CN101920018A - Pharmaceutic adjuvant and preparation method thereof - Google Patents
Pharmaceutic adjuvant and preparation method thereof Download PDFInfo
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- CN101920018A CN101920018A CN2009100527697A CN200910052769A CN101920018A CN 101920018 A CN101920018 A CN 101920018A CN 2009100527697 A CN2009100527697 A CN 2009100527697A CN 200910052769 A CN200910052769 A CN 200910052769A CN 101920018 A CN101920018 A CN 101920018A
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- Prior art keywords
- pharmaceutic adjuvant
- lactose
- mannitol
- preparation
- polyvinylpolypyrrolidone
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Links
- 239000000546 pharmaceutical excipient Substances 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 26
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims abstract description 33
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims abstract description 33
- 229930195725 Mannitol Natural products 0.000 claims abstract description 33
- 239000008101 lactose Substances 0.000 claims abstract description 33
- 239000000594 mannitol Substances 0.000 claims abstract description 33
- 235000010355 mannitol Nutrition 0.000 claims abstract description 33
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims abstract description 27
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims abstract description 27
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 21
- 239000000203 mixture Substances 0.000 claims abstract description 16
- 238000001694 spray drying Methods 0.000 claims abstract description 15
- 239000002904 solvent Substances 0.000 claims abstract description 9
- 239000006185 dispersion Substances 0.000 claims abstract description 6
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 claims description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 238000002156 mixing Methods 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 238000004945 emulsification Methods 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims 1
- 238000007907 direct compression Methods 0.000 abstract description 11
- 230000008569 process Effects 0.000 abstract description 7
- 239000006191 orally-disintegrating tablet Substances 0.000 abstract description 3
- 239000007787 solid Substances 0.000 abstract description 3
- 238000010008 shearing Methods 0.000 abstract description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 abstract 2
- 229960000913 crospovidone Drugs 0.000 abstract 2
- 239000000839 emulsion Substances 0.000 abstract 1
- 239000003826 tablet Substances 0.000 description 30
- 210000000214 mouth Anatomy 0.000 description 23
- 239000003795 chemical substances by application Substances 0.000 description 19
- 239000002671 adjuvant Substances 0.000 description 18
- 230000000694 effects Effects 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 239000000843 powder Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 6
- 239000008367 deionised water Substances 0.000 description 5
- 229910021641 deionized water Inorganic materials 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 239000007921 spray Substances 0.000 description 5
- 239000004744 fabric Substances 0.000 description 4
- HYWYRSMBCFDLJT-UHFFFAOYSA-N nimesulide Chemical compound CS(=O)(=O)NC1=CC=C([N+]([O-])=O)C=C1OC1=CC=CC=C1 HYWYRSMBCFDLJT-UHFFFAOYSA-N 0.000 description 4
- 229960000965 nimesulide Drugs 0.000 description 4
- FGXWKSZFVQUSTL-UHFFFAOYSA-N domperidone Chemical compound C12=CC=CC=C2NC(=O)N1CCCN(CC1)CCC1N1C2=CC=C(Cl)C=C2NC1=O FGXWKSZFVQUSTL-UHFFFAOYSA-N 0.000 description 3
- 229960001253 domperidone Drugs 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000035807 sensation Effects 0.000 description 2
- PPKXEPBICJTCRU-XMZRARIVSA-N (R,R)-tramadol hydrochloride Chemical compound Cl.COC1=CC=CC([C@]2(O)[C@H](CCCC2)CN(C)C)=C1 PPKXEPBICJTCRU-XMZRARIVSA-N 0.000 description 1
- 206010013886 Dysaesthesia Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000000748 compression moulding Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 238000011112 process operation Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000006104 solid solution Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000002352 surface water Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229960003107 tramadol hydrochloride Drugs 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the medical field and particularly relates to a pharmaceutic adjuvant and a preparation method thereof. The pharmaceutic adjuvant of the invention contains mannitol, lactose and crospovidone. The pharmaceutic adjuvant is prepared by performing high shearing dispersion and emulsion to the mixture of mannitol, lactose and crospovidone in solvent and performing spray drying. The pharmaceutic adjuvant of the invention has good fluidity and disintegration, good mouthfeel and high physical strength; and the pharmaceutic adjuvant can be widely used in various oral solid preparations and especially suitable for preparing orally disintegrating tablets through the direct compression process.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to a kind of pharmaceutic adjuvant and preparation method thereof.
Background technology
Pharmaceutic adjuvant (pharmaceutical excipients) is meant when preparation prescription designs, and adds the general designation of all the medicinal materials except that principal agent in the prescription for mouldability, effectiveness, stability, the safety that solves preparation.Pharmaceutic adjuvant is the basic material and the important component part of pharmaceutical preparation, is the material base that guarantees pharmaceutical preparation production and development, plays a part key at preparation formulation with in producing.It not only gives medicine certain dosage form.And with the curative effect that improves medicine, reduce untoward reaction very big relation arranged, its reliability and multiformity are the bases that guarantees dosage form and preparation advance.
Oral cavity disintegration tablet is that a kind of water that do not need in the oral cavity can disintegrate or dissolved tablet, and it has and absorbs soon, and the bioavailability height needn't be used water delivery service, taking convenience, and intestinal is residual few, and side effect is low, can reduce the advantages such as first pass effect of liver.The main preparation technology of oral cavity disintegration tablet has pressed disc method etc. behind freeze-drying, spray drying method, solid solution technology (solid state dissolution), lyophilization, compression moulding, direct compression process, wet method pressing and the wet granulation, wherein the direct compression process operation is the easiest, has industrialized prospect most.Direct compression process is had relatively high expectations to pharmaceutic adjuvant, and used pharmaceutic adjuvant requires not only that compressibility is good, good moldability, and also wanting can disintegrate rapidly in oral environment, and good mouthfeel is arranged after disintegrate.In addition, generally when the preparation oral cavity disintegration tablet, also need to add other components such as filler, disintegrating agent, correctives, fluidizer.The key of preparation oral cavity disintegration tablet is to seek proper supplementary material, when guaranteeing tabletting good fluidity, compressibility is strong, disintegrate is fast, requires prepared tablet mouthfeel to get well in addition.
A difficult problem of oral cavity disintegration tablet research is, because its have relatively high expectations (disintegrate generally should be no more than 1 minute) to disintegration time, therefore the disintegrating agent that necessary additional proportion is bigger in existing disintegrating agent is (usually more than 10%, what have more reaches 30%), but powerful disintegrating agent such as carboxymethyl starch sodium commonly used, granular sensation after disintegrate such as polyvinylpolypyrrolidone is all heavier, mouthfeel is bad, user's dysaesthesia, and these disintegrating agents is mobile bad, be difficult to mix homogeneously with principal agent and other adjuvants, problems such as it is big to be prone to tablet weight variation during direct compression, and finished product disintegration time difference is big.Simultaneously, if disintegrating agent adds too much, also may cause disintegrating tablet to be prone to " shielding of expanding " effect, in disintegrating procedue, moisture is difficult for entering disintegrating tablet inside, causes disintegration rate slack-off on the contrary; If disintegrating agent addition deficiency then easily causes the oral cavity disintegration tablet disintegration time long, can't practical requirement.And, in the prior art, generally be that principal agent is proportionally carried out common tabletting in other crude adjuvants, therefore in concrete production technology, producers need carry out the test of various proportionings to determine its ratio to the ratio of various adjuvants, cause the step complexity, process is loaded down with trivial details, and cost improves.To sum up, provide a kind of when reducing the disintegrating agent ratio, can guarantee good disintegrate effect and preferably the pharmaceutic adjuvant of mouthfeel become this area problem demanding prompt solution.
Summary of the invention
The objective of the invention is to provides a kind of pharmaceutic adjuvant and preparation method thereof at the deficiencies in the prior art.
In order to solve the problems of the technologies described above, technical scheme of the present invention is:
A kind of pharmaceutic adjuvant, contain mannitol, lactose and polyvinylpolypyrrolidone, wherein the weight ratio of mannitol, lactose and polyvinylpolypyrrolidone is 10.8～13.2: 5.4～6.6: 1, and this pharmaceutic adjuvant is made by following method: with the mixture of mannitol, lactose and polyvinylpolypyrrolidone in solvent behind high cut disperse emulsification spray drying.
Preferably, in the described pharmaceutic adjuvant, the weight ratio of mannitol, lactose and polyvinylpolypyrrolidone is 11.4～12.6: 5.7～6.3: 1.
Preferably, described solvent is a water.
Described high cut disperse emulsification is meant under the high-speed driving of motor, processed material bears the inferior shear action of hundreds of thousands at short notice, because the powerful kinetic energy that high linear speed that the rotor high-speed rotation is produced and high frequency machinery effect belt come, make that material is subjected to intensive machinery and fluid power shearing, centrifugal extruding, liquid layer friction in the accurate gap of stator and rotor, high-speed impact is torn with comprehensive function such as turbulent flow under division, broken, disperse, thereby make immiscible material in the abundant dispersion in moment uniform, fine ground, emulsifying, homogenizing, dissolving.
The preparation method of pharmaceutic adjuvant of the present invention comprises the steps:
1) mannitol, lactose and polyvinylpolypyrrolidone are made compound by weight weigh batching and after mixing;
2) add solvent in the compound that in step 1), makes, under 10000～20000 rev/mins rotating speed, stir and carried out the high shear dispersion in 30～90 minutes, make serosity;
3) with step 2) preparation serosity carry out spray drying.
Preferably, described step 2) in, the weight ratio of solvent and compound is 10～20: 1, more preferably 14～16: 1.
Preferably, described step 2) in, when high shear disperseed homogenate, rotating speed was 13000～17000 rev/mins; Mixing time is 45～75 minutes.
Preferably, in the described step 3), the spray drying temperature is 80～100 ℃, more preferably 85 ℃.
The main component of pharmaceutic adjuvant of the present invention is mannitol and lactose, these two kinds of compositions have certain fluidity, granular sensation is less after the disintegrate, patient is acceptant, but in the prior art, because the disintegrate effect relatively poor (disintegration time is generally more than ten minutes) of these two kinds of materials is difficult to reach the requirement (generally requiring in 1 minute) of oral cavity disintegration tablet, the powerful disintegrating agent that therefore generally needs to add more than 10% just can reach quickly disintegrated effect.And carry out processing such as high shear dispersion by disintegrating agent with mannitol, lactose and low ratio according to the method for the invention together, can be with the disintegrating agent homodisperse, and form the simple aggregation thing with mannitol and lactose, this polymer has kept mannitol and the good mouthfeel of lactose, have better flowability and disintegrate ability, and avoided in the prior art,, also saved cost owing to adding " shielding of expanding " effect that heavy dose of disintegrating agent occurs.
The compositions that pharmaceutic adjuvant of the present invention and independent mannitol, lactose, polyvinylpolypyrrolidone, these three kinds of compositions are simply mixed and organize in contrast with the compositions that different mixing modes makes according to identical proportioning, carry out performance respectively relatively, estimate from powder fluidity, disintegration time, mouthfeel, lustrous surface and these aspects of frangible degree, evaluation result shows: the ratio according to mannitol, lactose, these three kinds of materials of polyvinylpolypyrrolidone among the present invention has following characteristics with the pharmaceutic adjuvant that high cut disperse emulsification method of the present invention prepares:
1, powder fluidity is good: (angle of repose is θ) less than 30 degree, and less than other matched groups to be embodied in angle of repose;
2, disintegration time was less than 10 seconds, and disintegration rate is good;
3, good mouthfeel, have good lustrous surface, good through tablet friability somascope test physical strength simultaneously, be difficult for crisp broken.
And in the matched group, the compositions that independent mannitol, lactose, polyvinylpolypyrrolidone, these three kinds of compositions simply mix and all can't reach above-mentioned performance requirement with the compositions that different mixing modes makes according to identical proportioning, or can't good fluidity, disintegration time is short, mouthfeel is good and physical strength well (non-friable) these several respects be met simultaneously.
Pharmaceutic adjuvant of the present invention can be used as premixing auxiliary material, mix with principal agent, avoided in the prior art, the technical staff carries out the test of various proportionings to the ratio of various adjuvants, can be directly and principal agent carry out mixed pressuring plate, produce and the cost of research and development guaranteeing that mouth collapses to have reduced when medicament has superperformance.The invention provides and a kind ofly have good flowability and disintegrative, and the pharmaceutic adjuvant of good taste is arranged, this pharmaceutic adjuvant can be widely used in various oral solid formulations, is particularly useful for direct compression process and prepares oral cavity disintegration tablet.
The specific embodiment
The invention will be further described below by embodiment, but should not limit protection scope of the present invention with this.
Below in conjunction with specific embodiment this aspect is described
Embodiment 1
Get 108 kilograms in mannitol, 54 kilograms of lactose, 10 kilograms of polyvinylpolypyrrolidone, drop into retort, the deionized water that in retort, adds 1720 kilograms, disperse refiner under 10000 rev/mins rotating speed, to stir 30 minutes with high shear, make serosity, use spray dryer, spray drying under 80 ℃ of conditions of temperature, get 157 kilograms of finished products, yield is 91.3%.
Embodiment 2
Get 132 kilograms in mannitol, 66 kilograms of lactose, 10 kilograms of polyvinylpolypyrrolidone, drop into retort, the deionized water that in retort, adds 4160 kilograms, disperse refiner under 20000 rev/mins rotating speed, to stir 90 minutes with high shear, make serosity, use spray dryer, spray drying under 100 ℃ of conditions of temperature, get 183 kilograms of finished products, yield is 88.0%.
Embodiment 3
Get 122 kilograms in mannitol, 58 kilograms of lactose, 10 kilograms of polyvinylpolypyrrolidone, drop into retort, the deionized water that in retort, adds 2850 kilograms, disperse refiner under 15000 rev/mins rotating speed, to stir 60 minutes with high shear, make serosity, use spray dryer, spray drying under 85 ℃ of conditions of temperature, get 180 kilograms of finished products, yield is 94.7%.
Embodiment 4
Get 110 kilograms in mannitol, 64 kilograms of lactose, 10 kilograms of polyvinylpolypyrrolidone, drop into retort, the deionized water that in retort, adds 3130 kilograms, disperse refiner under 13000 rev/mins rotating speed, to stir 50 minutes with high shear, make serosity, use spray dryer, spray drying under 90 ℃ of conditions of temperature, get 160 kilograms of finished products, yield is 87.0%.
Embodiment 5
Get 128 kilograms in mannitol, 58 kilograms of lactose, 10 kilograms of polyvinylpolypyrrolidone, drop into retort, the deionized water that in retort, adds 2350 kilograms, disperse refiner under 17000 rev/mins rotating speed, to stir 70 minutes with high shear, make serosity, use spray dryer, spray drying under 95 ℃ of conditions of temperature, get 176 kilograms of finished products, yield is 89.8%.
Embodiment 6
The pharmaceutic adjuvant that makes among the embodiment 1 is carried out the Performance Detection of powder fluidity, disintegration time, mouthfeel, lustrous surface and frangible these several respects of degree.
Powder fluidity: the flowability of powder body is bigger to the weight differential and the normal running influence of preparations such as granule, capsule, tablet, for direct compression, more requires to have higher flowability.The flowability of powder body can't be expressed with single characteristic value, angle of repose commonly used (angle of repose, θ) expression.Be meant the free inclined-plane and the formed maximum angular of horizontal plane of powder body accumulation horizon angle of repose.Angle of repose is more little, and frictional force is more little, and flowability is good more, it is generally acknowledged good fluidity when θ≤30 are spent, and can satisfy the need for liquidity in the production process when θ≤40 are spent.
Disintegration time: oral cavity disintegration tablet is as a kind of special dosage form, and one of its technical essential is the disintegration time of control tablet in the oral cavity.Method commonly used at present is a JP dissolution improved method, installs mainly by stripping rotor, and stirring arm, the disintegrate basket is formed.The screen cloth that it adopted is 10 orders, and is screen cloth all on four sides, and after the stirring, water runs through screen cloth with fast speeds, and slice, thin piece is caused bigger mechanical impulse force.The granularity that this method is used for controlling oral cavity disintegration tablet seems too loose, thus change stainless steel mesh into 30 orders with reference to the oral cavity disintegration tablet meeting summary, and with the disintegrate basket be designed to can only the bottom surface water inlet form.Concrete disintegrating method process is as follows: the distilled water that adds 37 ℃ of 900mL is fixed on the disintegrate basket on the stripping wall of cup in stripping rotor, and its upper end flushes (water volume is 1.99mL in the disintegrate basket) with the water surface, and mixing speed is adjusted to 100rmin
-1Oral cavity disintegration tablet drops in the disintegrate basket, and record is the disintegration time of oral cavity disintegration tablet from dropping into tablet till the basic noresidue to the screen cloth during this period of time.The preparation method of oral cavity disintegration tablet to be measured is: do not adding in addition under the situation of other adjuvant, adjuvant under identical compression force that each is to be compared is pressed into blank.
Mouthfeel: test the comparison mouthfeel with the volunteer, select 36 healthy volunteers, 18 male 18 woman wherein, the age was explained the purpose and the meaning of test to it between 23～29 years old.Every volunteer sucks 1 blank oral cavity disintegration tablet at every turn, normal talk and activity during the pastille, but must not drink water, to the complete disintegrate of slice, thin piece, spue, gargle, write down every volunteer's the impression of taking with normal saline, with+expression volunteer to the evaluation of mouthfeel, be divided into level Four ,+for poor, ++ for generally, +++be is better, ++ ++ for fine.
Lustrous surface: visualization
Frangible degree: get 10 of oral cavity quick disintegrating slices, place tablet friability somascope, rotate 100 times, take out and observe
Comparative result sees following table for details:
The pharmaceutic adjuvant The performance test results that table 1 embodiment 1 makes
Annotate: contrast adjuvant 1 is identical with the ratio of the contained mannitol of the pharmaceutic adjuvant of embodiment 1, lactose and polyvinylpolypyrrolidone, just forms through simple mix homogeneously; Contrast adjuvant 2 is simple blended optimization ratios of taking each side index screenings such as the comprehensive flowability of orthogonal test method, disintegrative, outward appearance to go out mannitol, lactose and polyvinylpolypyrrolidone three, three's part by weight is a mannitol: lactose: polyvinylpolypyrrolidone=4: 3: 3, through simply mixing; Contrast adjuvant 3 with contrast adjuvant 2 and have identical component ratio, make by spray drying preparation behind the high-shear homogenate identical with embodiment 1.
By comparative test, as can be seen from above-mentioned correction data:
1, mannitol, lactose and polyvinylpolypyrrolidone are carried out the simple combination of arbitrary proportion, its direct compression adjuvant as oral cavity disintegration tablet all is difficult to be suitable for (though the disintegration time of optimized prescription was a little less than 1 minute, but be higher than 40 degree its angle of repose, can't satisfy and produce required flowability substantially);
2, be not the combination of mannitol, lactose and polyvinylpolypyrrolidone three arbitrary proportion all can obtain performance through spray-drying process behind the high-shear homogenate of the present invention lifting, with contrast adjuvant 2 and 3, after this method is handled, though mobile and mouthfeel slightly promotes, but disintegrating property descends obviously, and finished product is more frangible.Have only mannitol, the disintegrating agent of lactose and low ratio carries out processing such as high shear dispersion together, can be with the disintegrating agent homodisperse, and form the simple aggregation thing with mannitol and lactose, this polymer has kept mannitol and the good mouthfeel of lactose, have better flowability and good disintegrate ability, the mannitol that only meets proportionate relationship, lactose all has remarkable lifting in every respect with the performance of the pharmaceutic adjuvant that the polyvinylpolypyrrolidone three method among the present invention of passing through makes together, this and component ratio polymerization methods different relevant between each composition simultaneously not.
Embodiment 7
Prepare domperidone orally disintegrating tablet with embodiment 1 gained adjuvant, and compare with commercially available sample:
Preparation method: get domperidone 10 grams, add above embodiment 1 gained adjuvant 90 grams, mixing, direct compression, every heavy 0.1 gram gets 980 of domperidone orally disintegrating tablets.
Relatively see the following form:
| Title | Disintegration time | Mouthfeel | Lustrous surface | Frangible degree |
| From film-making | 9 seconds | ++++ | Good | Good |
| Commercially available | 27 seconds | +++ | Generally | Generally |
Embodiment 8
Prepare the nimesulide oral cavity disintegration tablet with embodiment 3 gained adjuvants, and compare with commercially available sample:
Preparation method: get nimesulide 100 grams, add above embodiment 3 gained adjuvants 100 grams, mixing, direct compression, every heavy 0.2 gram gets 977 of nimesulide oral cavity disintegration tablets.
Relatively see the following form:
| Title | Disintegration time | Mouthfeel | Lustrous surface | Frangible degree |
| From film-making | 12 seconds | ++++ | Good | Good |
| Commercially available | 29 seconds | +++ | Generally | Generally |
Embodiment 9
Prepare the tramado hydrochloride oral cavity disintegration tablet with embodiment 5 gained adjuvants, and compare with commercially available sample:
Preparation method: get acetaminophen 325 grams, tramadol hydrochloride 37.5 grams add above embodiment 5 gained adjuvants 72.5 grams, mixing, and direct compression, every heavy 0.435 gram gets 969 of nimesulide oral cavity disintegration tablets.
Relatively see the following form:
| Title | Disintegration time | Mouthfeel | Lustrous surface | Frangible degree |
| From film-making | 14 seconds | ++++ | Good | Good |
| Commercially available | 48 seconds | +++ | Generally | Generally |
Claims (7)
1. pharmaceutic adjuvant, contain mannitol, lactose and polyvinylpolypyrrolidone in this pharmaceutic adjuvant, wherein the weight ratio of mannitol, lactose and polyvinylpolypyrrolidone is 10.8～13.2: 5.4～6.6: 1, and this pharmaceutic adjuvant is made by following method: with the mixture of mannitol, lactose and polyvinylpolypyrrolidone in solvent behind high cut disperse emulsification spray drying.
2. the pharmaceutic adjuvant described in claim 1 is characterized in that, in the described pharmaceutic adjuvant, the weight ratio of mannitol, lactose and polyvinylpolypyrrolidone is 11.4～12.6: 5.7～6.3: 1.
3. the pharmaceutic adjuvant described in claim 1 is characterized in that, described solvent is a water.
4. the preparation method of the described pharmaceutic adjuvant of arbitrary claim among the claim 1-3 comprises the steps:
1) mannitol, lactose and polyvinylpolypyrrolidone are made compound by weight weigh batching and after mixing;
2) add solvent in the compound that in step 1), makes, under 10000～20000 rev/mins rotating speed, stir and carried out the high shear dispersion in 30～90 minutes, make serosity;
3) with step 2) preparation serosity carry out spray drying.
5. the preparation method of the pharmaceutic adjuvant described in claim 4 is characterized in that, described step 2) in, the weight ratio of solvent and compound is 10～20: 1.
6. the preparation method of the pharmaceutic adjuvant described in claim 4 is characterized in that, in the described step 3), the spray drying temperature is 80～100 ℃.
Among the claim 1-3 the described pharmaceutic adjuvant of arbitrary claim in the application in medication preparation field.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100527697A CN101920018B (en) | 2009-06-09 | 2009-06-09 | Pharmaceutic adjuvant and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100527697A CN101920018B (en) | 2009-06-09 | 2009-06-09 | Pharmaceutic adjuvant and preparation method thereof |
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| Publication Number | Publication Date |
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| CN101920018A true CN101920018A (en) | 2010-12-22 |
| CN101920018B CN101920018B (en) | 2012-11-28 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2009100527697A Expired - Fee Related CN101920018B (en) | 2009-06-09 | 2009-06-09 | Pharmaceutic adjuvant and preparation method thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101829332A (en) * | 2010-05-27 | 2010-09-15 | 上海华茂药业有限公司 | Rapidly disintegrable pharmaceutic adjuvant and preparation method thereof |
| CN102614519A (en) * | 2012-04-06 | 2012-08-01 | 安徽山河药用辅料股份有限公司 | Preparation method of premixed auxiliary material for dispersible tablet |
| CN105012955A (en) * | 2015-07-30 | 2015-11-04 | 湖南尔康制药股份有限公司 | Premixed auxiliary material for preparing orally disintegrating tablet through direct compression |
| WO2020150930A1 (en) * | 2019-01-23 | 2020-07-30 | 谭淞文 | Novel microcrystalline mannitol medicinal auxiliary agent |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1225241C (en) * | 2003-07-30 | 2005-11-02 | 北京中西经纬释药技术有限公司 | Oral disintegrant tablet and its preparation method |
| CN1237965C (en) * | 2003-12-09 | 2006-01-25 | 成都圣诺科技发展有限公司 | Oral disintegrating tablet of bambuterol hydrochloride and its preparation method |
-
2009
- 2009-06-09 CN CN2009100527697A patent/CN101920018B/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101829332A (en) * | 2010-05-27 | 2010-09-15 | 上海华茂药业有限公司 | Rapidly disintegrable pharmaceutic adjuvant and preparation method thereof |
| CN102614519A (en) * | 2012-04-06 | 2012-08-01 | 安徽山河药用辅料股份有限公司 | Preparation method of premixed auxiliary material for dispersible tablet |
| CN105012955A (en) * | 2015-07-30 | 2015-11-04 | 湖南尔康制药股份有限公司 | Premixed auxiliary material for preparing orally disintegrating tablet through direct compression |
| CN105012955B (en) * | 2015-07-30 | 2017-12-22 | 湖南尔康制药股份有限公司 | A kind of premixing auxiliary material that oral disintegrating tablet is prepared for direct tablet compressing |
| WO2020150930A1 (en) * | 2019-01-23 | 2020-07-30 | 谭淞文 | Novel microcrystalline mannitol medicinal auxiliary agent |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101920018B (en) | 2012-11-28 |
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