CN1692909A - Dosmalfate dispersion tablet and its prepn. method - Google Patents
Dosmalfate dispersion tablet and its prepn. method Download PDFInfo
- Publication number
- CN1692909A CN1692909A CN 200410027074 CN200410027074A CN1692909A CN 1692909 A CN1692909 A CN 1692909A CN 200410027074 CN200410027074 CN 200410027074 CN 200410027074 A CN200410027074 A CN 200410027074A CN 1692909 A CN1692909 A CN 1692909A
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- Prior art keywords
- dosmalfate
- starch
- dispersible tablet
- cellulose
- microcrystalline cellulose
- Prior art date
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Links
- 229950002968 dosmalfate Drugs 0.000 title claims description 68
- RIIQJLBJDMMSSK-RHFFRRHRSA-A tetradecaaluminum;[2-methoxy-5-[7-[(2s,3r,4s,5r,6r)-6-[[(2r,3r,4r,5s,6s)-6-methyl-3,4,5-trisulfonatooxyoxan-2-yl]oxymethyl]-3,4,5-trisulfonatooxyoxan-2-yl]oxy-4-oxo-5-sulfonatooxychromen-2-yl]phenyl] sulfate;pentatriacontahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Al+3].[Al+3].[Al+3].[Al+3].[Al+3].[Al+3].[Al+3].[Al+3].[Al+3].[Al+3].[Al+3].[Al+3].[Al+3].[Al+3].C1=C(OS([O-])(=O)=O)C(OC)=CC=C1C(OC1=C2)=CC(=O)C1=C(OS([O-])(=O)=O)C=C2O[C@H]1[C@H](OS([O-])(=O)=O)[C@@H](OS([O-])(=O)=O)[C@H](OS([O-])(=O)=O)[C@@H](CO[C@H]2[C@@H]([C@H](OS([O-])(=O)=O)[C@@H](OS([O-])(=O)=O)[C@H](C)O2)OS([O-])(=O)=O)O1 RIIQJLBJDMMSSK-RHFFRRHRSA-A 0.000 title claims description 66
- 238000000034 method Methods 0.000 title claims description 7
- 239000006185 dispersion Substances 0.000 title 1
- 238000002156 mixing Methods 0.000 claims abstract description 23
- 238000001035 drying Methods 0.000 claims abstract description 21
- 229920002472 Starch Polymers 0.000 claims abstract description 18
- 239000008107 starch Substances 0.000 claims abstract description 18
- 235000019698 starch Nutrition 0.000 claims abstract description 18
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims abstract description 16
- 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 claims abstract description 15
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims abstract description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 5
- 208000025865 Ulcer Diseases 0.000 claims abstract 2
- 210000001035 gastrointestinal tract Anatomy 0.000 claims abstract 2
- 231100000397 ulcer Toxicity 0.000 claims abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 44
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 44
- 239000007919 dispersible tablet Substances 0.000 claims description 34
- 239000000203 mixture Substances 0.000 claims description 33
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 25
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 25
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 25
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 25
- 235000019359 magnesium stearate Nutrition 0.000 claims description 22
- 239000008187 granular material Substances 0.000 claims description 20
- 239000007788 liquid Substances 0.000 claims description 20
- 239000007779 soft material Substances 0.000 claims description 20
- 238000005303 weighing Methods 0.000 claims description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 15
- 229950005770 hyprolose Drugs 0.000 claims description 15
- 239000000741 silica gel Substances 0.000 claims description 15
- 229910002027 silica gel Inorganic materials 0.000 claims description 15
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 14
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 14
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 12
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 12
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 12
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 claims description 11
- 229940013618 stevioside Drugs 0.000 claims description 11
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 claims description 11
- 235000019202 steviosides Nutrition 0.000 claims description 11
- 229920000881 Modified starch Polymers 0.000 claims description 10
- 238000004132 cross linking Methods 0.000 claims description 10
- -1 hydroxypropyl Chemical group 0.000 claims description 8
- 239000004368 Modified starch Substances 0.000 claims description 6
- 235000010980 cellulose Nutrition 0.000 claims description 6
- 229920002678 cellulose Polymers 0.000 claims description 6
- 239000001913 cellulose Substances 0.000 claims description 6
- 235000019426 modified starch Nutrition 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- 239000002671 adjuvant Substances 0.000 claims description 5
- 239000008101 lactose Substances 0.000 claims description 5
- 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
- 229920001353 Dextrin Polymers 0.000 claims description 4
- 239000004375 Dextrin Substances 0.000 claims description 4
- 229930195725 Mannitol Natural products 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 239000011230 binding agent Substances 0.000 claims description 4
- 235000019425 dextrin Nutrition 0.000 claims description 4
- 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 4
- 239000000945 filler Substances 0.000 claims description 4
- 239000001341 hydroxy propyl starch Substances 0.000 claims description 4
- 235000013828 hydroxypropyl starch Nutrition 0.000 claims description 4
- 239000000314 lubricant Substances 0.000 claims description 4
- 239000000594 mannitol Substances 0.000 claims description 4
- 235000010355 mannitol Nutrition 0.000 claims description 4
- 229920000609 methyl cellulose Polymers 0.000 claims description 4
- 239000001923 methylcellulose Substances 0.000 claims description 4
- 235000010981 methylcellulose Nutrition 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 235000000346 sugar Nutrition 0.000 claims description 4
- 229920002907 Guar gum Polymers 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
- 239000003292 glue Substances 0.000 claims description 3
- 239000000665 guar gum Substances 0.000 claims description 3
- 235000010417 guar gum Nutrition 0.000 claims description 3
- 229960002154 guar gum Drugs 0.000 claims description 3
- 239000002002 slurry Substances 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 2
- 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 2
- 108010011485 Aspartame Proteins 0.000 claims description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 2
- 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
- 239000001828 Gelatine Substances 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 2
- 229910021502 aluminium hydroxide Inorganic materials 0.000 claims description 2
- 235000010357 aspartame Nutrition 0.000 claims description 2
- 239000000605 aspartame Substances 0.000 claims description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 2
- 229960003438 aspartame Drugs 0.000 claims description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 2
- 239000004327 boric acid Substances 0.000 claims description 2
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 claims description 2
- 239000004568 cement Substances 0.000 claims description 2
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 claims description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 2
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 2
- 229920001249 ethyl cellulose Polymers 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 239000008172 hydrogenated vegetable oil Substances 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 2
- 229920000053 polysorbate 80 Polymers 0.000 claims description 2
- 229920006316 polyvinylpyrrolidine Polymers 0.000 claims description 2
- 235000015424 sodium Nutrition 0.000 claims description 2
- 229940032147 starch Drugs 0.000 claims description 2
- 239000006188 syrup Substances 0.000 claims description 2
- 235000020357 syrup Nutrition 0.000 claims description 2
- 239000000080 wetting agent Substances 0.000 claims description 2
- 239000000230 xanthan gum Substances 0.000 claims description 2
- 235000010493 xanthan gum Nutrition 0.000 claims description 2
- 229920001285 xanthan gum Polymers 0.000 claims description 2
- 229940082509 xanthan gum Drugs 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims 1
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 abstract 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 abstract 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 abstract 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 abstract 1
- 239000003826 tablet Substances 0.000 description 18
- 238000004090 dissolution Methods 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 208000008469 Peptic Ulcer Diseases 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 239000010419 fine particle Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 208000011906 peptic ulcer disease Diseases 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000007613 slurry method Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
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Abstract
A dispersing tablet of Duosima eter for treating the ulcer of digestive tract is prepared from Duosimazhi, starch, microcrystalline cellullose, polyvinyl pyrrolidone, carboxymethyl cellulose sodium, and hydroxypropyl cellulose through mixing part of them, granulating, drying, mixing with other and tabletting.
Description
● technical field
The present invention relates to a kind of pharmaceutical composition that contains dosmalfate, more particularly, the present invention relates to a kind of dosmalfate dispersible tablet.The invention still further relates to the preparation method of described dosmalfate dispersible tablet.
● background technology
Dosmalfate (English name: be a kind of novel gastric mucosa protectant dosmalfate), be used for the treatment of peptic ulcer.The dosage form of the external exploitation of this product is a conventional tablet.Domesticly ratify first on February 13rd, 2003 and enter clinical research, dosage form is an ordinary tablet.
Because dosmalfate poorly soluble in water, it is relatively poor that conventional tablet exists disintegrating property, and the deficiency that onset is slower limits and weakened dosmalfate to the gastrointestinal protective effect.The dosmalfate dosage is bigger, and exploitation dosmalfate dispersible tablet also helps always, the patient young and difficulty of swallowing takes.
● summary of the invention
The objective of the invention is at the deficiencies in the prior art, overcome the limitation of dosmalfate ordinary tablet, the methods and applications of preparation dosmalfate dispersible tablet are provided.This dosage form can significantly improve the disintegration rate and the dissolving out capability of medicine.
Purpose of the present invention is achieved by following technical proposals.
Except as otherwise noted, percent of the present invention is percetage by weight.
Dosmalfate dispersible tablet of the present invention, every contains dosmalfate 100～1000mg and pharmaceutic adjuvant, and described pharmaceutic adjuvant comprises filler 0～200mg, binding agent 0～200mg, disintegrating agent or swellability adjuvant 2～300mg, lubricant 0.1～20mg, fluidizer 0.1～15mg, antitack agent 0～15mg, aromatic and sweeting agent 0～15mg.Described filler is selected from a kind of in starch, dextrin, Icing Sugar, lactose, mannitol or the microcrystalline Cellulose or their mixture: described wetting agent is selected from water or ethanol or their mixture; Described binding agent is selected from a kind of of starch slurry, hydroxypropyl starch, modified starch, pregelatinized Starch, dextrin, Icing Sugar, syrup, microcrystalline Cellulose, cellulose derivative (comprising hydroxypropyl emthylcellulose, methylcellulose, sodium carboxymethyl cellulose, ethyl cellulose), polyvinylpyrrolidone rubber cement, gelatine size or their mixture; Described disintegrating agent or swellability adjuvant are selected from hydroxypropyl starch, modified starch, starch, carboxymethyl starch sodium, microcrystalline Cellulose, cellulose derivative (comprises hydroxypropyl emthylcellulose, methylcellulose, sodium carboxymethyl cellulose, low replacement-hyprolose, cross-linking sodium carboxymethyl cellulose, carboxy-propyl cellulose, carboxymethylcellulose calcium), crospolyvinylpyrrolidone, tween 80, sodium lauryl sulphate, guar gum, Herba Xanthii glue, a kind of in the xanthan gum or their mixture; Described lubricant, fluidizer, antitack agent are selected from a kind of in modified starch, microcrystalline Cellulose, aluminium hydroxide, boric acid, hydrogenated vegetable oil, Polyethylene Glycol, magnesium stearate, Pulvis Talci, Stepanol MG, sodium lauryl sulphate or the micropowder silica gel or their mixture; Described aromatic and sweeting agent are selected from a kind of in stevioside, essence or the aspartame or their mixture.
The preferential composition of dosmalfate dispersible tablet of the present invention is:
Every comprises dosmalfate 100～1000mg, starch 0～200mg, microcrystalline Cellulose 0～200mg, crospolyvinylpyrrolidone 2～200mg, cross-linking sodium carboxymethyl cellulose 0～200mg, low replacement-hyprolose 0～200mg, micropowder silica gel 0～15mg, magnesium stearate 0.1～20mg, sodium lauryl sulphate 0～15mg, stevioside 0～15mg.
Preparation method of the present invention comprises the step of following order:
1. take by weighing dosmalfate, starch, microcrystalline Cellulose, partial cross-linked polyvinylpyrrolidone, partial cross-linked sodium carboxymethyl cellulose, the low replacement-hyprolose of part, mix homogeneously;
2. Dropwise 5 % polyvinylpyrrolidone K30 ethanol liquid system soft material is crossed 18～24 mesh sieves and is granulated;
3. wet granular carries out drying under 50～80 ℃ of conditions;
4. with 18～24 mesh sieve granulate, add the residue crospolyvinylpyrrolidone, residue cross-linking sodium carboxymethyl cellulose, the low replacement-hyprolose of residue, magnesium stearate and micropowder silica gel mixing, tabletting promptly gets required dosmalfate dispersible tablet.
Dosmalfate dispersible tablet of the present invention is compared with common dosmalfate tablet, has following beneficial effect.
1. have extremely strong disintegrate and dissolving out capability.Rapidly disintegrate after dosmalfate dispersible tablet of the present invention is oral, and homodisperse becomes fine particle, has incomparable disintegrate of ordinary tablet and stripping property ability, better brings into play the gastric mucosal protective effect of this medicine.Below reflect relevant pharmaceutical properties by disintegration and dissolution determination.
(1) the dosmalfate dispersible tablet compares in the disintegrate situation of dosmalfate sheet
The mensuration of dispersing uniformity: get 2 dosmalfate dispersible tablets (medicine is according to the method preparation of embodiment 7) or common dosmalfate sheet (lot number: 030901), place the jolting of 100ml water respectively, under 20 ℃ ± 1 ℃ temperature, all disintegrate was also by No. 2 sieves in 3 minutes, and result of the test sees Table 1.
Table 1, disintegration time mensuration result
| Kind | Disintegration |
| The dosmalfate dispersible tablet | 35 seconds |
| The dosmalfate ordinary tablet | 250 seconds |
(2) dosmalfate dispersible tablet and ordinary tablet stripping situation are relatively
Dosmalfate can not dissolve after the disintegrate in water, because this product is brought into play drug effect under one's belt, adopts simulated gastric fluid 0.1mol/L hydrochloric acid to carry out determination of dissolution rate.According to slurry method (two methods) in two appendix of pharmacopeia, slurry speed adopts 100 rev/mins, and 37 ℃, the 1000ml dissolution fluid.
Get dosmalfate dispersible tablet (medicine is according to the method preparation of embodiment 7) and common dosmalfate sheet (lot number: 030901), under these conditions, respectively at 2,4,6,8,10,15,20,30,45,60 minutes timing spot samplings 5 milliliters of (replenishing same medium simultaneously), 45 μ m filtering with microporous membranes, measure stripping quantity, calculate accumulation stripping percentage rate relatively.Result of the test sees Table 2.
Table 2, dissolution determination result
| Time (min) | ??2 | ??4 | ??6 | ??8 | ??10 | ??15 | ??20 | ??30 | ??45 | ??60 |
| Ordinary tablet | ??3.35 | ??9.96 | ??12.21 | ??16.89 | ??21.09 | ??27.77 | ??50.68 | ??64.01 | ??81.58 | ??92.18 |
| Dispersible tablet | ??74.54 | ??84.45 | ??87.69 | ??89.40 | ??91.32 | ??93.07 | ??95.29 | ??95.41 | ??95.40 | ??95.48 |
Result of the test shows that the dissolution rate of dispersible tablet obviously is better than ordinary tablet.
2. dosmalfate dispersible tablet of the present invention is the rapid uniform tablet of disintegrate in water, forms the long term storage steady quality by medicine and specific disintegrating agent and other adjuvant mixing granulation tabletting.Rapid disintegrate of energy and homodisperse became fine particle after dispersible tablet was oral, had incomparable disintegrate of ordinary tablet and stripping property ability.
3. dispersible tablet of the present invention is that the dosage form of carrying out on the basis of former conventional tablet is improved, and the dosmalfate dispersible tablet is used for the treatment of peptic ulcer.
Description of drawings: (seeing Figure of description)
| Time (min) | ??0 | ???2 | ??4 | ???6 | ???8 | ???10 | ???15 | ???20 | ???30 | ???45 | ??60 |
| Ordinary tablet | ??0 | ???3.35 | ??8.96 | ???12.21 | ???16.89 | ???25.09 | ???37.77 | ???50.68 | ???64.01 | ???81.58 | ??89.18 |
| Dispersible tablet | ??0 | ???74.54 | ??84.5 | ???87.69 | ???89.4 | ???91.32 | ???93.07 | ???95.29 | ???95.41 | ???95.4 | ??95.48 |
Figure is the external stripping curve of dosmalfate dispersible tablet of the present invention and ordinary tablet.
Among the figure: the stripping curve of------dosmalfate ordinary tablet
--------the stripping curve of-----dosmalfate dispersible tablet
The result shows among the figure, and dosmalfate dispersible tablet drug accumulation stripping percentage rate had reached 80% in 4 minutes, and ordinary tablet just reached 80% in 45 minutes, and the dissolution rate that this shows dispersible tablet is apparently higher than ordinary tablet.
● the specific embodiment
By specific embodiment given below, can further be well understood to the present invention, but they not limitation of the invention.
Embodiment 1
Take by weighing dosmalfate 100g, pregelatinized Starch 20g, microcrystalline Cellulose 40g, crospolyvinylpyrrolidone 20g, mix homogeneously; Dropwise 5 %PVPK30 ethanol liquid system soft material is crossed 18～30 mesh sieves and is granulated, and wet grain carries out drying under 50～80 ℃ of conditions, with 18～30 mesh sieve granulate, adds magnesium stearate 3g and micropowder silica gel 1g mixing, and tabletting is made 1000 flake products.
Embodiment 2
Take by weighing dosmalfate 100g, microcrystalline Cellulose 20g, crospolyvinylpyrrolidone 10g, low replacement-hyprolose 10g, mix homogeneously; Dropwise 5 %PVPK30 ethanol liquid system soft material is crossed 18～30 mesh sieves and is granulated, and wet grain carries out drying under 50～80 ℃ of conditions, with 18～30 mesh sieve granulate, add crospolyvinylpyrrolidone 10g, low replacement-hyprolose 10g, magnesium stearate 5g mixing, tabletting is made 1000 flake products.
Embodiment 3
Take by weighing dosmalfate 100g, lactose 20g, guar gum 10g, crospolyvinylpyrrolidone 20g, sodium lauryl sulphate 1g, stevioside 2g, mix homogeneously; Dropwise 5 %PVPK30 ethanol liquid system soft material is crossed 18～30 mesh sieves and is granulated, and wet grain carries out drying under 50～80 ℃ of conditions, with 18～30 mesh sieve granulate, adds Pulvis Talci 2g and micropowder silica gel 1g mixing, and tabletting is made 1000 flake products.
Embodiment 4
Take by weighing dosmalfate 250g, pregelatinized Starch 5g, microcrystalline Cellulose 20g, cross-linking sodium carboxymethyl cellulose 20g, mix homogeneously; Dropwise 5 %PVPK30 ethanol liquid system soft material is crossed 18～30 mesh sieves and is granulated, and wet grain carries out drying under 50～80 ℃ of conditions, with 18～30 mesh sieve granulate, adds cross-linking sodium carboxymethyl cellulose 20g, magnesium stearate 5g mixing, and tabletting is made 1000 flake products.
Embodiment 5
Take by weighing dosmalfate 250g, microcrystalline Cellulose 20g, crospolyvinylpyrrolidone 25g, low replacement-hyprolose 20g, essence (Fructus Citri tangerinae) 5g, mix homogeneously; Dropwise 5 %PVPK30 ethanol liquid system soft material is crossed 18～30 mesh sieves and is granulated, and wet grain carries out drying under 50～80 ℃ of conditions, with 18～30 mesh sieve granulate, adds magnesium stearate 3g and micropowder silica gel 1.5g, mixing, and tabletting is made 1000 flake products.
Embodiment 6
Take by weighing dosmalfate 250g, lactose 20g, mannitol 10g, microcrystalline Cellulose 20g, crospolyvinylpyrrolidone 30g, mix homogeneously; Dropwise 5 %PVPK30 ethanol liquid system soft material is crossed 18～30 mesh sieves and is granulated, and wet grain carries out drying under 50～80 ℃ of conditions, with 18～30 mesh sieve granulate, adds crospolyvinylpyrrolidone 20g, magnesium stearate 5g mixing, and tabletting is made 1000 flake products.
Embodiment 7
Take by weighing dosmalfate 500g, microcrystalline Cellulose 20g, crospolyvinylpyrrolidone 30g, mix homogeneously; Dropwise 5 %PVPK30 ethanol liquid system soft material is crossed 18～30 mesh sieves and is granulated, and wet grain carries out drying under 50～80 ℃ of conditions, with 18～30 mesh sieve granulate, add crospolyvinylpyrrolidone 20g, magnesium stearate 3g and micropowder silica gel 2g, mixing, tabletting is made 1000 flake products.
Take by weighing dosmalfate 500g, crospolyvinylpyrrolidone 40g, mix homogeneously; Dropwise 5 %PVPK30 ethanol liquid system soft material is crossed 18～30 mesh sieves and is granulated, and wet grain carries out drying under 50～80 ℃ of conditions, with 18～30 mesh sieve granulate, adds crospolyvinylpyrrolidone 40g, magnesium stearate 5g mixing, and tabletting is made 1000 flake products.
Embodiment 9
Take by weighing dosmalfate 500g, starch 10g, microcrystalline Cellulose 40g, crospolyvinylpyrrolidone 20g, Stepanol MG 3g, stevioside 3g, mix homogeneously; Dropwise 5 %PVPK30 ethanol liquid system soft material is crossed 18～30 mesh sieves and is granulated, and wet grain carries out drying under 50～80 ℃ of conditions, with 18～30 mesh sieve granulate, adds magnesium stearate 5g and micropowder silica gel 1.5g, mixing, and tabletting is made 1000 flake products.
Embodiment 10
Take by weighing dosmalfate 500g, lactose 10g, microcrystalline Cellulose 100g, essence (Fructus Citri tangerinae) 5g, stevioside 3g, mix homogeneously; Dropwise 5 %PVPK30 ethanol liquid system soft material is crossed 18～30 mesh sieves and is granulated, and wet grain carries out drying under 50～80 ℃ of conditions, with 18～30 mesh sieve granulate, adds cross-linking sodium carboxymethyl cellulose 40g, magnesium stearate 5g, and mixing, tabletting is made 1000 flake products.
Embodiment 11
Take by weighing dosmalfate 500g, starch 10g, microcrystalline Cellulose 40g, low replacement-hyprolose 40g, sodium lauryl sulphate 3g, mix homogeneously; Dropwise 5 %PVPK30 ethanol liquid system soft material is crossed 18～30 mesh sieves and is granulated, and wet grain carries out drying under 50～80 ℃ of conditions, with 18～30 mesh sieve granulate, adds Pulvis Talci 2g and micropowder silica gel 2g, mixing, and tabletting is made 1000 flake products.
Embodiment 12
Take by weighing dosmalfate 750g, mannitol 10g, microcrystalline Cellulose 30g, crospolyvinylpyrrolidone 50g, sodium lauryl sulphate 6g, mix homogeneously; Dropwise 5 %PVPK30 ethanol liquid system soft material is crossed 18～30 mesh sieves and is granulated, and wet grain carries out drying under 50～80 ℃ of conditions, with 18～30 mesh sieve granulate, adds magnesium stearate 8g, mixing, and tabletting is made 1000 flake products.
Embodiment 13
Take by weighing dosmalfate 750g, crospolyvinylpyrrolidone 40g, low replacement-hyprolose 40g, sodium lauryl sulphate 6g, stevioside 5g, mix homogeneously; Dropwise 5 %PVPK30 ethanol liquid system soft material is crossed 18～30 mesh sieves and is granulated, and wet grain carries out drying under 50～80 ℃ of conditions, with 18～30 mesh sieve granulate, adds magnesium stearate 5g and micropowder silica gel 2g, mixing, and tabletting is made 1000 flake products.
Embodiment 14
Take by weighing dosmalfate 750g, starch 10g, crospolyvinylpyrrolidone 50g, Herba Xanthii glue 20g, Stepanol MG 3g, stevioside 3g, mix homogeneously; Dropwise 5 %PVPK30 ethanol liquid system soft material is crossed 18～30 mesh sieves and is granulated, and wet grain carries out drying under 50～80 ℃ of conditions, with 18～30 mesh sieve granulate, add crospolyvinylpyrrolidone 50g, magnesium stearate 5g and micropowder silica gel 1.5g, mixing, tabletting is made 1000 flake products.
Embodiment 15
Take by weighing dosmalfate 750g, microcrystalline Cellulose 80g, cross-linking sodium carboxymethyl cellulose 30g, stevioside 6g, mix homogeneously; Dropwise 5 %PVPK30 ethanol liquid system soft material is crossed 18～30 mesh sieves and is granulated, and wet grain carries out drying under 50～80 ℃ of conditions, with 18～30 mesh sieve granulate, add cross-linking sodium carboxymethyl cellulose 30g, magnesium stearate 4g and carboxymethyl starch sodium 3g, mixing, tabletting is made 1000 flake products.
Embodiment 16
Take by weighing dosmalfate 750g, starch 10g, microcrystalline Cellulose 60g, low replacement-hyprolose 60g, sodium lauryl sulphate 5g, mix homogeneously; Dropwise 5 %PVPK30 ethanol liquid system soft material is crossed 18～30 mesh sieves and is granulated, and wet grain carries out drying under 50～80 ℃ of conditions, with 18～30 mesh sieve granulate, adds magnesium stearate 7g, mixing, and tabletting is made 1000 flake products.
Embodiment 17
Take by weighing dosmalfate 1000g, microcrystalline Cellulose 40g, crospolyvinylpyrrolidone 50g, stevioside 6g, mix homogeneously; Dropwise 5 %PVPK30 ethanol liquid system soft material is crossed 18～30 mesh sieves and is granulated, and wet grain carries out drying under 50～80 ℃ of conditions, with 18～30 mesh sieve granulate, add crospolyvinylpyrrolidone 50g, magnesium stearate 6g and micropowder silica gel 2g, mixing, tabletting is made 1000 flake products.
Embodiment 18
Take by weighing dosmalfate 1000g, crospolyvinylpyrrolidone 100g, low replacement-hyprolose 60g, sodium lauryl sulphate 5g, mix homogeneously; Dropwise 5 %PVPK30 ethanol liquid system soft material is crossed 18～30 mesh sieves and is granulated, and wet grain carries out drying under 50～80 ℃ of conditions, with 18～30 mesh sieve granulate, adds magnesium stearate 8g, mixing, and tabletting is made 1000 flake products.
Claims (8)
1. contain dosmalfate (English name: dispersible tablet dosmalfate).
2. dosmalfate dispersible tablet according to claim 1 is characterized in that used dosmalfate can be the salt that any one can be medicinal.
3. according to the dispersible tablet of claim 1, every contains dosmalfate 100～1000mg and pharmaceutic adjuvant, and described pharmaceutic adjuvant comprises filler 0～200mg, binding agent 0～200mg, disintegrating agent or swellability adjuvant 2～300mg, lubricant 0.1～20mg, fluidizer 0.1～15mg, antitack agent 0～15mg, aromatic and sweeting agent 0～15mg.
4. according to the dosmalfate dispersible tablet of claim 3, wherein said described filler is selected from a kind of in starch, dextrin, Icing Sugar, lactose, mannitol or the microcrystalline Cellulose or their mixture: described wetting agent is selected from water or ethanol or their mixture; Described binding agent is selected from a kind of of starch slurry, hydroxypropyl starch, modified starch, pregelatinized Starch, dextrin, Icing Sugar, syrup, microcrystalline Cellulose, cellulose derivative (comprising hydroxypropyl emthylcellulose, methylcellulose, sodium carboxymethyl cellulose, ethyl cellulose), polyvinylpyrrolidone rubber cement, gelatine size or their mixture; Described disintegrating agent or swellability adjuvant are selected from hydroxypropyl starch, modified starch, starch, carboxymethyl starch sodium, microcrystalline Cellulose, cellulose derivative (comprises hydroxypropyl emthylcellulose, methylcellulose, sodium carboxymethyl cellulose, low replacement-hyprolose, cross-linking sodium carboxymethyl cellulose, carboxy-propyl cellulose, carboxymethylcellulose calcium), crospolyvinylpyrrolidone, tween 80, sodium lauryl sulphate, guar gum, Herba Xanthii glue, a kind of in the xanthan gum or their mixture; Described lubricant, fluidizer, antitack agent are selected from a kind of in modified starch, microcrystalline Cellulose, aluminium hydroxide, boric acid, hydrogenated vegetable oil, Polyethylene Glycol, magnesium stearate, Pulvis Talci, Stepanol MG, sodium lauryl sulphate or the micropowder silica gel or their mixture; Described aromatic and sweeting agent are selected from a kind of in stevioside, essence or the aspartame or their mixture.
5. dosmalfate dispersible tablet according to claim 4, every comprises dosmalfate 100～1000mg, starch 0～200mg, microcrystalline Cellulose 0～200mg, low replacement-hyprolose 0～200mg, crospolyvinylpyrrolidone 2～200mg, micropowder silica gel 0～15mg, magnesium stearate 0.1～20mg, sodium lauryl sulphate 0～15mg, stevioside 0～15mg.
6. dosmalfate dispersible tablet preparation method, this method comprises the step of following order:
6.1 take by weighing dosmalfate, starch, microcrystalline Cellulose, partial cross-linked polyvinylpyrrolidone, partial cross-linked sodium carboxymethyl cellulose, the low replacement-hyprolose of part, mix homogeneously;
6.2 Dropwise 5 % polyvinylpyrrolidone K30 ethanol liquid system soft material is crossed 18～24 mesh sieves and is granulated;
6.3 wet granular carries out drying under 50～80 ℃ of conditions;
6.4 with 18～24 mesh sieve granulate, add the residue crospolyvinylpyrrolidone, residue cross-linking sodium carboxymethyl cellulose, the low replacement-hyprolose of residue, magnesium stearate and micropowder silica gel mixing, tabletting promptly gets required dosmalfate dispersible tablet.
7. be 0～100% of recipe quantity according to the described part of claim 6.2.
8. require prepared dosmalfate dispersible tablet according to aforesaid right, be used for digestive tract ulcer clinically.
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2004100270740A CN100372540C (en) | 2004-05-08 | 2004-05-08 | Dosmalfate dispersion tablet and its prepn. method |
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2004100270740A CN100372540C (en) | 2004-05-08 | 2004-05-08 | Dosmalfate dispersion tablet and its prepn. method |
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| CN100372540C CN100372540C (en) | 2008-03-05 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102462669A (en) * | 2010-11-19 | 2012-05-23 | 北大方正集团有限公司 | Troxipide dispersible tablet and preparation method thereof |
| CN106137990A (en) * | 2016-07-29 | 2016-11-23 | 花园药业股份有限公司 | Azithromycin dispersible tablet and preparation technology thereof |
| WO2020224452A1 (en) * | 2019-05-05 | 2020-11-12 | 广州新创忆药物临床研究有限公司 | Compound for regulating body weight imbalance, composition thereof and application thereof |
| WO2021078110A1 (en) * | 2019-10-25 | 2021-04-29 | 广州新创忆药物临床研究有限公司 | Drug combination for preventing or treating irritable bowel syndrome |
-
2004
- 2004-05-08 CN CNB2004100270740A patent/CN100372540C/en not_active Expired - Lifetime
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102462669A (en) * | 2010-11-19 | 2012-05-23 | 北大方正集团有限公司 | Troxipide dispersible tablet and preparation method thereof |
| CN102462669B (en) * | 2010-11-19 | 2013-12-04 | 北大方正集团有限公司 | Troxipide dispersible tablet and preparation method thereof |
| CN106137990A (en) * | 2016-07-29 | 2016-11-23 | 花园药业股份有限公司 | Azithromycin dispersible tablet and preparation technology thereof |
| WO2020224452A1 (en) * | 2019-05-05 | 2020-11-12 | 广州新创忆药物临床研究有限公司 | Compound for regulating body weight imbalance, composition thereof and application thereof |
| WO2021078110A1 (en) * | 2019-10-25 | 2021-04-29 | 广州新创忆药物临床研究有限公司 | Drug combination for preventing or treating irritable bowel syndrome |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100372540C (en) | 2008-03-05 |
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Assignee: XIANGBEI WELMAN PHARMACEUTICAL Co.,Ltd. Assignor: Sun Mingjie|GUANGZHOU WELMAN NEW DRUG R&D Co.,Ltd.|Wang Ting Contract fulfillment period: 2008.11.5 to 2024.5.8 Contract record no.: 2008440000396 Denomination of invention: Dosmalfate dispersion tablet and its prepn. method Granted publication date: 20080305 License type: General permission Record date: 20081124 |
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