CN1067242C - Production of beta-form thiamine hydrochloride crystals - Google Patents
Production of beta-form thiamine hydrochloride crystals Download PDFInfo
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- CN1067242C CN1067242C CN93100007A CN93100007A CN1067242C CN 1067242 C CN1067242 C CN 1067242C CN 93100007 A CN93100007 A CN 93100007A CN 93100007 A CN93100007 A CN 93100007A CN 1067242 C CN1067242 C CN 1067242C
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- thiamine hydrochloride
- type thiamine
- granule
- beta
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- 229960000344 thiamine hydrochloride Drugs 0.000 title claims abstract description 59
- 235000019190 thiamine hydrochloride Nutrition 0.000 title claims abstract description 59
- 239000011747 thiamine hydrochloride Substances 0.000 title claims abstract description 59
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 title claims abstract description 59
- 239000013078 crystal Substances 0.000 title claims abstract description 18
- 238000004519 manufacturing process Methods 0.000 title abstract 3
- 239000011230 binding agent Substances 0.000 claims abstract description 14
- 239000008187 granular material Substances 0.000 claims description 26
- 239000000843 powder Substances 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 18
- 238000002425 crystallisation Methods 0.000 claims description 14
- 230000008025 crystallization Effects 0.000 claims description 14
- 238000003756 stirring Methods 0.000 claims description 12
- 239000002245 particle Substances 0.000 claims description 5
- 238000000034 method Methods 0.000 abstract description 26
- 238000002360 preparation method Methods 0.000 abstract description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 11
- 238000005054 agglomeration Methods 0.000 abstract 1
- 230000002776 aggregation Effects 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 description 8
- 239000000499 gel Substances 0.000 description 7
- 238000004898 kneading Methods 0.000 description 7
- 239000002243 precursor Substances 0.000 description 7
- 238000002156 mixing Methods 0.000 description 6
- 229920002472 Starch Polymers 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- -1 hydroxypropyl Chemical group 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 239000007921 spray Substances 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000005469 granulation Methods 0.000 description 3
- 230000003179 granulation Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000003232 water-soluble binding agent Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 229920003091 Methocel™ Polymers 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000011160 research Methods 0.000 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 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 239000004368 Modified starch Substances 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000005243 fluidization Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 238000000275 quality assurance Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
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Abstract
The invention produces a beta-type thiamine hydrochloride crystal which is more stable and hardly causes agglomeration and its preparation by a simple method. The objective method for producing a beta-type thiamine hydrochloride crystal is characterized in that a alpha-type thiamine hydrochloride crystal is moistened with water and then stirred in the presence of the beta-type thiamine hydrochloride crystal and the objective method for producing a preparation of beta-type thiamine hydrochloride crystal is characterized in that the alpha-type thiamine hydrochloride crystal is moistened with water together with a binder and then stirred in the presence of the preparation of beta-type thiamine hydrochloride crystal.
Description
The present invention relates to contain β-crystalline granule of type thiamine hydrochloride and reach the tablet that obtains by this granule.
Usually, thiamine hydrochloride is with solid dosage forms, and the form of tablet particularly separately, or combines administration with other one or more vitamin or other medicines.
These solid dosage formss need have the quality assurance before taking, therefore, thiamine hydrochloride needs heat and moist stable.And commercially available thiamine hydrochloride mostly is α-type, and it easily is heated and the moisture absorption and instability.Therefore, in the former technology, need adopt some measures to be heated and the moisture absorption preventing as far as possible for guaranteeing quality.
In order to guarantee the quality of thiamine hydrochloride and other medicines, many technological inventions on dosage form and appearance packaging, have been carried out.But in fact a kind of solution can be so that thiamine hydrochloride itself be more stable, if α type thiamine hydrochloride can be converted into β-type, that will be a kind of solution of letter knot, and β-type thiamine hydrochloride is non-hygroscopic, be difficult for bondingly, have good anti-cohesive and higher heat stability.
The method that easily α-type is converted into β-type comprises α-type is dissolved in the solvent, before recrystallization, adds β-type crystal seed in solution.But the method needs a large amount of liquors, and promptly time-consuming uneconomical again, when with an organic solvent, remaining in the product have organic solvent to form itself problem again, therefore, the method industrial be not method preferably.
Therefore, the purpose of this invention is to provide a kind of simply, easy row is suitable for the method for the β-type that α-type is converted into of commercial Application.
X-diffraction pattern (the CuK of the β that obtains in (Fig. 1) example 1-type thiamine hydrochloride powder
2, 40Kv, 40mA)
X-diffraction pattern (the CuK of the α that obtains in (Fig. 2) example 1-type thiamine hydrochloride powder
2, 40Kv, 40mA)
The present inventor is surprised to find that in the research of being devoted to address the above problem, to α-Add a small amount of water and pulverous β-type in the type, again through stirring, can make all α-Type will change β-type in very short time, this find on basis further research and Caused of the present invention finishing.
The invention provides:
(1) prepare the method for β-type thiamine hydrochloride, it is included in β-type thiamine hydrochloride crystal seed and exists down, with water-wet α-type thiamine hydrochloride, stirs the wet mix that obtains;
(2). the method described in (1), wherein used α-type thiamine hydrochloride is the α that the is no less than weight 95%-type thiamine hydrochloride crystalline powder by 100 mesh sieves;
(3). the method described in (1), wherein used α-type thiamine hydrochloride are the crystalline powder by the α that the is no less than weight 95%-type thiamine hydrochloride of 145 mesh sieves;
(4). the method described in (1), wherein 1-15% the water-wet of α-type thiamine hydrochloride with respect to total α-type thiamine hydrochloride weight;
(5). the method described in (1), wherein the amount of the β of Jia Ruing-type thiamine hydrochloride be α-type thiamine hydrochloride weight 1-30%;
(6). preparation contains the method for pharmaceutical formulation of β-type thiamine hydrochloride, and it is included in β-type thiamine hydrochloride and exists down, contains the α-type thiamine hydrochloride of binding agent with water-wet, stirs the wet mix of gained;
(7). the method described in (6), wherein the amount of adhesive therefor is 0.5-5% of a used thiamine hydrochloride weight;
(8) contain β-type thiamine hydrochloride grain amount be no less than dried granule gross weight 90% and
(9). with containing the tablet that tablet mixture compacting that β-type thiamine hydrochloride crystallization is no less than dried granule gross weight 90% forms.
α-type thiamine hydrochloride raw material can be powder or granule, if be crystallization, granular size can change.Specifically, the α-type thiamine hydrochloride powder that passes through 100 orders (JIS) sieve that is no less than weight 95% is comparatively desirable, more preferably is no less than the α-type thiamine hydrochloride powder that passes through 145 orders (JIS) sieve of weight 95%.Water can suitably add so that it exists with such amount, and the amount that adds entry is with respect to 1-15% of α-type thiamine hydrochloride weight, and preferred 1.4-8%.β-type thiamine hydrochloride preferably adds as crystal seed, and the amount of adding determines (generally being that added amount reduces according to the increase that adds the amount of entry) according to the amount of adding water, yet, from economic point of view.Add 1-30% weight ratio.Preferred 5-20% weight ratio, β-type crystal seed be enough to impel and fully become β-type.
According to the present invention, the preparation β-type thiamine hydrochloride (being β-type), or the preparation contain in the preparation of β-type, can add one or more binding agents, stabilizing agent, coloring agent, correctives and diluent.
α-type can promote by mechanical factor to the conversion of β-type.As stirring, stir, mix fusion or vibrate above-mentioned composition.Usually, preferably stir and mix.Stirring and mixing are carried out according to a conventional method, and stirring 10 minutes or longer time can make α-type be converted into β-type fully usually in blender or analog.Stirring and mixing intensity are also influential.Therefore, incorporation time should preferably be adjusted to the β-type that is converted into fully.After the mixing, converted product can be dry according to a conventional method, and as fluid bed drying, common drying or vacuum drying are granulated and obtained final products.
The conventional hybrid technology of some that mentioned, as fluidization, the centrifugal flow technology.Toss about in bed technology, grinding technique, the technology of kneading and stirring technique, every kind of used agitator all is applicable to this application.
Added water can spray or disposable adding, and above-mentioned mixing adds water, and dry and granulation step can be used in combination by suitable method, or changes these sequence of steps.For example, more preferably integrating step comprises mixing with fluidised bed granulator of being mentioned, and sprays, and granulates drying.
In the method, be used for changing α-type the moistening of β-type into and mix generally in room temperature and carry out to about 80 ℃.But the employing fluidised bed granulator comprises mixing, sprays, and granulates and exsiccant associated methods, can be used as above-mentioned typical method, and this method is usually at about 40 ℃-about 80 ℃, and preferred about 50 ℃-70 ℃ are carried out.The used binding agent of granulating can be water-soluble binder or solubility organic solvent binding agent.
Water-soluble binder comprises precursor gel starch, water-soluble cellulose derivative and water-soluble macromolecule.So-called " precursor gel starch " comprises by starch being scattered in the water the dry then products obtained therefrom of heating dispersion.Precursor gel starch comprises the precursor gel corn starch, precursor gel potato starch and precursor modified starch (as, The Code of FederalRegulation (U.S.A.) § 12.1.1031a, b, c, d, e, f, g or h, Deng put down in writing), gelling and exsiccant starch-based product such as Amikol C (Nichiden Kagaku K.K.), precursor gel (Hublinger Co, U.S.A.) and the clean gel of speed (NationalStarch δ Chemical Corp, U.S.A.).
Water-soluble cellulose derivative comprises hydroxypropyl cellulose, hydroxy methocel, and hydroxypropyl emthylcellulose, carboxymethyl cellulose, methylcellulose etc., water-soluble macromolecule comprise polyethylene pyrroles gastral cavity ketone, polyvinyl alcohol, dextrin, arabic gum, gelatin etc.
Solubility organic solvent binding agent comprises, for example: solubility organic cellulose derivant (as cellulose acetate-phthalate, Hydroxypropyl Methylcellulose Phathalate, ethyl cellulose etc.).
Be used for dissolving the solvent that joins the above-mentioned binding agent of the present invention above-mentioned water of mentioning and organic solvent (as alcohol (as methanol, ethanol, isopropyl alcohol), acetone etc.) are arranged
The concentration of the binding agent that is added can change according to practice, and as, 1-10% of weight, it changes mainly according to the combination of binding agent and solvent, can obtain certain viscosity, and the suitable viscosity that institute adds binding agent more preferably is that 1-1000cps is with the generation adhesive effect.Binding agent can add in any step, and binding agent can join in advance in α-type and to mix or join in granulation step in β-type product.
After the granulation, product can be used the conventional method drying, and can join in the air flow after spraying, keeps flow regime then, reaches the particular prediction value up to product temperature and comes dry.
The dried product of granulating, if necessary, agglomerate can or take that pulverizing is broken now with pulverizer such as electric mill, so that a material has Dispersion of Particles degree preferably.
Method of the present invention especially preferably is applicable to the preparation (as granule and tablet etc.) of direct compacted products of the thiamine hydrochloride of high level.Particularly can be used for making β-type thiamine hydrochloride cellulose content and be no less than 90%, more preferably 97%, granule.For example,, stir, can obtain being used for the granule that contains β-type of direct compression very soon when α-type thiamine hydrochloride crystallization and binding agent are used water-wet together.Reuse conventional method tabletting just can obtain tablet.For example, can contain the above-mentioned particulate tablet mixture of mentioning by compacting and obtain tablet, β in the granule-crystalline content of type thiamine hydrochloride is no less than 90%.Comprise as the example for preparing said preparation more specifically, in fluidized bed granulator, the α-type that is flowing with the water-soluble binder spray solution, in the presence of β-type crystal seed, the water wet mix, dry then, granulate.Gained granule and usual excipients, for example, lactose, magnesium stearate, corn starch and Talcum mix.Mixture can obtain tablet with the tablet machine tabletting.
The invention provides a kind of preparation β-crystalline method of type thiamine hydrochloride simple, that easily go, β-type thiamine hydrochloride is better than α-type thiamine hydrochloride in stability on hygroscopicity and the anti-caking performance (as prevented from caking).
Following example is used to further specify the present invention.
Example 1
Add α-type powder and the 200g β-type powder of 2Kg content 96% by 145 orders (JIS) sieve in FD-3S type fluidised bed granulator (Powrec), at 60 ℃, air mass flow is 0.5m
3/ minute the time, in mixture, spray 1.2 liter 7% hydroxypropyl emthylcellulose aqueous solution, the crystal form analysis result (the SSC/5200 type instrument with SEIKO records) of dry then gained granule (granule and mixture of powders are referred to as granule later on) DSC figure illustrates that dried particles nearly all is β-type crystallization.
X-diffraction pattern (the CuK of the exsiccant β-type powder that obtains
240KV 40mA) sees Fig. 1.
X-diffraction pattern (the CuK of raw material α-type powder
2, 40KV 40mA) sees Fig. 2.
Example 2.
Add α-type powder and the 150g β-type powder of 2Kg content 98% in the kneading machine by 145 (JIS) sieve, add 200g water then, kneading obtained the mixture of kneading in 60 minutes, and this DSC figure crystal analysis presentation of results powder of mediating mixture is made up of β-type crystallization fully.
Example 3.
Add 1Kg content in the kneading machine and be no less than 95% α-type powder and 50g β-type powder by 145 orders (JIS) sieve, the dextrin in aqueous solution that adds 70g 5% then, kneading obtained granule in 30 minutes, and the crystal form analysis explanation granule of the DSC figure of hybrid particles almost is β-type crystallization entirely.
Comparative example 1
Method in the example 1, but do not add β-type as crystal seed, the hybrid particles that obtains contains any β-type hardly and all is α-type crystallization.
Comparative example 2
Implement the method in 2, but do not add β-type crystallization, the mixture of kneading that obtains substantially all is α-type crystallization.
Comparative example 3
Method in the example 3, but do not add β-type crystallization, the granule that obtains substantially all is α-type crystallization.
Comparative example 4
Method in the example 3, but do not add entry, the granule that obtains substantially all is α-type crystallization.
Example 4
Utilize β-type granule (β of 97%-type thiamine hydrochloride of preparation in the example 1.3% hydroxypropyl cellulose), make tablet by following prescription and tabletting condition.
Prescription:
β-type granule 53.1mg
Lactose 145.9mg
Magnesium stearate 1.0mg
200.0mg
Tabletting condition: tablet machine: KIKUSUI CLEANPRESS Correct 6HUK mould, stamping machine: diameter 8.5mm, sweep 12mm rotating speed: 40 commentaries on classics/min principal pressures: 1000kg precompression: 300Kg
Comparative example 5
Press tablet formulation and tabletting condition in the example 4, be used in and obtain α-type granule (97% α-type thiamine hydrochloride, 3% hydroxy methocel) substituted beta-type granule tabletting in the comparative example 1 and make tablet.
Experiment embodiment
The stability of the α-matrix agent of preparation in the β-matrix agent of preparation and the comparative example 5 in the comparison example 4 of the present invention, with tablet after depositing the following time under the following condition, measure the percentage rate of thiamine hydrochloride remaining in the tablet separately with high-pressure liquid phase, gained the results are shown in the following table.
Table
Remaining percentage ratio preservation condition holding time example 4 comparative examples 5 xeothermic (40 ℃) 98.9 9.36 damp and hot 8 weeks 95.0 82.9 of 8 weeks (40 ℃, relative humidity: 75%)
Claims (2)
1. contain β-crystalline amount of type thiamine hydrochloride and be no less than the granule of dry weight total particle quantity 90%, wherein said β-type thiamine hydrochloride crystallization is following obtaining: in the presence of based on the β-type thiamine hydrochloride crystallization of α-crystalline 1-30wt% of type thiamine hydrochloride as crystal seed, 1-15wt% water-wet with described relatively α-type thiamine hydrochloride crystalline powder weight can and be no less than α-type thiamine hydrochloride crystalline powder of 95wt% and account for the heavy 0.5-5wt% binding agent of described α-type thiamine hydrochloride crystalline powder by 145 mesh sieves, stirs the wet mix of gained.
2. contain the tablet that right requires 1 particulate tablet mixture to obtain by compacting.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4222466A JPH05202039A (en) | 1991-09-19 | 1992-08-21 | Production of thiamine hydrochloride crystal |
| JP222466/92 | 1992-08-21 | ||
| JP222466/1992 | 1992-08-21 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1082405A CN1082405A (en) | 1994-02-23 |
| CN1067242C true CN1067242C (en) | 2001-06-20 |
Family
ID=16782862
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN93100007A Expired - Fee Related CN1067242C (en) | 1992-08-21 | 1993-01-01 | Production of beta-form thiamine hydrochloride crystals |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1067242C (en) |
-
1993
- 1993-01-01 CN CN93100007A patent/CN1067242C/en not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| CHEM PHAARM BULL17(11) 1979.1.1 ATSUSHI WATANABE 等，"POLYMORPHISM OF THIAMINE HYDROCHLORIDE II CRYSTAL STR" * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1082405A (en) | 1994-02-23 |
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