention Deficit Hyperactivity Disorder (ADHD) of children and teenagers. At present, clonidine hydrochloride is clinically used for treating hypertension, migraine, dysmenorrheal, menopausal hot flashes and attention deficit hyperactivity disorder.
Clonidine hydrochloride is already prepared into preparations such as oral quick-release tablets, sustained-release tablets, dripping pills, injection and transdermal patches on the market, the current preparation method of the clonidine hydrochloride oral sustained-release preparation comprises the steps of preparing a sustained-release capsule prepared by a patent CN105395518A for treating and relieving muscle spasm and severe pain of skeletal muscle accompanied by the muscle spasm, preparing multivesicular lipid to realize sustained-release action by CN101536981, using skeleton type sustained-release materials by CN105395506A, CN104138362A and CN104352473A, and preparing sustained-release pellets by using a coating film added with a pore-forming agent by CN104352447A and CN 102138906A. However, the inventor finds that the clonidine hydrochloride product and the preparation method thereof still have the problems of uneven content, complex preparation process, incomplete release and the like in the preparation process.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides the clonidine hydrochloride microporous membrane osmotic pump sustained release tablet and the preparation method thereof, so that the release speed of the sustained release tablet is not influenced by gastrointestinal tract variable factors such as peristalsis, pH, gastric emptying time and the like, and the sustained release tablet has good controlled release effect; and the preparation process is simple, the industrial production is easy, the defects of the existing clonidine hydrochloride controlled release tablet are effectively overcome, the cost is reduced, and therefore, the clonidine hydrochloride controlled release tablet has good practical application value.
The invention is realized by the following technical scheme:
the invention provides a clonidine hydrochloride microporous membrane osmotic pump sustained release tablet, which is prepared from a drug-containing layer tablet core and a semipermeable membrane coating,
wherein, the tablet core of the medicine-containing layer consists of the following raw materials (by weight percentage):
clonidine hydrochloride 0.1-0.2%
The penetration enhancer is 20 to 50 percent
10 to 20 percent of retarder
20 to 50 percent of filling agent
0.5 to 2 percent of lubricant
Further, the penetration enhancer can be any one or combination of sodium chloride, glucose, sucrose, lactose, magnesium sulfate, magnesium chloride, potassium sulfate, sodium sulfate, d-mannitol, urea, magnesium succinate and tartaric acid, preferably any one or combination of sodium chloride, glucose, mannitol and lactose;
the retardant can be hypromellose or sodium carboxymethylcellulose (CMC-Na), preferably sodium carboxymethylcellulose;
the filler is microcrystalline cellulose (MCC);
lubricant magnesium stearate or talc; magnesium stearate is preferred.
The semipermeable membrane coating comprises a film-forming material, a pore-forming agent and a plasticizer;
wherein the film forming material is ethyl cellulose, the pore-forming agent is PEG400, sucrose, polyvinylpyrrolidone (PVP) or propylene glycol, and the plasticizer is diethyl phthalate (DEP).
Specifically, the preparation method of the sustained-release tablet comprises the following steps:
-preparing a drug-containing layer core;
-preparing a semipermeable membrane coating;
spraying the semipermeable membrane coating solution on the tablet core containing the drug layer for coating.
Compared with the prior art, the invention has the beneficial effects that:
the invention provides a clonidine hydrochloride microporous membrane osmotic pump sustained release tablet and a preparation method thereof for the first time, so that the release speed of the sustained release tablet is not influenced by gastrointestinal tract variable factors such as peristalsis, pH, gastric emptying time and the like, and the sustained release tablet has good controlled release effect; and the preparation process is simple, the industrial production is easy, the defects of the existing clonidine hydrochloride controlled release tablet are effectively overcome, the cost is reduced, and therefore, the clonidine hydrochloride controlled release tablet has good practical application value.
Drawings
FIG. 1 is a graph of the release rate versus time for clonidine hydrochloride microporous membrane osmotic pump sustained release tablets prepared in example 1;
FIG. 2 is a graph of the release rate versus time for clonidine hydrochloride microporous membrane osmotic pump sustained release tablets prepared in example 2;
FIG. 3 is a graph of the release rate versus time for clonidine hydrochloride microporous membrane osmotic pump sustained release tablets prepared in example 3;
FIG. 4 is a graph of the release rate versus time for clonidine hydrochloride microporous membrane osmotic pump sustained release tablets prepared in example 4;
FIG. 5 is a graph of the release rate versus time for clonidine hydrochloride microporous membrane osmotic pump sustained release tablets prepared in example 5;
FIG. 6 is a graph of the release rate versus time for clonidine hydrochloride microporous membrane osmotic pump sustained release tablets prepared in example 6.
Detailed Description
It is to be understood that the following detailed description is exemplary and is intended to provide further explanation of the invention as claimed. 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.
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of example embodiments according to the present application. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, and it should be understood that when the terms "comprises" and/or "comprising" are used in this specification, they specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof, unless the context clearly indicates otherwise.
As mentioned above, the inventor finds that the existing clonidine hydrochloride product and the preparation method thereof still have the problems of uneven content in the preparation process, complex preparation process, incomplete release and the like.
In view of the above, one embodiment of the present invention provides a clonidine hydrochloride microporous membrane osmotic pump sustained release tablet, which can be made into oral osmotic pump tablets (capsules) and osmotic implants by using osmotic pressure principle, and can release drugs uniformly and constantly in vivo, and is also a controlled release membrane coating preparation. The osmotic pump tablet has the greatest characteristic of releasing drugs in vivo, the drug release rate is not influenced by gastrointestinal tract variable factors such as peristalsis, pH, gastric emptying time and the like except uniformity and constancy, and the osmotic pump tablet is suitable for preparing drugs with various solubilities and is the most ideal oral controlled release preparation so far. The osmotic pump tablet is prepared from materials for forming a semipermeable membrane, a pore-forming agent, a permeation enhancer, a pushing agent and the like besides the medicine, compared with mechanical perforation, the pore-forming agent is added into the coating membrane to improve the permeability of the membrane, the microporous osmotic pump can be prepared, and the medicine solution can be released through micropores on the spongy membrane, so that the preparation process of the osmotic pump is simplified, and the irritation caused by overhigh local medicine concentration due to a single medicine release hole is reduced.
The clonidine hydrochloride microporous membrane osmotic pump sustained release tablet is prepared by a medicine-containing layer tablet core and a semipermeable membrane coating,
wherein, the tablet core of the medicine-containing layer consists of the following raw materials (by weight percentage):
clonidine hydrochloride 0.1-0.2%
The penetration enhancer is 20 to 50 percent
10 to 20 percent of retarder
20 to 50 percent of filling agent
0.5 to 2 percent of lubricant
In another embodiment of the present invention, the penetration enhancer may be any one or combination of sodium chloride, glucose, sucrose, lactose, magnesium sulfate, magnesium chloride, potassium sulfate, sodium sulfate, d-mannitol, urea, magnesium succinate and tartaric acid, preferably any one or combination of sodium chloride, glucose, mannitol and lactose; the adoption of the penetration enhancer is beneficial to the construction of a microporous osmotic pump, and high osmotic pressure is generated by adding the penetration enhancer, so that an osmotic pump effect is formed, and the stable and lasting release of the medicine is promoted;
in yet another embodiment of the present invention, the retardant may be hypromellose or sodium carboxymethylcellulose (CMC-Na), preferably sodium carboxymethylcellulose; the retarder has good drug slow release effect, and the addition of sodium carboxymethylcellulose with certain mass is favorable for relieving the drug release speed and simultaneously avoiding the influence of gastrointestinal tract variable factors such as peristalsis, pH, gastric emptying time and the like on the active ingredients of the drug;
it should be noted that, the clonidine hydrochloride has a certain solubility in water, the addition of the penetration enhancer in the invention easily causes the early-stage drug release to be too fast, and the later-stage drug release to be more residual, so the invention screens the added penetration enhancer and retardant, and optimally controls the added amount, thereby ensuring the drug release speed to be stable, and reducing the drug residue at the later stage of the drug release;
in yet another embodiment of the present invention, the filler is microcrystalline cellulose (MCC); the microcrystalline cellulose is used as a filler, so that the compactness of a tablet core can be maintained, and the tablet forming rate of the tablet core is improved;
in yet another embodiment of the invention, the lubricant magnesium stearate or talc; magnesium stearate is preferred.
In yet another embodiment of the present invention, the semi-permeable membrane coating comprises a film-forming material, a pore-forming agent, and a plasticizer;
in another embodiment of the present invention, the film-forming material is ethyl cellulose, the pore-forming agent is PEG400, sucrose, polyvinylpyrrolidone (PVP) or propylene glycol, and the plasticizer is diethyl phthalate (DEP). Pore-forming agent is added into the coating film to improve the permeability of the film, and the drug solution can be released through micropores on the spongy film;
in another embodiment of the present invention, the method for preparing the sustained-release tablet comprises:
-preparing a drug-containing layer core: dissolving clonidine hydrochloride in 95% ethanol or 95% ethanol PVP solution, preparing into wetting agent, sieving medicinal layer adjuvants, adding wetting agent containing medicine, making soft material, sieving, granulating, drying, sieving, grading, adding lubricant, mixing, and tabletting;
in another embodiment of the present invention, the number of the drug layer excipients screened is 70 to 90 mesh (preferably 80 mesh); preparing a soft material, sieving with a 10-30 mesh sieve (preferably 20 meshes), granulating, drying at 35-45 ℃ (preferably 40 ℃) for 2-4 h (preferably 3h), and sieving with a 10-20 mesh sieve (preferably 18 meshes) for grading; the control of the parameters is beneficial to the stable release of the drug;
-preparing a semipermeable membrane coating: dissolving the film forming material, the pore-forming agent and the plasticizer by acetone to obtain a coating solution;
in another embodiment of the invention, the film forming material is ethyl cellulose, and the mass fraction of the ethyl cellulose is 2.5-3.5% (preferably 3.0%); the porosity of the semipermeable membrane coating liquid can be effectively improved by controlling the mass fraction of the ethyl cellulose;
spraying the semipermeable membrane coating solution on the tablet core containing the drug layer for coating.
In another embodiment of the invention, the temperature is controlled to be 45 +/-5 ℃ during the preparation process of the coating; is beneficial to improving the coating efficiency and reducing the generation of damaged tablets.
The invention is further illustrated by the following examples, which are not to be construed as limiting the invention thereto. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention.
Example 1
Preparation of medicine-containing chip
Dissolving clonidine hydrochloride in 95% ethanol solution of 5% PVP as medicine-containing wetting agent, sieving sodium chloride, CMC-Na and MCC with 80 mesh sieve, mixing, adding wetting agent to make soft mass, sieving with 20 mesh sieve, granulating, drying at 40 deg.C for 3 hr, sieving with 18 mesh sieve, adding lubricant magnesium stearate, mixing, and tabletting.
Preparation of semipermeable membrane coating solution
Dissolving ethyl cellulose, PEG400 and diethyl phthalate (DEP) in acetone to obtain a coating solution with the mass fraction of the ethyl cellulose being 3%, the mass fraction of the PEG400 being 15% of the ethyl cellulose and the mass fraction of the diethyl phthalate (DEP) being 3% of the ethyl cellulose.
Preparation of film-coated tablets: putting the tablet core into a coating pan, spraying coating liquid, increasing the weight of the tablet core by 3%, keeping the temperature at 45 +/-5 ℃, coating and packaging.
According to the first method of the four-part general rule of the 'Chinese pharmacopoeia' edition for measuring the dissolution rate and the release rate, the conditions of the digestive tract in vivo are simulated, the temperature is controlled to be 37 +/-0.5 ℃, degassed fresh purified water is used as a release medium, a drug release rate test is carried out on clonidine hydrochloride controlled release particles by using dilute hydrochloric acid, samples are respectively taken for 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours, the absorbance is measured according to the four-part general rule of the 'Chinese pharmacopoeia' edition of the ultraviolet-visible spectrophotometry, the accumulated release rate is calculated according to a standard curve, the release rate is measured to be 90.5 percent, and the long-acting constant-speed release of 16 hours is maintained, as shown in figure 1.
Example 2
Preparation of medicine-containing chip
Dissolving clonidine hydrochloride in 95% ethanol solution of 5% PVP as medicine-containing wetting agent, sieving lactose, CMC-Na and MCC with 80 mesh sieve, mixing, adding wetting agent to make soft mass, sieving with 20 mesh sieve, granulating, drying at 40 deg.C for 3 hr, sieving with 18 mesh sieve, adding lubricant magnesium stearate, mixing, and tabletting.
Preparing a semipermeable membrane coating solution: dissolving ethyl cellulose, PEG400 and diethyl phthalate (DEP) in acetone to obtain a coating solution with the mass fraction of the ethyl cellulose being 3%, the mass fraction of the PEG400 being 15% of the ethyl cellulose and the mass fraction of the diethyl phthalate (DEP) being 3% of the ethyl cellulose.
Preparation of film-coated tablets: putting the tablet core into a coating pan, spraying coating liquid, increasing the weight of the tablet core by 3%, keeping the temperature at 45 +/-5 ℃, coating and packaging. The release was measured to be 81.2% at 24h, see FIG. 2.
Example 3
Preparation of medicine-containing chip
Dissolving clonidine hydrochloride in 95% ethanol solution of 5% PVP as medicine-containing wetting agent, sieving sodium chloride, CMC-Na and MCC with 80 mesh sieve, mixing, adding wetting agent to make soft mass, sieving with 20 mesh sieve, granulating, drying at 40 deg.C for 3 hr, sieving with 18 mesh sieve, adding lubricant magnesium stearate, mixing, and tabletting.
Preparing a semipermeable membrane coating solution: dissolving ethyl cellulose, PEG400 and diethyl phthalate (DEP) in acetone to obtain a coating solution with the mass fraction of the ethyl cellulose being 3%, the mass fraction of the PEG400 being 15% of the ethyl cellulose and the mass fraction of the diethyl phthalate (DEP) being 3% of the ethyl cellulose.
Preparation of film-coated tablets: putting the tablet core into a coating pan, spraying coating liquid, increasing the weight of the tablet core by 3%, keeping the temperature at 45 +/-5 ℃, coating and packaging. The 24h cumulative release was found to be 75.2%, see FIG. 3.
Example 4
Preparation of medicine-containing chip
Dissolving clonidine hydrochloride in 95% ethanol solution of 5% PVP as medicine-containing wetting agent, sieving sodium chloride, CMC-Na and MCC with 80 mesh sieve, mixing, adding wetting agent to make soft mass, sieving with 20 mesh sieve, granulating, drying at 40 deg.C for 3 hr, sieving with 18 mesh sieve, adding lubricant magnesium stearate, mixing, and tabletting.
Preparing a semipermeable membrane coating solution: dissolving ethyl cellulose and PEG400 in acetone to obtain a coating solution with the mass fraction of the ethyl cellulose being 3% and the mass fraction of the PEG400 being 15% of the ethyl cellulose.
Preparation of film-coated tablets: putting the tablet core into a coating pan, spraying coating liquid, increasing the weight of the tablet core by 3%, keeping the temperature at 45 +/-5 ℃, coating and packaging. The 24h cumulative release was found to be 71.3%, see FIG. 4.
Example 5
Preparation of medicine-containing chip
Dissolving clonidine hydrochloride in 95% ethanol solution of 5% PVP as medicine-containing wetting agent, sieving sodium chloride, CMC-Na and MCC with 80 mesh sieve, mixing, adding wetting agent to make soft mass, sieving with 20 mesh sieve, granulating, drying at 40 deg.C for 3 hr, sieving with 18 mesh sieve, adding lubricant magnesium stearate, mixing, and tabletting.
Preparing a semipermeable membrane coating solution: dissolving ethyl cellulose, PEG600 and diethyl phthalate (DEP) in acetone to obtain a coating solution with the mass fraction of the ethyl cellulose being 3%, the mass fraction of PEG400 being 15% of the ethyl cellulose and the mass fraction of the diethyl phthalate (DEP) being 3% of the ethyl cellulose.
Preparation of film-coated tablets: putting the tablet core into a coating pan, spraying coating liquid, increasing the weight of the tablet core by 4%, keeping the temperature at 45 +/-5 ℃, coating and packaging. The 24h cumulative release was found to be 83.3%, see FIG. 5.
Example 6
Preparation of medicine-containing chip
Dissolving clonidine hydrochloride in 95% ethanol solution of 5% PVP as medicine-containing wetting agent, sieving sodium chloride, CMC-Na and MCC with 80 mesh sieve, mixing, adding wetting agent to make soft mass, sieving with 20 mesh sieve, granulating, drying at 40 deg.C for 3 hr, sieving with 18 mesh sieve, adding lubricant magnesium stearate, mixing, and tabletting.
Preparing a semipermeable membrane coating solution: dissolving ethyl cellulose, PEG400 and diethyl phthalate (DEP) in acetone to obtain a coating solution with the mass fraction of the ethyl cellulose being 3%, the mass fraction of PEG600 being 15% of the ethyl cellulose and the mass fraction of the diethyl phthalate (DEP) being 3% of the ethyl cellulose.
Preparation of film-coated tablets: putting the tablet core into a coating pan, spraying coating liquid, increasing the weight of the tablet core by 3%, keeping the temperature at 45 +/-5 ℃, coating and packaging. The cumulative release over 24h was found to be 80.5%, see FIG. 6.
It should be noted that the above examples are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to the examples given, those skilled in the art can modify the technical solution of the present invention as needed or equivalent substitutions without departing from the spirit and scope of the technical solution of the present invention.
Claims (3)
1. A clonidine hydrochloride microporous membrane osmotic pump sustained release tablet is characterized in that the clonidine hydrochloride microporous membrane osmotic pump sustained release tablet is prepared by a drug-containing layer tablet core and a semipermeable membrane coating,
wherein, the tablet core of the medicine-containing layer consists of the following raw materials:
clonidine hydrochloride 0.1mg, sodium chloride 30mg, CMC-Na 20mg, MCC 45mg, magnesium stearate 0.5mg, 5% PVP in 95% ethanol solution 10 mg;
the preparation method of the clonidine hydrochloride microporous membrane osmotic pump sustained release tablet comprises the following steps:
preparing a medicine-containing chip: dissolving clonidine hydrochloride in 95% ethanol solution of 5% PVP as medicine-containing wetting agent, sieving sodium chloride, CMC-Na and MCC with 80 mesh sieve, mixing, adding wetting agent to make soft mass, sieving with 20 mesh sieve, granulating, drying at 40 deg.C for 3 hr, sieving with 18 mesh sieve, adding lubricant magnesium stearate, mixing, and tabletting;
preparing a semipermeable membrane coating solution: dissolving ethyl cellulose, PEG400 and diethyl phthalate in acetone to obtain a coating solution with the mass fraction of the ethyl cellulose being 3%, the mass fraction of the PEG400 being 15% of the ethyl cellulose and the mass fraction of the diethyl phthalate being 3% of the ethyl cellulose;
preparation of film-coated tablets: putting the tablet core in a coating pan, spraying coating liquid, increasing the weight of the tablet core by 3%, keeping the temperature at 45 + -5 deg.C, coating, and packaging.
2. A clonidine hydrochloride microporous membrane osmotic pump sustained release tablet is characterized in that the clonidine hydrochloride microporous membrane osmotic pump sustained release tablet is prepared by a drug-containing layer tablet core and a semipermeable membrane coating,
wherein, the tablet core of the medicine-containing layer consists of the following raw materials:
clonidine hydrochloride 0.1mg, lactose 30mg, CMC-Na 20mg, MCC 45mg, magnesium stearate 0.5mg, 5% PVP in 95% ethanol solution 10mg,
the preparation method of the clonidine hydrochloride microporous membrane osmotic pump sustained release tablet comprises the following steps:
preparing a medicine-containing chip: dissolving clonidine hydrochloride in 95% ethanol solution of 5% PVP as medicine-containing wetting agent, sieving lactose, CMC-Na and MCC with 80 mesh sieve, mixing, adding wetting agent to make soft material, sieving with 20 mesh sieve, granulating, drying at 40 deg.C for 3 hr, sieving with 18 mesh sieve, adding lubricant magnesium stearate, mixing, and tabletting;
preparing a semipermeable membrane coating solution: dissolving ethyl cellulose, PEG400 and diethyl phthalate in acetone to obtain a coating solution with the mass fraction of the ethyl cellulose being 3%, the mass fraction of the PEG400 being 15% of the ethyl cellulose and the mass fraction of the diethyl phthalate being 3% of the ethyl cellulose;
preparation of film-coated tablets: putting the tablet core in a coating pan, spraying coating liquid, increasing the weight of the tablet core by 3%, keeping the temperature at 45 + -5 deg.C, coating, and packaging.
3. A clonidine hydrochloride microporous membrane osmotic pump sustained release tablet is characterized in that the clonidine hydrochloride microporous membrane osmotic pump sustained release tablet is prepared by a drug-containing layer tablet core and a semipermeable membrane coating,
wherein, the tablet core of the medicine-containing layer consists of the following raw materials:
clonidine hydrochloride 0.1mg, sodium chloride 20mg, CMC-Na 20mg, MCC 55mg, magnesium stearate 0.5mg, 5% PVP in 95% ethanol solution 10 mg;
the preparation method of the clonidine hydrochloride microporous membrane osmotic pump sustained release tablet comprises the following steps:
preparing a medicine-containing chip: dissolving clonidine hydrochloride in 95% ethanol solution of 5% PVP as medicine-containing wetting agent, sieving sodium chloride, CMC-Na and MCC with 80 mesh sieve, mixing, adding wetting agent to make soft mass, sieving with 20 mesh sieve, granulating, drying at 40 deg.C for 3 hr, sieving with 18 mesh sieve, adding lubricant magnesium stearate, mixing, and tabletting;
preparing a semipermeable membrane coating solution: dissolving ethyl cellulose, PEG400 and diethyl phthalate in acetone to obtain a coating solution with the mass fraction of the ethyl cellulose being 3%, the mass fraction of the PEG400 being 15% of the ethyl cellulose and the mass fraction of the diethyl phthalate being 3% of the ethyl cellulose;
preparation of film-coated tablets: putting the tablet core in a coating pan, spraying coating liquid, increasing the weight of the tablet core by 3%, keeping the temperature at 45 + -5 deg.C, coating, and packaging.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910227249.9A CN109966259B (en) | 2019-03-25 | 2019-03-25 | Clonidine hydrochloride microporous membrane osmotic pump sustained release tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910227249.9A CN109966259B (en) | 2019-03-25 | 2019-03-25 | Clonidine hydrochloride microporous membrane osmotic pump sustained release tablet and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109966259A CN109966259A (en) | 2019-07-05 |
| CN109966259B true CN109966259B (en) | 2020-12-18 |
Family
ID=67080296
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910227249.9A Active CN109966259B (en) | 2019-03-25 | 2019-03-25 | Clonidine hydrochloride microporous membrane osmotic pump sustained release tablet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109966259B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103550183A (en) * | 2013-09-05 | 2014-02-05 | 合肥立方制药股份有限公司 | Trimetazidine hydrochloride osmotic pump controlled-release tablet and preparation method thereof |
| CN104706614A (en) * | 2013-12-16 | 2015-06-17 | 四川科瑞德制药有限公司 | Tandospirone micropore osmotic pump preparation |
| CN105919943A (en) * | 2016-04-26 | 2016-09-07 | 青岛正大海尔制药有限公司 | Clonidine hydrochloride controlled-release granule and preparation method thereof |
-
2019
- 2019-03-25 CN CN201910227249.9A patent/CN109966259B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103550183A (en) * | 2013-09-05 | 2014-02-05 | 合肥立方制药股份有限公司 | Trimetazidine hydrochloride osmotic pump controlled-release tablet and preparation method thereof |
| CN104706614A (en) * | 2013-12-16 | 2015-06-17 | 四川科瑞德制药有限公司 | Tandospirone micropore osmotic pump preparation |
| CN105919943A (en) * | 2016-04-26 | 2016-09-07 | 青岛正大海尔制药有限公司 | Clonidine hydrochloride controlled-release granule and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109966259A (en) | 2019-07-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11253523B2 (en) | Tofacitinib oral sustained release dosage forms | |
| EP2085078B1 (en) | Controlled porosity osmotic pump tablet of high permeable drugs and the preparation method thereof | |
| US6641840B2 (en) | Sustained release formulations for growth hormone secretagogues | |
| CA1338552C (en) | Use of asymmetric membranes in delivery devices | |
| NO965539L (en) | Pharmaceutical tacrine preparations | |
| SK8572002A3 (en) | Hydrogel-driven drug dosage form | |
| JP2000229846A (en) | Release control type dosage form | |
| CA3050049A1 (en) | Modified-release dosage forms of 5-ht2c agonists useful for weight management | |
| EP2663310A1 (en) | Oral dosage forms for modified release comprising tasocitinib | |
| KR20120056864A (en) | Osmotic pump controlled release tablet and preparation method thereof | |
| JP2022500505A (en) | Sustained release composition containing trihexyphenidyl | |
| JP2021516260A (en) | Programmable pharmaceutical composition for time release of drug | |
| CN109966259B (en) | Clonidine hydrochloride microporous membrane osmotic pump sustained release tablet and preparation method thereof | |
| ES2912968T3 (en) | Extended Release Compositions Comprising Pyridostigmine | |
| WO2021014360A1 (en) | Oral modified release dosage forms | |
| CN114222562A (en) | Oral pharmaceutical composition | |
| JP2007520421A (en) | Controlled release drug delivery system for oral administration | |
| JP2009503011A (en) | Pharmaceutical forms with sustained pH-independent active ingredient release for active ingredients with strong pH-dependent solubility | |
| WO2018192000A1 (en) | Osmotic pump tablet of perindopril and salt thereof and preparation method of same | |
| CN114099499A (en) | Edaravone oral sustained-release composition, preparation method and application | |
| US20160228378A1 (en) | Sustained release formulations of lorazepam | |
| JP2013502427A (en) | Controlled release formulations of anabaseine compounds and uses thereof | |
| CN110917158A (en) | Gliclazide microporous membrane osmotic pump sustained-release tablet and preparation method thereof | |
| RU2632715C2 (en) | Sustained-release pharmaceutical composition containing asparaginates | |
| US20070212415A1 (en) | Sustained-release tablet containing doxazosin mesylate |
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 |