CN110327306B - Isradipine controlled release tablet and preparation method thereof - Google Patents
Isradipine controlled release tablet and preparation method thereof Download PDFInfo
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- 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
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0004—Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
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- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- 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
Abstract
The invention provides an isradipine controlled release tablet and a preparation method thereof, wherein the isradipine controlled release tablet comprises a double-layer tablet consisting of a drug layer and a boosting layer, a controlled release semi-permeable membrane, a drug release pore and a moisture-proof coat. The drug layer comprises a main drug isradipine and a carrier, wherein the carrier mainly comprises vinylpyrrolidone andor vinylpyrrolidone copolymer; the boosting layer mainly comprises penetration-promoting substances, insoluble polymers, osmotic pressure promoters and the like, and the controlled-release semi-permeable membrane mainly comprises cellulose acetate, a plasticizer and a pore-foaming agent. The invention releases the isradipine at a controlled rate after oral administration through the application of the high polymer material, so that the preparation can achieve the aim of maintaining 24-hour drug release after once daily administration, stabilize the blood concentration and improve the clinical treatment effect of the drug.
Description
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to a single-chamber double-layer osmotic pump controlled release preparation containing an active drug isradipine and a preparation method thereof.
Background
Isradipine (also known as: isradipine), chemical name: isopropylmethyl (+/-) -4- (4-benzofurazanyl) -1, 4-dihydro-2, 6-dimethyl-3, 6-pyridinedicarboxylate. Isradipine is a novel dihydropyridine calcium channel blocker, and like other dihydropyridine drugs, by blocking transmembrane calcium ion inflow, effectively and selectively inhibits contraction caused by depolarization to play a role on cardiac muscle and vascular smooth muscle, has high vascular selectivity, can dilate peripheral blood vessels, coronary blood vessels and cerebral vessels, has small effect on the heart, and only inhibits spontaneous activity of sinoatrial node. The product has strong vasodilatation effect, no cardiac inhibition effect, and hardly causes reflex tachycardia. The composition has obvious blood pressure lowering and atherosclerosis resisting effects, and can maintain or recover blood flow under left ventricular endothelium, prevent ischemic injury, improve motion of angina pectoris and congestive heart failure patients, treat hypertension, and protect heart.
The medicine has slow effect (2-4 weeks) and long duration, the peak time of blood concentration is 2 hours after oral administration, the binding rate of the medicine to protein in blood plasma is 95%, the medicine is metabolized in liver, and t is t1/2For about 9 hours. Isradipine can increase excretion of sodium ions and water, promote urination, expand renal output artery and output artery, reduce renal capillary pressure, and protect kidney. Can be used for treating hypertension, coronary heart disease, angina pectoris, and congestive heart failure.
Cardiovascular diseases have obvious time-dependent characteristics, and a large number of clinical experiments show that the attack frequency of the cardiovascular diseases is high from early morning, particularly before and after getting up to around 11-12 o' clock at noon. If an effective drug could be provided over this period of time, better prophylactic and therapeutic effects could be achieved. The timing medicine releasing system is one new kind of controlled release preparation developed in recent years, and can release effective amount of medicine automatically in the important time of disease attack to ensure the curative effect and reduce toxic side effect. Although the existing pulse type release system which is researched more has timing effect, the release time is short, and the treatment requirement cannot be met, so that the delayed-release type controlled release tablet becomes a new direction for the research of the oral timing release system.
Disclosure of Invention
The invention discloses a single-chamber double-layer osmotic pump preparation prepared by adding appropriate auxiliary materials into isradipine to control the release of a medicament, the single-chamber double-layer osmotic pump preparation consists of a semipermeable membrane, a medicament-containing layer containing a main medicament and a high polymer material capable of absorbing water and a boosting layer made of a swellable high polymer material, and the tablet expands after absorbing water so that the medicament is released from a small hole punched by laser at an approximately constant speed, thereby achieving the purposes of stabilizing and lasting blood concentration, reducing peak-valley phenomenon and reducing the medicament taking times.
In the patent and literature formula of the isradipine controlled release tablet, polyoxyethylene is added into a drug layer and a boosting layer, the hygroscopicity of the polyoxyethylene is very high, the problems of soft material adhesion, net adhesion, caking and the like are easy to occur in granulation, the solvent drying is difficult in the granulation process, the problem of high organic solvent residue is easy to cause due to the generally low drying temperature, and if the drying is complete, relatively long drying time is needed, so that the smooth implementation of large-scale production is influenced to a certain extent. In the high-speed tabletting process, when the temperature reaches about 50 ℃ due to heat generated after the die is repeatedly used, the unfavorable phenomena such as sticking and the like are easy to occur, so that a special cooling facility is needed to control the temperature of the die. Therefore, there is a strong need to find a better way to solve this problem.
The glass transition temperature range of the polyoxyethylene is 65-67 ℃, the thermal stability is poor, the storage temperature of the prepared tablet is not too high, the release behavior of the tablet is influenced because the property of the polyoxyethylene is changed easily if the storage temperature is high, and meanwhile, the prepared finished product is easy to absorb moisture and has the problem of stability of the medicine quality. The polyoxyethylene is unstable and easy to oxidize and deteriorate, needs to be stored in a nitrogen-filled cold place, has short effective period, and has influence on the continuity of large-scale production and production arrangement. The polyoxyethylene has a slow rate of water absorption and hydration, so that the time lag of drug release is long, and the drug cannot take effect quickly after being taken.
In order to fully exert the advantage that the current isradipine controlled release tablet can control the uniform and rapid release of the medicine and overcome the problems of the granulation process of the polyoxyethylene formula used in the traditional formula and the stability of the product, the invention specially utilizes the high polymer material with lower hygroscopicity and stronger water swelling property to carry out the double-layer tablet formula, such as: polyvidone, copovidone, hydroxypropyl methylcellulose, cross-linked sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose and the like, which not only ensure the uniform release of the medicine, but also successfully solve the product quality problems caused by granulation adhesion and easy moisture absorption of the product in the traditional prescription process.
Drawings
Figure 1 is a graph of the release profile of the sample of example 1,
figure 2 is a graph of the release profile of the sample of example 2,
Detailed Description
The invention will be further described below by means of specific embodiments. It should be understood by those skilled in the art that these descriptions are not intended to limit the scope of the present invention, and equivalents or corresponding modifications made based on the descriptions in the embodiments may still fall within the scope of the present invention.
EXAMPLE 1 preparation of controlled Release tablets of isradipine
(1) Preparation of bilayer tablet core
(ii) a drug layer
Isradipine 5g
Carbomer 70g
Povidone 30g
Silica 1g
Magnesium stearate 1g
The isradipine, the carbomer and the povidone in the formula amount are uniformly mixed, a proper amount of 60-80% ethanol is used for preparing a soft material, a 18-mesh nylon net is used for granulating, the prepared granules are subjected to ventilation drying at the temperature of 50 ℃, and then the silicon dioxide and the magnesium stearate are added and uniformly mixed for later use.
② boosting layer
Low-substituted hydroxypropylcellulose 30g
Cross-linked sodium carboxymethyl starch 60g
Sodium chloride 20g
Red iron oxide 2g
Silica 1g
Magnesium stearate 1g
Mixing the low-substituted hydroxypropyl cellulose, the cross-linked sodium carboxymethyl starch, the sodium chloride and the red iron oxide according to the prescription amount uniformly, preparing a soft material by using a proper amount of 60-80% ethanol, granulating by using a 18-mesh nylon net, ventilating and drying the prepared granules at 50 ℃, adding the silicon dioxide and the magnesium stearate, and mixing uniformly for later use.
③ tabletting
The medicine layer granule is 60%
40 percent of particles of the boosting layer
The tablets were punched with a shallow arc of 8mm diameter using a double layer tablet press at about 215mg tablet weight and hardness were measured during the compression process.
(2) Controlled release semi-permeable film coating preparation
Cellulose acetate 40g
Phthalic acid diethyl ester 3g
Polyethylene glycol 10004 g
Acetone 2000ml
The double-layer tablets prepared by the process are coated by a controlled-release semi-permeable membrane by using an efficient coating machine, the temperature of a tablet bed is 10-20 ℃, and the weight of the coating is increased by 18-22%.
Making into 1000 pieces
(3) Laser drilling
Punching holes with diameter of 0.8mm on the surface of the medicine layer by using a laser-beam drilling machine.
(4) Preparation of gastric soluble film coat
The tablets prepared by the process are coated with gastric-soluble film by an efficient coating machine, and the coating is increased by 2-3%.
(5) And packaging the prepared sheet with PVC aluminum foil.
And (3) measuring the release degree: the procedure was carried out in the dark, the in vitro release in example 1 was determined according to the first method of the second method of dissolution determination, XD, appendix D of the second edition of Chinese pharmacopoeia 2015, at a rotation speed of 50r/min, using 900ml of an aqueous solution of 0.1% (w/v) sodium lauryl sulfate as release medium at 37 ℃ and tablets were placed in a dissolution cup, 5ml were sampled at 2, 4, 6, 8, 10, 12, 16, 20, 24h, respectively, and simultaneously supplemented with an aqueous solution of 0.1% (w/v) sodium lauryl sulfate at the same temperature and volume.
Example 2 preparation of isradipine controlled Release tablets
(1) Preparation of bilayer tablet core
(ii) a drug layer
Isradipine 10g
Carbomer 90g
Povidone 45g
Silica 1g
Magnesium stearate 1g
The isradipine, the carbomer and the povidone in the formula amount are uniformly mixed, a proper amount of 60-80% ethanol is used for preparing a soft material, a 18-mesh nylon net is used for granulating, the prepared granules are subjected to ventilation drying at the temperature of 50 ℃, and then the silicon dioxide and the magnesium stearate are added and uniformly mixed for later use.
② boosting layer
Crosslinked sodium carboxymethyl starch 70g
Hydroxypropyl methylcellulose 40g
22g of sodium chloride
Red iron oxide 2g
Silica 1g
Magnesium stearate 1g
Uniformly mixing hydroxypropyl methylcellulose, cross-linked sodium carboxymethyl starch, sodium chloride and red iron oxide according to the prescription amount, preparing a soft material by using a proper amount of 60-80% ethanol, granulating by using a 18-mesh nylon net, ventilating and drying the prepared granules at 50 ℃, adding silicon dioxide and magnesium stearate, and uniformly mixing for later use.
③ tabletting
The medicine layer granule is 60%
40 percent of particles of the boosting layer
And punching the tablets by using a double-layer tablet press with a shallow arc with the diameter of 9mm according to the weight of the tablets being about 285mg, and detecting the weight and the hardness of the tablets in the tabletting process.
(2) Controlled release semi-permeable film coating preparation
Cellulose acetate 45g
Phthalic acid diethyl ester 4g
Polyethylene glycol 10005 g
Acetone 2000ml
The double-layer tablets prepared by the process are coated by a controlled-release semi-permeable membrane by using an efficient coating machine, the temperature of a tablet bed is 10-20 ℃, and the weight of the coating is increased by 18-22%.
(3) Laser drilling
Punching holes with diameter of 0.8mm on the surface of the medicine layer by using a laser-beam drilling machine.
(4) Preparation of gastric soluble film coat
The tablets prepared by the process are coated with gastric-soluble film by an efficient coating machine, and the coating is increased by 2-3%.
(5) And packaging the prepared sheet with PVC aluminum foil.
Example 1 sample detection and Mass stability analysis
The procedure was carried out in the dark, the in vitro release in example 1 was determined according to the first method of the second method of dissolution determination, XD, appendix D of the second edition of Chinese pharmacopoeia 2015, at a rotation speed of 50r/min, using 900ml of an aqueous solution of 0.1% (w/v) sodium lauryl sulfate as release medium at 37 ℃ and tablets were placed in a dissolution cup, 5ml were sampled at 2, 4, 6, 8, 10, 12, 16, 20, 24h, respectively, and simultaneously supplemented with an aqueous solution of 0.1% (w/v) sodium lauryl sulfate at the same temperature and volume.
Example 1 results of measuring the degree of release of the sample are shown in the following table
The release curve is shown in figure 1 of the specification
Example 2 sample detection and Mass stability analysis
The procedure was carried out in the dark, the in vitro release in example 1 was determined according to the first method of the second method of dissolution determination, XD, appendix D of the second edition of Chinese pharmacopoeia 2015, at a rotation speed of 50r/min, using 900ml of an aqueous solution of 0.1% (w/v) sodium lauryl sulfate as release medium at 37 ℃ and tablets were placed in a dissolution cup, 5ml were sampled at 2, 4, 6, 8, 10, 12, 16, 20, 24h, respectively, and simultaneously supplemented with an aqueous solution of 0.1% (w/v) sodium lauryl sulfate at the same temperature and volume.
Example 2 results of measuring the degree of release of the sample are shown in the following table
The release curve is shown in figure 2 of the specification
Accelerated tests and long-term test investigation are carried out according to the commercially available package, and the results show that the indexes of the product do not change obviously under the packaging condition, and the product can meet the requirements of the medicine on storage and transportation conditions. The esomeprazole magnesium enteric capsule and the preparation method thereof have the advantages of stable product quality, low impurity content, simple and convenient formula and smooth process, ensure the product quality and clinical treatment effect, and can obtain remarkable social benefit and economic benefit.
Claims (2)
1. An isradipine controlled release tablet, which is characterized in that: the preparation method of the isradipine controlled release tablet comprises the following steps:
(1) preparation of bilayer tablet core
(ii) a drug layer
Isradipine 5g
Carbomer 70g
Povidone 30g
Silica 1g
Magnesium stearate 1g
Uniformly mixing the isradipine, the carbomer and the povidone according to the formula amount, preparing a soft material by using a proper amount of 60-80% ethanol, granulating by using an 18-mesh nylon net, carrying out ventilation drying on the prepared granules at 50 ℃, and then adding silicon dioxide and magnesium stearate to be uniformly mixed for later use;
② boosting layer
Low-substituted hydroxypropylcellulose 30g
Cross-linked sodium carboxymethyl starch 60g
Sodium chloride 20g
Red iron oxide 2g
Silica 1g
Magnesium stearate 1g
Uniformly mixing the low-substituted hydroxypropyl cellulose, the cross-linked sodium carboxymethyl starch, the sodium chloride and the red iron oxide according to the prescription amount, preparing a soft material by using a proper amount of 60-80% ethanol, granulating by using a 18-mesh nylon net, ventilating and drying the prepared granules at 50 ℃, adding silicon dioxide and magnesium stearate, and uniformly mixing for later use;
③ tabletting
The medicine layer granule is 60%
40 percent of particles of the boosting layer
Punching the tablets by using a double-layer tablet press in a shallow arc manner with the diameter of 8mm according to the weight of the tablets being about 215mg, and detecting the weight and the hardness of the tablets in the tabletting process;
(2) controlled release semi-permeable film coating preparation
Cellulose acetate 40g
Phthalic acid diethyl ester 3g
Polyethylene glycol 10004 g
Acetone 2000ml
Coating the double-layer tablet prepared by the process with a controlled release semi-permeable membrane by using a high-efficiency coating machine, wherein the temperature of a tablet bed is 10-20 ℃, and the weight of the coating is increased by 18-22%;
making into 1000 pieces
(3) Laser drilling
Punching the surface of the medicine layer by using a laser-beam drilling machine, wherein the diameter of each hole is 0.8 mm;
(4) preparation of gastric soluble film coat
Coating the tablets prepared by the process with a gastric-soluble film by using a high-efficiency coating machine, wherein the weight of the coating is increased by 2-3%;
(5) and packaging the prepared sheet with PVC aluminum foil.
2. An isradipine controlled release tablet, which is characterized in that: the preparation method of the isradipine controlled release tablet comprises the following steps:
(1) preparation of bilayer tablet core
(ii) a drug layer
Isradipine 10g
Carbomer 90g
Povidone 45g
Silica 1g
Magnesium stearate 1g
Uniformly mixing the isradipine, the carbomer and the povidone according to the formula amount, preparing a soft material by using a proper amount of 60-80% ethanol, granulating by using an 18-mesh nylon net, carrying out ventilation drying on the prepared granules at 50 ℃, and then adding silicon dioxide and magnesium stearate to be uniformly mixed for later use;
② boosting layer
Crosslinked sodium carboxymethyl starch 70g
Hydroxypropyl methylcellulose 40g
22g of sodium chloride
Red iron oxide 2g
Silica 1g
Magnesium stearate 1g
Uniformly mixing hydroxypropyl methylcellulose, cross-linked sodium carboxymethyl starch, sodium chloride and red iron oxide according to the prescription amount, preparing a soft material by using a proper amount of 60-80% ethanol, granulating by using a 18-mesh nylon net, drying the prepared granules at 50 ℃ in a ventilating way, and adding silicon dioxide and magnesium stearate to be uniformly mixed for later use;
③ tabletting
The medicine layer granule is 60%
40 percent of particles of the boosting layer
Punching tablets by using a double-layer tablet press in a shallow arc manner with the diameter of 9mm according to the weight of the tablets being about 285mg, and detecting the weight and the hardness of the tablets in the tabletting process;
(2) controlled release semi-permeable film coating preparation
Cellulose acetate 45g
Phthalic acid diethyl ester 4g
Polyethylene glycol 10005 g
Acetone 2000ml
Coating the double-layer tablet prepared by the process with a controlled release semi-permeable membrane by using a high-efficiency coating machine, wherein the temperature of a tablet bed is 10-20 ℃, and the weight of the coating is increased by 18-22%;
(3) laser drilling
Punching the surface of the medicine layer by using a laser-beam drilling machine, wherein the diameter of each hole is 0.8 mm;
(4) preparation of gastric soluble film coat
Coating the tablets prepared by the process with a gastric-soluble film by using a high-efficiency coating machine, wherein the weight of the coating is increased by 2-3%;
(5) and packaging the prepared sheet with PVC aluminum foil.
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Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4946687A (en) * | 1987-10-02 | 1990-08-07 | Alza Corporation | Dosage form for treating cardiovascular diseases |
| WO2003051341A1 (en) * | 2001-12-18 | 2003-06-26 | Alza Corporation | Dosage form for providing time-varying patterns of drug delivery |
| CN1761453A (en) * | 2003-06-26 | 2006-04-19 | 韩国化学研究院 | Controlled release-drug delivery system for oral administration |
| CN101161242A (en) * | 2006-10-13 | 2008-04-16 | 北京红林制药有限公司 | A explosive core composition of controlled release administer drug and controlled release preparation as well as its preparing method |
| CN101167700A (en) * | 2006-10-24 | 2008-04-30 | 北京红林制药有限公司 | Nifedipine controlled-releasing tablet and preparation method thereof |
| CN101172101A (en) * | 2006-10-30 | 2008-05-07 | 北京红林制药有限公司 | Glipizide controlled release tablets and preparation method thereof |
| CN102349880A (en) * | 2011-10-12 | 2012-02-15 | 合肥华方医药科技有限公司 | Isradipine controlled-release tablets and preparation method thereof |
| CN102846574A (en) * | 2012-10-10 | 2013-01-02 | 德州德药制药有限公司 | Nifedipine controlled release composition and preparation method thereof |
| CN104208035A (en) * | 2014-08-22 | 2014-12-17 | 苏州大学 | Sustained-release tablet containing isradipine |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6764697B1 (en) * | 1991-06-27 | 2004-07-20 | Alza Corporation | System for delaying drug delivery up to seven hours |
| US20040005359A1 (en) * | 2002-06-27 | 2004-01-08 | Cheng Xiu Xiu | Controlled release oral dosage form |
| US20070128280A1 (en) * | 2005-12-02 | 2007-06-07 | Patel Hasmukh B | Oral osmotic drug delivery system |
| CN108578380A (en) * | 2017-07-25 | 2018-09-28 | 广州玻思韬控释药业有限公司 | Controlled releasing penetrant pump |
-
2019
- 2019-06-15 CN CN201910518649.5A patent/CN110327306B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4946687A (en) * | 1987-10-02 | 1990-08-07 | Alza Corporation | Dosage form for treating cardiovascular diseases |
| WO2003051341A1 (en) * | 2001-12-18 | 2003-06-26 | Alza Corporation | Dosage form for providing time-varying patterns of drug delivery |
| CN1761453A (en) * | 2003-06-26 | 2006-04-19 | 韩国化学研究院 | Controlled release-drug delivery system for oral administration |
| CN101161242A (en) * | 2006-10-13 | 2008-04-16 | 北京红林制药有限公司 | A explosive core composition of controlled release administer drug and controlled release preparation as well as its preparing method |
| CN101167700A (en) * | 2006-10-24 | 2008-04-30 | 北京红林制药有限公司 | Nifedipine controlled-releasing tablet and preparation method thereof |
| CN101172101A (en) * | 2006-10-30 | 2008-05-07 | 北京红林制药有限公司 | Glipizide controlled release tablets and preparation method thereof |
| CN102349880A (en) * | 2011-10-12 | 2012-02-15 | 合肥华方医药科技有限公司 | Isradipine controlled-release tablets and preparation method thereof |
| CN102846574A (en) * | 2012-10-10 | 2013-01-02 | 德州德药制药有限公司 | Nifedipine controlled release composition and preparation method thereof |
| CN104208035A (en) * | 2014-08-22 | 2014-12-17 | 苏州大学 | Sustained-release tablet containing isradipine |
Non-Patent Citations (1)
| Title |
|---|
| 伊拉地平单室渗透泵控释片的制备及在犬体内的生物等效性研究;严明志，等;《中国药房》;20131231;第24卷(第41期);第3876-3878页 * |
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Inventor after: Bian Jiangang Inventor after: Pan Xiuzhi Inventor after: Li Chengwen Inventor after: Yin Lifang Inventor after: Liu Jing Inventor after: Kong Chenxi Inventor after: Zhang Huawei Inventor after: Ma Hao Inventor after: Liu Wei Inventor before: Bian Jiangang Inventor before: Pan Xiuzhi Inventor before: Li Chengwen Inventor before: Liu Jing Inventor before: Kong Chenxi Inventor before: Zhang Huawei Inventor before: Ma Hao Inventor before: Liu Wei |
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Correction item: Inventor Correct: Bian Jiangang|Pan Xiuzhi|Li Chengwen|Yin Lifang|Liu Jing|Kong Chenxi|Zhang Huawei|Ma Hao|Liu Wei False: Bian Jiangang|Pan Xiuzhi|Li Chengwen|Yin Lifang|Liu Jing|Kong Chenxi|Zhang Huawei|Ma Hao|Liu Wei Number: 52-01 Volume: 36 |
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