CN1155888A - Powdered hydroxypropyl-beta-cyclodextrin compositions and methods of making the same - Google Patents
Powdered hydroxypropyl-beta-cyclodextrin compositions and methods of making the same Download PDFInfo
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- CN1155888A CN1155888A CN 96190627 CN96190627A CN1155888A CN 1155888 A CN1155888 A CN 1155888A CN 96190627 CN96190627 CN 96190627 CN 96190627 A CN96190627 A CN 96190627A CN 1155888 A CN1155888 A CN 1155888A
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- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 title claims abstract description 22
- 238000000034 method Methods 0.000 title claims description 15
- 239000002245 particle Substances 0.000 claims abstract description 18
- 239000000243 solution Substances 0.000 claims description 30
- 238000002360 preparation method Methods 0.000 claims description 16
- 238000004090 dissolution Methods 0.000 claims description 14
- 238000006253 efflorescence Methods 0.000 claims description 13
- 206010037844 rash Diseases 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 239000007787 solid Substances 0.000 claims description 11
- 238000012360 testing method Methods 0.000 claims description 9
- 239000003595 mist Substances 0.000 claims description 4
- 238000005507 spraying Methods 0.000 claims description 4
- 239000006104 solid solution Substances 0.000 claims description 3
- 230000008901 benefit Effects 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 239000012736 aqueous medium Substances 0.000 abstract 1
- 239000010419 fine particle Substances 0.000 abstract 1
- 229920000858 Cyclodextrin Polymers 0.000 description 13
- 239000003826 tablet Substances 0.000 description 13
- 239000000843 powder Substances 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000005516 engineering process Methods 0.000 description 8
- 239000007921 spray Substances 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 6
- 238000007599 discharging Methods 0.000 description 6
- -1 really Chemical compound 0.000 description 6
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 5
- 239000001116 FEMA 4028 Substances 0.000 description 4
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 4
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 4
- 229960004853 betadex Drugs 0.000 description 4
- 230000006835 compression Effects 0.000 description 4
- 238000007906 compression Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
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- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
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- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
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Landscapes
- Medicinal Preparation (AREA)
Abstract
The present invention relates to a novel powdered hydroxypropyl-beta-cyclodextrin composition having a cored particle size without fine particles and significantly improved solubility in aqueous media. Such compositions also have good flow properties and have the advantage of compressibility. The invention also relates to a process for preparing such a powdered hydroxypropyl-beta-cyclodextrin composition.
Description
The present invention relates to a kind of new powdery hydroxypropyl-beta-cyclodextrin composition with specified particle size and good dissolution rate.
The invention still further relates to ad hoc approach and its industrial purposes of being used to prepare this composition.
According to whether be α-, β-or γ-Huan Hujing and contain the cyclodextrin of the big ring of 6,7 or 8 glucose units surely, particularly done a large amount of descriptions in the literature for their dissolving and the character of stable all cpds.These are to possess real advantage owing to they form the character that the ability of title complex has in the presence of the compound that can be embedded into fully or partly in these big rings in equipment protection, pharmacy and foodstuffs industry basically.In addition, also having studied cyclodextrin derivative itself, is not very high water-soluble in order to improve cyclodextrin particularly: really, for example for beta-cyclodextrin, water-soluble have only per 100 milliliters of 1.8 grams.In these derivatives, cyclodextrin ethers, the hydroxyalkyl cyclodextrin of more specifically saying so is owing to its high water-soluble, harmless and produce easily and be subjected to special concern.
These hydroxyalkyl cyclodextrin are with wherein all or part of hydroxyl is corresponding by the cyclodextrin of hydroxyalkyl etherificate.
The characteristic of these derivatives has inspired scientist that it is tested in various fields, particularly in pharmacy, makeup and equipment protection field.
Really, but these derivative good water-solubility for the water-soluble form of itself slightly soluble or insoluble effective ingredient in water and further to have an exploitation of form of high stability extremely beneficial.
Therefore, protected the pharmaceutical composition of the unformed title complex that contains pharmaceutically active agents and a kind of cyclodextrin compound that particularly comprises hydroxypropyl-beta-cyclodextrin by the United States Patent (USP) 4727064 of Pitha application.This title complex can improve the solvability of effective constituent and therefore improve the absorptivity of health.
Janssen Pharmaceutica company has also obtained European patent EP 149197, it relates to by being insoluble in water or unsettled containing by the beta-cyclodextrin of part etherificate in water, the pharmaceutical preparation formed of the inclusion compound of the medicine of hydroxypropyl-beta-cyclodextrin particularly is to improve solvability and the stability of these medicines in water.
The European patent EP 366154 that Shiseido company obtains has been protected the purposes of hydroxypropyl-beta-cyclodextrin in makeup.The title complex of this compound that is slightly soluble in water by ultraviolet sequestering agent, sanitas and perfume compound has good water-solubility, and the makeup that contain them have gratifying stability and needn't adopt the solubilizing agent of skin irritation.
Recently, it is also noted that and particularly in 1068303 and the NihonNoyaku63079802 of Japanese Patent Sun Oil, also described the purposes that hydroxypropyl-beta-cyclodextrin is used for the equipment protection field.This illustrated relevant cooperation compound toxicity and about the advantage of the solvability of this title complex and stability.
What also will replenish is to have mentioned that in these documents many other specifically describes the title complex of particular active agent and hydroxypropyl-beta-cyclodextrin.
This hydroxyalkyl derivant of cyclodextrin normally according to being included under specified temp, pressure and the time conditions, prepares in the method for water-bearing media and alkaline ph value reaction by propylene oxide and beta-cyclodextrin.Usually select sodium hydroxide as catalysts.
This reaction is normally finished under at least 70 ℃ temperature.
When reaction finishes, neutralization reaction medium, separation, purifying and reclaim hydroxypropyl-beta-cyclodextrin with the form of the aqueous solution.
Solid form if desired, can adopt various technology, therefore, be entitled as " NeW Trends inCyclodextrins and Derivatives " what chapter 2 related to hydroxypropyl-beta-cyclodextrin by what Prof.Duchene published in 1991, L.Szente and C.E.Strattan one book have been quoted freeze-drying, injection and evaporation technology.
Freeze-drying and spray also the method that is designed in order to reclaim cyclodextrin ethers in the patent 2597485 of France by American Maize Products.
But, as by L.Szente and C.E.Strattan described in the above-mentioned citing document, have many shortcomings according to the powder of these different technology preparations, particularly poorly soluble.
In addition, these powder are difficult for flowing and having inferior compression property.
Also have, these technology can produce superfine particle, and they have caused quite serious public hazards in the reinforced of loading hopper and chute and packing bag and discharging operation.Furtherly, these particulates can set off an explosion, and may produce stimulation for the operator.
Rely on these analyses; the powdery hydroxypropyl-beta-cyclodextrin composition that therefore the application company attempts to develop a kind of dissolution rate height and be suitable for all industrial requirements more; it does not have flowing and constrictive defective of the known powder type of hydroxypropyl-beta-cyclodextrin, and can not become the source of production plant's dust or blast simultaneously.
The application company commendablely has successfully prepared a kind of powdery hydroxypropyl-beta-cyclodextrin composition that does not have above-mentioned defective, has " having the inclination " granularity that does not have particulate simultaneously and has significantly improved dissolving power in water-bearing media.
Therefore the present invention relates to a kind of powdery hydroxypropyl-beta-cyclodextrin composition, being characterised in that it contains is less than about 25% granularity less than 100 microns particle, and the dissolution rate that is determined in the water-bearing media according to test I is less than 5 minutes at 21 ℃ for containing 20% solid solution.
The invention still further relates to and prepare powdery hydroxypropyl-beta-cyclodextrin method for compositions with above-mentioned physics and functional property.
According to first key character of powdery hydroxypropyl-beta-cyclodextrin composition of the present invention (below be abbreviated as HP β CD), it has specific and granularity that have the inclination.Really, it contains and is less than about 25% granularity less than 100 microns particle.
This powdery HP β CD composition preferably contains and is no more than about 10% granularity less than 40 microns particle, more preferably contains to be less than about 40% granularity greater than 315 microns particle.
Can adopt by the commercially available konimeter of Henbach engineering corporation (II type) and prove there is not subparticle, this is a particularly advantageous characteristic of the present composition just.The principle of measuring is test products is placed in the rotating cylinder of motion; Contained subparticle will be taken away by airflow, compiles on strainer again.This strainer before being in motion and weight afterwards just provided the amount of accumulative subparticle on strainer.
For powdery HP β CD composition of the present invention, the amount that adopts powder is 100 grams, and air velocity is 8 liters of per minutes, and run duration is 5 minutes.The gained result clearlys show that when comparing with prior art compositions the amount of the subparticle that contains in the present composition can be ignored.
Second key character of powdery HP β CD composition of the present invention comprises its dissolving power fast.
The dissolution time of measuring under the test I condition that will be described below is 21 ℃ temperature and is less than 5 minutes for containing 20% solid HP β CD solution, preferably be less than 3 minutes, more preferably less than 2 minutes, this dissolution rate with known HP β CD powder was compared to have had and is significantly improved.In addition, under the condition that adopts HP β CD more widely, especially receive an acclaim in the improvement aspect the quick dissolving.
In order to measure the dissolution rate of second key character that constitutes powdery HP β CD composition of the present invention, I carries out this method according to test, dissolves fully in the softening water and the required time of HP β CD that contains the corresponding different amounts of 5,10,20,30 and 40% solid composition comprising being determined at.Measure for this, with finally prepare 100 grams contain 5,10,20,30 or the softening water of the composition aequum of 40%HP β CD join in 150 milliliters of high beakers, again with 1250 rev/mins speed with bar magnet (length: 25mm, diameter: 6mm) stir this solution, add the HP β CD of selected amount.Under two temperature, carry out this test: 21 ℃ and 60 ℃.
Selected dissolution time is and reaches the suitable time of complete visually-clear in the suspension of preparation like this.
No matter no matter be in room temperature or much at high temperature and HP β CD concentration, the dissolution time of powder composition of the present invention is generally more than the weak point of prior art compositions.
In addition, it should be noted for prior art compositions that powder can be at surface aggregation under the high situation of solids content, and then overflow may take place in this gathering.This problem causes adding HP β CD in batches.
Except that dissolution time, the application has also further proved other particularly advantageous functional character of the present composition, mobile and its rate of compression as it.
Flowability is to adopt by the commercially available measuring apparatus of Hosokawa company.This equipment can standard with reproducible condition under measure the flowability of powder, and calculate the grade that flows, just refer to the Ka Er number.Powdery HP β CD composition of the present invention has good mobile grade, between 60 and 90.This grade is preferably between 70 and 85.Flowing of therefore visible powder of the present invention obviously is better than the prior art powder.
This characteristic is particularly advantageous in industrial application, because this facilitates hopper and container or selectable medicament forms, as the operation of medicine bag and capsular adding and discharge.
For same equipment with according to the method that the producer proposes, can measure the inflation apparent density.The value that records by the present composition generally 300 and 650g/l between, preferred 350 to 600g/l, and the inflation apparent density of prior art combinations is less than 300g/l.
For compressibility, II determines by test, and it comprises measures the power of pulverizing by required usefulness newton (N) expression of the tablet of wanting underproof preparation of compositions, that is to say in the main body that constitutes this tablet to present the required power of rupture line.Therefore this power has been reacted the band convex surface, diameter is that 13mm, the thick 5mm of being and weight are 0.499 gram, density is the ultimate compression strength of the cylindric tablet of 1.15g/ml in other words, said power puts on the outside surface of tablet at its rotating shaft direction by the mode that props up said surface with a moveable piston along generatrix, and said tablet is fixed and props up a fixing plug, and this fixing plug also props up the outside surface of this tablet along the generatrix of the surface opposite that props up with moveable piston.
In order to prepare these tablets, add the lubricant that is called Magnesium Stearate of 0.5% weight in this subject composition.
These two kinds of products adopt TurbulaT2C mixing tanks (by Willy A.BachofenAG, Switzerland is commercially available) with 42 rev/mins actuating speed homogenizing 5 minutes.
Adopt the Frogerais alternation punch press of AM type for the mixture of suppressing this preparation.This punch press has assembled that diameter is arranged is the round punch of 13 millimeters concave surfaces.
In order to obtain the characteristic of above-mentioned tablet, adjust the degree of depth of upper plunger and the reinforced volume of matrix, the latter's adjustment can access the pulverulent mixture of aequum by weight, is 0.499 gram in this case.
For the ultimate compression strength of measuring these tablets adopts Schleuniger 2E sclerometer (being sold by Frogerais company in France).
Different with the prior art compositions of (it is because the viscous that produces in adopting press process can not be used to prepare tablet with dissociating problem) preparation according to known technique, powdery HP β CD composition of the present invention has the compressibility that is entirely satisfactory.This is that hardness by tablet reflects, and hardness all is higher than 30N for density is the tablet of 1.15g/ml in all cases, preferably is higher than 60N, more preferably is higher than 100N.
This compressibility is for pharmacy field or candy field, is that the preparation lozenge that will be sucked or chew is desirable.
Powdery HP β CD composition of the present invention can according to spray hydroxypropyl-beta-cyclodextrin solution under given conditions the preparation of some similar methods arranged, although this technology does not have to prepare the powdery hydroxypropyl-beta-cyclodextrin composition with present composition granularity and functional performance so far.This method mainly is included in sprays HP β CD solution on the HP β CD particulate motion efflorescence bed.
Particularly, this method that is used in particular for present composition preparation comprises the following steps:
-preparation contains at least 30% solid HP β CD solution,
-this solution mist is ejected on the HP β CD particulate motion efflorescence bed, this temperature is between 40 ℃ and 110 ℃, and this amount is at least 0.5 times of the solution amount of per hour spraying always,
-dry efflorescence bed and solution is with preparation powdery HP β CD composition,
-this composition that may partly circulate is so that it constitutes new efflorescence HP β CD bed.
Therefore this technology can prepare and has powdery HP β CD composition specific and that have good dissolution rate when having the inclination granularity.These features with and mobile and compressibility can by change solids content in the HP β CD solution of wanting injected, spray fineness, make particle motion mode, bed tempertaure, drying temperature and bed and the relative quantity of sprayed solution adjust.
As for the solids content in the HP β CD solution, preferably it is more than or equal to 50%.
And, preferably to avoid the thick injection of solution, otherwise can see particulate viscous.
Therefore, have above-mentioned specific character, should select to make solution to form fine droplets or even the equipment of mist in order to make powdery HP β CD composition.
For the HP β CD particulate character that constitutes the efflorescence bed, it is the HP β CD particle with powdery HP β CD composition all characteristics of the present invention that this ideal is selected.This can obtain by the present composition of following as HP β CD particulate efflorescence bed that partly circulates.
The particle that constitutes the efflorescence bed mechanically or by blowing with air is moved.The latter is because it can may be preferred by selecting air themperature to come easily bed tempertaure to be adjusted between 40 ℃ and 110 ℃.
Usually bed tempertaure preferably remains between 50 and 80 ℃.
Spraying syrupy efflorescence bed thereon must be dried and be no more than 5%, preferred 3% composition to prepare final water content.
This application has is verified, and " multiple-effect " or the M.S.D. type spray tower continuous production powdery HP β CD composition that are provided by Niro Atomizer company for example are provided is favourable, preferred back one type.This spray tower can repeat all key steps of the inventive method owing to its design.
Really, this equipment can be by means of its nozzle with temperature between 30 and 100 ℃, contain 30 to 70% solid solution be ejected into superfinely adopt air and carry out and the HP β CD grain bed that keeps moving on.Furtherly, this equipment can adopt warm air to finish drying operation simultaneously.Can advantageously be chosen in the bubbling air temperature between 160 and 300 ℃ and add the velocity of flow of material so that make the air themperature of discharging from tower between 45 and 130 ℃, preferably still between 60 and 90 ℃.This equipment can also optionally be finished the part circulation of powdery HP β CD composition and it is dispersed in the tower superfinely, preferably around the solution nozzle.
Because its characteristic, powdery HP β CD composition of the present invention can be advantageously be used as raising at pharmacy, makeup and agrochemical field and wants the solvability of active compound in water and/or the reagent of stability in the prescription of dissolved powder or tablet.
Read the back pass through that diagramatic way provides and do not imply on the embodiment basis of any qualification will be better appreciated by advantage of the present invention, these embodiment are based on the specific embodiments of powdery HP β CD composition of the present invention.Embodiment:
Three kinds of powdery HP of product preparation β CD composition according to the present invention and against existing technologies.
According to standard method, a kind of HP β CD solution of preparation under following condition:
The commercially available beta-cyclodextrin of 1275 grams (be equivalent to 1134 gram anhydrous) is dissolved in 6% sodium hydroxide solution of 1600g (96 gram dissolution of sodium hydroxide are in 1504 gram softening waters), keeps about 80 ℃ temperature simultaneously.
In the reactor of this solution added assembling under the inert gas environment that is in nitrogen agitator and condenser.406 gram propylene oxides are added drop-wise in the reactor that this simultaneous temperature remains on 80-100 ℃, and after propylene oxide all adds, continue to react 4 hours.Then with the reaction mixture cooling, and by adding the concentrated hydrochloric acid neutralization.
Reaction mixture is selectively carried out purifying according to required purity by the known technology of prior art (filter, by with activated carbon treatment decolouring, demineralize, with washing with alcohol, with acetone extraction, dialysis).
For these three present compositions each, then finish this method by following approach respectively:
-No. 1 composition
Regulate this composition to containing 60% solid, and temperature is 50 ℃ before in " multiple-effect " type tower that it is injected into provided by Niro Atomizer company.
Then this solution mist is ejected on the particulate motion efflorescence bed corresponding with the particle that when operation begins, forms.
Temperature regulation to 50 ℃ with the bed of moving particle.
Between 175 and 195 ℃, the temperature of the air of discharging from tower is between 45 and 60 ℃ in the temperature of the dry air of the upper inlet of tower.
-No. 2 compositions
This solution be adjusted to contain 35% solid, and make its in the M.S.D. type tower that provides by Niro Atomizer company is provided before temperature be 70 ℃.
The bed temperature of moving particle is adjusted to 75 ℃.
Between 200 and 230 ℃, the temperature of the air of discharging from tower is between 65 and 85 ℃ in the temperature of the dry air of the upper inlet of tower.
-No. 3 compositions
This solution be adjusted to contain 55% solid, and make its in the M.S.D. type tower that provides by Niro Atomizer company is provided before temperature be 70 ℃.
The bed temperature of moving particle is adjusted to 62 ℃.
Between 180 and 200 ℃, the temperature of the air of discharging from tower is between 60 and 80 ℃ in the temperature of the dry air of the upper inlet of tower.
-prior art combinations
Prepare this composition according to being included in without any containing the standard spraying technique that 35% solid HP β CD solution is ejected in the standard spray tower under the HP β CD particle efflorescence bed situation.
The temperature of the dry air of tower inlet is between 230 and 280 ℃, and the temperature of the air of discharging from tower is between 100 and 130 ℃.
The main physical and the functional performance of Zhi Bei No. 1, No. 2 and No. 3 composition provide in following table under these conditions.
| Composition of the present invention | Prior art compositions | |||||||
| No. 1 | No. 2 | No. 3 | ||||||
| Granularity＜40 μ＜100 μ＞315 μ | ??????????????0％ ??????????????9％ ??????????????25％ | ?????????????0％ ?????????????21％ ?????????????6％ | ????????????0％ ????????????1％ ????????????11％ | ?????????????50％ ?????????????100％ ??????????????0％ | ||||
| Inflation apparent density g/l | ??????????????478 | ?????????????386 | ????????????381 | ?????????????263 | ||||
| Dissolution time | At 21 ℃ | At 60 ℃ | At 21 ℃ | At 60 ℃ | At 21 ℃ | At 60 ℃ | At 21 ℃ | At 60 ℃ |
| 5% solution, 10% solution, 20% solution, 30% solution, 40% solution | 15 seconds 35 seconds 50 seconds 2 minutes 15 seconds 4 minutes | ＜10 seconds 10 seconds 15 seconds 35 seconds 1 minute 10 seconds | 15 seconds 30 seconds 45 seconds 1 minute 10 seconds 2 minutes 30 seconds | ＜10 seconds 10 seconds 20 seconds 35 seconds 1 minute 10 seconds | 15 seconds 35 seconds 50 seconds 1 minute 15 seconds 2 minutes 40 seconds | ＜10 seconds 10 seconds 20 seconds 35 seconds 1 minute 10 seconds | 1 minute 15 seconds 4 minutes 8 minutes *11 minutes *17 minutes * | 40 seconds 1 minute 10 seconds 4 minutes 6 minutes 15 seconds *8 minutes 50 seconds * |
| Ash oontent g | ?????????????0.15 | ???????????????0.03 | ??????????????0.03 | ??????????????0.64 | ||||
| Grade flows | ???????????????77 | ?????????????????76 | ???????????????78 | ???????????????44 | ||||
| Compressibility | ??????????????34N | ???????????????147N | ??????????????116N | Can not compress | ||||
* part adds required HP β CD
Different with prior art combinations, composition of the present invention advantageously combines the character of also not finding simultaneously so far.Really, they have simultaneously that these are water-soluble fast, can pressurized, flow easily and do not produce the characteristic of subparticle.
Claims (8)
1. powdery hydroxypropyl-beta-cyclodextrin composition is characterized in that containing and is less than about 25% granularity less than 100 microns particle, and the dissolution time of measuring according to test I in water medium is less than 5 minutes at 21 ℃ for containing 20% solid solution.
2. according to the powdery hydroxypropyl-beta-cyclodextrin composition of claim 1, it is characterized in that being less than 3 minutes, preferably be less than 2 minutes according to the dissolution time that test I measures.
3. according to any one composition in claim 1 and 2, it is characterized in that containing and be no more than about 10% granularity less than 40 microns particle.
4. according to any one composition in the claim 1 to 3, it is characterized in that containing and be less than about 40% granularity greater than 315 microns particle.
5. according to any one composition in the claim 1 to 4, it is characterized in that its mobile grade between 60 and 90, preferably between 70 and 85.
6. according to any one composition in the claim 1 to 5, it is characterized in that its inflation apparent density 300 and 650g/l between, preferably 350 and 600g/l between.
7. according to any one composition in the claim 1 to 6, the compressibility that it is characterized in that determining according to test II is preferably greater than 60N, more preferably greater than 100N greater than 30N.
8. preparation powdery HP β CD method for compositions is characterised in that it comprises the following steps:
-preparation contains at least 30% solid HP β CD solution,
-this solution mist is ejected on the HP β CD particulate motion efflorescence bed, this temperature is between 40 ℃ and 110 ℃, and this amount is at least 0.5 times of the solution amount of per hour spraying always,
-dry efflorescence bed and solution is with preparation powdery HP β CD composition,
-may partly recycle this composition, so that it constitutes new efflorescence HP β CD bed.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 96190627 CN1155888A (en) | 1995-06-08 | 1996-06-06 | Powdered hydroxypropyl-beta-cyclodextrin compositions and methods of making the same |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR95/06772 | 1995-06-08 | ||
| CN 96190627 CN1155888A (en) | 1995-06-08 | 1996-06-06 | Powdered hydroxypropyl-beta-cyclodextrin compositions and methods of making the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1155888A true CN1155888A (en) | 1997-07-30 |
Family
ID=5128116
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 96190627 Pending CN1155888A (en) | 1995-06-08 | 1996-06-06 | Powdered hydroxypropyl-beta-cyclodextrin compositions and methods of making the same |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1155888A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100374555C (en) * | 2006-01-19 | 2008-03-12 | 山东大学 | Method for preparing beta-cyclodextrin by yeast |
| CN112334494A (en) * | 2018-06-29 | 2021-02-05 | 罗盖特公司 | Novel hydroxypropyl-beta-cyclodextrin and method for producing the same |
-
1996
- 1996-06-06 CN CN 96190627 patent/CN1155888A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100374555C (en) * | 2006-01-19 | 2008-03-12 | 山东大学 | Method for preparing beta-cyclodextrin by yeast |
| CN112334494A (en) * | 2018-06-29 | 2021-02-05 | 罗盖特公司 | Novel hydroxypropyl-beta-cyclodextrin and method for producing the same |
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