CN102600109B - Dexlansoprazole sustained release capsule and preparation method thereof - Google Patents
Dexlansoprazole sustained release capsule and preparation method thereof Download PDFInfo
- Publication number
- CN102600109B CN102600109B CN201210107787.2A CN201210107787A CN102600109B CN 102600109 B CN102600109 B CN 102600109B CN 201210107787 A CN201210107787 A CN 201210107787A CN 102600109 B CN102600109 B CN 102600109B
- Authority
- CN
- China
- Prior art keywords
- parts
- micropill
- mass
- lansoprazole
- composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- MJIHNNLFOKEZEW-RUZDIDTESA-N dexlansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1C[S@@](=O)C1=NC2=CC=CC=C2N1 MJIHNNLFOKEZEW-RUZDIDTESA-N 0.000 title claims abstract description 47
- 229960003568 dexlansoprazole Drugs 0.000 title claims abstract description 46
- 239000002775 capsule Substances 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 238000013268 sustained release Methods 0.000 title abstract 3
- 239000012730 sustained-release form Substances 0.000 title abstract 3
- 239000012055 enteric layer Substances 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 31
- 238000007789 sealing Methods 0.000 claims description 26
- 239000010410 layer Substances 0.000 claims description 24
- 239000011248 coating agent Substances 0.000 claims description 22
- 238000000576 coating method Methods 0.000 claims description 22
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 16
- 229920000053 polysorbate 80 Polymers 0.000 claims description 16
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 14
- 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 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 13
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims description 13
- 239000001069 triethyl citrate Substances 0.000 claims description 13
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims description 13
- 235000013769 triethyl citrate Nutrition 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- 229920003135 Eudragit® L 100-55 Polymers 0.000 claims description 12
- GDCRSXZBSIRSFR-UHFFFAOYSA-N ethyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.CCOC(=O)C=C GDCRSXZBSIRSFR-UHFFFAOYSA-N 0.000 claims description 12
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 229960000502 poloxamer Drugs 0.000 claims description 9
- 229920001983 poloxamer Polymers 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 239000000741 silica gel Substances 0.000 claims description 7
- 229910002027 silica gel Inorganic materials 0.000 claims description 7
- 239000004408 titanium dioxide Substances 0.000 claims description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- 229920002472 Starch Polymers 0.000 claims description 6
- 239000012530 fluid Substances 0.000 claims description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 6
- 239000008107 starch Substances 0.000 claims description 6
- 235000019698 starch Nutrition 0.000 claims description 6
- 239000004375 Dextrin Substances 0.000 claims description 5
- 229920001353 Dextrin Polymers 0.000 claims description 5
- 235000019425 dextrin Nutrition 0.000 claims description 5
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 5
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 5
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 5
- 229960003943 hypromellose Drugs 0.000 claims description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 5
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 4
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 4
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 4
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 4
- 239000004925 Acrylic resin Substances 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 3
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 3
- 239000000347 magnesium hydroxide Substances 0.000 claims description 3
- 229910001862 magnesium hydroxide Inorganic materials 0.000 claims description 3
- 235000019359 magnesium stearate Nutrition 0.000 claims description 3
- 239000002994 raw material Substances 0.000 claims description 3
- 239000000377 silicon dioxide Substances 0.000 claims description 3
- 235000012239 silicon dioxide Nutrition 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- 229920002594 Polyethylene Glycol 8000 Polymers 0.000 claims description 2
- 210000004211 gastric acid Anatomy 0.000 abstract description 5
- 239000008188 pellet Substances 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 3
- 230000006378 damage Effects 0.000 abstract 1
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract 1
- 239000000825 pharmaceutical preparation Substances 0.000 abstract 1
- 239000008363 phosphate buffer Substances 0.000 description 8
- 239000002253 acid Substances 0.000 description 6
- 239000006184 cosolvent Substances 0.000 description 5
- 230000000968 intestinal effect Effects 0.000 description 5
- 239000000314 lubricant Substances 0.000 description 5
- 239000000872 buffer Substances 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 3
- 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 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000000857 drug effect Effects 0.000 description 3
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000004014 plasticizer Substances 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 206010063655 Erosive oesophagitis Diseases 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000000767 anti-ulcer Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000003605 opacifier Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- MMJMSRMOAUITKN-UHFFFAOYSA-N 2-sulfinylbenzimidazole Chemical compound C1=CC=CC2=NC(=S=O)N=C21 MMJMSRMOAUITKN-UHFFFAOYSA-N 0.000 description 1
- 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 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 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
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- 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 description 1
- 206010070840 Gastrointestinal tract irritation Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 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 description 1
- 241000590002 Helicobacter pylori Species 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 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 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 201000008629 Zollinger-Ellison syndrome Diseases 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N ferric oxide Chemical compound O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 230000027119 gastric acid secretion Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 201000000052 gastrinoma Diseases 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 208000024798 heartburn Diseases 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 229940037467 helicobacter pylori Drugs 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 230000008855 peristalsis Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 229920000333 poly(propyleneimine) Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 230000003578 releasing effect Effects 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of pharmaceutical preparation, and particularly relates to a dexlansoprazole sustained release capsule and a preparation method thereof. Two kinds of pellets are arranged in the capsule, and the weight ratio of dexlansoprazole contained in the first kind of pellets and the second kind of pellets is 1:3-4. The dexlansoprazole sustained release capsule disclosed by the invention can avoid the destruction of the dexlansoprazole in gastric acid, and is released in the intestinal tract in a fixed position so as to achieve the purposes of taking effect rapidly and improving bioavailability.
Description
Technical field
The invention belongs to technical field of medicine, be specifically related to a kind of R-lansoprazole slowbreak capsule and preparation method thereof.
Background technology
The molecular formula of R-lansoprazole (dexlansoprazole) is:
Chemistry is by name: (+)-2-[(R)-[[3-methyl-4-(2,2,2-trifluoro ethoxy)-2-pyridine radicals] methyl] sulfinyl]-1H-benzimidazole.
R-lansoprazole is proton pump inhibitor class antiulcerative newly developed, its oral formulations is the exploitation of Japanese Takeda Pharmaceutical Company Limited, commodity are called Kapilax, sustainable gastric acid secretion inhibiting, so can improve GERD symptom, effect significantly and better tolerance, obtains U.S. FDA in January, 2009 and ratifies " heartburn " symptom and the erosive esophagitis that cause for Non-erosive GERD, and for the treatment that maintains of erosive esophagitis.
R-lansoprazole belongs to and draws azole PPIs antiulcerative, in R-lansoprazole structure, there is the chemical constitution of sulfinyl benzimidazole, its stability is subject to light, heavy metal ion, the impact of the many factors such as oxidisability and reproducibility composition, especially in the time of acid condition, can there is destructive variation in the chemical constitution of R-lansoprazole, there is variable color and polymerism, thereby R-lansoprazole is unstable in the diluent of slant acidity, make after oral formulations, drug absorption need be passed through medicine disintegrate dispose procedure, and because causing R-lansoprazole to destroy, decomposes in gastric acid in stomach, and reduction drug effect speed and bioavailability, how making R-lansoprazole capsule mainly under intestinal environment, discharge is very large key point.
Summary of the invention
The invention provides a kind of R-lansoprazole slowbreak capsule and preparation method thereof.
The present invention is by the following technical solutions:
A kind of R-lansoprazole slowbreak capsule, is equipped with two kinds of micropills in capsule, the mass ratio of the first micropill and the second micropill is 1:1-4;
The first micropill is followed successively by celphere, medicated layer, sealing coat and enteric layers from inside to outside, and the mass parts of celphere is 800 parts, and the composition of medicated layer and mass parts are R-lansoprazole: 300 parts,
Stabilizing agent: 5-20 part,
Cosolvent: 1-5 part,
Excipient: 50-200 part,
Lubricant: 5-30 part,
Binding agent: 50-300 part,
The composition of sealing coat and mass parts are binding agent: 30-60 part,
Cosolvent: 3-10 part,
Opacifier: 3-8 part,
Lubricant: 5-10 part,
The composition of enteric layers and mass parts are coating materials: 50-150 part,
Plasticizer: 5-20 part,
Cosolvent: 5-15 part,
Lubricant: 5-15 part;
The difference of the second micropill and the first micropill is that the composition of enteric layers and mass parts are: EUDRAGIT L100-55 (1:2): 100-300 part,
Plasticizer: 10-40 part,
Cosolvent: 2-8 part,
Lubricant: 50-100 part.
Described stabilizing agent is magnesium hydroxide, magnesium carbonate, sodium carbonate or sodium hydroxide, cosolvent is poloxamer or tween, excipient is microcrystalline Cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, lactose, mannitol, dextran, glucose, sorbitol, Pulvis Talci, starch or sucrose, lubricant is magnesium stearate, Pulvis Talci, stearic acid, micropowder silica gel, one or more in colloidality silicon dioxide or Polyethylene Glycol, binding agent is polyvinylpyrrolidone, starch slurry, sodium carboxymethyl cellulose, hydroxypropyl cellulose, methylcellulose, ethyl cellulose, hypromellose, gelatin, dextrin or sucrose, opacifier is titanium dioxide, coating materials is EUDRAGIT L100-55 (1:1) or polyacrylic resin Ⅱ, plasticizer is triethyl citrate or Polyethylene Glycol.
The preparation method of R-lansoprazole slowbreak capsule, comprises the following steps when preparation:
(1) prepare the first micropill:
A, get each raw material in proportion;
B, each component of medicated layer is mixedly configured into medicated layer coating solution, medicated layer coating solution is added medicine to celphere, dry;
C, bag sealing coat, be mixedly configured into sealing coat coating solution by each component of sealing coat, and the ball core medicine-feeding of sealing coat coating solution to step b gained is dry;
D, bag enteric layers, be configured to enteric layers coating solution by each component of enteric layers, and the ball core medicine-feeding of enteric layers coating solution to step c gained is dry;
(2) prepare the second micropill
Identical with the preparation process of the first micropill;
(3) the first micropill and the second micropill are mixed with mass ratio 1:1-4, incapsulate.
Celphere is 40-60 object sucrose ball core, microcrystalline Cellulose ball core or starch ball core.
R-lansoprazole slowbreak capsule of the present invention selects suitable adjuvant to reach that stable, dissolubility strengthens, the object of slowbreak controlled release, fundamentally solves medicine and decomposes the problem that reduces drug effect speed and bioavailability because gastric acid causes destroying, two kinds of micropills are housed in capsule of the present invention, according to the difference of two kinds of coating of pellets layer coating materials used, thereby realize two kinds of micropills and can under specific pH environment, decompose release, the first micropill decomposes under pH6.8 environment, the second micropill is to decompose under 7.0 to 7.6 environment at pH, the burst size that finally realizes R-lansoprazole slowbreak capsule of the present invention 2h in pH1.2 acid is less than 10% of labelled amount, in the buffer of pH6.8, the burst size of 0.5 hour is labelled amount 10-25%'s, be that in 7.0 to 7.6 buffer, the burst size of 1 hour is less than 40% of labelled amount at pH, the burst size of 1.5 hours is not less than 75% of labelled amount, can avoid R-lansoprazole destroyed in gastric acid, and location discharges in intestinal, rapid to reach onset, improve the object of bioavailability.
R-lansoprazole slowbreak capsule of the present invention adopts micropill to adopt micropill release technology, it is little that micropill absorption is affected by the gastrointestinal peristalsis rhythm and pace of moving things, multiple-unit release makes intestinal wall contact area large, absorb rapidly, gastrointestinal irritation is less, prevents that the medicine does no good to because single preparation defect causes, drug effect predictability is higher, capsule can be taken apart taking individually inconvenient old man and child, directly take the micropill in capsule, can not cause pharmacodynamic change.R-lansoprazole slowbreak capsule of the present invention is used for the treatment of gastric ulcer, duodenal ulcer, erosive stomach-esophageal reflux disease, helicobacter pylori, zollinger-ellison syndrome.
Detailed description of the invention
Embodiment 1
R-lansoprazole slowbreak capsule, is equipped with two kinds of micropills in capsule, the mass ratio (taking R-lansoprazole) of the first micropill and the second micropill is 1:3;
The first micropill is followed successively by celphere, medicated layer, sealing coat and enteric layers from inside to outside, and the mass parts of celphere is 800 parts, and the composition of medicated layer and mass parts are R-lansoprazole: 300 parts,
Sodium hydroxide: 16 parts,
Tween 80: 5 parts,
Carboxymethyl starch sodium: 50 parts,
Colloidality silicon dioxide: 20 parts,
Hypromellose: 200 parts,
The composition of sealing coat and mass parts are hypromellose: 50 parts,
Tween 80: 6 parts,
Titanium dioxide: 6 parts,
PEG 8000: 10 parts,
The composition of enteric layers and mass parts are EUDRAGIT L100-55 (1:1): 60 parts,
Triethyl citrate: 10 parts,
Tween 80: 10 parts,
Pulvis Talci: 10 parts;
The difference of the second micropill and the first micropill is that the composition of enteric layers and mass parts are: EUDRAGIT L100-55 (1:2): 150 parts,
Triethyl citrate: 30 parts,
Tween 80: 5 parts,
Pulvis Talci: 85 parts.
Embodiment 2
R-lansoprazole slowbreak capsule, is equipped with two kinds of micropills in capsule, the mass ratio (R-lansoprazole meter) of the first micropill and the second micropill is 1:3;
The first micropill is followed successively by celphere, medicated layer, sealing coat and enteric layers from inside to outside, and the mass parts of celphere is 800 parts, and the composition of medicated layer and mass parts are R-lansoprazole: 300 parts,
Magnesium hydroxide: 5 parts,
Poloxamer: 1 part,
Microcrystalline Cellulose: 200 parts,
Magnesium stearate: 5 parts,
Polyvinylpyrrolidone: 50 parts,
The composition of sealing coat and mass parts are polyvinylpyrrolidone: 30 parts,
Poloxamer: 3 parts,
Titanium dioxide: 3 parts,
Micropowder silica gel: 5 parts,
The composition of enteric layers and mass parts are polyacrylic resin Ⅱ: 50 parts,
Triethyl citrate: 5 parts,
Poloxamer: 15 parts,
Micropowder silica gel: 15 parts;
The difference of the second micropill and the first micropill is that the composition of enteric layers and mass parts are: EUDRAGIT L100-55 (1:2): 100 parts,
Triethyl citrate: 10 parts,
Poloxamer: 2 parts,
Pulvis Talci: 100 parts.
Embodiment 3
R-lansoprazole slowbreak capsule, is equipped with two kinds of micropills in capsule, the mass ratio (R-lansoprazole meter) of the first micropill and the second micropill is 1:4;
The first micropill is followed successively by celphere, medicated layer, sealing coat and enteric layers from inside to outside, and the mass parts of celphere is 800 parts, and the composition of medicated layer and mass parts are R-lansoprazole: 300 parts,
Sodium carbonate: 20 parts,
Tween 80: 3 parts,
Low-substituted hydroxypropyl cellulose: 100 parts,
Pulvis Talci: 30 parts,
Dextrin: 300 parts,
The composition of sealing coat and mass parts are dextrin: 60 parts,
Tween 80: 10 parts,
Titanium dioxide: 8 parts,
Pulvis Talci: 8 parts,
The composition of enteric layers and mass parts are EUDRAGIT L100-55 (1:1): 150 parts,
Triethyl citrate: 20 parts,
Tween 80: 5 parts,
Micropowder silica gel: 5 parts;
The difference of the second micropill and the first micropill is that the composition of enteric layers and mass parts are: EUDRAGIT L100-55 (1:2): 300 parts,
Triethyl citrate: 40 parts,
Tween 80: 8 parts,
Pulvis Talci: 50 parts.
Embodiment 1-3 comprises the following steps while preparation:
(1) prepare the first micropill:
A, get each raw material in proportion;
B, each component of medicated layer is mixed, is configured to the ethanol of volume fraction 75-95% the medicated layer coating solution of mass fraction 15-45%, in fluid bed, medicated layer coating solution is added medicine to celphere, controls fluidized-bed temperature 35-45 DEG C, and 30-60 DEG C is dried;
C, bag sealing coat, each component of sealing coat is mixed, is configured to the ethanol of volume fraction 75-95% to the sealing coat coating solution of mass fraction 15-45%, in fluid bed, the ball core medicine-feeding of sealing coat coating solution to step b gained, controls fluidized-bed temperature 35-55 DEG C, and 30-60 DEG C dry;
D, bag enteric layers, each component of enteric layers is mixed, is configured to the ethanol of volume fraction 75-95% to the one-tenth enteric layers coating solution of mass fraction 15-45%, in fluid bed, the ball core medicine-feeding of enteric layers coating solution to step c gained, controls fluidized-bed temperature 35-55 DEG C, and 30-60 DEG C dry;
(2) prepare the second micropill
Identical with the preparation process of the first micropill;
(3) the first micropill and the second micropill are mixed according to required mass ratio, incapsulate.
Umber in embodiment 1-3 is weight portion.
Under varying environment, the burst size of embodiment 1-3 capsule is tested respectively, result is that the burst size of embodiment 1 2h in pH1.2 acid is labelled amount 0.2%, in the phosphate buffer of pH6.8, the burst size of 0.5 hour is labelled amount 24%, the burst size of 33%, 1.5 hour that in the phosphate buffer that is 7.0 at pH, the burst size of 1 hour is labelled amount is labelled amount 96%; The burst size of embodiment 2 2h in pH1.2 acid is labelled amount 0.5%, in the phosphate buffer of pH6.8, the burst size of 0.5 hour is labelled amount 23%, the burst size of 34%, 1.5 hour that in the phosphate buffer that is 7.0 at pH, the burst size of 1 hour is labelled amount is labelled amount 95%; The burst size of embodiment 3 2h in pH1.2 acid is labelled amount 0.4%, in the phosphate buffer of pH6.8, the burst size of 0.5 hour is labelled amount 18%, the burst size of 31%, 1.5 hour that in the buffer that is 7.0 at pH, the burst size of 1 hour is labelled amount is labelled amount 94%.In the above phosphate buffer that is 7.0 at pH, having same pH is essentially identical releasing effect in 7.0 buffer.
Found out by above data, the burst size of the capsule of embodiment 1-3 2h in acid is all less than 10%, can avoid R-lansoprazole destroyed in gastric acid, in the phosphate buffer of pH6.8, the burst size of 0.5 hour is labelled amount 10-25%, can make R-lansoprazole be absorbed rapidly in small intestinal, onset immediately, be that in 7.0 to 7.6 phosphate buffer, the burst size of 1 hour is less than 40% of labelled amount at pH, the burst size of 1.5 hours is all greater than 75% of labelled amount, can ensure that R-lansoprazole discharges in intestinal pH environment, and play slow release effect.
Claims (4)
1. a R-lansoprazole slowbreak capsule, is characterized in that: two kinds of micropills are housed in capsule, and the mass ratio of the first micropill and the contained R-lansoprazole of the second micropill is 1:3;
The first micropill is followed successively by celphere, medicated layer, sealing coat and enteric layers from inside to outside, and the mass parts of celphere is 800 parts, and the composition of medicated layer and mass parts are R-lansoprazole: 300 parts,
Sodium hydroxide: 16 parts,
Tween 80: 5 parts,
Carboxymethyl starch sodium: 50 parts,
Colloidality silicon dioxide: 20 parts,
Hypromellose: 200 parts,
The composition of sealing coat and mass parts are hypromellose: 50 parts,
Tween 80: 6 parts,
Titanium dioxide: 6 parts,
PEG 8000: 10 parts,
The composition of enteric layers and mass parts are the EUDRAGIT L100-55 of 1:1: 60 parts,
Triethyl citrate: 10 parts,
Tween 80: 10 parts,
Pulvis Talci: 10 parts;
The difference of the second micropill and the first micropill is that the composition of enteric layers and mass parts are: the EUDRAGIT L100-55 of 1:2: 150 parts,
Triethyl citrate: 30 parts,
Tween 80: 5 parts,
Pulvis Talci: 85 parts.
2. a R-lansoprazole slowbreak capsule, is characterized in that: two kinds of micropills are housed in capsule, and the mass ratio of the first micropill and the contained R-lansoprazole of the second micropill is 1:3;
The first micropill is followed successively by celphere, medicated layer, sealing coat and enteric layers from inside to outside, and the mass parts of celphere is 800 parts, and the composition of medicated layer and mass parts are R-lansoprazole: 300 parts,
Magnesium hydroxide: 5 parts,
Poloxamer: 1 part,
Microcrystalline Cellulose: 200 parts,
Magnesium stearate: 5 parts,
Polyvinylpyrrolidone: 50 parts,
The composition of sealing coat and mass parts are polyvinylpyrrolidone: 30 parts,
Poloxamer: 3 parts,
Titanium dioxide: 3 parts,
Micropowder silica gel: 5 parts,
The composition of enteric layers and mass parts are polyacrylic resin Ⅱ: 50 parts,
Triethyl citrate: 5 parts,
Poloxamer: 15 parts,
Micropowder silica gel: 15 parts;
The difference of the second micropill and the first micropill is that the composition of enteric layers and mass parts are: the EUDRAGIT L100-55 of 1:2: 100 parts,
Triethyl citrate: 10 parts,
Poloxamer: 2 parts,
Pulvis Talci: 100 parts.
3. a R-lansoprazole slowbreak capsule, is characterized in that: two kinds of micropills are housed in capsule, and the mass ratio of the first micropill and the contained R-lansoprazole of the second micropill is 1:4;
The first micropill is followed successively by celphere, medicated layer, sealing coat and enteric layers from inside to outside, and the mass parts of celphere is 800 parts, and the composition of medicated layer and mass parts are R-lansoprazole: 300 parts,
Sodium carbonate: 20 parts,
Tween 80: 3 parts,
Low-substituted hydroxypropyl cellulose: 100 parts,
Pulvis Talci: 30 parts,
Dextrin: 300 parts,
The composition of sealing coat and mass parts are dextrin: 60 parts,
Tween 80: 10 parts,
Titanium dioxide: 8 parts,
Pulvis Talci: 8 parts,
The composition of enteric layers and mass parts are the EUDRAGIT L100-55 of 1:1: 150 parts,
Triethyl citrate: 20 parts,
Tween 80: 5 parts,
Micropowder silica gel: 5 parts;
The difference of the second micropill and the first micropill is that the composition of enteric layers and mass parts are: the EUDRAGIT L100-55 of 1:2: 300 parts,
Triethyl citrate: 40 parts,
Tween 80: 8 parts,
Pulvis Talci: 50 parts.
4. the preparation method of the R-lansoprazole slowbreak capsule described in claim 1-3 any one, is characterized in that:
When preparation, comprise the following steps:
(1) prepare the first micropill:
A, get each raw material in proportion;
B, each component of medicated layer is mixed, is configured to the ethanol of volume fraction 75-95% the medicated layer coating solution of mass fraction 15-45%, in fluid bed, medicated layer coating solution is added medicine to celphere, controls fluidized-bed temperature 35-45 DEG C, and 30-60 DEG C is dried;
C, bag sealing coat, each component of sealing coat is mixed, is configured to the ethanol of volume fraction 75-95% to the sealing coat coating solution of mass fraction 15-45%, in fluid bed, the ball core medicine-feeding of sealing coat coating solution to step b gained, controls fluidized-bed temperature 35-55 DEG C, and 30-60 DEG C dry;
D, bag enteric layers, each component of enteric layers is mixed, is configured to the ethanol of volume fraction 75-95% to the one-tenth enteric layers coating solution of mass fraction 15-45%, in fluid bed, the ball core medicine-feeding of enteric layers coating solution to step c gained, controls fluidized-bed temperature 35-55 DEG C, and 30-60 DEG C dry;
(2) prepare the second micropill
Identical with the preparation process of the first micropill;
(3) the first micropill and the second micropill are mixed according to required mass ratio, incapsulate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210107787.2A CN102600109B (en) | 2012-04-13 | 2012-04-13 | Dexlansoprazole sustained release capsule and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210107787.2A CN102600109B (en) | 2012-04-13 | 2012-04-13 | Dexlansoprazole sustained release capsule and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102600109A CN102600109A (en) | 2012-07-25 |
| CN102600109B true CN102600109B (en) | 2014-09-17 |
Family
ID=46518139
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210107787.2A Active CN102600109B (en) | 2012-04-13 | 2012-04-13 | Dexlansoprazole sustained release capsule and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102600109B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103565770A (en) * | 2012-07-31 | 2014-02-12 | 北京阜康仁生物制药科技有限公司 | Dexlansoprazole enteric-coated slow controlled-release pellet tablets |
| CN104523654A (en) * | 2014-12-15 | 2015-04-22 | 北京红太阳药业有限公司 | Dexlansoprazole sustained-release capsule and preparation method thereof |
| CN104940169B (en) * | 2015-06-26 | 2017-10-10 | 山东省药学科学院 | A kind of R-lansoprazole spansule and preparation method thereof |
| CN105796532B (en) * | 2016-03-28 | 2018-12-21 | 中国医药集团总公司四川抗菌素工业研究所 | A kind of RABEPRAZOLE SODIUM spansule and preparation method thereof |
| CN106822045B (en) * | 2017-03-28 | 2019-11-05 | 乐普药业科技有限公司 | A kind of R-lansoprazole sustained release preparation and preparation method thereof and drug |
| KR102227486B1 (en) * | 2017-06-30 | 2021-03-12 | 롯데정밀화학 주식회사 | Oral solid formulation composition comprising proton pump inhibitor, oral solid formulation comprising the same and manufacturing method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102014638A (en) * | 2007-10-12 | 2011-04-13 | 武田制药北美公司 | Methods of treating gastrointestinal disorders independent of the intake of food |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120058194A1 (en) * | 2010-08-27 | 2012-03-08 | Navin Vaya | Pharmaceutical formulations comprising substituted benzimidazole derivatives |
-
2012
- 2012-04-13 CN CN201210107787.2A patent/CN102600109B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102014638A (en) * | 2007-10-12 | 2011-04-13 | 武田制药北美公司 | Methods of treating gastrointestinal disorders independent of the intake of food |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102600109A (en) | 2012-07-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2227556T3 (en) | PHARMACEUTICAL PREPARATION OF MULTIPLE UNITS CONTAINING A PROTON PUMP INHIBITOR. | |
| CN102600109B (en) | Dexlansoprazole sustained release capsule and preparation method thereof | |
| JP5118962B2 (en) | Stabilizing composition | |
| EP1078628B1 (en) | Multiple unit tableted dosage form | |
| EP2596791B1 (en) | Stable solid preparations | |
| ES2338009T3 (en) | SOLID COMPOSITION INCLUDING A PROTON PUMP INHIBITOR. | |
| CA2448760A1 (en) | Solid preparation | |
| JP2012153712A (en) | Heartburn treatment | |
| CA2290824A1 (en) | Benzimidazole pharmaceutical composition and process of preparation | |
| PT1746980E (en) | Pharmaceutical dosage form comprising pellets as well as its manufacturing process | |
| PT1624869E (en) | Dosage form containing pantoprazole as active ingredient | |
| EP2319504A1 (en) | Pharmaceutical solid dosage form | |
| CN114569575B (en) | Enteric coated pellets, process for their preparation and formulations containing them | |
| JP7541617B2 (en) | Enteric-coated pellets, their manufacturing method and preparations containing the same | |
| US9040564B2 (en) | Stabilized composition | |
| JP4331930B2 (en) | High content granules of acid labile drugs | |
| CN114569580B (en) | Enteric coated pellets, process for their preparation and formulations containing them | |
| RU2821366C1 (en) | Enteric coated pellets, method for their production and compositions containing them | |
| CN104606168A (en) | Drug composition for treating digestive system diseases | |
| CN104739801A (en) | Pharmaceutical composition for treating digestive system disease | |
| KR960015143B1 (en) | New oral preparations containing benzimidazole derivative and its manufacturing method | |
| CN104606169A (en) | Preparation method of drug composition for treating digestive system diseases | |
| JPH10504288A (en) | Novel oral pharmaceutical formulations containing magnesium salt of omeprazole |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C53 | Correction of patent for invention or patent application | ||
| CB02 | Change of applicant information |
Address after: Xiangcheng City, Zhoukou City, Henan province 466200 Peace Avenue East No. 216 Applicant after: LEPU PHARMACEUTICAL CO., LTD. Address before: Xiangcheng City, Zhoukou City, Henan province 466200 Peace Avenue East No. 216 Applicant before: Henan Xinshuaike Pharmaceutical Co., Ltd. |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: APPLICANT; FROM: HENAN XINSHUAIKE PHARMACEUTICAL CO., LTD. TO: LEPU PHARMACEUTICAL CO., LTD. |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20170303 Address after: 466200 Xiangcheng City, Henan Province Industrial Zone, No. two weft Road No. 36, No. Patentee after: Henan Meihua Pharmaceutical Co., Ltd. Address before: Xiangcheng City, Zhoukou City, Henan province 466200 Peace Avenue East No. 216 Patentee before: LEPU PHARMACEUTICAL CO., LTD. |
|
| CP03 | Change of name, title or address | ||
| CP03 | Change of name, title or address |
Address after: 466200 Xiangcheng City, Henan Province Industrial Zone, No. two weft Road No. 36, No. Patentee after: Joy Pharmaceutical Technology Co., Ltd. Address before: No. two, No. 36, weft Road, Xiangcheng Industrial Agglomeration Area Patentee before: Henan Meihua Pharmaceutical Co., Ltd. |