CN103202817B - Preparation method for mannitol grains capable of being directly pressed - Google Patents
Preparation method for mannitol grains capable of being directly pressed Download PDFInfo
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- CN103202817B CN103202817B CN201310154224.3A CN201310154224A CN103202817B CN 103202817 B CN103202817 B CN 103202817B CN 201310154224 A CN201310154224 A CN 201310154224A CN 103202817 B CN103202817 B CN 103202817B
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- lactose
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- 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 title claims abstract description 94
- 229930195725 Mannitol Natural products 0.000 title claims abstract description 94
- 239000000594 mannitol Substances 0.000 title claims abstract description 94
- 235000010355 mannitol Nutrition 0.000 title claims abstract description 94
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 239000000843 powder Substances 0.000 claims abstract description 32
- 238000005469 granulation Methods 0.000 claims abstract description 13
- 230000003179 granulation Effects 0.000 claims abstract description 13
- 239000007864 aqueous solution Substances 0.000 claims abstract description 10
- 239000011230 binding agent Substances 0.000 claims description 48
- 239000002245 particle Substances 0.000 claims description 42
- 239000008187 granular material Substances 0.000 claims 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 description 19
- 239000008101 lactose Substances 0.000 claims description 19
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 18
- 238000007906 compression Methods 0.000 claims description 18
- 230000006835 compression Effects 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 239000012530 fluid Substances 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 16
- 239000007921 spray Substances 0.000 claims description 16
- 229920000881 Modified starch Polymers 0.000 claims description 14
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 14
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 13
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 13
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 11
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 11
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 10
- 229940071676 hydroxypropylcellulose Drugs 0.000 claims description 10
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 claims description 9
- 229920001287 Chondroitin sulfate Polymers 0.000 claims description 9
- 102000008186 Collagen Human genes 0.000 claims description 9
- 108010035532 Collagen Proteins 0.000 claims description 9
- 229940059329 chondroitin sulfate Drugs 0.000 claims description 9
- 235000013325 dietary fiber Nutrition 0.000 claims description 9
- 229920000609 methyl cellulose Polymers 0.000 claims description 9
- 239000001923 methylcellulose Substances 0.000 claims description 9
- 235000010981 methylcellulose Nutrition 0.000 claims description 9
- 230000002572 peristaltic effect Effects 0.000 claims description 9
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 7
- 238000010298 pulverizing process Methods 0.000 claims description 4
- 230000036760 body temperature Effects 0.000 claims description 2
- 229920002678 cellulose Polymers 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims description 2
- 235000010980 cellulose Nutrition 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 14
- 239000002002 slurry Substances 0.000 abstract description 10
- 239000000853 adhesive Substances 0.000 abstract description 5
- 230000001070 adhesive effect Effects 0.000 abstract description 5
- 238000007873 sieving Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 17
- 238000007689 inspection Methods 0.000 description 14
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
- 239000013078 crystal Substances 0.000 description 12
- 238000004519 manufacturing process Methods 0.000 description 10
- 239000007788 liquid Substances 0.000 description 8
- 239000004568 cement Substances 0.000 description 7
- 238000001514 detection method Methods 0.000 description 7
- 238000009826 distribution Methods 0.000 description 7
- 235000019359 magnesium stearate Nutrition 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 238000004321 preservation Methods 0.000 description 7
- 239000008213 purified water Substances 0.000 description 7
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000007909 melt granulation Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- -1 poor fluidity Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010019133 Hangover Diseases 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 239000003005 anticarcinogenic agent Substances 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 230000004410 intraocular pressure Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000011782 vitamin Substances 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
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The invention discloses a preparation method for mannitol grains capable of being directly pressed. The preparation method is characterized by comprising the following steps of: taking mannitol, crushing and passing through a 80-mesh sieve, so as to obtain a mannitol powder; and performing top-jet granulation on the mannitol powder by virtue of a fluidized bed, by using adhesive aqueous solution as top-jet slurry, granulating and then sieving, so as to obtain the mannitol grains capable of being directly pressed. The preparation method disclosed by the invention is simple in granulation process and saving in labour; a mixed adhesive is preferentially chosen; and the obtained grains are capable of meeting requirements in the aspects of brittleness, uniformity and hardness, better in uniformity, flowability and dispersity, and more convenient to package and transport.
Description
Technical field
The preparation method that the present invention relates to medicine tablet vertical compression granule, concrete is the preparation method of vertical compression mannitol particles.
Background technology
Mannitol (mannitol) be again mannitol, molecular formula C
6h
8(OH)
6, molecular weight is 182.17, is white crystal, its structural formula is as follows:
Mannitol is being pharmaceutically good diuretic, reduces the diluent of intracranial pressure, intraocular pressure and treatment kidney medicine, dehydrant, sugar succedaneum, the excipient that is also used as tablet and solid, liquid.As the excipient of tablet, mannitol no hygroscopicity, fast drying, chemical stability is good, and has the features such as tasty and refreshing, pelletize is good, for most of tablets such as anticarcinogen, antimicrobial drug, antihistaminic and vitamin.In addition, also for chewing tablets such as hangover medicine, mouthful fresheners.
At present the domestic mannitol often making is acicular crystal, poor fluidity, and crystal can not be directly used in tabletting, and the dissolution velocity of crystal is also slow than granule, and domestic tablet producer is mainly by import vertical compression mannitol particles.Vertical compression mannitol particles preparation method has following several at present:
US Patent No. 5160680 discloses a kind of production method of mannitol particles that can vertical compression, the method is by the moisture Hybrid Heating of mannitol crystal or powder and 2-4% at 166 DEG C, bar-shaped to being squeezed into after the mannitol melting of 50-80%, then knock and pulverize and sieve.Its particle size distribution is the about 18-60 order of 1000-250 μ m(Tyler screen), average 620 μ m.
US Patent No. 3341415 discloses the preparation method of the mannitol particles of a kind of mannitol content >50%, after the method is mannitol melting, is added to other saccharides of many 50%, continues heating and melting, then cooling, pulverizes and sieves.
Above two kinds of methods all adopt melt granulation, do not use binding agent, and melt granulation technical requirement is high, operate waywardly, and material high-temperature discoloration can affect outward appearance; The mannitol particles mannitol content making is low, and close structure is not soluble, and operation is difficult for, and is difficult to carry out suitability for industrialized production.
The patent 200610019626.2 of Nanning chemical pharmacy discloses a kind of preparation method of vertical compression mannitol, the method is by aqueous solution and the abundant mix homogeneously of mannitol of binding agent (binding agent that the method is used has maltose alcohol, sorbitol, xylitol etc.), then vacuum drying, pulverizing, screening.The particle size distribution that the method is produced is the about 9-100 order of 2000 μ m-154 μ m(Tyler screen), apparent density is that 0.3-0.7g/ml, fusing point are 164-168 DEG C, mannitol content is greater than 95%.But the mannitol product yield of the method is too low, it is 60% left and right.
The preparation method of vertical compression type mannitol formulations in the patent 201110340624.4 of rivers and mountains, Jiangsu pharmacy, a kind of speed is disclosed and has collapsed, the method is the aqueous solution that the binding agent of 0.2-5% is prepared into 8-20%, then stir granulation with the mannitol powder of pulverizing, then granulate sieves.Wherein, the binding agent that the method is used has starch, maltodextrin, hydroxypropyl emthylcellulose, polyvinylpyrrolidone.The method is easy operating relatively, but needs the granule of granulate too much, and granulate easily produces powder, reduces overall flow, is difficult for and other auxiliary materials and mixing.
And the particle size distribution that existing fluidized bed prilling technology makes is even, compressibility is strong, but granule brittleness is too high, frangible, and in packaging and transportation, grain graininess diminishes, easily produces powder, and vertical compression effect and the mobility of product all can reduce.
Summary of the invention
The preparation method that the object of this invention is to provide a kind of vertical compression mannitol particles, the method is simple to operate, products obtained therefrom even particle distribution, compressibility is strong, and broken brittleness is low, and hardness is high.
Inventor conducts in-depth research mannitol granulating process, prilling, binding agent are chosen and carried out screening widely, obtained economical, adhesive formula and granulation process parameters efficiently by repeatedly testing, thus make that gained mannitol particles vertical compression is good, particle size distribution is little, broken brittleness and hardness high.
The concrete technical scheme of the present invention is as follows:
A preparation method for vertical compression mannitol particles, is characterized in that: get mannitol, by its pulverizing mistake 80 mesh sieves, obtain mannitol powder body; Adopt fluid bed to carry out top spray granulation mannitol powder body, taking binder aqueous solution as top spray serosity, after pelletize, sieve, obtain vertical compression mannitol particles.
The present invention, taking water as solvent, is crushed to mannitol below 80 orders, and granularity is low, while using binder aqueous solution as top spray serosity, and the crystallisation problems can effectively avoid mannitol fluidized bed prilling time, granulating is effective.
In above-mentioned preparation method, described binding agent is two or more in pre-gelatinized starch, lactose, carboxymethyl cellulose (CMC), water soluble dietary fiber, methylcellulose (MC), hydroxypropyl cellulose (HPC), chondroitin sulfate and collagen protein.
In above-mentioned preparation method, binding agent is preferably the mixture of pre-gelatinized starch, lactose and carboxymethyl cellulose (CMC), and wherein pre-gelatinized starch content is 35-45wt%, and lactose content is 20-30wt%, carboxymethyl cellulose surplus.
In above-mentioned preparation method, binding agent is preferably the mixture of water soluble dietary fiber, methylcellulose (MC) and hydroxypropyl cellulose (HPC), wherein hydroxy propyl cellulose cellulose content is 20-30wt%, and methylcellulose content is 30-35wt%, water soluble dietary fiber surplus.
In above-mentioned preparation method, binding agent is preferably the mixture of chondroitin sulfate, lactose, collagen protein and carboxymethyl cellulose, and wherein the content of chondroitin sulfate is 0.5-1.5wt%, and the content of collagen protein is 1-3wt%, the content of lactose is 35-40wt%, carboxymethyl cellulose surplus.
The present invention, by screening and great many of experiments to binding agent, has drawn preferred adhesive formula, and preferred binder content can be below 3%, can also make the uniformity of granule, broken brittleness and hardness all be improved preferably.
In above-mentioned preparation method, in mannitol particles, binder content is 1-3%, and mannitol content is 97-99%, preferred: binder content is 1-2%, and mannitol content is 98-99%.
In above-mentioned preparation method, the concentration of binder aqueous solution is 5-10wt%.
In above-mentioned preparation method, when top spray is granulated, atomizing pressure is 20-80kPa, and intake is 40-80m3/h, peristaltic pump rotating speed 8-20r/min, and inlet temperature is 50-90 DEG C, and mannitol powder body temperature is 25-45 DEG C, and binder aqueous solution temperature is 60-85 DEG C.
In above-mentioned preparation method, the granule of pelletize gained is successively crossed 20 orders, 80 order Tyler screens, obtains vertical compression mannitol particles.
More widely compared with wet granulation, the present invention has following advantage with current application:
(1) prilling is simple, saves labour force, binding agent cost, and integrated cost significantly declines;
(2) response rate is high, mobility of particle is high, compressibility is strong, and in finished particle, fine powder content is low, just can produce the tablet that hardness is high under lower tabletting pressure;
(3) preferentially select mixed adhesive, gained granule all can meet the demands aspect broken brittleness, the uniformity, hardness, and pellet hardness is high, non-friable, and mobility, vertical compression performance are not affected by the extraneous factors such as packaging, transport substantially;
(4) mannitol particles making has better uniformity, mobility and dispersibility, mixes more evenly with other adjuvants, is more suitable for tablet manufacturing.
Detailed description of the invention
According to following embodiment, can better understand the present invention.But, those skilled in the art will readily understand, the described concrete technology condition of embodiment, material proportion and result thereof be only for the present invention is described, and should also can not limit the present invention described in claims.
embodiment 1make the mannitol particles of binding agent production 97% of hydroxypropyl cellulose (HPC), methylcellulose (MC) and water soluble dietary fiber
1. mannitol crystal is ground into the following powder of 80 orders (Tyler screen) with impact grinder.
2. getting 12.5g water soluble dietary fiber adjusts in 250ml purified water and makes solution.
3. getting 10gMC is dissolved in 250 ml step 2 solution (45 DEG C) and makes serosity.
4. getting 7.5gHPC is dissolved in step 2 solution and makes binding agent serosity
5. take 970 g mannitol powder (<80 order) and in fluid bed, carry out the granulation of fluid bed top spray, technological parameter is: atomizing pressure 25-35KPa, peristaltic pump rotating speed 8r/min, intake 45-55m3/h, inlet temperature 75-90 DEG C, material (mannitol powder) temperature is controlled at 25-45 DEG C, and cement slurry liquid temp is controlled at 70-80 DEG C.
6. after pelletize finishes, pelletize reclaims 97.7%, pours out the mannitol particles making from silo, crosses 20 orders, 80 mesh sieves, then carries out the detection of indices, packs, and room temperature preservation is for subsequent use.
7. after Tyler screen sieves, 20 orders are following 99.2%, and wherein 80 orders account for 5.9% below, apparent density 0.446g/cm3,37.00 ° of angles of repose.
8. tabletting inspection
(1) mannitol tabletting: add 1% magnesium stearate to mix gained granule, mix rear moisture and account for 0.21%, with the round row tabletting of rushing in of 10mm;
(2) tablet inspection: the heavy 0.51g of average sheet, friability 0.57%, can press hardness 119N, disintegration time 46s.
embodiment 2make the mannitol particles of binding agent production 99% of lactose, pre-gelatinized starch and carboxymethyl cellulose (CMC)
1. mannitol crystal is ground into the following powder of 80 orders (Tyler screen) with impact grinder.
2. getting 3g lactose is dissolved in 200ml purified water and makes solution.
3. getting 3.5g pre-gelatinized starch is dissolved in 200 mL step 2 solution (45 DEG C).
4. getting 3.5gCMC is dissolved in and in step 3 solution, is prepared into binding agent serosity (top spray serosity).
5. take 990 g mannitol powder (<80 order) and in fluid bed, carry out the granulation of fluid bed top spray, technological parameter is: atomizing pressure 55-65KPa, peristaltic pump rotating speed 10r/min, intake 65-75m3/h, inlet temperature 50-65 DEG C, temperature of charge is controlled at 25-45 DEG C, and cement slurry liquid temp is controlled at 60-70 DEG C.
6. after pelletize finishes, pelletize reclaims 98.1%, pours out the mannitol particles making from silo, crosses 20 orders, 80 mesh sieves, then carries out the detection of indices, packs, and room temperature preservation is for subsequent use.
7. after Tyler screen sieves, 20 orders are following 99.0%, and wherein 80 orders account for 5.1% below, apparent density 0.514g/cm3,36.81 ° of angles of repose.
8. tabletting inspection
(1) mannitol tabletting: add 1% magnesium stearate to mix gained granule, mix rear moisture and account for 0.20%, with the round row tabletting of rushing in of 10mm;
(2) tablet inspection: the heavy 0.52g of average sheet, friability 0.49%, can press hardness 117N, disintegration time 45s.
embodiment 3make the mannitol particles of binding agent production 98.5% of lactose, pre-gelatinized starch and carboxymethyl cellulose (CMC)
1. mannitol crystal is ground into the following powder of 80 orders (Tyler screen) with impact grinder.
2. getting 3g lactose is dissolved in 200ml purified water and makes solution.
3. getting 6.7g pre-gelatinized starch is dissolved in 200 mL step 2 solution (45 DEG C).
4. getting 5.3gCMC is dissolved in and in step 3 solution, is prepared into binding agent serosity (top spray serosity).
5. take 985 g mannitol powder (<80 order) and in fluid bed, carry out the granulation of fluid bed top spray, technological parameter is: atomizing pressure 70-80KPa, peristaltic pump rotating speed 18r/min, intake 60-70m3/h, inlet temperature 70-85 DEG C, temperature of charge is controlled at 25-45 DEG C, and cement slurry liquid temp is controlled at 80-85 DEG C.
6. after pelletize finishes, pelletize reclaims 98.2%, pours out the mannitol particles making from silo, crosses 20 orders, 80 mesh sieves, then carries out the detection of indices, packs, and room temperature preservation is for subsequent use.
7. after Tyler screen sieves, 20 orders are following 99.3%, and wherein 80 orders account for 5.8% below, apparent density 0.532g/cm3,36.21 ° of angles of repose.
8. tabletting inspection
(1) mannitol tabletting: add 1% magnesium stearate to mix gained granule, mix rear moisture and account for 0.21%, with the round row tabletting of rushing in of 10mm;
(2) tablet inspection: the heavy 0.57g of average sheet, friability 0.23%, can press hardness 114N, disintegration time 47s.
embodiment 4a kind of binding agent and two kinds of granule effect comparisons that binding agent is produced
1. be that the granule effect of producing with embodiment 3 is made comparisons, establish two contrast experiments, contrast 1: binding agent is 15gCMC; Contrast 2: binding agent is 15g pre-gelatinized starch; Contrast 3: binding agent is 15g lactose.Other steps and technological parameter are identical with embodiment 3.
2. respectively the 150g granule of embodiment 3, contrast 1 and contrast 2 is poured in V-Mixer and rotated and mix 30min, make granule rotate up and down to check the fragility of granule with mixer, then 20 orders, 40 orders, 60 orders, 80 order Tyler screens carry out particle size distribution more excessively.
3. before and after pair mixing, particle size distribution result compares analysis
4. interpretation of result:
As can be seen from the above data:
4.1. while only using CMC or lactose to do binding agent, granule fragility is too high, frangible, in V-arrangement mixer, rotate 30min after average particle size have the trend of diminishing, and the following fine powder amount of 80 order obviously increases, this all can obviously reduce the mobility of granule and compressibility.
4.2. while only using pre-gelatinized starch to do binding agent, pellet hardness is high, but grain graininess is inhomogeneous, and it is a lot of to exceed 20 object bulky grains.
embodiment 5make the mannitol particles of binding agent production 98% of chondroitin sulfate, collagen protein, lactose and carboxymethyl cellulose
1. mannitol crystal is ground into the following powder of 80 orders (Tyler screen) with impact grinder.
2. getting 8g lactose adjusts in 200ml purified water and makes solution.
3. getting 11.5g carboxymethyl cellulose is dissolved in 200 mL step 2 solution (45 DEG C).
4. getting 0.1g chondroitin sulfate and 0.4g collagen protein is dissolved in 200 mL step 2 solution (45 DEG C) and makes binding agent serosity.
5. take 980 g mannitol powder (<80 order) and in fluid bed, carry out the granulation of fluid bed top spray, technological parameter is: atomizing pressure 50-55KPa, peristaltic pump rotating speed 12r/min, intake 65-75m3/h, inlet temperature 70-75 DEG C, material (mannitol powder) temperature is controlled at 25-45 DEG C, and cement slurry liquid temp is controlled at 70-80 DEG C.
6. after pelletize finishes, pelletize reclaims 98.7%, pours out the mannitol particles making from silo, crosses 20 orders, 80 mesh sieves, then carries out the detection of indices, packs, and room temperature preservation is for subsequent use.
7. after Tyler screen sieves, 20 orders are following 99.5%, and wherein 80 orders account for 4.1% below, apparent density 0.571g/cm3,35.93 ° of angles of repose.
8. tabletting inspection
(1) mannitol tabletting: add 1% magnesium stearate to mix gained granule, mix rear moisture and account for 0.17%, with the round row tabletting of rushing in of 10mm;
(2) tablet inspection: the heavy 0.61g of average sheet, friability 0.10 %, can press hardness 112N, disintegration time 46s.
embodiment 6make the mannitol particles of binding agent production 99% of chondroitin sulfate, collagen protein, lactose and carboxymethyl cellulose
1. mannitol crystal is ground into the following powder of 80 orders (Tyler screen) with impact grinder.
2. getting 3.5g lactose adjusts in 200ml purified water and makes solution.
3. getting 6.25g carboxymethyl cellulose is dissolved in 200 mL step 2 solution (45 DEG C).
4. getting 0.15g chondroitin sulfate and 0.1g collagen protein is dissolved in 200 mL step 2 solution (45 DEG C) and makes binding agent serosity.
5. take 990 g mannitol powder (<80 order) and in fluid bed, carry out the granulation of fluid bed top spray, technological parameter is: atomizing pressure 65-75KPa, peristaltic pump rotating speed 12r/min, intake 60-70m3/h, inlet temperature 65-75 DEG C, material (mannitol powder) temperature is controlled at 25-45 DEG C, and cement slurry liquid temp is controlled at 70-80 DEG C.
6. after pelletize finishes, pelletize reclaims 98.7%, pours out the mannitol particles making from silo, crosses 20 orders, 80 mesh sieves, then carries out the detection of indices, packs, and room temperature preservation is for subsequent use.
7. after Tyler screen sieves, 20 orders are following 99.4%, and wherein 80 orders account for 4.2% below, apparent density 0.498g/cm3,38.56 ° of angles of repose.
8. tabletting inspection
(1) mannitol tabletting: add 1% magnesium stearate to mix gained granule, mix rear moisture and account for 0.18%, with the round row tabletting of rushing in of 10mm;
(2) tablet inspection: the heavy 0.59g of average sheet, friability 0.11 %, can press hardness 119N, disintegration time 51s.
embodiment 7 use carboxymethyl celluloses (CMC) and water soluble dietary fiber do the mannitol particles of binding agent production 97%
1. mannitol crystal is ground into the following powder of 80 orders (Tyler screen) with impact grinder.
2. getting 15g water soluble dietary fiber adjusts in 600ml purified water and makes solution.
3. getting 15gCMC is dissolved in 600 mL step 2 solution (45 DEG C) and makes binding agent serosity.
4. take 970 g mannitol powder (<80 order) and in fluid bed, carry out the granulation of fluid bed top spray, technological parameter is: atomizing pressure 55-65KPa, peristaltic pump rotating speed 10r/min, intake 65-75m3/h, inlet temperature 50-65 DEG C, temperature of charge is controlled at 25-45 DEG C, and cement slurry liquid temp is controlled at 60-70 DEG C.
5. after pelletize finishes, pelletize reclaims 97.7%, pours out the mannitol particles making from silo, crosses 20 orders, 80 mesh sieves, then carries out the detection of indices, packs, and room temperature preservation is for subsequent use.
6. after Tyler screen sieves, 20 orders are following 99.0%, and wherein 80 orders account for 7.9% below, apparent density 0.446g/cm3,37.00 ° of angles of repose.
7. tabletting inspection
(1) mannitol tabletting: add 1% magnesium stearate to mix gained granule, mix rear moisture and account for 0.21%, with the round row tabletting of rushing in of 10mm;
(2) tablet inspection: the heavy 0.51g of average sheet, friability 0.64%, can press hardness 112N, disintegration time 46s.
embodiment 8 use hydroxypropyl celluloses (HPC) and pre-gelatinized starch do the mannitol particles of binding agent production 97%
1. mannitol crystal is ground into the following powder of 80 orders (Tyler screen) with impact grinder.
2. getting 10g pre-gelatinized starch adjusts in 400ml purified water and makes slurry.
3. getting 20 gHPC is dissolved in 400 mL pre-gelatinized starches slurries (45 DEG C) and makes binding agent serosity.
4. take 970 g mannitol powder (<80 order) and in fluid bed, carry out the granulation of fluid bed top spray, technological parameter is: atomizing pressure 25-35KPa, peristaltic pump rotating speed 8r/min, intake 45-55m3/h, inlet temperature 75-90 DEG C, material (mannitol powder) temperature is controlled at 25-45 DEG C, and cement slurry liquid temp is controlled at 70-80 DEG C.
5. after pelletize finishes, pelletize reclaims 98.2%, pours out the mannitol particles making from silo, crosses 20 orders, 80 mesh sieves, then carries out the detection of indices, packs, and room temperature preservation is for subsequent use.
6. after Tyler screen sieves, 20 orders are following 99.1%, and wherein 80 orders account for 7.5% below, apparent density 0.532g/cm3,36.21 ° of angles of repose.
7. tabletting inspection
(1) mannitol tabletting: add 1% magnesium stearate to mix gained granule, mix rear moisture and account for 0.21%, with the round row tabletting of rushing in of 10mm;
(2) tablet inspection: the heavy 0.57g of average sheet, friability 0.67%, can press hardness 114N, disintegration time 47s.
Claims (4)
1. a preparation method for vertical compression mannitol particles, is characterized in that: get mannitol, by its pulverizing mistake 80 mesh sieves, obtain mannitol powder body; Adopt fluid bed to carry out top spray granulation mannitol powder body, taking binder aqueous solution as top spray serosity, after pelletize, sieve, obtain vertical compression mannitol particles, in mannitol particles, binder content is 1-3wt%, and mannitol content is 97-99wt%;
Described binding agent is any in following a, b, c:
A. described binding agent is the mixture of pre-gelatinized starch, lactose and carboxymethyl cellulose, and wherein pre-gelatinized starch content is 35-45wt%, and lactose content is 20-30wt%, carboxymethyl cellulose surplus;
B. described binding agent is the mixture of water soluble dietary fiber, methylcellulose and hydroxypropyl cellulose, and wherein hydroxy propyl cellulose cellulose content is 20-30wt%, and methylcellulose content is 30-35wt%, water soluble dietary fiber surplus;
C. described binding agent is the mixture of chondroitin sulfate, lactose, collagen protein and carboxymethyl cellulose, and wherein the content of chondroitin sulfate is 0.5-1.5wt%, and the content of collagen protein is 1-3wt%, and the content of lactose is 35-40wt%, carboxymethyl cellulose surplus.
2. preparation method according to claim 1, is characterized in that: when top spray is granulated, atomizing pressure is 20-80kPa, intake is 40-80m3/h, peristaltic pump rotating speed 8-20r/min, and inlet temperature is 50-90 DEG C, mannitol powder body temperature is 25-45 DEG C, and binder aqueous solution temperature is 60-85 DEG C.
3. preparation method according to claim 1, is characterized in that: the concentration of binder aqueous solution is 5-10wt%.
4. preparation method according to claim 1, is characterized in that: the granule of pelletize gained is successively crossed 20 orders, 80 order Tyler screens, obtains vertical compression mannitol particles.
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| CN116510026B (en) * | 2023-07-04 | 2023-09-19 | 山东天力药业有限公司 | Mannitol compound pharmaceutical adjuvant and preparation method thereof |
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| PL187160B1 (en) * | 1994-01-31 | 2004-05-31 | Yamanouchi Pharma Co Ltd | A method of producing a soluble intraoral compression molded molding |
| KR101400064B1 (en) * | 2006-04-13 | 2014-05-27 | 니폰 조키 세야쿠 가부시키가이샤 | Dry direct compression fast disintegrating tablet |
| CN100413834C (en) * | 2006-07-11 | 2008-08-27 | 广西南宁化学制药有限责任公司 | Method for preparing compressible mannite particle |
| JP5766899B2 (en) * | 2007-04-11 | 2015-08-19 | ニプロ株式会社 | Oral disintegrant and method for producing the same |
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