CN104645336B - A kind of composite auxiliary material and its production and use - Google Patents
A kind of composite auxiliary material and its production and use Download PDFInfo
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- CN104645336B CN104645336B CN201510003814.5A CN201510003814A CN104645336B CN 104645336 B CN104645336 B CN 104645336B CN 201510003814 A CN201510003814 A CN 201510003814A CN 104645336 B CN104645336 B CN 104645336B
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Abstract
The invention provides a kind of composite auxiliary material, the composite auxiliary material is the spherical or spherical particle obtained by mannitol and PVPP cocrystallization.The properties such as the mobility and compressibility of the composite auxiliary material are satisfied by the requirement of direct tablet compressing technique.Present invention also offers a kind of preparation method of composite auxiliary material, comprise the following steps：PVPP suspension is added in mannitol saturated solution, under ice-water bath and stirring, the mannitol is set to carry out cocrystallization with the PVPP, after the completion for the treatment of crystallization of mannitol, suction filtration, dry, grind after sieving, produce the composite auxiliary material, the composite auxiliary material is to carry out the spherical or spherical particle that cocrystallization is obtained by mannitol and PVPP.The preparation method technique of the composite auxiliary material is simple, and cost is low, is conducive to industrialized production.Composite auxiliary material produced by the present invention is used to prepare oral disnitegration tablet, and the disintegration time for the tablet being made is within 1min.
Description
Technical field
The present invention relates to field of medicaments, and in particular to a kind of composite auxiliary material and its production and use.
Background technology
Tablet is as traditional formulation, because its property is stable, carry and easy to use, manufacture mechanization degree height, cost
Low, yield is high, divided dose is accurate and turns into one of formulation the most frequently used at present.But because tablet needs extrusion forming, disintegration is relatively slow,
Bioavilability is relatively low and the elderly, children, mental patient etc. swallow more difficult, thus makes the promoting the use of one of tablet
Determine to be restricted in degree.Therefore in the research of solid pharmaceutical preparation, various quick releasing formulations have been increasingly becoming new drug in recent years
One focus of research and development, particularly oral disnitegration tablet.Oral disnitegration tablet is a kind of water is not required in oral cavity can be disintegrated or dissolve
Tablet, it, which has, absorbs fast, and bioavilability is high, it is not necessary to use water delivery service, convenient to take, and enteron aisle residual is few, and side effect is low, can
The advantages of reducing the first pass effect of liver.The disintegrant commonly used at present in conventional oral disnitegration tablet such as sodium carboxymethyl starch, low take
Granular sensation after being disintegrated for hydroxypropyl cellulose and PVPP etc. is heavier, and mouthfeel is bad, and these disintegrants
Mobility is bad, and main ingredient and other auxiliary materials are difficult to be well mixed, and causes during direct tablet compressing easily to occur that tablet weight variation is big, finished product collapses
Solve the quality problems such as time difference is big.
To solve the problem, Publication No. CN101829333 invention provides a kind of new multi-functional auxiliary material, the auxiliary material
It is processed into by mannitol, isobide and PVPP, although the mobility and disintegration ability of obtained auxiliary material have been carried
Height, but auxiliary material is prepared using spray drying process, method is complex, and spraying apparatus floor space is big, and production cost is higher；
Also need to add isobide in preparation process as adhesive, further increase production cost.
The content of the invention
To solve the above problems, the invention provides a kind of composite auxiliary material and its production and use.The present invention is provided
Composite auxiliary material obtained by mannitol with PVPP cocrystallization, preparation method technique is simple, in preparation process not
Large-scale instrument and equipment is needed, cost is low, is conducive to industrialized production, solve prior art composite auxiliary material preparation method complexity
Problem.
First aspect present invention provides a kind of composite auxiliary material, and the composite auxiliary material is to be entered by mannitol with PVPP
The spherical or spherical particle that row cocrystallization is obtained.
The composite auxiliary material is spherical or spherical particle, and the composite auxiliary material particle rounding, sphericity is preferable, Ke Yiti
The mobility of the high composite auxiliary material.
Preferably, the mannitol is 98~40 in mass ratio with the PVPP:2~60 carry out cocrystallization.
Under the ratio, preferably, obtained composite auxiliary material mobility and compressibility can be full for mannitol and PVPP mixed effect
The need for sufficient direct tablet compressing, defect of the PVPP separately as disintegrant is overcome.
It is highly preferred that the mannitol is 98~75 in mass ratio with the PVPP:2~25 are tied jointly
It is brilliant.
It is further preferred that the mannitol is 90~75 in mass ratio with the PVPP:10~25 are total to
The syncrystallization.
The composite auxiliary material that first aspect present invention is provided, is obtained by mannitol and PVPP cocrystallization, wherein sweet
Dew alcohol has the advantages that agent of low hygroscopicity, high stability, height endurability, low in calories and sweet taste are pure, in oral disnitegration tablet is prepared
Primarily serve the effect of excipient and flavouring.The excipient that currently available technology prepares tablet uses lactose mostly, this
Allowing for patient's particularly functions of intestines and stomach with lactose intolerance does not have fully grown children to be made in drug administration
Into certain puzzlement.The composite auxiliary material of the present invention fundamentally solves this problem.During PVPP is oral disnitegration tablet
Conventional disintegrant, in good taste, no feeling of grittiness.The composite auxiliary material prepared by mannitol and PVPP cocrystallization, flowing
Property and compressibility can reach the requirement of direct tablet compressing technique, the piece method of double differences moderate using tablet hardness made from the composite auxiliary material
Different smaller, a small amount of water can be so that it be swelled rapidly disintegration and good mouthfeel in oral cavity.
Second aspect of the present invention provides a kind of preparation method of composite auxiliary material, comprises the following steps：
PVPP suspension is added in mannitol saturated solution, under ice-water bath and stirring, made described sweet
Reveal alcohol and carry out cocrystallization with the PVPP, treat after the completion of crystallization of mannitol, suction filtration is dried, ground after sieving, produces
The composite auxiliary material, the composite auxiliary material be by mannitol and PVPP carry out that cocrystallization obtains it is spherical or spherical
Particle.
The composite auxiliary material is spherical or spherical granular particles rounding, and sphericity preferably, can improve described multiple
Close the mobility of auxiliary material.
Preferably, the mannitol saturated solution is placed in ice-water bath and stirred to when beginning with crystallization precipitation, added
The PVPP suspension, continues to stir, the mannitol is carried out cocrystallization with the PVPP.
Preferably, the mannitol is 98~40 in mass ratio with the PVPP:2~60 carry out cocrystallization.
It is highly preferred that the mannitol is 98~75 in mass ratio with the PVPP:2~25 are tied jointly
It is brilliant.
It is further preferred that the mannitol is 90~75 in mass ratio with the PVPP:10~25 are total to
The syncrystallization.
Preferably, the one or more PVPP being dispersed in water, ethanol and ethyl acetate are obtained
The PVPP suspension.
It is highly preferred that the PVPP is dispersed in into water obtains the PVPP suspension.
Preferably, in the PVPP suspension, the concentration of the PVPP is 0.4g/mL~0.8g/mL.
Preferably, the one or more mannitol being dissolved in water, ethanol and ethyl acetate obtain the sweet dew
Alcohol saturated solution.
Stirred it is highly preferred that the mannitol is added in 80~90 DEG C of hot water, be completely dissolved it and obtain described
Mannitol saturated solution.
Preferably, the drying temperature is 65 DEG C.
Preferably, the sieving is sieved using 65 mesh sieves.
The preparation method for the composite auxiliary material that second aspect of the present invention is provided, only need to be by the mannitol and the poly- dimension of the crosslinking
Ketone can be prepared by the composite auxiliary material using the method for cocrystallization, and obtained composite auxiliary material mobility and compressibility preferably, is adopted
The tablet prepared with the composite auxiliary material has the cohesive between certain hardness, any surface finish, composite auxiliary material preferable, tabletting
Obtained tablet is come off without piece powder, and the oral disnitegration tablet prepared using the composite auxiliary material is disintegrated soon, in good taste.The present invention is provided
Preparation method it is simple to operation, it is not necessary to large-scale instrument and equipment, cost is low, is conducive to industrialized production.Solve existing skill
Art prepares the problem of composite auxiliary material method is complicated, auxiliary material has waste, cost is higher using spray drying process.
Third aspect present invention provides a kind of purposes of composite auxiliary material, and the composite auxiliary material is used to prepare Orally disintegrating
Piece.
The obtained composite auxiliary material that third aspect present invention is provided can be used for preparing oral disnitegration tablet, and obtained oral cavity collapses
The disintegration time of piece is solved within 1min, disintegration is very fast, good mouthfeel, without feeling of grittiness, and there is suitable hardness, it is suitable to
Transport and storage, tablet weight variation are smaller.
To sum up, a kind of beneficial effect of composite auxiliary material that the present invention is provided and its production and use includes following
Aspect：
(1), the property such as the mobility of the composite auxiliary material, compressibility can reach the requirement of direct tablet compressing technique；
(2), the preparation method technique of the composite auxiliary material is simple, and cost is low, is conducive to industrialized production；
(3) oral disnitegration tablet, is prepared using the composite auxiliary material, the disintegration time of obtained oral disnitegration tablet is in 1min
Within.
Brief description of the drawings
The electronic scanner microscope figure of Fig. 1 composite auxiliary materials made from the product and embodiment 1 of comparative example 1~3；
Differential scanning calorimetry (DSC) figure of Fig. 2 composite auxiliary materials made from the product and embodiment 1 of comparative example 1~3
Spectrum；
The X-ray powder diffraction (XRD) of Fig. 3 composite auxiliary materials made from the product and embodiment 1 of comparative example 1~3 is bent
Line；
Infrared spectrum (FT-IR) spectrogram of Fig. 4 composite auxiliary materials made from the product and embodiment 1 of comparative example 1~3.
Embodiment
As described below is the preferred embodiment of the present invention, it is noted that for those skilled in the art
For, under the premise without departing from the principles of the invention, some improvements and modifications can also be made, these improvements and modifications are also considered as
Protection scope of the present invention.
Embodiment 1：
A kind of preparation method of composite auxiliary material, comprises the following steps：
Weigh PVPP 20g to be placed in beaker, add water the PVPP suspension for being made that concentration is 0.8g/mL；
Weigh mannitol 80g to be placed in beaker, adding 80 DEG C of hot water stirs is completely dissolved it, and mannitol saturated solution is made, will be sweet
Dew alcohol saturated solution be placed in ice-water bath cool and stir into beaker begin with crystallization separate out when, add PVPP be suspended
Liquid, under low temperature stirring, makes mannitol carry out cocrystallization with PVPP, treats after the completion of crystallization of mannitol, will burn
Material in cup carries out suction filtration, and 65 DEG C of drying, grinding is crossed 65 mesh sieves and sieved, produces composite auxiliary material.
Embodiment 2：
A kind of preparation method of composite auxiliary material, comprises the following steps：
Weigh PVPP 15g to be placed in beaker, add water the PVPP suspension for being made that concentration is 0.6g/mL；
Weigh mannitol 85g to be placed in beaker, adding 90 DEG C of hot water stirs is completely dissolved it, and mannitol saturated solution is made, will be sweet
Dew alcohol saturated solution be placed in ice-water bath cool and stir into beaker begin with crystallization separate out when, add PVPP be suspended
Liquid, under low temperature stirring, makes mannitol carry out cocrystallization with PVPP, treats after the completion of crystallization of mannitol, will burn
Material in cup carries out suction filtration, and 65 DEG C of drying, grinding is crossed 65 mesh sieves and sieved, produces composite auxiliary material.
Embodiment 3：
A kind of preparation method of composite auxiliary material, comprises the following steps：
Weigh PVPP 10g to be placed in beaker, add water the PVPP suspension for being made that concentration is 0.4g/mL；
Weigh mannitol 90g to be placed in beaker, adding 80 DEG C of hot water stirs is completely dissolved it, and mannitol saturated solution is made, will be sweet
Dew alcohol saturated solution be placed in ice-water bath cool and stir into beaker begin with crystallization separate out when, add PVPP be suspended
Liquid, under low temperature stirring, makes mannitol carry out cocrystallization with PVPP, treats after the completion of crystallization of mannitol, will burn
Material in cup carries out suction filtration, and 65 DEG C of drying, grinding is crossed 65 mesh sieves and sieved, produces composite auxiliary material.
Embodiment 4：
A kind of preparation method of composite auxiliary material, comprises the following steps：
Weigh PVPP 2g to be placed in beaker, add water the PVPP suspension for being made that concentration is 0.4g/mL；Claim
Mannitol 98g is taken to be placed in beaker, adding 80 DEG C of hot water stirs is completely dissolved it, mannitol saturated solution is made, by sweet dew
Alcohol saturated solution be placed in ice-water bath cool and stir into beaker begin with crystallization separate out when, add PVPP be suspended
Liquid, under low temperature stirring, makes mannitol carry out cocrystallization with PVPP, treats after the completion of crystallization of mannitol, will burn
Material in cup carries out suction filtration, and 65 DEG C of drying, grinding is crossed 65 mesh sieves and sieved, produces composite auxiliary material.
Embodiment 5：
A kind of preparation method of composite auxiliary material, comprises the following steps：
Weigh PVPP 40g to be placed in beaker, add water the PVPP suspension for being made that concentration is 0.8g/mL；
Weigh mannitol 60g to be placed in beaker, adding 80 DEG C of hot water stirs is completely dissolved it, and mannitol saturated solution is made, will be sweet
Dew alcohol saturated solution be placed in ice-water bath cool and stir into beaker begin with crystallization separate out when, add PVPP be suspended
Liquid, under low temperature stirring, makes mannitol carry out cocrystallization with PVPP, treats after the completion of crystallization of mannitol, will burn
Material in cup carries out suction filtration, and 65 DEG C of drying, grinding is crossed 65 mesh sieves and sieved, produces composite auxiliary material.
Embodiment 6：
A kind of preparation method of composite auxiliary material, comprises the following steps：
Weigh PVPP 25g to be placed in beaker, add water the PVPP suspension for being made that concentration is 0.6g/mL；
Weigh mannitol 75g to be placed in beaker, adding 80 DEG C of hot water stirs is completely dissolved it, and mannitol saturated solution is made, will be sweet
Dew alcohol saturated solution be placed in ice-water bath cool and stir into beaker begin with crystallization separate out when, add PVPP be suspended
Liquid, under low temperature stirring, makes mannitol carry out cocrystallization with PVPP, treats after the completion of crystallization of mannitol, will burn
Material in cup carries out suction filtration, and 65 DEG C of drying, grinding is crossed 65 mesh sieves and sieved, produces composite auxiliary material.
Embodiment 7：
American Pharmacopeia committee expert points out in the article for the relevant composite auxiliary material that American Pharmacopeia forum delivers, for making
The one-component of standby auxiliary material is clear and legible under physical mixed state, and during common processing, between single auxiliary material
It can not chemically react, so being combined mechanism for the composite auxiliary material prepared by the present invention and sign state is studied
And explain.
Comparative example 1：Single mannitol (being represented with A) is weighed to be tested.
Comparative example 2：Single PVPP (being represented with B) is weighed to be tested.
Comparative example 3：Mannitol 80g and PVPP 20g are weighed, is well mixed, physics mixed accessories is made and (use C tables
Show), tested.
Composite auxiliary material (being represented with D) made from the product of comparative example 1~3 and embodiment 1 is analyzed.Specifically
It is analyzed as follows described.
1st, electronic scanner microscope is analyzed
Composite auxiliary material made from the product and embodiment 1 of comparative example 1~3 is taken to carry out bonding mechanism and sign between auxiliary material
Research：
Using metal spraying method observe surface texture, by sample (be respectively mannitol (A), PVPP (B), mannitol and
Composite auxiliary material (D) made from above-mentioned PVPP physical mixture (C), embodiment 1) it is placed in glass dish, after ion sputtering
Sample surfaces structure is observed with SEM, accelerating potential is 25.0kV.
The electronic scanner microscope figure of Fig. 1 composite auxiliary materials made from the product and embodiment 1 of comparative example 1~3.By scheming
1A understands that comparative example 1 has the obvious crystal formation of the single auxiliary material of mannitol；Figure 1B is the structure of the PVPP of comparative example 2；Figure
1C is physical mixed auxiliary material made from comparative example 3, it is observed that the independent feature of mannitol and PVPP.Fig. 1 D are real
Composite auxiliary material made from example 1 is applied, the composite auxiliary material that mannitol and PVPP are obtained after cocrystallization is integral particle,
Outward appearance is spherical or spherical, and the independent spy of the obvious crystal formation of the single auxiliary material of mannitol and single PVPP is not observed
Levy, both are well combined.And physical mixed auxiliary material is observed that the independent feature of mannitol and PVPP, both can not
It is combined together well.Illustrating the preparation method of the present invention well can be combined mannitol one with PVPP
Rise, be not simple mixing, the reason for advantage for further illustrating composite auxiliary material physical property is improved.
2nd, differential calorimetric scan (DSC) is analyzed
Respectively by appropriate mannitol (A), PVPP (B), mannitol and PVPP physical mixture (C), reality
Apply mannitol made from example 1 and PVPP composite auxiliary material (D) is placed in an aluminum pot, using empty aluminium crucible as reference substance, heating
Speed：10.00℃·min-1；Temperature elevating range：0~500 DEG C, the differential calorimetric scan curve of sample is recorded respectively, and Fig. 2 is contrast
Differential scanning calorimetry (DSC) collection of illustrative plates of composite auxiliary material made from the product and embodiment 1 of example 1~3.
As can be seen from Figure 2, the DSC spectral lines of contrast mixed accessories (C) and composite auxiliary material (D), it is known that mannitol in composite auxiliary material
Do not produce new endothermic peak with PVPP, illustrate that the two is without the change in chemical constituent in composite auxiliary material.
3rd, x-ray powder diffraction (XRD) is analyzed
Respectively by appropriate mannitol (A), PVPP (B), mannitol and PVPP physical mixture (C), sweet
Reveal alcohol and PVPP composite auxiliary material (D) carries out X-ray powder diffraction analysis.Test condition is Cu targets (40kV, 40mV)；
Step-scan：0.02 °/step；Scanning range：5 °~60 °；Sweep speed：0.02°·min-1.The X-ray of sample is recorded respectively
Powder diffraction pattern, is shown in accompanying drawing 3.
The X-ray powder diffraction (XRD) of Fig. 3 composite auxiliary materials made from the product and embodiment 1 of comparative example 1~3 is bent
Line；As can be seen from Figure 3, mannitol has multiple strong crystalline characteristics diffraction maximums in the range of 10 °~50 °；PVPP is non-knot
Crystallization compound, without obvious diffraction maximum；Mannitol is still with the presence of crystal diffraction peak in the spectral line of mixed accessories, remitted its fury,
Illustrate that mannitol crystal formation does not change, chemical constituent does not also change；And in the spectral line of composite auxiliary material crystallization of mannitol
Diffraction maximum part is present, it may be possible to because part mannitol is divided in the technical process of crystallization with amorphous state or molecular state
It is dispersed in composite auxiliary material.
4th, infrared spectrum (FT-IR) is analyzed
Respectively by appropriate mannitol (A), PVPP (B), mannitol and PVPP physical mixture (C), reality
Apply mannitol made from example 1 and PVPP composite auxiliary material (D) is mixed after film-making in dry environments with KBr, 400~
4000cm-1In the range of carry out infrared spectrum measurement, obtain accompanying drawing 4.
Infrared spectrum (FT-IR) spectrogram of Fig. 4 composite auxiliary materials made from the product and embodiment 1 of comparative example 1~3.
As can be seen from Figure 4, the characteristic peak of mixed accessories spectral line is the simple superposition of mannitol and PVPP.The spectral line of composite auxiliary material with
Mixed accessories are compareed, and have no new absworption peak in the spectral line of composite auxiliary material, thus it is speculated that do not given birth between mannitol and PVPP
Cheng Xin chemical bond.
To sum up, by the way that by mannitol and PVPP cocrystallization, obtained composite auxiliary material is integral particle, granularity
It is uniformly dispersed, outward appearance is spherical or spherical, and the single feature of mannitol and PVPP, composite auxiliary material are not observed
Learn component also not change relative to simple physical mixed accessories, new change is not generated between mannitol and PVPP
Learn key.
Effect example 1
Obtained pharmaceutic adjuvant in embodiment 1~3 is carried out to the performance test in terms of powder fluidity, compressibility.
Powder fluidity：Weight differential influence of the mobility of powder on preparations such as granule, capsule, tablets is larger,
It is the important step for ensureing product quality.And direct compression method prepares tablet has specific requirement to the mobility of powder.Stop
(Angle of Repose) refers to the maximum angular that the free inclined-plane of powder accumulation horizon and horizontal plane are formed at angle, is to be commonly used to table
Show the index of powder fluidity.It is generally acknowledged that angle of repose is smaller, the frictional force between particle is smaller, and mobility is better.When stopping
The demand of mobility in production process can be met during angle≤35 °.The composite auxiliary material obtained in embodiment 1~3 is justified with fixed
Bore bottom method and determine angle of repose, as a result as shown in table 1.
Bulk density, tap density, carr's index：The compressibility and filling capacity of carr's index reaction powder.Carr's index
Big powder compressibility is good, but poor fluidity；The small powder fillibility of carr's index and good fluidity,
But poor compressibility.Generally, when carr's index between 15%~25% when, the mobility and compressibility of powder
The requirement of rotary tablet machine direct powder compression can be reached.Determine embodiment 1~3 in obtain composite auxiliary material it is loose close
Degree, tap density, carr index, as a result as shown in table 1.
The dry jet mixing pile of the composite auxiliary material of table 1
The result of table 1 shows that the angle of repose of composite auxiliary material produced by the present invention and carr index are satisfied by direct compression method
Requirement to auxiliary material.
The product of obtained composite auxiliary material in embodiment 2 and comparative example 1~3 is carried out to the comparison of mobility, as a result such as table 2
It is shown.
The single auxiliary material of table 2, physical mixed and composite auxiliary material dry jet mixing pile
The result of table 2 shows that composite auxiliary material dry jet mixing pile produced by the present invention is better than its single auxiliary material and simple thing
The auxiliary material being mixed to get is managed, the performance for illustrating composite auxiliary material produced by the present invention is not that the simple of the performance of two kinds of single auxiliary materials adds
With composite auxiliary material dry jet mixing pile of the invention is advantageously.
Effect example 2
Blank oral disnitegration tablet is made in the case of without adding auxiliary material with the composite auxiliary material of the gained of embodiment 1~3,
And hardness, disintegration time limited, mouthfeel, surface smoothness and the friability of blank oral disnitegration tablet are determined, three groups of each point is surveyed
It is fixed.As a result it is as shown in table 3：
Disintegration time：Oral disnitegration tablet is as a kind of special formulation, and one of technical points are control tablets in oral cavity
Disintegration time.It is measured using extremely big day hair KB-1 Orally disintegrating instrument.Specific continuous mode is as follows：Plus 37 DEG C of 900mL
Distilled water is in stripping rotor, and in oral disnitegration tablet input disintegration basket, click starts, and disintegration basket teetertotters, and records from input piece
Agent untill basic noresidue on screen cloth this period be oral disnitegration tablet disintegration time.
Mouthfeel：Mouthfeel is compared with volunteer's experiment.6 healthy volunteers are selected, wherein 3 male 3 female, the age was at 18~36 years old
Between, using three opinion ratings, A：It is good；B：Typically；C：Difference.
Lustrous surface：Visually observation.
Friability：Press《Chinese Pharmacopoeia》Friability determination method is measured.
Blank oral disnitegration tablet characteristic research made from the composite auxiliary material of table 3
As a result：Blank oral disnitegration tablet any surface finish made from the composite auxiliary material, good mouthfeel, without feeling of grittiness, during disintegration
Between within 1min, and with certain hardness, suitable for transporting and depositing.
Application Example 1
Ibuprofen oral disintegrating tablets are prepared with composite auxiliary material made from embodiment 2, preparation method is as follows：
Brufen 18g, plus the gained composite auxiliary material 27g of above example 2 are taken, appropriate magnesium stearate is eventually adding, mixes, adopts
Prepared with direct powder compression, every piece 0.2g compressing with 8mm punch dies, hardness is controlled in 70~80N, brufen is made
Oral disnitegration tablet 200.
Ibuprofen oral disintegrating tablets obtained above are tested：Test result shows the complete bright and clean, color of gained tablet
It is damp uniform, 70~80N of tablet hardness, disintegration time is within 40s, the micro- sweet tea of taste, no feeling of grittiness, good mouthfeel.Tablet weight variation control
System is within 0.75%.
Application Example 2
Vitamin C oral disintegration tablet is prepared with composite auxiliary material made from embodiment 3, preparation method is as follows：
Vitamin C 6g, plus the gained composite auxiliary material 56g of above example 3 are taken, appropriate magnesium stearate is eventually adding, mixed,
Prepared using direct powder compression, every piece 0.2g compressing with 8mm punch dies, hardness is controlled in 70~80N, dimension life is made
Plain C oral disnitegration tablets 260.
Vitamin C oral disintegration tablet obtained above is tested：Test result shows the complete bright and clean, color of gained tablet
It is damp uniform, 70~80N of tablet hardness, disintegration time is within 40s, the micro- sweet tea of taste, no feeling of grittiness, good mouthfeel.Tablet weight variation control
System is within 0.75%.
To sum up, than two kinds auxiliary materials of performance that the embodiment of the present invention passes through composite auxiliary material made from simple cocrystallization method
The auxiliary material performance that is mixed to get of simple physical it is more excellent, the property such as its mobility, compressibility can reach direct tablet compressing work
The requirement of skill；Using the disintegration time of oral disnitegration tablet made from composite auxiliary material of the present invention within 1min.The composite auxiliary material
Can be well mixed with other auxiliary materials and main ingredient, after direct tablet compressing, obtained tablet weight difference is small, in addition, Orally disintegrating
Any surface finish of piece, good mouthfeel, without feeling of grittiness, and with certain hardness, suitable for transporting and depositing.
Embodiment described above only expresses the several embodiments of the present invention, and it describes more specific and detailed, but simultaneously
Therefore the limitation to the scope of the claims of the present invention can not be interpreted as.It should be pointed out that for one of ordinary skill in the art
For, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to the guarantor of the present invention
Protect scope.Therefore, the protection domain of patent of the present invention should be determined by the appended claims.
Claims (8)
1. a kind of composite auxiliary material, it is characterised in that it by mannitol and PVPP is 98 in mass ratio that the composite auxiliary material, which is,
~40:2~60 in the mixed solvents formed in water or at least one of ethanol and ethyl acetate with water are tied jointly
The spherical or spherical particle that crystalline substance is obtained.
2. a kind of preparation method of composite auxiliary material, it is characterised in that comprise the following steps：
PVPP suspension is added in mannitol saturated solution, under ice-water bath and stirring, makes the mannitol
It is 98~40 in mass ratio with the PVPP:2~60 in water or at least one of ethanol and ethyl acetate with
The in the mixed solvent of water formation carries out cocrystallization, treats after the completion of crystallization of mannitol, suction filtration is dried, ground after sieving, produces institute
Composite auxiliary material is stated, the composite auxiliary material is to carry out spherical or spherical that cocrystallization is obtained by mannitol and PVPP
Grain.
3. the preparation method of composite auxiliary material as claimed in claim 2, it is characterised in that the mannitol and the poly- dimension of the crosslinking
Ketone is 98~75 in mass ratio:2~25 carry out cocrystallization.
4. the preparation method of composite auxiliary material as claimed in claim 3, it is characterised in that the mannitol and the poly- dimension of the crosslinking
Ketone is 90~75 in mass ratio:10~25 carry out cocrystallization.
5. the preparation method of composite auxiliary material as claimed in claim 2, it is characterised in that be placed in the mannitol saturated solution
In ice-water bath and stir to when beginning with crystallization and separating out, add the PVPP suspension, continue to stir, make the sweet dew
Alcohol carries out cocrystallization with the PVPP.
6. the preparation method of composite auxiliary material as claimed in claim 2, it is characterised in that the PVPP is dispersed
One or more in water, ethanol and ethyl acetate obtain the PVPP suspension.
7. the preparation method of composite auxiliary material as claimed in claim 2, it is characterised in that be dissolved in water the mannitol
To the mannitol saturated solution.
8. a kind of purposes of composite auxiliary material, it is characterised in that be combined made from the preparation method as described in claim any one of 2-7
Auxiliary material is used to prepare oral disnitegration tablet.
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|---|---|---|---|---|
| CN111166891B (en) * | 2018-11-13 | 2022-04-05 | 中国药科大学 | Mannitol eutectic auxiliary material and preparation method and application thereof |
| CN109481690A (en) * | 2019-01-23 | 2019-03-19 | 谭淞文 | A kind of Novel microcrystalline mannitol pharmaceutic adjuvant |
| CN114504559B (en) * | 2022-03-01 | 2023-05-05 | 安徽山河药用辅料股份有限公司 | Preparation method of pharmaceutical adjuvant lactose cellulose co-processed product |
| CN116459347B (en) * | 2023-06-07 | 2024-06-21 | 江苏西典药用辅料有限公司 | Mannitol and microcrystalline cellulose-based composite auxiliary material and preparation method thereof |
| CN118453884B (en) * | 2024-07-12 | 2024-09-27 | 山东天力药业有限公司 | Mannitol-containing pharmaceutical adjuvant and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1494418A (en) * | 2001-03-06 | 2004-05-05 | Э�ͷ���ҵ��ʽ���� | Tablets quickly disintegrating in oral cavity |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP5100391B2 (en) * | 2005-10-05 | 2012-12-19 | 京都薬品工業株式会社 | Oral composition |
| TWI547282B (en) * | 2007-07-02 | 2016-09-01 | 愛戴爾製藥股份有限公司 | Orally disintegrating tablet compositions of lamotrigine |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1494418A (en) * | 2001-03-06 | 2004-05-05 | Э�ͷ���ҵ��ʽ���� | Tablets quickly disintegrating in oral cavity |
Non-Patent Citations (1)
| Title |
|---|
| Studies of Rapidly Disintegrating Tablets in the Oral Cavity Using Co-ground Mixtures of Mannitol with Crospovidone;Toshifusa SHU et al.;《Chem. Pharm. Bull.》;20020228;第50卷(第2期);193-198页 * |
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