CN1228045C - Fast collapsed and fast dissolved preparation for oral cavity and producing method - Google Patents
Fast collapsed and fast dissolved preparation for oral cavity and producing method Download PDFInfo
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- CN1228045C CN1228045C CN 200310107658 CN200310107658A CN1228045C CN 1228045 C CN1228045 C CN 1228045C CN 200310107658 CN200310107658 CN 200310107658 CN 200310107658 A CN200310107658 A CN 200310107658A CN 1228045 C CN1228045 C CN 1228045C
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- Prior art keywords
- levalbuterol
- mannitol
- lactose
- eudragit
- preparation
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- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- 238000000034 method Methods 0.000 title claims abstract description 12
- 210000000214 mouth Anatomy 0.000 title abstract description 7
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 32
- 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 abstract description 25
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims abstract description 25
- 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 abstract description 25
- 229930195725 Mannitol Natural products 0.000 claims abstract description 25
- 239000008101 lactose Substances 0.000 claims abstract description 25
- 239000000594 mannitol Substances 0.000 claims abstract description 25
- 235000010355 mannitol Nutrition 0.000 claims abstract description 25
- 229920003149 Eudragit® E 100 Polymers 0.000 claims abstract description 24
- NEDGUIRITORSKL-UHFFFAOYSA-N butyl 2-methylprop-2-enoate;2-(dimethylamino)ethyl 2-methylprop-2-enoate;methyl 2-methylprop-2-enoate Chemical compound COC(=O)C(C)=C.CCCCOC(=O)C(C)=C.CN(C)CCOC(=O)C(C)=C NEDGUIRITORSKL-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000003814 drug Substances 0.000 claims abstract description 20
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 16
- 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 abstract description 14
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229960002052 salbutamol Drugs 0.000 claims abstract description 13
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims abstract description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims abstract description 5
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 52
- 239000008187 granular material Substances 0.000 claims description 47
- 238000002156 mixing Methods 0.000 claims description 33
- 229950008204 levosalbutamol Drugs 0.000 claims description 31
- 238000003756 stirring Methods 0.000 claims description 31
- NDAUXUAQIAJITI-LBPRGKRZSA-N (R)-salbutamol Chemical compound CC(C)(C)NC[C@H](O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-LBPRGKRZSA-N 0.000 claims description 29
- 239000000203 mixture Substances 0.000 claims description 27
- 229910001220 stainless steel Inorganic materials 0.000 claims description 22
- 239000010935 stainless steel Substances 0.000 claims description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 15
- 206010013786 Dry skin Diseases 0.000 claims description 11
- 239000011248 coating agent Substances 0.000 claims description 11
- 238000000576 coating method Methods 0.000 claims description 11
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 11
- 239000012153 distilled water Substances 0.000 claims description 11
- 238000001035 drying Methods 0.000 claims description 11
- 229960004756 ethanol Drugs 0.000 claims description 11
- 238000010792 warming Methods 0.000 claims description 11
- BNPSSFBOAGDEEL-UHFFFAOYSA-N albuterol sulfate Chemical compound OS(O)(=O)=O.CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1.CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 BNPSSFBOAGDEEL-UHFFFAOYSA-N 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- OWNWYCOLFIFTLK-YDALLXLXSA-N 4-[(1r)-2-(tert-butylamino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol;hydron;chloride Chemical compound Cl.CC(C)(C)NC[C@H](O)C1=CC=C(O)C(CO)=C1 OWNWYCOLFIFTLK-YDALLXLXSA-N 0.000 claims description 3
- 238000007906 compression Methods 0.000 claims description 3
- 230000006835 compression Effects 0.000 claims description 3
- 229940087642 levalbuterol hydrochloride Drugs 0.000 claims description 3
- 239000007916 tablet composition Substances 0.000 claims description 3
- VNVNZKCCDVFGAP-FPDJQMMJSA-N 4-[(1r)-2-(tert-butylamino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol;(2r,3r)-2,3-dihydroxybutanedioic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.CC(C)(C)NC[C@H](O)C1=CC=C(O)C(CO)=C1.CC(C)(C)NC[C@H](O)C1=CC=C(O)C(CO)=C1 VNVNZKCCDVFGAP-FPDJQMMJSA-N 0.000 claims description 2
- BNPSSFBOAGDEEL-NMFAMCKASA-N 4-[(1r)-2-(tert-butylamino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol;sulfuric acid Chemical compound OS(O)(=O)=O.CC(C)(C)NC[C@H](O)C1=CC=C(O)C(CO)=C1.CC(C)(C)NC[C@H](O)C1=CC=C(O)C(CO)=C1 BNPSSFBOAGDEEL-NMFAMCKASA-N 0.000 claims description 2
- -1 Levalbuterol oxalates Chemical class 0.000 claims description 2
- 229940076884 levalbuterol tartrate Drugs 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract description 7
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 abstract description 7
- 238000005516 engineering process Methods 0.000 abstract description 5
- 239000000463 material Substances 0.000 abstract 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 abstract 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 abstract 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 abstract 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 abstract 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 abstract 1
- 229950005770 hyprolose Drugs 0.000 abstract 1
- 229940057948 magnesium stearate Drugs 0.000 abstract 1
- 229940041616 menthol Drugs 0.000 abstract 1
- 229940095064 tartrate Drugs 0.000 abstract 1
- 235000019441 ethanol Nutrition 0.000 description 10
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 235000019658 bitter taste Nutrition 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000012738 dissolution medium Substances 0.000 description 2
- 238000011978 dissolution method Methods 0.000 description 2
- 238000007922 dissolution test Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- 210000003296 saliva Anatomy 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- OWNWYCOLFIFTLK-UHFFFAOYSA-N 4-[2-(tert-butylamino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol;hydron;chloride Chemical compound Cl.CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 OWNWYCOLFIFTLK-UHFFFAOYSA-N 0.000 description 1
- 230000009748 deglutition Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
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- 231100000017 mucous membrane irritation Toxicity 0.000 description 1
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to the field of medicine preparation, and provides a preparation and a preparation method thereof. The preparation is rapidly disintegrated or dissolved in the oral cavity. The present invention takes Eudragit E-100, lactose, mannitol, low-replaced hyprolose, magnesium stearate and menthol as materials, adopts a wet granulating and tabletting method, and respectively takes salbutamol, salbutamol sulphate, salbutamol, and hydrochloride, sulfate, tartrate, oxalate, citrate, maleate, etc. of salbutamol as medicine. All the materials are made into tablets which are rapidly disintegrated and dissolved in the oral cavity. The present invention does not need particular apparatuses, adopts a common tabletting machine, and has the advantages of simple technology and low cost.
Description
Technical field: the present invention relates to field of medicine preparations, belong to the rapid release drug-supplying system, be oral rapidly disintegrating, rapid-dissolve tablet formulations and preparation method thereof.
Background technology: oral cavity quick disintegrating slice (also being oral instant-dissolving tablet) is a kind of novel dosage form that emerges rapidly in the medicament field in recent years.It has taking convenience, it is fast to absorb, bioavailability is high and to advantages such as the effect of digestive tract mucous membrane irritation are little.Water can not needed when taking, disintegrate rapidly in the 15s in the oral cavity.Though the lyophilization sheet is comparatively ripe in numerous preparation technologies, too high, the complex process of cost is very strict to the requirement of preparation condition, is difficult to be suitable for the reality of domestic pharmacy.At present oral rapidly disintegrating, instant preparation forward cost direction low, that technology is simple, mouthfeel good, quality is high develop.
Summary of the invention: for the cost that solves instant of present production oral rapidly disintegrating too high, complex process, to the very strict problem of the requirement of preparation condition, development and design of the present invention a kind of fast at Orally disintegrating or dissolving preparation and preparation method thereof, medicine is selected from albuterol, salbutamol sulfate, Levalbuterol, Levalbuterol hydrochloride, Levalbuterol sulfate, the Levalbuterol tartrate, the Levalbuterol oxalates, the Levalbuterol citrate, a kind of in the Levalbuterol maleate, with Eudragit E-100, lactose, mannitol, low-substituted hydroxypropyl cellulose, magnesium stearate, Mentholum is a pharmaceutic adjuvant, medicine and Eudragit E-100, lactose, mannitol, low-substituted hydroxypropyl cellulose, magnesium stearate, the proportioning of these pharmaceutic adjuvants of Mentholum is 1: 0.2～1.5: 20～100: 10～60: 1.0～5.0: 0.2～1.0: 0.4～2.0, utilize common tablet machine, by control process parameters, make instant of oral rapidly disintegrating.Its preparation method adopts the wet granule compression tablet method, the first step at first is dissolved in Eudragit E-100 that to make concentration in the dehydrated alcohol be 100mg/ml～300mg/ml, add medicine by proportioning then and stir coating fast, and in 20 ℃～50 ℃ dryings, it is stand-by that porphyrize is crossed 80 mesh sieves, second step crossed 80 mesh sieve mixings with the lactose and the mannitol of proportional quantity, the Mentholum ethanol solution 80mg/ml～120mg/ml that adds proportional quantity stirs, mixing, stand-by in 30 ℃～50 ℃ oven dry, the 3rd step is with the first and second step gains mix homogeneously, adding an amount of distilled water mixes, granulate with 16 mesh sieves, the granule that makes is tiled in stainless steel disc immediately puts into the baking oven baking 20～40 minutes that is warming up to 40 ℃～60 ℃, the 4th step will be dried by the fire good granule and be put to room temperature, behind the granulate, add the low-substituted hydroxypropyl cellulose and the magnesium stearate mixing of proportional quantity, select the suitable low pressure tabletting that dashes for use, with the sheet of being pressed be put in stainless steel disc 30 ℃～50 ℃ down baking promptly got instant of oral rapidly disintegrating in 3-6 hour.The mouthfeel that this oral rapidly disintegrating is instant is good, and disintegration time is at 15-30 between second.
The present invention is Orally disintegrating, solution tablet preparation, and it is main adopting water soluble adjuvant, and said preparation is disintegrate and the most of dissolving of adjuvant rapidly when running into saliva.After the medicine liquefy, with the natural swallowing act of human body, follow the saliva clothes down, need not drink water good mouthfeel, no sand feeling and bitterness sense.This tablet is taken medicine to some function of deglutition patient bad and water intaking inconvenience convenience is provided.Adopt the wet granule compression tablet method, utilize common tablet machine, the simple cost of technology is low, has vast market prospect.
Description of drawings:
Fig. 1 is a dissolution comparison diagram in instant of Levalbuterol oral rapidly disintegrating and the Levalbuterol ordinary tablet water;
Fig. 2 is a dissolution comparison diagram in instant of Levalbuterol oral rapidly disintegrating and the Levalbuterol ordinary tablet hydrochloric acid.
The specific embodiment:
Embodiment 1: the preparation that the Levalbuterol oral rapidly disintegrating is instant
Get Levalbuterol 1.25g, Eudragit E-100 0.5g, earlier Eudragit E-100 is dissolved in that to make concentration in the dehydrated alcohol be 100mg/ml～300mg/ml, add Levalbuterol then and stir coating fast, and in 40 ℃ of dryings, it is stand-by that porphyrize is crossed 80 mesh sieves, second step: get lactose 29.6g, mannitol 35.8g crosses 80 mesh sieve mixings; get Mentholum 1.0g; add 10ml absolute ethyl alcohol and stirring dissolving; the ethanol solution 100mg/ml of Mentholum is joined in the mixture of lactose and mannitol and stir; mixing, and is stand-by in 40 ℃ of oven dry, the 3rd step: with the first and second step gains mix homogeneously; add an amount of distilled water and mix; granulate with 16 mesh sieves, the granule that makes is tiled in stainless steel disc immediately puts into the baking oven baking 30 minutes that is warming up to 50 ℃, the 4th step: will dry by the fire granule well and put to room temperature; behind the granulate, adding 2.5g low-substituted hydroxypropyl cellulose and 0.5g magnesium stearate mixing.Select for use 6.0mm towards the low pressure tabletting, the sheet of being pressed is put in stainless steel disc dries by the fire 4 hours down promptly at 50 ℃.
Through the volunteer oral test, disintegration time is between the 15-30S in the oral cavity, and mouthfeel does not have bitterness well.Pharmacopeia disintegration inspection method improved method: (2000 editions two appendix XA of Chinese Pharmacopoeia) do not add jolting, survey its disintegration time between 15-25 S.
Get instant of Levalbuterol oral rapidly disintegrating, press dissolution method (2000 editions two appendix XC three therapeutic methods of traditional Chinese medicine of Chinese Pharmacopoeia), be dissolution medium with water, hydrochloric acid 0.1mol/l solution 100ml respectively, 100 rev/mins of rotating speeds, measure the drug release situation by medicine intelligence dissolution test instrument (Radio Factory of Tianjin Univ.'s product), the results are shown in Figure 1, Fig. 2, show that instant of Levalbuterol oral rapidly disintegrating compares with ordinary tablet and have tangible rapid release characteristic, can discharge at stomach, intestinal rapidly after medicine enters in the body and produce drug effect.
Embodiment 2: the preparation that the albuterol oral rapidly disintegrating is instant
Get albuterol 2.4g, Eudragit E-100 1.2g, earlier EudragitE-100 is dissolved in that to make concentration in the dehydrated alcohol be 100mg/ml～300mg/ml, add albuterol then and stir coating fast, and in 40 ℃ of dryings, it is stand-by that porphyrize is crossed 80 mesh sieves, second step: get lactose 44.5g, mannitol 30.8g crosses 80 mesh sieve mixings, gets Mentholum 1.2g, adds the dissolving of 10ml absolute ethyl alcohol and stirring.The ethanol solution (100mg/ml) of Mentholum is joined in the mixture of lactose and mannitol stir, mixing, stand-by in 40 ℃ of oven dry, the 3rd step: with the first and second step gains mix homogeneously, adding an amount of distilled water mixes, granulate with 16 mesh sieves, the granule that makes is tiled in stainless steel disc immediately puts into the baking oven baking 30 minutes that is warming up to 50 ℃, the 4th step: will dry by the fire good granule and put to room temperature, behind the granulate, add 3.8g low-substituted hydroxypropyl cellulose and 0.7g magnesium stearate mixing.Select for use 6.0mm towards the low pressure tabletting, the sheet of being pressed is put in stainless steel disc dries by the fire 4 hours down promptly at 50 ℃.
Through the volunteer oral test, disintegration time is between the 15-30S in the oral cavity, and mouthfeel does not have bitterness well.Pharmacopeia disintegration inspection method improved method: (2000 editions two appendix XA of Chinese Pharmacopoeia) do not add jolting, survey its disintegration time between 15-25 S.
Get instant of albuterol oral rapidly disintegrating, press dissolution method (2000 editions two appendix XC three therapeutic methods of traditional Chinese medicine of Chinese Pharmacopoeia), be dissolution medium with water, hydrochloric acid 0.1mol/l solution 100ml respectively, 100 rev/mins of rotating speeds, measure the drug release situation by medicine intelligence dissolution test instrument (Radio Factory of Tianjin Univ.'s product), the result shows that instant of albuterol oral rapidly disintegrating compares with ordinary tablet and have tangible rapid release characteristic, can discharge at stomach, intestinal rapidly after medicine enters in the body to produce drug effect.
Embodiment 3: Levalbuterol hydrochloride orally collapses instant preparation
Get albuterol hydrochloride 1.25g, Eudragit E-100 0.5g, earlier Eudragit E-100 is dissolved in that to make concentration in the dehydrated alcohol be 100mg/ml～300mg/ml, add Levalbuterol then and stir coating fast, and in 40 ℃ of dryings, it is stand-by that porphyrize is crossed 80 mesh sieves, second step: get lactose 29.6g, mannitol 35.8g crosses 80 mesh sieve mixings; get Mentholum 1.0g; add 10ml absolute ethyl alcohol and stirring dissolving; the ethanol solution 100mg/ml of Mentholum is joined in the mixture of lactose and mannitol and stir; mixing, and is stand-by in 40 ℃ of oven dry, the 3rd step: with the first and second step gains mix homogeneously; add an amount of distilled water and mix; granulate with 16 mesh sieves, the granule that makes is tiled in stainless steel disc immediately puts into the baking oven baking 30 minutes that is warming up to 50 ℃, the 4th step: will dry by the fire granule well and put to room temperature; behind the granulate, adding 2.5g low-substituted hydroxypropyl cellulose and 0.5g magnesium stearate mixing.Select for use 6.0mm towards the low pressure tabletting, the sheet of being pressed is put in stainless steel disc dries by the fire 4 hours down promptly at 50 ℃.
Embodiment 4: the preparation that sulphuric acid Levalbuterol oral rapidly disintegrating is instant
Get sulphuric acid Levalbuterol 1.25g, Eudragit E-100 0.5g, earlier Eudragit E-100 is dissolved in that to make concentration in the dehydrated alcohol be 100mg/ml～300mg/ml, add Levalbuterol then and stir coating fast, and in 40 ℃ of dryings, it is stand-by that porphyrize is crossed 80 mesh sieves, second step: get lactose 29.6g, mannitol 35.8g crosses 80 mesh sieve mixings; get Mentholum 1.0g; add 10ml absolute ethyl alcohol and stirring dissolving; the ethanol solution 100mg/ml of Mentholum is joined in the mixture of lactose and mannitol and stir; mixing, and is stand-by in 40 ℃ of oven dry, the 3rd step: with the first and second step gains mix homogeneously; add an amount of distilled water and mix; granulate with 16 mesh sieves, the granule that makes is tiled in stainless steel disc immediately puts into the baking oven baking 30 minutes that is warming up to 50 ℃, the 4th step: will dry by the fire granule well and put to room temperature; behind the granulate, adding 2.5g low-substituted hydroxypropyl cellulose and 0.5g magnesium stearate mixing.Select for use 6.0mm towards the low pressure tabletting, the sheet of being pressed is put in stainless steel disc dries by the fire 4 hours down promptly at 50 ℃.
Embodiment 5: the preparation that tartaric acid Levalbuterol oral rapidly disintegrating is instant
Get tartaric acid Levalbuterol 1.25g, Eudragit E-100 0.5g, earlier Eudragit E-100 is dissolved in that to make concentration in the dehydrated alcohol be 100mg/ml～300mg/ml, add Levalbuterol then and stir coating fast, and in 40 ℃ of dryings, it is stand-by that porphyrize is crossed 80 mesh sieves, second step: get lactose 29.6g, mannitol 35.8g crosses 80 mesh sieve mixings; get Mentholum 1.0g; add 10ml absolute ethyl alcohol and stirring dissolving; the ethanol solution 100mg/ml of Mentholum is joined in the mixture of lactose and mannitol and stir; mixing, and is stand-by in 40 ℃ of oven dry, the 3rd step: with the first and second step gains mix homogeneously; add an amount of distilled water and mix; granulate with 16 mesh sieves, the granule that makes is tiled in stainless steel disc immediately puts into the baking oven baking 30 minutes that is warming up to 50 ℃, the 4th step: will dry by the fire granule well and put to room temperature; behind the granulate, adding 2.5g low-substituted hydroxypropyl cellulose and 0.5g magnesium stearate mixing.Select for use 6.0mm towards the low pressure tabletting, the sheet of being pressed is put in stainless steel disc dries by the fire 4 hours down promptly at 50 ℃.
Embodiment 6: the preparation that oxalic acid Levalbuterol oral rapidly disintegrating is instant
Get oxalic acid Levalbuterol 1.25g, Eudragit E-100 0.5g, earlier Eudragit E-100 is dissolved in that to make concentration in the dehydrated alcohol be 100mg/ml～300mg/ml, add Levalbuterol then and stir coating fast, and in 40 ℃ of dryings, it is stand-by that porphyrize is crossed 80 mesh sieves, second step: get lactose 29.6g, mannitol 35.8g crosses 80 mesh sieve mixings; get Mentholum 1.0g; add 10ml absolute ethyl alcohol and stirring dissolving; the ethanol solution 100mg/ml of Mentholum is joined in the mixture of lactose and mannitol and stir; mixing, and is stand-by in 40 ℃ of oven dry, the 3rd step: with the first and second step gains mix homogeneously; add an amount of distilled water and mix; granulate with 16 mesh sieves, the granule that makes is tiled in stainless steel disc immediately puts into the baking oven baking 30 minutes that is warming up to 50 ℃, the 4th step: will dry by the fire granule well and put to room temperature; behind the granulate, adding 2.5g low-substituted hydroxypropyl cellulose and 0.5g magnesium stearate mixing.Select for use 6.0mm towards the low pressure tabletting, the sheet of being pressed is put in stainless steel disc dries by the fire 4 hours down promptly at 50 ℃.
Embodiment 7: the preparation that citric acid Levalbuterol oral rapidly disintegrating is instant
Get citric acid Levalbuterol 1.25g, Eudragit E-100 0.5g, earlier Eudragit E-100 is dissolved in that to make concentration in the dehydrated alcohol be 100mg/ml～300mg/ml, add Levalbuterol then and stir coating fast, and in 40 ℃ of dryings, it is stand-by that porphyrize is crossed 80 mesh sieves, second step: get lactose 29.6g, mannitol 35.8g crosses 80 mesh sieve mixings; get Mentholum 1.0g; add 10ml absolute ethyl alcohol and stirring dissolving; the ethanol solution 100mg/ml of Mentholum is joined in the mixture of lactose and mannitol and stir; mixing, and is stand-by in 40 ℃ of oven dry, the 3rd step: with the first and second step gains mix homogeneously; add an amount of distilled water and mix; granulate with 16 mesh sieves, the granule that makes is tiled in stainless steel disc immediately puts into the baking oven baking 30 minutes that is warming up to 50 ℃, the 4th step: will dry by the fire granule well and put to room temperature; behind the granulate, adding 2.5g low-substituted hydroxypropyl cellulose and 0.5g magnesium stearate mixing.Select for use 6.0mm towards the low pressure tabletting, the sheet of being pressed is put in stainless steel disc dries by the fire 4 hours down promptly at 50 ℃.
Embodiment 8: the preparation that maleic acid levo albuterol oral rapidly disintegrating is instant
Get maleic acid levo albuterol 1.25g, Eudragit E-100 0.5g, earlier Eudragit E-100 is dissolved in that to make concentration in the dehydrated alcohol be 100mg/ml～300mg/ml, add Levalbuterol then and stir coating fast, and in 40 ℃ of dryings, it is stand-by that porphyrize is crossed 80 mesh sieves, second step: get lactose 29.6g, mannitol 35.8g crosses 80 mesh sieve mixings; get Mentholum 1.0g; add 10ml absolute ethyl alcohol and stirring dissolving; the ethanol solution 100mg/ml of Mentholum is joined in the mixture of lactose and mannitol and stir; mixing, and is stand-by in 40 ℃ of oven dry, the 3rd step: with the first and second step gains mix homogeneously; add an amount of distilled water and mix; granulate with 16 mesh sieves, the granule that makes is tiled in stainless steel disc immediately puts into the baking oven baking 30 minutes that is warming up to 50 ℃, the 4th step: will dry by the fire granule well and put to room temperature; behind the granulate, adding 2.5g low-substituted hydroxypropyl cellulose and 0.5g magnesium stearate mixing.Select for use 6.0mm towards the low pressure tabletting, the sheet of being pressed is put in stainless steel disc dries by the fire 4 hours down promptly at 50 ℃.
Embodiment 9: the preparation that the salbutamol sulfate oral rapidly disintegrating is instant
Get salbutamol sulfate 2.4g, Eudragit E-100 1.2g, earlier Eudragit E-100 is dissolved in that to make concentration in the dehydrated alcohol be 100mg/ml～300mg/ml, add albuterol then and stir coating fast, and in 40 ℃ of dryings, it is stand-by that porphyrize is crossed 80 mesh sieves, second step: get lactose 44.5g, mannitol 30.8g crosses 80 mesh sieve mixings, gets Mentholum 1.2g, adds the dissolving of 10ml absolute ethyl alcohol and stirring.The ethanol solution 100mg/ml of Mentholum is joined in the mixture of lactose and mannitol stir, mixing, stand-by in 40 ℃ of oven dry, the 3rd step: with the first and second step gains mix homogeneously, adding an amount of distilled water mixes, granulate with 16 mesh sieves, the granule that makes is tiled in stainless steel disc immediately puts into the baking oven baking 30 minutes that is warming up to 50 ℃, the 4th step: will dry by the fire the granule of getting well and put to room temperature, behind the granulate, add 3.8g low-substituted hydroxypropyl cellulose and 0.7g magnesium stearate mixing.Select for use 6.0mm towards the low pressure tabletting, the sheet of being pressed is put in stainless steel disc dries by the fire 4 hours down promptly at 50 ℃.
Claims (1)
1. oral rapidly disintegrating rapid-dissolve tablet formulations, medicine is selected from albuterol, salbutamol sulfate, Levalbuterol, Levalbuterol hydrochloride, Levalbuterol sulfate, the Levalbuterol tartrate, the Levalbuterol oxalates, the Levalbuterol citrate, a kind of in the Levalbuterol maleate, with Eudragit E-100, lactose, mannitol, low-substituted hydroxypropyl cellulose, magnesium stearate, Mentholum is a pharmaceutic adjuvant, it is characterized in that: medicine and Eudragit E-100, lactose, mannitol, low-substituted hydroxypropyl cellulose, magnesium stearate, the proportioning of these pharmaceutic adjuvants of Mentholum is 1: 0.2～1.5: 20～100: 10～60: 1.0～5.0: 0.2～1.0: 0.4～2.0, preparation method adopts the wet granule compression tablet method, the first step at first is dissolved in Eudragit E-100 that to make concentration in the dehydrated alcohol be 100mg/ml～300mg/ml, add medicine by proportioning then and stir coating fast, and in 20 ℃～50 ℃ dryings, it is stand-by that porphyrize is crossed 80 mesh sieves, second step crossed 80 mesh sieve mixings with the lactose and the mannitol of proportional quantity, the Mentholum ethanol solution 80mg/ml～120mg/ml that adds proportional quantity stirs, mixing, stand-by in 30 ℃～50 ℃ oven dry, the 3rd step is with the first and second step gains mix homogeneously, adding an amount of distilled water mixes, granulate with 16 mesh sieves, the granule that makes is tiled in stainless steel disc immediately puts into the baking oven baking 20～40 minutes that is warming up to 40 ℃～60 ℃, the 4th step will be dried by the fire good granule and be put to room temperature, behind the granulate, the low-substituted hydroxypropyl cellulose and the magnesium stearate mixing that add proportional quantity, select the suitable low pressure tabletting that dashes for use, with the sheet of being pressed be put in stainless steel disc 30 ℃～50 ℃ down baking promptly got instant of oral rapidly disintegrating in 3-6 hour.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200310107658 CN1228045C (en) | 2003-11-03 | 2003-11-03 | Fast collapsed and fast dissolved preparation for oral cavity and producing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200310107658 CN1228045C (en) | 2003-11-03 | 2003-11-03 | Fast collapsed and fast dissolved preparation for oral cavity and producing method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1539408A CN1539408A (en) | 2004-10-27 |
| CN1228045C true CN1228045C (en) | 2005-11-23 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200310107658 Expired - Fee Related CN1228045C (en) | 2003-11-03 | 2003-11-03 | Fast collapsed and fast dissolved preparation for oral cavity and producing method |
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| Country | Link |
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| CN (1) | CN1228045C (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007020204A2 (en) * | 2005-08-12 | 2007-02-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Hfc solution formulations for inhalation containing salbutamol hydrochloride or salbutamol citrate |
| CN107137367A (en) * | 2017-04-01 | 2017-09-08 | 重庆康刻尔制药有限公司 | Salbutamol sulfate oral disnitegration tablet and preparation method thereof |
| CN115645374B (en) * | 2022-12-25 | 2024-04-26 | 山东理工职业学院 | Preparation method of salbutamol sulfate tablet |
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2003
- 2003-11-03 CN CN 200310107658 patent/CN1228045C/en not_active Expired - Fee Related
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| CN1539408A (en) | 2004-10-27 |
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