CN101455666A - Nimodipine double-layer osmotic pump controlled release tablet and preparation technique thereof - Google Patents
Nimodipine double-layer osmotic pump controlled release tablet and preparation technique thereof Download PDFInfo
- Publication number
- CN101455666A CN101455666A CNA2007103021226A CN200710302122A CN101455666A CN 101455666 A CN101455666 A CN 101455666A CN A2007103021226 A CNA2007103021226 A CN A2007103021226A CN 200710302122 A CN200710302122 A CN 200710302122A CN 101455666 A CN101455666 A CN 101455666A
- Authority
- CN
- China
- Prior art keywords
- controlled release
- release tablet
- boosting
- nimodipine
- osmotic pump
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 230000003204 osmotic effect Effects 0.000 title claims abstract description 69
- 238000013270 controlled release Methods 0.000 title claims abstract description 52
- UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 title claims abstract description 48
- 229960000715 nimodipine Drugs 0.000 title claims abstract description 48
- 238000002360 preparation method Methods 0.000 title claims description 19
- 238000000034 method Methods 0.000 title description 8
- 238000000576 coating method Methods 0.000 claims abstract description 35
- 239000011248 coating agent Substances 0.000 claims abstract description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 32
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 27
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 24
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical group [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 claims description 22
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 22
- 239000013543 active substance Substances 0.000 claims description 21
- 239000011230 binding agent Substances 0.000 claims description 19
- 239000003795 chemical substances by application Substances 0.000 claims description 19
- 239000000314 lubricant Substances 0.000 claims description 19
- 230000000149 penetrating effect Effects 0.000 claims description 19
- -1 polyoxyethylene, hydroxypropyl Polymers 0.000 claims description 14
- 235000019359 magnesium stearate Nutrition 0.000 claims description 12
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 11
- 239000011780 sodium chloride Substances 0.000 claims description 11
- 239000003086 colorant Substances 0.000 claims description 10
- 239000002245 particle Substances 0.000 claims description 10
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 10
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 9
- 239000000463 material Substances 0.000 claims description 7
- 239000012528 membrane Substances 0.000 claims description 7
- 239000004014 plasticizer Substances 0.000 claims description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- 229920002301 cellulose acetate Polymers 0.000 claims description 6
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 6
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 6
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 239000003361 porogen Substances 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 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 claims description 5
- 239000002202 Polyethylene glycol Substances 0.000 claims description 5
- 229920002125 Sokalan® Polymers 0.000 claims description 5
- 239000008101 lactose Substances 0.000 claims description 5
- 229920001223 polyethylene glycol Polymers 0.000 claims description 5
- 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 claims description 4
- 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 claims description 4
- 229930195725 Mannitol Natural products 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- 239000000594 mannitol Substances 0.000 claims description 4
- 235000010355 mannitol Nutrition 0.000 claims description 4
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 3
- 239000001856 Ethyl cellulose Substances 0.000 claims description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 2
- 239000005715 Fructose Substances 0.000 claims description 2
- 229930091371 Fructose Natural products 0.000 claims description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 2
- FNJSWIPFHMKRAT-UHFFFAOYSA-N Monomethyl phthalate Chemical compound COC(=O)C1=CC=CC=C1C(O)=O FNJSWIPFHMKRAT-UHFFFAOYSA-N 0.000 claims description 2
- 229920002472 Starch Polymers 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims description 2
- 235000010489 acacia gum Nutrition 0.000 claims description 2
- 239000001785 acacia senegal l. willd gum Substances 0.000 claims description 2
- 239000008121 dextrose Substances 0.000 claims description 2
- 235000013681 dietary sucrose Nutrition 0.000 claims description 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims description 2
- 229920001249 ethyl cellulose Polymers 0.000 claims description 2
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 2
- 229960003511 macrogol Drugs 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 238000010298 pulverizing process Methods 0.000 claims description 2
- 238000004080 punching Methods 0.000 claims description 2
- 239000000377 silicon dioxide Substances 0.000 claims description 2
- 235000012239 silicon dioxide Nutrition 0.000 claims description 2
- 239000002002 slurry Substances 0.000 claims description 2
- 239000008107 starch Substances 0.000 claims description 2
- 235000019698 starch Nutrition 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 229960004793 sucrose Drugs 0.000 claims description 2
- 239000001069 triethyl citrate Substances 0.000 claims description 2
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims description 2
- 235000013769 triethyl citrate Nutrition 0.000 claims description 2
- 239000010410 layer Substances 0.000 abstract description 51
- 239000003814 drug Substances 0.000 abstract description 19
- 239000008280 blood Substances 0.000 abstract description 3
- 210000004369 blood Anatomy 0.000 abstract description 3
- 239000002355 dual-layer Substances 0.000 abstract 1
- 230000001737 promoting effect Effects 0.000 abstract 1
- 229940079593 drug Drugs 0.000 description 10
- 239000002356 single layer Substances 0.000 description 10
- 239000002671 adjuvant Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 238000010586 diagram Methods 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 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 4
- 239000000523 sample Substances 0.000 description 4
- 229960003943 hypromellose Drugs 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical compound OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 0.000 description 2
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 229940093430 polyethylene glycol 1500 Drugs 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 206010061373 Sudden Hearing Loss Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 208000001286 intracranial vasospasm Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 230000007654 ischemic lesion Effects 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a dual-layer osmotic pump controlled release tablet of nimodipine, comprising a medicament contained layer core, promoting layer core, a coating, and a single medicine releasing hole on surface of a controlled release tablet at side of the medicine contained layer core. The inventive osmotic pump controlled release tablet is released in a special time for letting the blood concentration stable and effective during taking the medicament, reducing time of taking medicine, and improving safety and efficiency of the medicament.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of nimodipine osmotic pump controlled release tablet and preparation method thereof.
Background technology
Nimodipine is 1, the calcium-channel antagonists of 4-dihydropyridines, and the level that can regulate intracellular Ca2+ effectively makes it to keep normal physiological function; It is particularly outstanding to cerebrovascular effect, can combine with the special receptor of nervus centralis, effectively prevent and treat the cerebral tissue ischemic lesions that causes because of the caused cerebral vasospasm of subarachnoid hemorrhage, subarachnoid hemorrhage, ischemic cerebrovascular, migraine, sudden deafness and various dementia are all had better therapeutic effect.Nimodipine is water insoluble, is dissolved in ethanol, and is easily molten in acetone, chloroform, its in vivo the half-life only be 1～2 hour, therefore, conventional tablet or capsule needed take once in per 4 hours, blood concentration fluctuation is big, has increased untoward reaction.
The oral osmotic pump controlled-releasing tablet is not because its release is subjected to factor affecting such as gastrointestinal tract pH value, feature with zero-order release, avoided the interior blood concentration fluctuation of body excessive, thereby reduced poisonous side effect of medicine, drug effectiveness and safety have been improved, simultaneously also reduced the medication number of times, and this dosage form is less with respect to the individual variation influence, is comparatively ideal oral controlled release formulation.
The oral osmotic pump controlled-releasing tablet is divided into different kinds such as single chamber, multicell, " Shenyang Pharmaceutical University's journal " 2004 the 21st volumes the 3rd phase 168-172 page or leaf discloses the development of nimodipine osmotic pump controlled release tablet and release influence factor's investigation, and the document has been introduced the mono-layer osmotic pump controlled release tablets and the preparation technology thereof of nimodipine.
Yet because nimodipine is an insoluble drug, its dissolubility in water is very low, need the osmotic pressure of high concentration just can keep the certain drug release rate of nimodipine, and mono-layer osmotic pump controlled release tablets is difficult to realize above-mentioned technique effect, and mono-layer osmotic pump controlled release tablets also exists active constituents of medicine and discharges not exclusively, and the drug release reality of nimodipine mono-layer osmotic pump controlled release tablets only is 75% of recipe quantity in the documents; Poor reproducibility between criticizing and criticizing, quality is difficult to the defective of control; Double-layer osmotic pump controlled-release tablet undoubtedly can fine solution insoluble drug constant release problem.
Summary of the invention
At above technological deficiency, the invention provides a kind of Nimodipine double-layer osmotic pump controlled release tablet and preparation technology thereof.
Nimodipine double-layer osmotic pump controlled release tablet of the present invention comprises medicated layer label, boosting synusia core, coating membrane and in the single small delivery aperture on medicated layer label one side controlled release tablet surface, wherein, the medicated layer label comprises following composition, in the percentage ratio of the gross weight that accounts for medicated layer label and boosting synusia core:
Nimodipine is 5%-40%;
The osmotic pressure active substance is 0%-10%;
Penetrating agent is 20%-60%;
Binding agent is 1%-5%; With
Lubricant is 0.1%-3%;
Boosting synusia core comprises following composition, in the percentage ratio of the gross weight that accounts for medicated layer label and boosting synusia core:
Penetrating agent is 10%-40%;
The osmotic pressure active substance is 5%-25%;
Binding agent is 0%-5%;
Lubricant is 0.1%-3%; With
Coloring agent is 0.1%-5%.
Nimodipine double-layer osmotic pump controlled release tablet of the present invention more preferably medicated layer label comprises following composition, in the percentage ratio of the gross weight that accounts for medicated layer label and boosting synusia core:
Nimodipine is 14%-15%;
The osmotic pressure active substance is 0%-5%;
Penetrating agent is 40%-50%;
Binding agent is 3%-4%; With
Lubricant is 1%-1.5%;
Boosting synusia core comprises following composition, in the percentage ratio of the gross weight that accounts for medicated layer label and boosting synusia core:
Penetrating agent is 15%-30%;
The osmotic pressure active substance is 10%-15%;
Binding agent is 0%-3%;
Lubricant is 0.1%-2%; With
Coloring agent is 0.1%-1%.
In the Nimodipine double-layer osmotic pump controlled release tablet of the present invention, penetrating agent is selected from one or more in polyoxyethylene, hydroxypropyl emthylcellulose, carbopol and the arabic gum; The osmotic pressure active substance is selected from one or more in sodium chloride, lactose, mannitol, fructose, the dextrose plus saccharose; Wetting agent or binding agent are selected from one or more in water, ethanol, starch slurry, polyvidone and the hydroxypropyl emthylcellulose; Lubricant is selected from one or more in stearic acid, magnesium stearate, Pulvis Talci and the silicon dioxide; Coloring agent is selected from iron oxide red, iron oxide yellow or its combination.
Among the present invention in the Nimodipine double-layer osmotic pump controlled release tablet osmotic pressure active substance in the osmotic pressure active substance in the medicated layer label and the boosting synusia core can be with a kind of adjuvant, as in the medicated layer label and boosting synusia core in the osmotic pressure active substance can be sodium chloride, also can be adjuvant not of the same race; Equally, in the medicated layer label with boosting synusia core in penetrating agent can be with a kind of adjuvant, also can be adjuvant not of the same race; In the medicated layer label with boosting synusia core in binding agent can be with a kind of adjuvant, also can be adjuvant not of the same race; In the medicated layer label with boosting synusia core in lubricant can be with a kind of adjuvant, also can be adjuvant not of the same race.
In the Nimodipine double-layer osmotic pump controlled release tablet of the present invention, osmotic pressure active substance in the preferred medicated layer label is selected from sodium chloride, lactose or its combination, penetrating agent is selected from polyoxyethylene, carbopol or its combination, binding agent is selected from polyvidone, hydroxypropyl methylcellulose or its combination, and lubricant is selected from magnesium stearate; Osmotic pressure active substance in the boosting synusia core is selected from sodium chloride, and penetrating agent is selected from polyoxyethylene, and binding agent is selected from hydroxypropyl methylcellulose, and lubricant is selected from magnesium stearate, and coloring agent is selected from iron oxide red or iron oxide yellow.
The coating membrane of Nimodipine double-layer osmotic pump controlled release tablet of the present invention can be selected this area coating membrane commonly used for use, but the present invention preferably comprises following composition, to account for the percentage calculation of coatings weight:
Coating material is 80%-95%;
Plasticizer is 5%-10%; With
Porogen is 0%-10%.
Wherein coating material is selected from cellulose acetate, ethyl cellulose or its combination; Plasticizer is selected from one or more in Methyl Benzene-o-dicarboxylate, ethyl phthalate, triethyl citrate, Polyethylene Glycol and the polyvidone; Porogen is selected from one or more in Polyethylene Glycol, polyvidone and the mannitol, and wherein Polyethylene Glycol is preferably one or more in Macrogol 200-400, polyethylene glycol 1500, Macrogol 4000 and the polyethylene glycol 6000.
Nimodipine double-layer osmotic pump controlled release tablet of the present invention is 0.2～1.0 millimeter in the aperture of the single small delivery aperture on medicated layer label one side controlled release tablet surface; Be preferably 0.4～0.8 millimeter.
Nimodipine double-layer osmotic pump controlled release tablet of the present invention can adopt this area routine techniques to be prepared, but preferably adopts following method to be prepared, and this method specifically comprises the steps:
(1) granulate after the auxiliary materials and mixing such as nimodipine after will pulverizing and penetrating agent, osmotic pressure active substance, binding agent, lubricant, promptly get medicated layer sheet slug particle, standby;
(2) will granulate behind penetrating agent, osmotic pressure active substance, binding agent, lubricant and the coloring agent mixing, promptly get boosting synusia slug particle, standby;
(3) medicated layer sheet slug particle, boosting synusia slug particle are made double-deck label core body behind twice tabletting; Form coating solution with coating dissolution with solvents coating material and plasticizer and/or porogen, and with coating solution to double-deck label core body coating to 5%～7% of label weight, dried coating solvent volatilizees; In the diaphragm-operated surface punching of medicated layer label one side coating promptly.
In preparation medicated layer sheet slug particle and boosting synusia slug particle process, use ethanol as wetting agent among the present invention.
Coating solvent among the present invention is selected from one or more in acetone, isopropyl alcohol, dichloromethane, the second alcohol and water; The combination of the preferred acetone of the present invention or acetone and water.
As required, also Nimodipine double-layer osmotic pump controlled release tablet of the present invention can be wrapped the protecting film clothing of one deck routine again, make it more attractive in appearance.
The present invention finds the different proportion scope through screening test adjuvant has bigger influence to the release of medicine of the present invention, and when less than use amount scope of the present invention, drug releasing rate is slow and discharge not exclusively; When greater than the scope of use amount of the present invention, tablet volume is too big, takes inconvenience, and drug releasing rate is too fast.Compared with prior art have through the present invention prescription of screening more stable, discharge more complete, better efficacy, side effect characteristics still less; And by having prepared the nimodipine mono-layer osmotic pump controlled release tablets, and under same test conditions, carried out the comparative study of release in vitro degree with the Nimodipine double-layer osmotic pump controlled release tablet of the present invention's development with reference to disclosed optimization prescription of nimodipine mono-layer osmotic pump controlled release tablets in the documents and preparation technology; The result shows that nimodipine mono-layer osmotic pump controlled release tablets drug release is incomplete, and reality only is 75% of recipe quantity; And Nimodipine double-layer osmotic pump controlled release tablet drug release of the present invention surpasses 90% (see figure 3) of recipe quantity.
Description of drawings
Fig. 1 is the Nimodipine double-layer osmotic pump controlled release tablet releasing curve diagram according to embodiment 1 preparation;
Fig. 2 is the Nimodipine double-layer osmotic pump controlled release tablet releasing curve diagram according to embodiment 2 preparations;
Fig. 3 is according to the contrast releasing curve diagram of the nimodipine mono-layer osmotic pump controlled release tablets of optimizing prescription and prepared in the documents with the Nimodipine double-layer osmotic pump controlled release tablet for preparing according to embodiment 1.
The specific embodiment
The present invention is further elaborated by the following examples, but and unrestricted the present invention.
Embodiment 1
(1) medicated layer label
Nimodipine 15%
Polyoxyethylene 44%
Polyvidone 3.0%
Magnesium stearate 1.5%
Ethanol is an amount of
(2) boosting synusia core
Polyoxyethylene 25%
Sodium chloride 11%
Iron oxide red 0.2%
Magnesium stearate 0.3%
Ethanol is an amount of
(3) coatings
Cellulose acetate 95%
Macrogol 4000 5%
Acetone: water 2.0% (v/v)
Preparation method:
(1) according to the above-mentioned recipe quantity mixing granulation that respectively medicated layer label, boosting synusia core supplementary material sieved, adopt twice pressed-disc technique that medicated layer, boosting layer are made double-deck label;
(2) coating solution preparation: Macrogol 4000 is dissolved in the suitable quantity of water, slowly joins stirring and evenly mixing in the acetone, add cellulose acetate, be stirred to whole dissolvings, continue to stir standby;
(3) the double-deck label that will make is used and is stated the coating solution coating to 6% of label;
(4) make a call to an aperture that diameter is about 0.5 millimeter with laser at medicated layer label one side coating membrane surface.
(1) medicated layer label
Nimodipine 14%
Polyoxyethylene 49%
Sodium chloride 1.5%
Hypromellose 3.5%
Magnesium stearate 1.0%
Ethanol is an amount of
(2) boosting synusia core
Polyoxyethylene 17%
Sodium chloride 11%
Hypromellose 2.5%
Iron oxide yellow 0.2%
Magnesium stearate 0.3%
Ethanol is an amount of
(3) coatings
Cellulose acetate 95%
Polyethylene glycol 1500 5%
Acetone is an amount of
Preparation method: with embodiment 1.
Embodiment 3
(1) medicated layer label
Nimodipine 14%
Carbopol 43%
Lactose 5.0%
Polyvidone 3.0%
Magnesium stearate 1.0%
Ethanol is an amount of
(2) boosting synusia core
Polyoxyethylene 19%
Hypromellose 2.5%
Iron oxide red 0.2%
Magnesium stearate 0.3%
Ethanol is an amount of
(3) coatings
Cellulose acetate 95%
Macrogol 4000 5%
Acetone: water 2.0% (v/v)
Preparation method: with embodiment 1.
The determination experiment of experimental example 1 release
Sample thief A, B, C (sample A: according to the Nimodipine double-layer osmotic pump controlled release tablet of the embodiment of the invention 1 preparation; Sample B: according to the Nimodipine double-layer osmotic pump controlled release tablet of the embodiment of the invention 2 preparations; Sample C: according to the nimodipine mono-layer osmotic pump controlled release tablets of optimization prescription in the documents of the present invention and prepared), respectively according to dissolution method (Chinese Pharmacopoeia version appendix in 2005 X C first method), lauryl sodium sulfate aqueous solution 1000ml with 0.5% is a release medium, rotating speed is that per minute 100 changes, and operation in accordance with the law was respectively at the 2nd, 4,6,8,12 hour, sampling 5ml, and replenish with the volume release medium, filter, get subsequent filtrate as need testing solution.It is an amount of that other gets the nimodipine reference substance, accurate claims surely, and the solution product solution in contrast that contains 20 μ g among every 1ml is approximately made in the lauryl sodium sulfate aqueous solution dissolving with 0.5% and quantitatively diluting.Get above-mentioned sample solution and reference substance solution, measure trap at the wavelength place of 357nm, calculate every stripping quantity according to spectrophotography (Chinese Pharmacopoeia version appendix in 2005 IV A).
The result sees Fig. 1, Fig. 2, Fig. 3 respectively; Wherein Fig. 1 is the Nimodipine double-layer osmotic pump controlled release tablet releasing curve diagram according to embodiment 1 preparation; Fig. 2 is the Nimodipine double-layer osmotic pump controlled release tablet releasing curve diagram according to embodiment 2 preparations; Fig. 3 is according to the contrast releasing curve diagram of the nimodipine mono-layer osmotic pump controlled release tablets of optimizing prescription and prepared in the documents with the Nimodipine double-layer osmotic pump controlled release tablet for preparing according to embodiment 1.
Claims (10)
1, a kind of Nimodipine double-layer osmotic pump controlled release tablet is characterized in that comprising medicated layer label, boosting synusia core, coating membrane and in the single small delivery aperture on medicated layer one side controlled release tablet surface, wherein,
The medicated layer label comprises following composition, in the percentage ratio of the gross weight that accounts for medicated layer label and boosting synusia core:
Nimodipine is 5%-40%;
The osmotic pressure active substance is 0%-10%;
Penetrating agent is 20%-60%;
Binding agent is 1%-5%; With
Lubricant is 0.1%-3%;
Boosting synusia core comprises following composition, in the percentage ratio of the gross weight that accounts for medicated layer label and boosting synusia core:
Penetrating agent is 10%-40%;
The osmotic pressure active substance is 5%-25%;
Binding agent is 0%-5%;
Lubricant is 0.1%-3%; With
Coloring agent is 0.1%-5%.
2, osmotic pump controlled release tablet according to claim 1 is characterized in that, described medicated layer label comprises following composition, in the percentage ratio of the gross weight that accounts for medicated layer label and boosting synusia core:
Nimodipine is 14%-15%;
The osmotic pressure active substance is 0%-5%;
Penetrating agent is 40%-50%;
Binding agent is 3%-4%; With
Lubricant is 1%-1.5%;
Boosting synusia core comprises following composition, in the percentage ratio of the gross weight that accounts for medicated layer label and boosting synusia core:
Penetrating agent is 15%-30%;
The osmotic pressure active substance is 10%-15%;
Binding agent is 0%-3%;
Lubricant is 0.1%-2%; With
Coloring agent is 0.1%-1%.
3, osmotic pump controlled release tablet according to claim 2 is characterized in that, wherein said penetrating agent is selected from one or more in polyoxyethylene, hydroxypropyl emthylcellulose, carbopol and the arabic gum; The osmotic pressure active substance is selected from one or more in sodium chloride, lactose, mannitol, fructose, the dextrose plus saccharose; Binding agent is selected from one or more in water, ethanol, starch slurry, polyvidone and the hydroxypropyl emthylcellulose; Lubricant is selected from one or more in stearic acid, magnesium stearate, Pulvis Talci and the silicon dioxide; Coloring agent is selected from iron oxide red, iron oxide yellow or its combination.
4, osmotic pump controlled release tablet according to claim 3, it is characterized in that, osmotic pressure active substance in the described medicated layer label is selected from sodium chloride, lactose or its combination, penetrating agent is selected from polyoxyethylene, carbopol or its combination, binding agent is selected from polyvidone, hydroxypropyl methylcellulose or its combination, and lubricant is selected from magnesium stearate; Osmotic pressure active substance in the boosting synusia core is selected from sodium chloride, and penetrating agent is selected from polyoxyethylene, and binding agent is selected from hydroxypropyl emthylcellulose, and lubricant is selected from magnesium stearate, and coloring agent is selected from iron oxide red or iron oxide yellow.
5, osmotic pump controlled release tablet according to claim 4 is characterized in that, described coating membrane comprises following composition, to account for the percentage ratio of coatings weight:
Coating material is 80%-95%;
Plasticizer is 5%-10%; With
Porogen is 0%-10%.
6, osmotic pump controlled release tablet according to claim 5 is characterized in that, described porogen is selected from one or more in Polyethylene Glycol, polyvidone and the mannitol; Plasticizer is selected from one or more in Methyl Benzene-o-dicarboxylate, ethyl phthalate, triethyl citrate, Polyethylene Glycol and the polyvidone; Coating material is selected from cellulose acetate, ethyl cellulose or its combination.
7, controlled release tablet according to claim 6 is characterized in that, described plasticizer is selected from one or more in Macrogol 200-400, ethylene glycol 1500, ethylene glycol 4000 and the ethylene glycol 6000.
8, osmotic pump controlled release tablet according to claim 7 is characterized in that, the aperture of described single small delivery aperture on medicated layer label one side controlled release tablet surface is 0.2～1.0 millimeter.
9, according to the preparation method of the arbitrary described osmotic pump controlled release tablet of claim 1-8, it is characterized in that, comprise the steps:
(1) granulate behind nimodipine after will pulverizing and penetrating agent, osmotic pressure active substance, binding agent, the lubricant mixing, promptly get medicated layer sheet slug particle, standby;
(2) will granulate behind penetrating agent, osmotic pressure active substance, binding agent, lubricant and the coloring agent mixing, promptly get boosting synusia slug particle, standby;
(3) medicated layer sheet slug particle, boosting synusia slug particle are made double-deck label core body behind twice tabletting; Form coating solution with coating dissolution with solvents coating material and plasticizer and/or porogen, and with coating solution to double-deck label core body coating to 5%～7% of label weight, dried coating solvent volatilizees; In the punching of medicated layer label one side coating membrane surface promptly.
10, preparation method according to claim 9 is characterized in that, described coating solvent is selected from one or more in acetone, isopropyl alcohol, dichloromethane, the second alcohol and water.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007103021226A CN101455666A (en) | 2007-12-14 | 2007-12-14 | Nimodipine double-layer osmotic pump controlled release tablet and preparation technique thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007103021226A CN101455666A (en) | 2007-12-14 | 2007-12-14 | Nimodipine double-layer osmotic pump controlled release tablet and preparation technique thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101455666A true CN101455666A (en) | 2009-06-17 |
Family
ID=40766965
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007103021226A Pending CN101455666A (en) | 2007-12-14 | 2007-12-14 | Nimodipine double-layer osmotic pump controlled release tablet and preparation technique thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101455666A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101732276B (en) * | 2009-12-26 | 2012-09-12 | 鲁南制药集团股份有限公司 | Tablet of isosorbide mononitrate |
| CN103040785A (en) * | 2013-01-23 | 2013-04-17 | 上海奥科达生物医药科技有限公司 | Permeable gastric retention tablets and preparation method thereof |
| CN105560200A (en) * | 2015-12-21 | 2016-05-11 | 沈阳药科大学 | Insoluble medicine controlled-release tablets and preparation method thereof |
| CN115607544A (en) * | 2021-07-12 | 2023-01-17 | 上海博志研新药物技术有限公司 | Sustained release composition of sacubitril and valsartan sodium, its preparation method and application |
-
2007
- 2007-12-14 CN CNA2007103021226A patent/CN101455666A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101732276B (en) * | 2009-12-26 | 2012-09-12 | 鲁南制药集团股份有限公司 | Tablet of isosorbide mononitrate |
| CN103040785A (en) * | 2013-01-23 | 2013-04-17 | 上海奥科达生物医药科技有限公司 | Permeable gastric retention tablets and preparation method thereof |
| CN105560200A (en) * | 2015-12-21 | 2016-05-11 | 沈阳药科大学 | Insoluble medicine controlled-release tablets and preparation method thereof |
| CN105560200B (en) * | 2015-12-21 | 2018-10-23 | 沈阳药科大学 | Insoluble drug controlled release tablet and preparation method thereof |
| CN115607544A (en) * | 2021-07-12 | 2023-01-17 | 上海博志研新药物技术有限公司 | Sustained release composition of sacubitril and valsartan sodium, its preparation method and application |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6314188B2 (en) | Tofacitinib oral sustained release dosage form | |
| DE69720778T2 (en) | MEDICINES FOR DELAYED RELEASE OF HMG-CoA REDUCTASE INHIBITOR FLUVASTATIN | |
| CZ17801U1 (en) | Peroral application form with opioid protracted release | |
| JP2009137956A (en) | Sustained-release oral preparation of fasudil hydrochloride | |
| JP2003518487A (en) | Hydrogel-driven laminated drug formulation | |
| US11504345B2 (en) | Extended release liquid compositions of metformin | |
| CN105878204B (en) | A kind of Metformin hydrochloride osmotic pump controlled release tablet and preparation method thereof | |
| WO2021223480A1 (en) | Controlled-release ticagrelor tablet and preparation method therefor | |
| Ahmad et al. | Pharmaceutical micro encapsulation technology for development of controlled release drug delivery systems | |
| JPH08253413A (en) | Slow-releasing oral preparation of low-molecular medicine | |
| CN101455666A (en) | Nimodipine double-layer osmotic pump controlled release tablet and preparation technique thereof | |
| WO2020157730A1 (en) | A controlled release pharmaceutical composition of selexipag or it's active metabolite | |
| NL1032148C1 (en) | Oral dosing form for opiates, especially painkillers, has dosing structure designed to provide more prolonged release of opiate in presence of alcohol | |
| EP4371559A1 (en) | Osmotic pump controlled-release tablet of insoluble drug and preparation method therefor | |
| CN102028668B (en) | Simvastatin osmotic pump controlled-release tablet | |
| CN102670545A (en) | Carvedilol push-pull osmotic pump type controlled release preparation and preparation method thereof | |
| CN110251475A (en) | A kind of 9-hydroxy-risperidone tablet and preparation method thereof | |
| CN111407744B (en) | A kind of preparation method of tofacitinib citrate long-acting sustained-release microspheres | |
| CN106727407B (en) | A kind of metformin controlled release preparation and preparation method thereof | |
| JPS58502097A (en) | Expandable lattice of polyvinyl alcohol and polyethylene glycol | |
| Magulal et al. | Development and Evaluation of Swellable Elementary Osmotic Pump Tablet of Glipizide | |
| Pandey et al. | Evaluation of the effect of hydrophilic polymer blend to extend the release of clarithromycin from prepared microcapsules | |
| HK1106451B (en) | Methods of reducing alcohol-induced dose dumping for opioid sustained release oral dosage forms | |
| NZ613031A (en) | Solid molecular dispersion |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20090617 |