CN104800180A - Dual sustained release tablet composition prepared from potassium citrate and preparation method of dual sustained release tablet composition - Google Patents
Dual sustained release tablet composition prepared from potassium citrate and preparation method of dual sustained release tablet composition Download PDFInfo
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- CN104800180A CN104800180A CN201510153777.6A CN201510153777A CN104800180A CN 104800180 A CN104800180 A CN 104800180A CN 201510153777 A CN201510153777 A CN 201510153777A CN 104800180 A CN104800180 A CN 104800180A
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- Prior art keywords
- potassium citrate
- sustained
- release
- sustained release
- dual
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- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 title claims abstract description 53
- 239000001508 potassium citrate Substances 0.000 title claims abstract description 52
- 229960002635 potassium citrate Drugs 0.000 title claims abstract description 52
- 235000011082 potassium citrates Nutrition 0.000 title claims abstract description 52
- 238000002360 preparation method Methods 0.000 title claims description 11
- 230000009977 dual effect Effects 0.000 title abstract description 8
- 239000000203 mixture Substances 0.000 title description 19
- 239000007939 sustained release tablet Substances 0.000 title description 13
- 239000000463 material Substances 0.000 claims abstract description 31
- 238000013268 sustained release Methods 0.000 claims abstract description 29
- 239000012730 sustained-release form Substances 0.000 claims abstract description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims abstract description 12
- 235000021355 Stearic acid Nutrition 0.000 claims abstract description 10
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229920000642 polymer Polymers 0.000 claims abstract description 10
- 239000008117 stearic acid Substances 0.000 claims abstract description 10
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 claims abstract description 9
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims abstract description 9
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000004203 carnauba wax Substances 0.000 claims abstract description 8
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 5
- 239000004359 castor oil Substances 0.000 claims abstract description 4
- 235000019438 castor oil Nutrition 0.000 claims abstract description 4
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims abstract description 4
- 239000011248 coating agent Substances 0.000 claims description 39
- 238000000576 coating method Methods 0.000 claims description 39
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 27
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 claims description 11
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 claims description 11
- 238000005550 wet granulation Methods 0.000 claims description 3
- 241001597008 Nomeidae Species 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 15
- 229940079593 drug Drugs 0.000 abstract description 8
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 abstract description 7
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
- 239000007888 film coating Substances 0.000 abstract 2
- 238000009501 film coating Methods 0.000 abstract 2
- 235000013869 carnauba wax Nutrition 0.000 abstract 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 abstract 1
- 229940069328 povidone Drugs 0.000 abstract 1
- 230000002035 prolonged effect Effects 0.000 abstract 1
- 230000002459 sustained effect Effects 0.000 abstract 1
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 24
- 229920003081 Povidone K 30 Polymers 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- 239000008187 granular material Substances 0.000 description 15
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 12
- 235000019359 magnesium stearate Nutrition 0.000 description 12
- 229920000193 polymethacrylate Polymers 0.000 description 12
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 11
- 239000008101 lactose Substances 0.000 description 11
- 238000000034 method Methods 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 6
- 239000002671 adjuvant Substances 0.000 description 6
- 239000004014 plasticizer Substances 0.000 description 6
- 239000003361 porogen Substances 0.000 description 6
- 210000002700 urine Anatomy 0.000 description 6
- 239000001993 wax Substances 0.000 description 6
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- NAVWVHRQSDHCHD-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;potassium Chemical compound [K].OC(=O)CC(O)(C(O)=O)CC(O)=O NAVWVHRQSDHCHD-UHFFFAOYSA-N 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 235000004443 Ricinus communis Nutrition 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 208000009911 Urinary Calculi Diseases 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- QXDMQSPYEZFLGF-UHFFFAOYSA-L calcium oxalate Chemical compound [Ca+2].[O-]C(=O)C([O-])=O QXDMQSPYEZFLGF-UHFFFAOYSA-L 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 230000002485 urinary effect Effects 0.000 description 2
- 230000004584 weight gain Effects 0.000 description 2
- 235000019786 weight gain Nutrition 0.000 description 2
- 206010007027 Calculus urinary Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 229920003163 Eudragit® NE 30 D Polymers 0.000 description 1
- 208000019025 Hypokalemia Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 239000008118 PEG 6000 Substances 0.000 description 1
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000007500 overflow downdraw method Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- PJAHUDTUZRZBKM-UHFFFAOYSA-K potassium citrate monohydrate Chemical compound O.[K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O PJAHUDTUZRZBKM-UHFFFAOYSA-K 0.000 description 1
- 208000024896 potassium deficiency disease Diseases 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000007962 solid dispersion Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the field of pharmaceutical preparations, and relates to a dual sustained tablet prepared from a drug soluble in water easily. Stearic acid, a stearic acid derivative, carnauba wax, hydrogenated castor oil and the like are taken as framework materials, a drug-containing tablet core is prepared from the framework materials and other auxiliary materials, an ethyl acrylate and methyl methacrylate polymer (2:1) material is adopted as a sustained release film coating material, and a sustained release film is prepared from the sustained release film coating material, a certain proportion of polyethylene glycol 400 and a certain proportion of povidone K60. The tablet weight is reduced, and the release time of potassium citrate is prolonged greatly.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, relate to a kind of to the fairly soluble medicine potassium citrate of water and have dual-sustained-release working composition and method, specifically relate to the dual potassium sustained release tablets of citric acid and preparation method.
Background technology
Urinary system calculus is a kind of commonly encountered diseases, and foreign study finds that the probability suffering from urinary system calculus in normal person is about 8% ~ 15%, and has the calculus patient of 50% ratio to recur.Potassium citrate has the effect of supplementary potassium ion and alkalized urine, clinically for preventing and treating the hypokalemia that a variety of causes causes, and treatment distal renal tubular urine poisoning, hypocitruria calcium oxalate stone and urate calculus.Research shows, potassium citrate is a kind of medicine of up-and-coming control urinary stone recurrence, but conventional potassium citrate preparation is difficult to guarantee that urine continued alkalization in 1 day, therefore make slow releasing preparation, to avoid, because drug metabolism causes urine acid-base value shakiness and crystallization thereof, reaching the good efficacy that whole day suppresses calcium oxalate crystal growth in healthy urine crystallization to be formed.
As the medicine that potassium citrate sustained-release tablets goes on the market in the U.S., commodity are called UROCIT-K
?, it is that to have employed Brazil wax be slow-release material, is prepared into potassium citrate sustained-release tablets, in U.S.'s listing for many years.
Potassium citrate pharmacological action is clear and definite, is the active drug for the treatment of urinary calculus.But potassium citrate sustained-release tablets dosage is too large, every sheet reaches 1080mg containing potassium citrate, adds the additive of adjuvant and other necessity, and total tablet is heavy can reach about 2g, and cause difficulty of swallowing, patient's compliance is poor.Potassium citrate is very easily water-soluble simultaneously, is dissolved in ethanol hardly, insoluble in organic solvent.Therefore also substantially increase that to be made into sheet heavily low, be easy to the difficulty taking slow releasing preparation.
Described in Chinese patent CN200910020454.4, slow releasing pill is prepared into by adding the inertia wax class of potassium citrate weight 20 ~ 40%, calcium hydrogen phosphate, PEG6000 and magnesium stearate, then coating, but this technology needs special equipment, complex process, higher to equipment requirements, general very difficult extensive industrialization.Described in Chinese patent CN201110433102.9; granule is prepared respectively by potassium citrate being adopted two kinds of methods; the first granule adopts fusion method to prepare by the wax of potassium citrate and high meltbility; the second granule adopts wet granulation or dry granulation by the wax of potassium citrate and high meltbility; carry out tabletting by after two kinds of granule mixing, but this technology needs the operation simultaneously of two equipment, adds mixing difficulty; the 2g nearly and sheet weighs, patient's compliance is poor.
This invention exploits a kind of potassium citrate slow-releasing preparation of dual release, by the dual function of sustained-release matrix and release membranes.Slow down the speed of potassium citrate release greatly, maintain the citrate level in urine, the adjuvant simultaneously adopted is less, is easy to take, and compliance is good.
Summary of the invention
The invention discloses a kind of potassium citrate dual-sustained-release sheet and preparation method, this preparation method adopts dual-sustained-release system, first potassium citrate is made slow-releasing granules, carry out tabletting again and be prepared into slow release label, by slow release label bag sustained release film clothing, sheet is heavy little, is easy to take, and can obtains the potassium citrate sustained-release tablets of desirable release profiles.
The preparation method of potassium citrate dual-sustained-release sheet of the present invention, by potassium citrate and erodible inertia Wax, as stearic acid, Brazil wax, hydrogenated castor wet goods, adopt wet granulation, other adjuvants are Polyethylene Glycol, lactose, PVP K30, add lubricant and be pressed into slow release label, then with polymethacrylate material mixed liquor coating material coating and get final product.Two release is formed by polymethacrylates film and slow release framework material.Significantly extend the pharmaceutical release time of potassium citrate sustained-release tablets.
In the present invention, the effective dose of single dose potassium citrate is 500-1500mg, and wherein preferred dosage is 800-1300 mg, and most preferred dosage is 1000-1200 mg.
Principal character of the present invention is using potassium citrate as active component, adopts stearic acid and derivant thereof, Brazil wax, hydrogenated castor wet goods as framework material.This kind of material mostly is erodible framework material, is suitable for the medicine that water solublity is fabulous.According to the difference of kind and viscosity, select one or more inertia Wax combinations thereof, ensureing the consumption greatly reducing adjuvant under potassium citrate release prerequisite, its addition is the heavy 10-40%(weight ratio of whole slow release blade), preferred adjuvant addition is 20-35%(weight ratio).
The lubricant adopted in the present invention is for selecting magnesium stearate, and the amount of use is the 1-2% of whole tablet weight.
Material for sustained release coating is a lot, comprises polymethacrylate, cellulose derivative class, ethene polymers class and other kinds.Be combined into sustained release film clothing layer, good toughness at the special discovery ethyl acrylate of the present invention and methyl methacrylate polymer (2:1) and PEG400,30 POVIDONE K 30 BP/USP 60, can greatly delay to control citric acid Potassium release.
Specifically PEG400,30 POVIDONE K 30 BP/USP 60 and propylene glycol are slowly added to the water, continuous stirring and dissolving, then this solution are joined in ethyl acrylate and methyl methacrylate polymer aqueous dispersion, stir, form slow release layer coating solution.
In the present invention, adopt the polymeric material of ethyl acrylate and methyl methacrylate polymer (2:1) as sustained release film coat material, ethyl acrylate and methyl methacrylate polymer (2:1) are applied in enteric-coating material, are combined into sustained release film clothing layer in the present invention with PEG400,30 POVIDONE K 30 BP/USP 60.Ethyl acrylate and methyl methacrylate polymer (2:1) have had business-like product to occur at present, and commodity are called EUDRAGIT NE30D, are the aqueous dispersion coating solution containing 30% solids, are called for short NE30D below.
The independent coating of aqueous dispersion coating material produces obvious time lag sometimes, for promoting drug release.In the dosage form using filmogen, often plasticizer need be added.Plasticizer refers to the pliability, the plastic adjuvant that add in filmogen and improve film.The coating material used due to the present invention is water soluble film-forming material, generally selects water-soluble plasticizer better, as propylene glycol, glycerol, mannitol etc., is preferably propylene glycol.General plasticizer consumption is excessive, and the film of formation is excessively soft; And consumption is too small, the coating membrane of formation lacks pliability, easily breaks.In the present invention, the consumption of plasticizer is that 2% ~ 10%(converts with amount of solid).
Polyethylene Glycol is formed by ethylene oxide polymerization, has good water solublity.With the carrier for solvent, lubricant, porogen, wetting agent, solid dispersion in pharmacy, the present invention shows through many experimental results, adopt PEG400 can as the porogen of dual release release membranes, again can as the plasticizer of polymethacrylates film.Polymethacrylates and PEG400, can very effective control citric acid Potassium release after tablet surface film forming.
Adopt PEG400 to be porogen in the present invention, according to variety classes and molecular weight, its addition is the 2-8%(weight ratio of whole weight), preferred amount is 3-5%.
In the present invention with 30 POVIDONE K 30 BP/USP 60 for auxiliary porogen, addition is 1%-3%, and preferred addition is 1.5%-2.5%.Meanwhile, in the combination Sustained release coating materials of polymethacrylates, exist as porogen, the problem that potassium citrate sustained-release tablets drug release in early stage is few can be avoided.
30 POVIDONE K 30 BP/USP 60 also can be used as the porogen of sustained release coating, insoluble matrix sustained release tablet and erodible matrix sustained release tablet.Polyvidone and polymethacrylate copolymer are share as sustained release coating, and its drug release behavior does not affect by pH.
Coating solution is sprayed onto on slow release label by spray gun, and after dry, the weight of weightening finish is exactly the weight of solid content in the coating solution used, and also claims coating weight gain.Gain in weight larger, coating film forming is thicker, and medicine is more not easy release.Coating weight gain mass fraction is that 3% ~ 8%(is as the criterion with label weight in the present invention), preferred weightening finish mass fraction is 3% ~ 5%.
Potassium citrate sustained-release tablets release profiles prepared by preparation method of the present invention is desirable, and the burst size when 1h, 2h, 6h is respectively 35%-55%, the 50%-70% and more than 85% of labelled amount.
Dual-sustained-release mechanism control citric acid Potassium release is adopted in the present invention.Slow release label adopts erodible inertia Wax, if stearic acid, Brazil wax, hydrogenated castor wet goods are skeleton, control citric acid Potassium release, the coating solution that ethyl acrylate and methyl methacrylate polymer, PEG4000 and 30 POVIDONE K 30 BP/USP 60 form is coated on drug core simultaneously, is controlled Slack time and the release of medicine by macromolecule membrane further.
The potassium citrate sustained-release tablets that the present invention prepares dual release has the characteristic of sustained release 6h.Compared with common slow releasing tablet, this slow releasing tablet significantly effectively slow down the rate of release of medicine, stabilizes drug effect, is conducive to the safety, the effectiveness that ensure medication, improves the compliance of patient simultaneously.
Accompanying drawing explanation
Fig. 1 is the releasing curve diagram of potassium citrate dual-sustained-release sheet exemplary embodiments in water.
Embodiment
Embodiment 1 slow release label
Supplementary material mg/ sheet
Potassium citrate 1080
Stearic acid 120
PEG4000 30
Lactose 15
Magnesium stearate 15
Coating solution
NE30D(is in solid) 200g
30 POVIDONE K 30 BP/USP 60 3.5 g
PEG400 10 g
Propylene glycol 20 g
Water 600ml
Technical process:
Take potassium citrate 1.080kg, stearic acid 0.12kg, 0.03kg Macrogol 4000 and lactose 0.015kg, pulverize, cross 80 mesh sieves, mix homogeneously, granulate with 5% PVP K30 aqueous solution, dry 2h for 50 DEG C, cross 16 eye mesh screen granulate, add recipe quantity magnesium stearate mix homogeneously, it is 1080mg that mixture is pressed into containing potassium citrate, sheet is heavily about the blank label of about 1310mg, above formula is prepared into polymethacrylate material and makes coating solution coating, weightening finish 7%.
Embodiment 2 slow release label
Supplementary material mg/ sheet
Potassium citrate 1080
Stearic acid 160
PEG4000 30
Lactose 20
Magnesium stearate 15
Coating solution
NE30D(is in solid) 200g
30 POVIDONE K 30 BP/USP 60 8 g
PEG400 15 g
Propylene glycol 10 g
Water 600ml
Technical process:
Take potassium citrate 1.08kg, stearic acid 0.16kg, 0.03kg Macrogol 4000 and lactose 0.02kg, pulverize, cross 80 mesh sieves, mix homogeneously, granulate with 5% PVP K30 aqueous solution, dry 2h for 50 DEG C, cross 16 eye mesh screen granulate, add recipe quantity magnesium stearate mix homogeneously, it is 1080mg that mixture is pressed into containing potassium citrate, sheet is heavily about the blank label of about 1360mg, then makes coating solution coating with the polymethacrylate material of above-mentioned formula, weightening finish 7%.
Embodiment 3 slow release label
Supplementary material mg/ sheet
Potassium citrate 1080
Stearic acid 200
PEG4000 30
Lactose 20
Magnesium stearate 20
Coating solution
NE30D(is in solid) 200g
30 POVIDONE K 30 BP/USP 60 6 g
PEG400 10 g
Propylene glycol 5 g
Water 600ml
Technical process:
Take potassium citrate 1.08kg, stearic acid 0.20kg, 0.03kg Macrogol 4000 and lactose 0.02kg, pulverize, cross 80 mesh sieves, mix homogeneously, granulate with 5% PVP K30 aqueous solution, dry 2h for 50 DEG C, cross 16 eye mesh screen granulate, add recipe quantity magnesium stearate mix homogeneously, it is 1080mg that mixture is pressed into containing potassium citrate, sheet is heavily about the blank label of about 1330mg, then makes coating solution coating with the polymethacrylate material of above-mentioned formula, weightening finish 5%.
Embodiment 4 slow release label
Supplementary material mg/ sheet
Potassium citrate 1080
Brazil wax 160
PEG4000 30
Lactose 20
Magnesium stearate 20
Coating solution
NE30D(is in solid) 200g
30 POVIDONE K 30 BP/USP 60 3g
PEG400 5g
Propylene glycol 10g
Water 400ml
Technical process:
Take potassium citrate 1.08kg, Brazil wax 0.16kg, 0.03kg Macrogol 4000 and lactose, pulverize 0.02kg, cross 80 mesh sieves, mix homogeneously, granulate with 5% PVP K30 aqueous solution, dry 2h for 50 DEG C, cross 16 eye mesh screen granulate, add recipe quantity magnesium stearate mix homogeneously, it is 1080mg that mixture is pressed into containing potassium citrate, sheet is heavily about the blank label of about 1290mg, more above-mentioned formula make coating solution coating with polymethacrylate material, weightening finish 7%.
Embodiment 5 slow release label
Supplementary material mg/ sheet
Potassium citrate 1080
Castor oil hydrogenated 160
PEG4000 30
Lactose 20
Magnesium stearate 15
Coating solution
NE30D(is in solid) 200g
30 POVIDONE K 30 BP/USP 60 3g
PEG400 12g
Propylene glycol 15g
Water 500ml
Technical process:
Take potassium citrate 1.080kg, castor oil hydrogenated 0.16kg, Macrogol 4000 is 0.03kg and lactose 0.02kg, pulverize, cross 80 mesh sieves, mix homogeneously, granulate with 5% PVP K30 aqueous solution, dry 2h for 50 DEG C, cross 16 eye mesh screen granulate, add recipe quantity magnesium stearate mix homogeneously, it is 1080mg that mixture is pressed into containing potassium citrate, sheet is heavily about the blank label of about 1290mg, then coating solution formula makes coating solution coating with polymethacrylate material, weightening finish 8%.
Claims (6)
1. a potassium citrate dual-sustained-release sheet, contain that slow release label containing potassium citrate is gentle releases film-coat layer, wherein the slow release label of potassium citrate is prepared from by erodible framework material, and sustained release film clothing layer forms sustained release film clothing material by ethyl acrylate and methyl methacrylate polymer (2:1), PEG400, polyvidone k60.
2. potassium citrate dual-sustained-release sheet described in claim 1, slow release label wherein adopts stearic acid and derivant, Brazil wax, castor oil hydrogenated framework material, and wet granulation compacting forms.
3. framework material as claimed in claim 2, the amount added is 10-40%(weight ratio), preferred addition is 20-35%(weight ratio).
4. the sustained release film clothing layer of potassium citrate dual-sustained-release sheet according to claim 1, coating solution forms by by ethyl acrylate and methyl methacrylate polymer (2:1) polymeric material, propylene glycol, PEG400, polyvidone k60 and water, and the weight after coating shared by sustained release film clothing layer is the 5-8% of slow release label weight.
5. sustained release film clothing layer as claimed in claim 4, in the coating solution of described preparation, the amount of PEG400 is 2-10%(weight ratio), preferred amount is 3-6%(weight ratio).
6. coating solution as claimed in claim 5, wherein the amount of polyvidone k60 is 1%-3%, and preferred amount is 1.5%-2.5%
As claim 1,2, the effective dose of the potassium citrate dual-sustained-release sheet described in 4 is 500-1500mg, and wherein preferred dosage is 800-1300mg, and most preferred dosage is 1000-1200mg.
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| US20240167531A1 (en) * | 2019-11-14 | 2024-05-23 | Siemens Gamesa Renewable Energy A/S | Damper for a wind turbine |
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