CN106344535B - A kind of fluvastatin sodium controlled porosity osmotic pump tablets and preparation method thereof - Google Patents
A kind of fluvastatin sodium controlled porosity osmotic pump tablets and preparation method thereof Download PDFInfo
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- CN106344535B CN106344535B CN201610752919.5A CN201610752919A CN106344535B CN 106344535 B CN106344535 B CN 106344535B CN 201610752919 A CN201610752919 A CN 201610752919A CN 106344535 B CN106344535 B CN 106344535B
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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
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
-
- 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
-
- 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
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—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
- A61K9/2886—Dragees; Coated pills or tablets, e.g. with film or compression coating having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer
Abstract
The present invention relates to a kind of fluvastatin sodium controlled porosity osmotic pump tablets and preparation method thereof, said preparation includes drug containing label and the semi permeability clothing film being wrapped in outside label and general thin clothing film.Contain fluvastatin sodium, filler, retarding agent, osmotic pressure active material, alkali stabilizer and lubricant in label；Semi permeability clothing film includes cellulose acetate, pore-foaming agent and plasticizer；General thin clothing film is film coating pre-mix dose stomach dissolution type Opadry.The present invention slows down drug release rate by the way of macromolecule retarding agent is added in label, then successively packet semi permeability clothing film and the common clothing film with interception outside label, to which fluvastatin sodium controlled porosity osmotic pump preparation be prepared, said preparation is able to maintain constant speed release medicine in 24 hours, and blood concentration is more steady, and curative effect is lasting, toxic side effect is small, good patient compliance, and said preparation preparation process is simple, it is easy to industrialized production.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, and in particular to a kind of fluvastatin sodium controlled porosity osmotic pump tablets and its preparation
Method.
Background technique
With the development of the social economy, the raising of living standards of the people and the variation of life style, the average serum of crowd
TC (total cholesterol) level is just stepped up, and at the same time, closely related diabetes and metabolic syndrome exist with dyslipidemia
China is also very common, studies have shown that China announcing of professor Yang Wenying of China-Japan Friendship Hospital, the Ministry of Public Health 20 years old or more
In crowd, the illness rate of hypercholesterolemia is 9.0%, and the illness rate of criticality hypercholesterolemia is 22.5%, and is presented
The trend of liter.
At present the common drug of clinical treatment hypercholesterolemia be statins, as Lovastatin, Simvastatin,
Pravastatin, Atorvastatin and Fluvastatin etc., wherein Fluvastatin is metabolized in liver through cytochrome P450 2C9, compared with it
His statins are highly-safe, and toxic side effect is small, and therefore, the line that Fluvastatin becomes clinical treatment hyperlipemia is used
Medicine has entered national medical insurance.
Fluvastatin (Fluvastatin) is first fully synthetic hydroxyl first pentanedioyl acyl coenzyme of " SANDOS " company exploitation
A (HMG-CoA) reductase inhibitor, is clinically usually used with sodium salt, there was only conventional capsule (rule on domestic and international market at present
Lattice: 20mg or 40mg, in terms of Fluvastatin) and two kinds of dosage forms of sustained release tablets (specification: 80mg, in terms of Fluvastatin), wherein commonly
Capsule needs multiple dosing daily, and blood concentration fluctuation is big, and adverse reaction is serious；And fluvastatin sodium extended-released tablets, it is every to be administered day by day
Once, the compliance of patient medication is improved to a certain extent, but that there are slow release effects is inhomogenous, non-constant velocity drug release is asked
Topic.
If United States Patent (USP) US6242003B1 discloses the pharmaceutical composition of commercially available fluvastatin sodium extended-released tablets, the medicine group
Closing object includes fluvastatin sodium, hypromellose and other drugs excipient, but is sustained release bone with hypromellose
The fluvastatin sodium sustained release preparation of frame material after long-term place (such as storage 18 months or more), slow release effect obviously drops
It is low；A kind of technical side of osmotic pump controlled release preparation composition for treating hyperlipidemia of patent CN101385729A and preparation method thereof
A kind of label being made of Acipimox, Fluvastatin, penetration enhancer, filler, lubricant and one layer are disclosed in case 2
The controlled releasing penetrant pump of the film coating composition of semi-permeable property containing macromolecule filming material, plasticizer and pore-foaming agent,
Fluvastatin sodium 12h releases the drug completely in said preparation, but Fluvastatin absorbs rapidly, is administered at empty stomach in 1h that can to reach peak dense
Degree, and its half-life short, only 0.5~0.8h, therefore, the Acipimox and fluorine that take once day prepared using the technical solution
It cuts down statin micropore permeation pump preparation to be difficult to maintain to release the drug for 24 hours, drug effective acting time is short.
Patent CN102755284A discloses a kind of fluvastatin sodium sustained release pharmaceutical composition, the Fluvastatin slow releasing pharmaceutical
Composition uses Pluronic F-127 as controlled release matrix material and the coating coordinated containing light screening material, can effective solution
The problem of slow release effect is substantially reduced is placed for a long time using hypromellose as existing for controlled release matrix material；Above-mentioned sustained release
Although piece solves the frequent trouble of ordinary preparation administration, but since its non-constant velocity releases the drug, the release of drug and absorption rate are again
It will receive the influence of the factors such as patient's body gastro-intestinal Fluid pH；Further, since fluvastatin sodium solubility with higher, sustained release system
Agent is easy to appear burst drug release, and the fluctuation of blood concentration is still larger, and the size of effective acting time and side effect varies with each individual,
With uncontrollability；Therefore, it is necessary that exploitation, which has the fluvastatin sodium controlled release preparation of constant speed release medicine rate,.
Summary of the invention
In view of the above problems, technical scheme is as follows:
The rate of release for slowing down drug by the way of macromolecule retarding agent is added in label first, then outside label
Successively packet semi permeability clothing film and the common clothing film with interception, to obtain satisfactory fluvastatin sodium micropore
Osmotic pump controlled release tablet.
Fluvastatin sodium controlled porosity osmotic pump tablets of the invention include drug containing label, the semi permeability being wrapped in outside label
Clothing film and general thin clothing film, wherein semi permeability clothing film weight is the 8~12% of label weight, general thin clothing film
Weight is the 2~4% of label weight.
Fluvastatin sodium controlled porosity osmotic pump tablets of the invention, the weight percent of each component in drug containing label are as follows:
The component of semi permeability clothing film in the present invention are as follows: cellulose acetate, plasticizer, pore-foaming agent, plasticizer weight are
The 10~30% of cellulose acetate weight, pore-foaming agent weight are the 15~30% of cellulose acetate weight；General thin clothing film is
Film coating pre-mix dose stomach dissolution type Opadry.
Filler in the present invention is selected from one of microcrystalline cellulose, starch, lactose, dextrin, pregelatinized starch or more
Kind.
It is fine that retarding agent in the present invention is selected from polyoxyethylene WSR N-60K NF, polyoxyethylene WSR-301NF, hydroxypropyl
Tie up one of element K4M, hypromellose K15M, hydroxypropyl cellulose HPC-H or a variety of.
Osmotic pressure active material in the present invention is selected from one of sodium chloride, potassium chloride, sucrose, glucose, mannitol
Or it is a variety of.
Lubricant in the present invention is selected from one of magnesium stearate, talcum powder, superfine silica gel powder or a variety of；The choosing of alkali stabilizer
From saleratus.
In the present invention in clothing film plasticizer in diethyl phthalate, triethyl citrate, triglycerides
It is one or more；Pore-foaming agent is selected from one of polyethylene glycol 400, Macrogol 600, sucrose, mannitol in clothing film
Or it is a variety of.
The preparation method of fluvastatin sodium controlled porosity osmotic pump tablets provided by the invention includes the following steps:
(1), prepared by label: the fluvastatin sodium of recipe quantity, filler, retarding agent, osmotic pressure active material and alkali is steady
Determine agent and cross 60 meshes to be uniformly mixed, is added appropriate dehydrated alcohol softwood, 20 meshes granulation, 40 DEG C of dryings, 18 mesh sieves add
Tabletting is after entering lubricant mixing to get label；
(2), it is mixed that the cellulose acetate, plasticizer and pore-foaming agent of recipe quantity packet clothing film: are dissolved in acetone-purified water
It closes and is configured to the coating solution that solid content is 4~6% in solution, label is placed in coating pan and is coated, weight gain to required weight will
Coating tablet, which is placed in 40 DEG C of baking ovens, to be solidified 12 hours；
(3), film coating film: film coating pre-mix dose stomach dissolution type Opadry is dissolved in dehydrated alcohol-purification of aqueous solutions
It is configured to the coating solution that solid content is 7~10%, label is placed in coating pan and is coated, weight gain to required weight stops whitewashing,
By coating tablet in coating pan in 40 DEG C of dry 30min to get fluvastatin sodium controlled porosity osmotic pump tablets.
Acetone-purified water weight ratio described in the preparation method step (2) is 95:5~98:2.
Dehydrated alcohol-purified water weight ratio described in the preparation method step (3) is 6:4~8:2.
Inventors have found that fluvastatin sodium is soluble easily in water, itself higher osmotic pressure can be generated after drug dissolution, cause to release
It is too fast to put rate, it is easy to generate phenomenon of burst release, therefore, macromolecule retarding agent need to be added in label to slow down the release of drug
Rate.Macromolecule retarding agent polyoxyethylene WSRN-60KNF, the polyoxyethylene WSR-301NF, hypromellose of the application
K4M, hypromellose K15M, hydroxypropyl cellulose HPC-H are hydrophilic polymer, and hydration shape can occur after meeting water
At gel layer, delay the rate of release of drug by the barrier action of gel.
Inventor also found that the viscosity of retarding agent has a significant impact drug release rate in the technical program, polymer
Viscosity it is big, the diffusion rate of drug reduces, and drug release slows down, and therefore, need to use the high molecular polymer tune of appropriate viscosity
The rate of release for saving drug enables the fluvastatin sodium micro hole seep irrigation of preparation to achieve the purpose that release the drug for 24 hours.Inventor
Found by a large number of experiments, use molecular weight for 2,000,000 polyoxyethylene WSRN-60KNF, molecular weight be 4,000,000 polyoxy second
Alkene WSR-301NF, HPMC K4M that viscosity (20 DEG C, the viscosity in 2%w/v aqueous solution) is 4000cps, viscosity are
The hydroxypropyl cellulose HPC-H that the hydroxypropyl methylcellulose K15M and viscosity of 15000cps are 1000~4000cps is macromolecule
When retarding agent, the fluvastatin sodium controlled porosity osmotic pump tablets with good drug release behavior can be obtained.
The invention has the benefit that
The present invention can be very good to slow down drug release rate by the way of macromolecule retarding agent is added in label,
Fluvastatin sodium controlled porosity osmotic pump tablets are made to maintain release the drug for 24 hours, so as to effectively extend the action time of drug.
Fluvastatin sodium controlled porosity osmotic pump tablets prepared by the present invention have zero-order release feature, and blood concentration is more
Steadily, peak valley phenomenon is avoided, toxic side effect is small, good patient compliance, and drug release is not by pH value and gastrointestinal motility etc.
The influence of factor, individual difference are small.
Fluvastatin sodium controlled porosity osmotic pump tablets prepared by the present invention are not necessarily to laser boring, and preparation process is simple, production
It is at low cost, it is easier to industrialized production.
Detailed description of the invention
Fig. 1 is embodiment 1-5 fluvastatin sodium controlled porosity osmotic pump tablets and commercially available sustained release tablets in pH6.8 phosphate-buffered
Releasing curve diagram in liquid；
Fig. 2 is the release of embodiment 1-5 fluvastatin sodium controlled porosity osmotic pump tablets and commercially available sustained release tablets in purified water
Curve graph；
Specific embodiment
The present invention makees fluvastatin sodium controlled porosity osmotic pump tablets and preparation method thereof by following embodiment further
It illustrates, but the present invention is not limited in following embodiment.
Embodiment 1
Composition:
(1) label forms:
(2) semi permeability clothing film forms:
(3) outer membrane clothing film forms:
Composition weight/g
Opadry (stomach dissolution type, model: 95F620004) 6.75
Preparation process:
(1), label prepare: by the fluvastatin sodium of recipe quantity, starch, dextrin, polyoxyethylene WSR-301NF, potassium chloride,
Saleratus is crossed 60 meshes and is uniformly mixed, and appropriate dehydrated alcohol softwood is added, and 20 meshes are pelletized, 40 DEG C of dryings, and 18 meshes are whole
Grain, tabletting is after superfine silica gel powder mixing is added to get label；
(2), recipe quantity cellulose acetate, triethyl citrate and PEG600 packet clothing film: are dissolved in acetone-purified water
It is configured to the coating solution that solid content is 4% in the mixed solution of (weight ratio 98:2), label is placed in coating pan and is coated, increases
Coating tablet is placed in 40 DEG C of baking ovens and solidifies 12 hours to the 8% of label weight by weight；
(3), Opadry (stomach dissolution type, model: 95F620004) film coating film: is dissolved in dehydrated alcohol-purified water (weight
Amount ratio be 8:2) solid content is configured in solution as 7% coating solution, label is placed in coating pan and is coated, is increased weight to plate core weight
Amount 2%, stop whitewashing, by coating tablet in coating pan in 40 DEG C of dry 30min to get fluvastatin sodium micropore permeation pump control
Release piece.
Embodiment 2
Composition:
(1) label forms:
(2) semi permeability clothing film forms:
(3) outer membrane clothing film forms:
Composition weight/g
Opadry (stomach dissolution type, model: 95F620004) 10.10
Preparation process:
(1), prepared by label: by recipe quantity fluvastatin sodium, microcrystalline cellulose, lactose, polyoxyethylene WSRN-60KNF, chlorine
Change sodium, saleratus are crossed 60 meshes and are uniformly mixed, and appropriate dehydrated alcohol softwood, the granulation of 20 meshes, 40 DEG C of dryings, 18 mesh are added
Whole grain is sieved, tabletting is after magnesium stearate mixing is added to get label；
(2), it is pure that recipe quantity cellulose acetate, diethyl phthalate and PEG400 packet clothing film: are dissolved in acetone-
Change and be configured to the coating solution that solid content is 5% in the mixed solution of water (weight ratio 95:5), label is placed in coating pan and is wrapped
Clothing increases weight to the 10% of label weight, coating tablet is placed in 40 DEG C of baking ovens and is solidified 12 hours；
(3), Opadry (stomach dissolution type, model: 95F620004) film coating film: is dissolved in dehydrated alcohol-purified water (weight
Amount ratio be 7:3) solid content is configured in solution as 8% coating solution, label is placed in coating pan and is coated, is increased weight to plate core weight
Amount 3%, stop whitewashing, by coating tablet in coating pan in 40 DEG C of dry 30min to get fluvastatin sodium micropore permeation pump control
Release piece.
Embodiment 3
Composition:
(1) label forms:
(2) semi permeability clothing film forms:
(3) outer membrane clothing film forms:
Composition weight/g
Opadry (stomach dissolution type, model: 95F620004) 10.10
Preparation process:
(1), prepared by label: by recipe quantity fluvastatin sodium, pregelatinized starch, lactose, hydroxypropyl methylcellulose K15M, chlorination
Sodium, glucose, saleratus are crossed 60 meshes and are uniformly mixed, and appropriate dehydrated alcohol softwood are added, the granulation of 20 meshes, 40 DEG C dry
Dry, 18 mesh sieves, tabletting is after talcum powder and magnesium stearate mixing is added to get label；
(2), recipe quantity cellulose acetate, triglycerides and mannitol packet clothing film: are dissolved in acetone-purified water (weight
Amount ratio be 97:3) mixed solution in be configured to solid content for 6% coating solution, label is placed in coating pan and is coated, weight gain
To the 11% of label weight, coating tablet is placed in 40 DEG C of baking ovens and is solidified 12 hours；
(3), Opadry (stomach dissolution type, model: 95F620004) film coating film: is dissolved in dehydrated alcohol-purified water (weight
Amount ratio be 7:3) solid content is configured in solution as 9% coating solution, label is placed in coating pan and is coated, is increased weight to plate core weight
Amount 3%, stop whitewashing, by coating tablet in coating pan in 40 DEG C of dry 30min to get fluvastatin sodium micropore permeation pump control
Release piece.
Embodiment 4
Composition:
(1) label forms:
(2) semi permeability clothing film forms:
(3) outer membrane clothing film forms:
Composition weight/g
Opadry (stomach dissolution type, model: 95F620004) 13.50
Preparation process:
(1), prepared by label: by recipe quantity fluvastatin sodium, microcrystalline cellulose, HPMC K4M, potassium chloride, sugarcane
Sugar, saleratus are crossed 60 meshes and are uniformly mixed, and appropriate dehydrated alcohol softwood, the granulation of 20 meshes, 40 DEG C of dryings, 18 meshes are added
Whole grain, tabletting is after magnesium stearate mixing is added to get label；
(2), packet clothing film: recipe quantity cellulose acetate, diethyl phthalate, triglycerides and sucrose are dissolved in
It is configured to the coating solution that solid content is 4% in acetone-purified water (weight percent 96:4) mixed solution, label is placed in
It is coated in coating pan, increases weight to the 12% of label weight, coating tablet is placed in 40 DEG C of baking ovens and is solidified 12 hours；
(3), Opadry (stomach dissolution type, model: 95F620004) film coating film: is dissolved in dehydrated alcohol-purified water (weight
Amount percentage is 6:4) coating solution that solid content is 10% is configured in solution, label is placed in coating pan and is coated, weight gain is extremely
The 4% of label weight stops whitewashing, and coating tablet is seeped in coating pan in 40 DEG C of dry 30min to get fluvastatin sodium micropore
Saturating pump controlled-releasing tablet.
Embodiment 5
Composition:
(1) label forms:
(2) semi permeability clothing film forms:
(3) outer membrane clothing film forms:
Composition weight/g
Opadry (stomach dissolution type, model: 95F620004) 10.10
Preparation process:
(1), prepared by label: by recipe quantity fluvastatin sodium, microcrystalline cellulose, pregelatinized starch, hydroxypropyl cellulose
HPC-H, polyoxyethylene WSR N-60K, sodium chloride, mannitol, saleratus are crossed 60 meshes and are uniformly mixed, and appropriate anhydrous second is added
Alcohol softwood, the granulation of 20 meshes, 40 DEG C of dryings, 18 mesh sieves, tabletting is after talcum powder mixing is added to get label.
(2), recipe quantity cellulose acetate, triethyl citrate and PEG400 packet clothing film: are dissolved in acetone-purified water
The coating solution that solid content is 5% is made in the mixed solution of (weight ratio 95:5), label is placed in coating pan and is coated, weight gain is extremely
Coating tablet is placed in 40 DEG C of baking ovens and solidifies 12 hours by the 10% of label weight.
(3), Opadry (stomach dissolution type, model: 95F620004) film coating film: is dissolved in dehydrated alcohol-purified water (weight
Measure than 7:3) coating solution that solid content is 8% is made in solution, label is placed in coating pan and is coated, weight gain to label weight
3%, stop whitewashing, by coating tablet in coating pan in 40 DEG C of dry 30min to get fluvastatin sodium controlled porosity osmotic pump
Piece.
6 release of embodiment is investigated
According to 2015 editions four 0931 dissolution rates of general rule of Chinese Pharmacopoeia and the second method of drug release determination method paddle method, detects fluorine and cut down
The vitro release of statin sodium controlled porosity osmotic pump tablets, release method are as follows:
Fluvastatin sodium controlled porosity osmotic pump tablets made from Example 1-5 and commercially available sustained release tablets each 6, according to dissolution
Degree is measured with the second method of drug release determination method (paddle method adds sedimentation basket): measuring temperature is (37 ± 0.5) DEG C, medium volume
For 900ml, revolving speed is 50 revs/min, operates according to methods, took solution 5.0ml respectively in 2,4,6,8,10,12,16,20,24 hours,
Through 0.45 μm of filtering with microporous membrane, and isothermal is replenished in time, same volume dissolution medium.Then subsequent filtrate 2.0ml to 10ml is taken
In measuring bottle, dissolution medium is used to be diluted to scale as test solution；It separately takes fluvastatin sodium reference substance appropriate, uses dissolution medium
Solution of the 1ml containing about 20 μ g is made as reference substance solution, according to spectrophotometry (2015 editions four general rules of Chinese Pharmacopoeia in dilution
0401 UV-VIS spectrophotometry) measure trap respectively at 302nm, calculate accumulative releasing degree.
Measure fluvastatin sodium controlled porosity osmotic pump tablets and the city in embodiment 1-5 respectively using above-mentioned release method
Release behavior of the sustained release tablets in pH6.8 phosphate buffer and purified water is sold, and draws release profiles, as a result such as Fig. 1-2 institute
Show, the right R of Linear Quasi2Such as table 1.
Linear Quasi right R of the 1 fluvastatin sodium micro hole seep irrigation of table in pH6.8 phosphate buffer and purified water2
| The right R of Linear Quasi2 | PH6.8 phosphate buffer | Purified water |
| Embodiment 1 | 0.9892 | 0.9849 |
| Embodiment 2 | 0.9913 | 0.9893 |
| Embodiment 3 | 0.9644 | 0.9791 |
| Embodiment 4 | 0.9747 | 0.9873 |
| Embodiment 5 | 0.9799 | 0.9901 |
By release profiles and the right R of Linear Quasi2It is found that the fluvastatin sodium controlled porosity osmotic pump tablets in embodiment 1-5
Zero-order release behavior is significant in pH6.8 phosphate buffer and purified water, the right R of the Linear Quasi of drug release profiles20.95
More than, wherein fluvastatin sodium controlled porosity osmotic pump tablets release process and Zero order release models fitting in Examples 1 and 2
Highest is spent, and 24 hours drug releases are more complete, release is 95% or more；Compared with commercially available sustained release tablets, present invention preparation
Rate of releasing drug of the fluvastatin sodium controlled porosity osmotic pump tablets in pH6.8 phosphate buffer and purified water more slowly,
Steadily, it can reach 24 hours and release the drug, and drug release behavior is not influenced by medium pH, blood concentration is more steady.
Claims (7)
1. a kind of fluvastatin sodium controlled porosity osmotic pump tablets, which is characterized in that said preparation includes drug containing label, is wrapped in label
Outer semi permeability clothing film and general thin clothing film, the semi permeability clothing film weight is the 8~12% of label weight, general
Logical film clothing film weight is the 2~4% of label weight；
The weight percent of each component in the drug containing label are as follows:
The retarding agent be selected from polyoxyethylene WSR N-60K NF, polyoxyethylene WSR-301 NF, hypromellose K4M,
One of hypromellose K15M or hydroxypropyl cellulose HPC-H and polyoxyethylene WSR N-60K NF；
The component of the semi permeability clothing film are as follows: cellulose acetate, plasticizer, pore-foaming agent, the plasticizer weight are acetic acid
The 10~30% of cellulose, pore-foaming agent weight are the 15~30% of cellulose acetate weight；The general thin clothing film is
Film coating pre-mix dose stomach dissolution type Opadry；
The preparation methods of the controlled porosity osmotic pump tablets the following steps are included:
(1), prepared by label: by the fluvastatin sodium of recipe quantity, filler, retarding agent, osmotic pressure active material and alkali stabilizer
It crosses 60 meshes to be uniformly mixed, appropriate dehydrated alcohol softwood, the granulation of 20 meshes, 40 DEG C of dryings, 18 mesh sieves, addition profit is added
Tabletting is after lubrication prescription mixes to get label；
(2), it is molten that the cellulose acetate, plasticizer and pore-foaming agent of recipe quantity packet clothing film: are dissolved in the mixing of acetone-purified water
It is configured to the coating solution that solid content is 4~6% in liquid, label is placed in coating pan and is coated, increases weight to required weight, will be coated
Piece, which is placed in 40 DEG C of baking ovens, to be solidified 12 hours；
(3), film coating film: film coating pre-mix dose stomach dissolution type Opadry is dissolved in dehydrated alcohol-purification of aqueous solutions and is prepared
The coating solution for being 7~10% at solid content, label is placed in coating pan and is coated, and weight gain to required weight stops whitewashing, will wrap
Garment piece is in coating pan in 40 DEG C of dry 30min to get fluvastatin sodium controlled porosity osmotic pump tablets.
2. a kind of fluvastatin sodium controlled porosity osmotic pump tablets according to claim 1, which is characterized in that the filler
Selected from one of microcrystalline cellulose, starch, lactose, dextrin, pregelatinized starch or a variety of.
3. a kind of fluvastatin sodium controlled porosity osmotic pump tablets according to claim 1, which is characterized in that the osmotic pressure
Active material is selected from one of sodium chloride, potassium chloride, sucrose, glucose, mannitol or a variety of.
4. a kind of fluvastatin sodium controlled porosity osmotic pump tablets according to claim 1, which is characterized in that the lubricant
Selected from one of magnesium stearate, talcum powder, superfine silica gel powder or a variety of；The alkali stabilizer is selected from saleratus.
5. a kind of fluvastatin sodium controlled porosity osmotic pump tablets according to claim 1, which is characterized in that the controlled release clothing
Plasticizer is selected from one of diethyl phthalate, triethyl citrate, triglycerides or a variety of in film；The controlled release clothing
Pore-foaming agent is selected from one of polyethylene glycol 400, Macrogol 600, sucrose, mannitol or a variety of in film.
6. a kind of fluvastatin sodium controlled porosity osmotic pump tablets according to claim 1, which is characterized in that in step (2)
The weight ratio of the acetone-purified water is 95:5~98:2.
7. a kind of fluvastatin sodium controlled porosity osmotic pump tablets according to claim 1, which is characterized in that in step (3)
The weight ratio of the dehydrated alcohol-purified water is 6:4~8:2.
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Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5021053A (en) * | 1989-07-14 | 1991-06-04 | Alza Corporation | Oral osmotic device with hydrogel driving member |
| CN1328454A (en) * | 1998-10-14 | 2001-12-26 | 诺瓦提斯公司 | Sustained release pharmaceutical composition and method of releasing pharmaceutically active agent |
| CN1720912A (en) * | 2000-04-13 | 2006-01-18 | 诺瓦提斯公司 | Pharmaceutical compositions |
| CN101385729A (en) * | 2007-09-10 | 2009-03-18 | 鲁南制药集团股份有限公司 | Osmotic pump controlled release preparation composition for treating hyperlipemia and preparation method thereof |
| EP2260832A2 (en) * | 2001-10-25 | 2010-12-15 | DepoMed, Inc. | Optimal polymer mixtures for gastric retentive tablets |
| CN102670575A (en) * | 2011-03-09 | 2012-09-19 | 中国药科大学 | Ketoprofen osmotic pump type controlled release preparation and preparation method thereof |
| CN102755284A (en) * | 2011-12-22 | 2012-10-31 | 深圳信立泰药业股份有限公司 | Fluvastatin sustained-release medicinal composition |
| CN103908435A (en) * | 2013-01-04 | 2014-07-09 | 江苏天士力帝益药业有限公司 | Flutamide sustained release preparation and its preparation method |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100144800A1 (en) * | 2008-06-11 | 2010-06-10 | Ranbaxy Laboratories Limited | extended release tablet formulation of niacin |
-
2016
- 2016-08-29 CN CN201610752919.5A patent/CN106344535B/en not_active Expired - Fee Related
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5021053A (en) * | 1989-07-14 | 1991-06-04 | Alza Corporation | Oral osmotic device with hydrogel driving member |
| CN1328454A (en) * | 1998-10-14 | 2001-12-26 | 诺瓦提斯公司 | Sustained release pharmaceutical composition and method of releasing pharmaceutically active agent |
| CN1720912A (en) * | 2000-04-13 | 2006-01-18 | 诺瓦提斯公司 | Pharmaceutical compositions |
| EP2260832A2 (en) * | 2001-10-25 | 2010-12-15 | DepoMed, Inc. | Optimal polymer mixtures for gastric retentive tablets |
| CN101385729A (en) * | 2007-09-10 | 2009-03-18 | 鲁南制药集团股份有限公司 | Osmotic pump controlled release preparation composition for treating hyperlipemia and preparation method thereof |
| CN102670575A (en) * | 2011-03-09 | 2012-09-19 | 中国药科大学 | Ketoprofen osmotic pump type controlled release preparation and preparation method thereof |
| CN102755284A (en) * | 2011-12-22 | 2012-10-31 | 深圳信立泰药业股份有限公司 | Fluvastatin sustained-release medicinal composition |
| CN103908435A (en) * | 2013-01-04 | 2014-07-09 | 江苏天士力帝益药业有限公司 | Flutamide sustained release preparation and its preparation method |
Non-Patent Citations (3)
| Title |
|---|
| Formulation and evaluation of fluvastatin sodium bilayered osmotic tablets;Latha et al.;《Farmacia》;20151231;第63卷(第5期);第701页左栏第1段、右栏第1-4段 * |
| 卡乐康中国公司.欧巴代®CA，一种基于醋酸纤维素的全配方的半透膜包衣系统的应用.《中国医药工业杂志》.2014,第45卷(第6期),第S73-S75页. * |
| 微孔型渗透泵控释制剂的研究进展;张婧 等;《中国医院药学杂志》;20130831;第33卷(第16期);第1351页左栏第2段、右栏第1段、第2节，第1352页第2.1.3节、第2.2.1-2.2.2、2.2.4节,第1353页第5节 * |
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| CN106344535A (en) | 2017-01-25 |
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