CN102784126A - Rifampicin composition freeze-dried orally disintegrating tablet and preparation method thereof - Google Patents
Rifampicin composition freeze-dried orally disintegrating tablet and preparation method thereof Download PDFInfo
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- CN102784126A CN102784126A CN2012103025158A CN201210302515A CN102784126A CN 102784126 A CN102784126 A CN 102784126A CN 2012103025158 A CN2012103025158 A CN 2012103025158A CN 201210302515 A CN201210302515 A CN 201210302515A CN 102784126 A CN102784126 A CN 102784126A
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- rifampicin
- oral cavity
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- disintegration tablet
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- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 title claims abstract description 73
- 229960001225 rifampicin Drugs 0.000 title claims abstract description 73
- 239000000203 mixture Substances 0.000 title claims abstract description 65
- 238000002360 preparation method Methods 0.000 title claims abstract description 34
- 239000006191 orally-disintegrating tablet Substances 0.000 title abstract description 6
- 239000003814 drug Substances 0.000 claims abstract description 51
- 229940079593 drug Drugs 0.000 claims abstract description 23
- 239000004376 Sucralose Substances 0.000 claims abstract description 12
- 235000019408 sucralose Nutrition 0.000 claims abstract description 12
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims abstract description 12
- 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 7
- 108010010803 Gelatin Proteins 0.000 claims abstract description 7
- 229930195725 Mannitol Natural products 0.000 claims abstract description 7
- 229920000159 gelatin Polymers 0.000 claims abstract description 7
- 239000008273 gelatin Substances 0.000 claims abstract description 7
- 235000019322 gelatine Nutrition 0.000 claims abstract description 7
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract description 7
- 239000000594 mannitol Substances 0.000 claims abstract description 7
- 235000010355 mannitol Nutrition 0.000 claims abstract description 7
- 238000004108 freeze drying Methods 0.000 claims description 56
- 210000000214 mouth Anatomy 0.000 claims description 50
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 41
- 239000000243 solution Substances 0.000 claims description 35
- 238000003756 stirring Methods 0.000 claims description 20
- 239000008215 water for injection Substances 0.000 claims description 16
- 239000007788 liquid Substances 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 10
- 238000011068 loading method Methods 0.000 claims description 10
- 230000008014 freezing Effects 0.000 claims description 8
- 238000007710 freezing Methods 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 6
- 238000012856 packing Methods 0.000 claims description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 5
- 239000004615 ingredient Substances 0.000 claims description 4
- 238000010579 first pass effect Methods 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 8
- 238000010521 absorption reaction Methods 0.000 abstract description 6
- 230000008901 benefit Effects 0.000 abstract description 4
- 210000004185 liver Anatomy 0.000 abstract description 4
- 235000019640 taste Nutrition 0.000 abstract description 3
- ZQXSFZAMFNRZOQ-UHFFFAOYSA-N 2-methylpropan-2-ol;hydrate Chemical compound O.CC(C)(C)O ZQXSFZAMFNRZOQ-UHFFFAOYSA-N 0.000 abstract 1
- 239000003826 tablet Substances 0.000 description 42
- 238000005516 engineering process Methods 0.000 description 6
- 239000006184 cosolvent Substances 0.000 description 5
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000019634 flavors Nutrition 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000019505 Deglutition disease Diseases 0.000 description 2
- 241000194017 Streptococcus Species 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
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- 238000002425 crystallisation Methods 0.000 description 2
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- 208000002925 dental caries Diseases 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000004744 fabric Substances 0.000 description 2
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- 210000003296 saliva Anatomy 0.000 description 2
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- 108010011485 Aspartame Proteins 0.000 description 1
- 241000193738 Bacillus anthracis Species 0.000 description 1
- 241000193468 Clostridium perfringens Species 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 241000194033 Enterococcus Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000186781 Listeria Species 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- 241000186362 Mycobacterium leprae Species 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 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 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 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 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
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- 230000000052 comparative effect Effects 0.000 description 1
- 229940109275 cyclamate Drugs 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
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- 230000036267 drug metabolism Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
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- 230000002496 gastric effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
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- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
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- 229910001220 stainless steel Inorganic materials 0.000 description 1
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- 238000004659 sterilization and disinfection Methods 0.000 description 1
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- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The invention provides a rifampicin composition freeze-dried orally disintegrating tablet and a preparation method thereof, relates to the technical field of medicines and medicine preparation methods, and mainly solves the problem that a common rifampicin preparation is excessive in first-pass effect and strong in side effect after repeated administration, and is difficultly swallowed by old people and children. The rifampicin composition freeze-dried orally disintegrating tablet is prepared from components including, by weight, 30%-60% of rifampicin, 25%-70% of mannitol, 2%-4% of gelatin, 0.1%-0.15% of sucralose and 50%-70% of tert-butanol-water. The rifampicin composition freeze-dried orally disintegrating tablet prepared from the components according to the weight percent is simple in preparation process and composition, mainly aims to meet the administration requirements of the children, and has the advantages of rapidness in disintegration and effectiveness, sufficiency in medicine absorption, convenience in taking, fine taste and avoidance of the first-pass effect of livers.
Description
Technical field:
The present invention relates to the method for preparing technical field of medicine and medicine, relate in particular to a kind of rifampicin composition freeze-drying oral cavity disintegration tablet and preparation method thereof.
Background technology:
Rifampicin is scarlet or the kermesinus crystalline powder; Odorless, tasteless.In chloroform, be prone to dissolve, in methanol, the tert-butyl alcohol, dissolve, almost insoluble in water.The pH value of its 1% aqueous suspension is 4 ~ 6.5.Chance light is perishable, and aqueous solution is prone to oxidational losses and tires.Rifampicin all has the obvious sterilization effect to mycobacterium tuberculosis and part non-tuberculous mycobacteria (comprising Mycobacterium leprae etc.) inside and outside host cell.Rifampicin comprises staphylococcus product enzyme strain and methicillin resistance strain, streptococcus pneumoniae, other Streptococcus, Enterococcus, listeria, anthrax bacillus, bacillus perfringens, diphtheria corynebacterium, anaerobic cocci etc. to the good antibacterial action of aerobic gram positive bacteria tool.Its oral absorption can reach 90% ~ 95%, reaches the peak in 1-2 hour blood drug level.These article are prone to infiltrate in body tissue, the body fluid (comprising cerebrospinal fluid).Behind the oral common dose, major metabolite still has antibacterial activity.Drug disposition is many to be drained in bile, and about 1/3 medicine is by homaluria, and urine Chinese medicine concentration can reach treatment level, and t1/2 is 2-5 hour.These article are by enzymatic catalysis, and after the medication, drug metabolism (comprising first pass effect) is strengthened repeatedly, and after 2 weeks, t1/2 shortens to 2 hours.
The structure of rifampicin is following:
The characteristics of oral cavity disintegration tablet:
1, absorption is fast, bioavailability is high.Oral cavity disintegration tablet can influence the rate of dissolution of medicine, particularly to the influence of insoluble medicine rate of dissolution, can improve bioavailability of medicament so process oral cavity disintegration tablet.
2, taking convenience.Oral cavity disintegration tablet needn't be used water delivery service, and saliva can make its disintegrate or dissolving, both can swallow by common dose, can be placed in the water again to take after the disintegrate, can also not need to take medicine with water swallow, is particularly useful for the patient of old man, children's's dysphagia and the inconvenient person that fetches water.If adopt certain method to improve the mouthfeel of preparation in the preparation, then can improve the drug compliance of child patient greatly, solve the problem that it is difficult that infant is taken medicine.
3, reduce side effect.The rapid disintegrate of oral cavity disintegration tablet ability before medicine arrives gastrointestinal tract also is dispersed into trickle granule, causes medicine to distribute in the gastrointestinal tract large tracts of land, and absorption point increases, thereby has reduced medicine to the gastrointestinal local excitation.
4, avoid first pass effect.Because oral cavity disintegration tablet is rapidly disintegrate in the oral cavity, except that major part gets into the gastrointestinal tract with swallowing act, also have the considerable part trans-oral to lick film and absorb, thereby rapid-action, first pass effect is little.
The dosage form of listing is mainly conventional tablet, eye drop, capsule, injection at present.
The present invention is directed to the characteristics that first pass effect is big, side effect reaches old man, child's dysphagia by force behind the rifampicin general formulation repetitively administered, develop a kind of new rifampicin composition freeze-drying oral cavity disintegration tablet; To children's, old man's drug compliance, add novel correctives sucralose, its stability is strong, and it is respond well to rectify flavor; Long to traditional disintegration time of orally disintegrating tablets on the market, bioavailability is low, develops a kind of new Orally disintegrating piece preparation method; To the rifampicin slightly water-soluble, provide a kind of tertiary butanol and water cosolvent as the solvent in the lyophilizing preparation.Given this, the present invention is proposed.
Summary of the invention:
Technical problem to be solved by this invention is to overcome the defective of prior art, provides a kind of composition simple, easily manufactured, rapid-action rifampicin compositions and contain rifampicin composition freeze-drying oral cavity disintegration tablet that above-mentioned composition processes and preparation method thereof.
Technical problem to be solved by this invention adopts following technical scheme to realize.
A kind of rifampicin compositions, the prescription of said composition is made up of principal agent and accessory drugs, it is characterized in that: principal agent is a rifampicin, accessory drugs be chosen as skeleton agent (mannitol), forming agent (gelatin), correctives (sucralose).
A kind of rifampicin compositions is characterized in that, said composition comprises following component and component quantity ratio:
The preferred ingredient quantity ratio of said each component of rifampicin compositions is:
Another object of the present invention provides a kind of rifampicin composition freeze-drying oral cavity disintegration tablet that contains above-mentioned rifampicin compositions.This freeze-dry orally disintegrating tablet component is simple, need not water when taking, and need not to chew, and disintegration time was no more than for 2 seconds in human oral cavity; Rapid-action, intestinal is residual few, and liver first-pass effect is little, absorbs fully; Side effect is low, and mouthfeel is good, is particularly suitable for the infant patient and takes.
A kind of rifampicin composition freeze-drying oral cavity disintegration tablet that contains above-mentioned rifampicin compositions is characterized in that, is prepared from following component and component quantity ratio:
The preferred ingredient quantity ratio of each component of preparation rifampicin composition freeze-drying oral cavity disintegration tablet is:
A further object of the present invention provides a kind of method for preparing of rifampicin composition freeze-drying oral cavity disintegration tablet; This method for preparing with the tertiary butanol and water cosolvent as solvent; Can accelerate the distillation cycle of medicine, shorten lyophilization cycle, increase the rifampicin dissolving; Strengthen medicine stability, promote the crystallization of medicine.
For realizing a further object of the present invention, a kind of method for preparing of rifampicin composition freeze-drying oral cavity disintegration tablet is provided, adopt following technical scheme:
A) rifampicin with recipe quantity is dissolved in the tert-butyl alcohol of recipe quantity, and stirring and dissolving continues to stir at normal temperatures, preparation solution a;
B) mannitol, the sucralose with recipe quantity is dissolved in the water for injection of prescription with water for injection total amount 70%-80%, preparation solution b;
C) again the gelatin of recipe quantity is dissolved in the water for injection of prescription water consumption 20%-30%, is heated to dissolving fully, preparation solution c;
D) merge above-mentioned b, two kinds of solution of c become solution d, and stir, mixed then solution is cooled to below 5 ℃;
E) mix a, two kinds of solution of d, and stir, regulate pH value to 4 ~ 6.5 with sodium bicarbonate;
F) according to rifampicin composition freeze-drying oral cavity disintegration tablet specification; After confirming loading amount, the medicinal liquid after merging is moved in the drug-containing dish by loading amount, and put into freeze drying box; Medicinal liquid is carried out freezing (cryogenic temperature is-20 ℃--50 ℃); Evacuation dry (baking temperature is at+0 ℃-+5 ℃, vacuum be-more than the 0.09MPa) is controlled moisture and is no more than 1.0%;
G) treat rifampicin composition freeze-drying oral cavity disintegration tablet drying after, in freeze drying box, seal;
H) cut drug-containing dish after the medicament that freezes is taken out freeze drying box, and carry out finished product packing.
Said rifampicin composition freeze-drying oral cavity disintegration tablet specification is 150mg/ sheet, 300mg/ sheet.
We have formulated relevant detection method to the disintegration rate of rifampicin composition freeze-drying oral cavity disintegration tablet:
Disintegration
According to inspection technique disintegration (two appendix ⅹ of Chinese Pharmacopoeia version in 2010 A); The stainless steel shaft of hanging basket through the upper end hung on the metal rack; Immerse in the 1000ml beaker; And screen cloth fills temperature and is 37 ℃ ± 1 ℃ water apart from beaker bottom 25mm in the beaker when regulating the hanging basket position it being descended, when regulating height of water level hanging basket being risen screen cloth in the underwater 15mm place.
Except as otherwise herein provided, get 4 groups of test samples (every group of dosage is 600mg), put respectively in the glass tubing of above-mentioned hanging basket, add baffle plate, start disintegration tester and check, each sheet all should all disintegrates in 1.2 seconds.Result such as following table:
Dosage equates, the disintegration time and the medicine of different rifampicin tablets reach peak concentration
As stated above to rifampicin composition freeze-drying oral cavity disintegration tablet of the present invention and rifampicin ordinary tablet comparative determination; The present invention is up to specification; The rifampicin ordinary tablet disintegration can not be qualified, and the disintegration rate of rifampicin composition freeze-drying oral cavity disintegration tablet of the present invention is far longer than the rifampicin ordinary tablet.
The selected adjuvant of rifampicin composition freeze-drying oral cavity disintegration tablet of the present invention all is the adjuvants that are suitable for this tablet of preparation.According to discovering; The water solublity of rifampicin is very poor, and the present invention adopts the tertiary butanol and water cosolvent as solvent in technology, is insoluble in the rifampicin of water with tert-butyl alcohol dissolving; With other adjuvants of water for injection dissolving; Both mix with suitable ratio then, are dissolved the clear and bright cosolvent of water solublity and liposoluble substance jointly, use this technology to have multiple advantage.
The first, because the freezing point of the tert-butyl alcohol is high; Just can freeze at normal temperatures; With also can just can solidify after water mixes in the subzero several years, and tert-butyl alcohol vapour pressure is high, the vapour pressure height helps distillation; So use the tertiary butanol and water cosolvent can shorten freeze-drying time as solvent, the obtained freeze-drying product still keeps porous simultaneously.
The second, the tert-butyl alcohol and water can be with any mixed, and the medicine with slightly water-soluble is dissolved in the tert-butyl alcohol like this, can strengthen stability of drug.
Three, the adding of the tert-butyl alcohol can change the crystalline state of water, and then the drug crystallization state that is dissolved in the water is changed, and improves freezing point, and rate of sublimation improves greatly.
Four, tert-butyl alcohol toxicity is low, and after the lyophilizing almost there is not residual quantity, and this has just guaranteed the safety of drug use.
Since rifampicin composition freeze-drying oral cavity disintegration tablet of the present invention mainly in order to satisfy child's medication demand, and the rifampicin taste is pungent, for improving the compliance of children, in prescription, has added the correctives sucralose.In traditional production application, aspartame flavour mouthfeel is pretty good, but is prone to decompose instability; Cyclamate, glucide safety receive dispute to a certain degree, and are prone to produce the back bitterness.And the sucralose sweet feel is very near sucrose, and is very stable, safe to heat, acid, alkali.Simultaneously, sucralose is not utilized by the dental caries pathogenic bacteria, can reduce pathogenic bacteria in the oral cavity, and the acid amount of generation and streptococcus cell effectively play the dental caries effect in the adhesion of dental surface, and useful especially teenager teeth is healthy; The sucralose good stability can long term storage, and in freezing dry process, can not be damaged, and is fit to industrial applications.
The present invention has following beneficial effect:
The first, disintegrate is rapid, and drug effect is fast.Rifampicin composition freeze-drying oral cavity disintegration tablet of the present invention is disintegrate rapidly in 2 seconds in mouth, is beneficial to the rapid stripping of medicine, shortens dissolution time, accelerates to absorb, and liver first-pass effect is little, makes its performance curative effect fast.
The second, drug absorption is abundant.Rifampicin composition freeze-drying oral cavity disintegration tablet of the present invention is disintegrate fully in the oral cavity, makes the absorption of medicine more abundant, helps improving bioavailability of medicament like this.
Three, taking convenience, mouthfeel is good.Rifampicin composition freeze-drying oral cavity disintegration tablet of the present invention needn't be used water delivery service, and saliva can make its complete disintegrate, and no foreign body sensation in mouthful is owing to wherein add the compliance that the sweet child of helping of suitable correctives cool taste flavor takes medicine.Compare with liquid preparation and dosage advantage accurately arranged.
Four, avoid the first pass effect of liver, because rifampicin composition freeze-drying oral cavity disintegration tablet of the present invention disintegrate rapidly in mouth except that major part gets into the gastrointestinal tract with swallowing act, also has the considerable part trans-oral to absorb, thereby rapid-action, first pass effect is little.
The specific embodiment:
For technological means, creation characteristic that the present invention is realized, reach purpose and effect and be easy to understand and understand, below in conjunction with specific embodiment, further set forth the present invention.
Embodiment 1
With the 150mg/ sheet is that example prepares rifampicin composition freeze-drying oral cavity disintegration tablet
Prescription: 1000 amounts
Preparation technology:
The rifampicin of recipe quantity is dissolved in the tert-butyl alcohol of recipe quantity, and stirring and dissolving continues to stir at normal temperatures, preparation solution a; Mannitol, the sucralose of recipe quantity are dissolved in the water for injection of prescription with water for injection total amount 70%-80% preparation solution b; Gelatin with recipe quantity is dissolved in the water for injection of prescription water consumption 20%-30% again, is heated to dissolving fully, preparation solution c; Merge above-mentioned b, two kinds of solution of c become solution d, and stir, mixed then solution is cooled to below 5 ℃; Mix a, two kinds of solution of d, and stir, regulate pH value to 4.0 ~ 6.5 with sodium bicarbonate; According to rifampicin composition freeze-drying oral cavity disintegration tablet specification; After confirming loading amount, the medicinal liquid after merging is moved in the drug-containing dish by loading amount, and put into freeze drying box; Medicinal liquid is carried out freezing (cryogenic temperature is-20 ℃--50 ℃); Evacuation dry (baking temperature is at+0 ℃-+5 ℃, vacuum be-more than the 0.09MPa) is controlled moisture and is no more than 1.0%; After treating rifampicin composition freeze-drying oral cavity disintegration tablet drying, in freeze drying box, seal; Cut drug-containing dish after the medicament that freezes taken out freeze drying box, and carry out finished product packing.
Embodiment 2
With the 150mg/ sheet is that example prepares rifampicin composition freeze-drying oral cavity disintegration tablet
Prescription: 1000 amounts
Preparation technology:
The rifampicin of recipe quantity is dissolved in the tert-butyl alcohol of recipe quantity, and stirring and dissolving continues to stir at normal temperatures, preparation solution a; Mannitol, the sucralose of recipe quantity are dissolved in the water for injection of prescription with water for injection total amount 70%-80% preparation solution b; Gelatin with recipe quantity is dissolved in the water for injection of prescription water consumption 20%-30% again, is heated to dissolving fully, preparation solution c; Merge above-mentioned b, two kinds of solution of c become solution d, and stir, mixed then solution is cooled to below 5 ℃; Mix a, two kinds of solution of d, and stir, regulate pH value to 4.0 ~ 6.5 with sodium bicarbonate; According to rifampicin composition freeze-drying oral cavity disintegration tablet specification; After confirming loading amount, the medicinal liquid after merging is moved in the drug-containing dish by loading amount, and put into freeze drying box; Medicinal liquid is carried out freezing (cryogenic temperature is-20 ℃--50 ℃); Evacuation dry (baking temperature is at+0 ℃-+5 ℃, vacuum be-more than the 0.09MPa) is controlled moisture and is no more than 1.0%; After treating rifampicin composition freeze-drying oral cavity disintegration tablet drying, in freeze drying box, seal; Cut drug-containing dish after the medicament that freezes taken out freeze drying box, and carry out finished product packing.
Embodiment 3
With the 150mg/ sheet is that example prepares rifampicin composition freeze-drying oral cavity disintegration tablet
Prescription: 1000 amounts
Preparation technology:
The rifampicin of recipe quantity is dissolved in the tert-butyl alcohol of recipe quantity, and stirring and dissolving continues to stir at normal temperatures, preparation solution a; Mannitol, the sucralose of recipe quantity are dissolved in the water for injection of prescription with water for injection total amount 70%-80% preparation solution b; Gelatin with recipe quantity is dissolved in the water for injection of prescription water consumption 20%-30% again, is heated to dissolving fully, preparation solution c; Merge above-mentioned b, two kinds of solution of c become solution d, and stir, mixed then solution is cooled to below 5 ℃; Mix a, two kinds of solution of d, and stir, regulate pH value to 4.0 ~ 6.5 with sodium bicarbonate; According to rifampicin composition freeze-drying oral cavity disintegration tablet specification; After confirming loading amount, the medicinal liquid after merging is moved in the drug-containing dish by loading amount, and put into freeze drying box; Medicinal liquid is carried out freezing (cryogenic temperature is-20 ℃--50 ℃); Evacuation dry (baking temperature is at+0 ℃-+5 ℃, vacuum be-more than the 0.09MPa) is controlled moisture and is no more than 1.0%; After treating rifampicin composition freeze-drying oral cavity disintegration tablet drying, in freeze drying box, seal; Cut drug-containing dish after the medicament that freezes taken out freeze drying box, and carry out finished product packing.
More than show and described ultimate principle of the present invention, principal character and advantage of the present invention.The technical staff of the industry should understand; The present invention is not restricted to the described embodiments; That describes in the foregoing description and the description is merely preference of the present invention, is not used for limiting the present invention, under the prerequisite that does not break away from spirit and scope of the invention; The present invention also has various changes and modifications, and these variations and improvement all fall in the scope of the invention that requires protection.The present invention requires protection domain to be defined by appending claims and equivalent thereof.
Claims (6)
1. a rifampicin compositions is characterized in that, said composition comprises following component and component quantity ratio:
2. rifampicin compositions according to claim 1 is characterized in that, the preferred ingredient quantity ratio of said each component of rifampicin compositions is:
3. a rifampicin composition freeze-drying oral cavity disintegration tablet that contains the said compositions of claim 1 is characterized in that, is prepared from following component and component quantity ratio:
4. rifampicin composition freeze-drying oral cavity disintegration tablet according to claim 3 is characterized in that, the preferred ingredient quantity ratio of each component of preparation rifampicin composition freeze-drying oral cavity disintegration tablet is:
5. the method for preparing of the said rifampicin composition freeze-drying of claim 3 oral cavity disintegration tablet is characterized in that the concrete steps of this method for preparing are:
A) rifampicin with recipe quantity is dissolved in the tert-butyl alcohol of recipe quantity, and stirring and dissolving continues to stir at normal temperatures, preparation solution a;
B) mannitol, the sucralose with recipe quantity is dissolved in the water for injection of prescription with water for injection total amount 70%-80%, preparation solution b;
C) again the gelatin of recipe quantity is dissolved in the water for injection of prescription water consumption 20%-30%, is heated to dissolving fully, preparation solution c;
D) merge above-mentioned b, two kinds of solution of c become solution d, and stir, mixed then solution is cooled to below 5 ℃;
E) mix a, two kinds of solution of d, and stir, regulate pH value to 4 ~ 6.5 with sodium bicarbonate;
F) according to rifampicin composition freeze-drying oral cavity disintegration tablet specification, confirm loading amount after, the medicinal liquid after merging is moved in the drug-containing dish by loading amount, and puts into freeze drying box, medicinal liquid is carried out freezing, the dry control moisture of evacuation is no more than 1.0%;
G) treat rifampicin composition freeze-drying oral cavity disintegration tablet drying after, in freeze drying box, seal;
H) cut drug-containing dish after the medicament that freezes is taken out freeze drying box, and carry out finished product packing.
6. the method for preparing of rifampicin composition freeze-drying oral cavity disintegration tablet according to claim 5 is characterized in that: said rifampicin composition freeze-drying oral cavity disintegration tablet specification is 150mg/ sheet, 300mg/ sheet.
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| CN2012103025158A CN102784126A (en) | 2012-08-23 | 2012-08-23 | Rifampicin composition freeze-dried orally disintegrating tablet and preparation method thereof |
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| CN2012103025158A CN102784126A (en) | 2012-08-23 | 2012-08-23 | Rifampicin composition freeze-dried orally disintegrating tablet and preparation method thereof |
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| CN1689649A (en) * | 2004-04-30 | 2005-11-02 | 量子高科（北京）研究院有限公司 | Oral cavity quick dissolving preparation and production method thereof |
| CN101925349A (en) * | 2007-12-21 | 2010-12-22 | 欧兰德股份有限公司 | Orally disintegrating tablet compositions of temazepam |
| US20120076858A1 (en) * | 2009-06-04 | 2012-03-29 | Basf Se | Orally Disintegrating Dosage Forms Containing Taste-Masked Active Ingredients |
| CN102579378A (en) * | 2012-02-07 | 2012-07-18 | 海南卫康制药(潜山)有限公司 | Child cefdinir composition freeze-dried oral disintegrating tablet and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1689649A (en) * | 2004-04-30 | 2005-11-02 | 量子高科（北京）研究院有限公司 | Oral cavity quick dissolving preparation and production method thereof |
| CN101925349A (en) * | 2007-12-21 | 2010-12-22 | 欧兰德股份有限公司 | Orally disintegrating tablet compositions of temazepam |
| US20120076858A1 (en) * | 2009-06-04 | 2012-03-29 | Basf Se | Orally Disintegrating Dosage Forms Containing Taste-Masked Active Ingredients |
| CN102579378A (en) * | 2012-02-07 | 2012-07-18 | 海南卫康制药(潜山)有限公司 | Child cefdinir composition freeze-dried oral disintegrating tablet and preparation method thereof |
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Application publication date: 20121121 |