CN104645336A - Composite auxiliary material as well as preparation method and application thereof - Google Patents
Composite auxiliary material as well as preparation method and application thereof Download PDFInfo
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- CN104645336A CN104645336A CN201510003814.5A CN201510003814A CN104645336A CN 104645336 A CN104645336 A CN 104645336A CN 201510003814 A CN201510003814 A CN 201510003814A CN 104645336 A CN104645336 A CN 104645336A
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Abstract
The invention provides a composite auxiliary material which is spherical or spherical-like particles obtained by virtue of co-crystallization between mannitol and crospovidone. The properties of fluidity, compressibility and the like of the compound auxiliary material meet requirements of a direct tablet compressing process. The invention also provides a preparation method of the composite auxiliary material. The preparation method comprises the following steps: adding a crospovidone suspension into a mannitol saturated solution; performing co-crystallization on mannitol and crospovidon in an ice water bath while stirring; and when the crystallization of mannitol is finished, performing suction filtration, drying, grinding and screening to obtain the composite auxiliary material which is the spherical or spherical-like particles obtained by virtue of co-crystallization between mannitol and crospovidone. The preparation method of the composite auxiliary material is simple in process and low in cost, and is beneficial for industrial production. The composite auxiliary material prepared by the method provided by the invention is used for preparing orally disintegrating tablets, and the disintegrating time of the prepared tablets is within 1 minute.
Description
Technical field
The present invention relates to field of medicaments, be specifically related to a kind of composite auxiliary material and its production and use.
Background technology
Tablet as traditional dosage form, because of its stable in properties, carry with easy to use, manufacturing machine degree is high, cost is low, output is high, divided dose is accurate and become one of the most frequently used at present dosage form.But because tablet needs extrusion forming, disintegrate comparatively slowly, bioavailability is lower and old people, child, psychotic etc. swallow comparatively difficult, thus makes promoting the use of of tablet be restricted to a certain extent.Therefore, in the research of solid preparation, various quick releasing formulation has become a focus, particularly oral cavity disintegration tablet of new drug development in recent years gradually.Oral cavity disintegration tablet is that a kind of water that do not need in oral cavity can the tablet of disintegrate or dissolving, and it has and absorbs fast, and bioavailability is high, need not use water delivery service, taking convenience, and intestinal is residual to be lacked, and side effect is low, can reduce the advantages such as the first pass effect of liver.Disintegrating agent conventional in conventional oral cavity disintegration tablet is at present as all heavier in the granular sensation after the disintegrates such as carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose and polyvinylpolypyrrolidone, mouthfeel is bad, and the mobility of these disintegrating agents is bad, be difficult to mix homogeneously with principal agent and other adjuvants, cause during direct compression, easily occurring the quality problems such as tablet weight variation is large, finished product disintegration time difference is large.
For solving this problem, publication number is that the invention of CN101829333 provides a kind of new multi-functional auxiliary material, this adjuvant is processed into by mannitol, isosorbide and polyvinylpolypyrrolidone, although mobility and the disintegrate ability of obtained adjuvant increase, but use spray drying method to prepare adjuvant, method is comparatively complicated, and spraying apparatus floor space is large, and production cost is higher; Also need to add isosorbide as binding agent in preparation process, further increase production cost.
Summary of the invention
For solving the problem, the invention provides a kind of composite auxiliary material and its production and use.Composite auxiliary material provided by the invention is obtained by mannitol and polyvinylpolypyrrolidone cocrystallization, preparation method technique is simple, and do not need large-scale instrument and equipment in preparation process, cost is low, be conducive to suitability for industrialized production, solve the problem of prior art composite auxiliary material preparation method complexity.
First aspect present invention provides a kind of composite auxiliary material, and described composite auxiliary material carries out by mannitol and polyvinylpolypyrrolidone the spherical or spherical particle that cocrystallization obtains.
Described composite auxiliary material is spherical or spherical particle, described composite auxiliary material granule rounding, and sphericity is better, can improve the mobility of described composite auxiliary material.
Preferably, described mannitol and described polyvinylpolypyrrolidone are that cocrystallization is carried out in 98 ~ 40:2 ~ 60 in mass ratio.Under this ratio, better, obtained composite auxiliary material mobility and compressibility all can meet the needs of direct compression, overcome polyvinylpolypyrrolidone separately as the defect of disintegrating agent for mannitol and polyvinylpolypyrrolidone mixed effect.
More preferably, described mannitol and described polyvinylpolypyrrolidone are that cocrystallization is carried out in 98 ~ 75:2 ~ 25 in mass ratio.
Further preferably, described mannitol and described polyvinylpolypyrrolidone are that cocrystallization is carried out in 90 ~ 75:10 ~ 25 in mass ratio.
The composite auxiliary material that first aspect present invention provides, obtained by mannitol and polyvinylpolypyrrolidone cocrystallization, wherein mannitol has the advantages such as agent of low hygroscopicity, high stability, height endurability, low in calories and sweet taste be pure, is preparing the effect mainly playing excipient and correctives in oral cavity disintegration tablet.The excipient that currently available technology prepares tablet uses lactose mostly, and this patient just making to suffer from lactose intolerance particularly gastrointestinal function does not have fully grown child to cause certain puzzlement when drug administration.Composite auxiliary material of the present invention fundamentally solves this problem.Polyvinylpolypyrrolidone is disintegrating agent conventional in oral cavity disintegration tablet, and mouthfeel is good, without grains of sand sense.The composite auxiliary material prepared by mannitol and polyvinylpolypyrrolidone cocrystallization, mobility and compressibility all can reach the requirement of direct compression technique, the tablet hardness using this composite auxiliary material obtained is moderate, and tablet weight variation is less, and namely water a small amount of in oral cavity can make its rapid swelling disintegrate and good mouthfeel.
Second aspect present invention provides a kind of preparation method of composite auxiliary material, comprises the following steps:
Polyvinylpolypyrrolidone suspension is added in mannitol saturated solution, under ice-water bath and stirring, described mannitol and described polyvinylpolypyrrolidone is made to carry out cocrystallization, after crystallization of mannitol completes, sucking filtration, dry, grinding obtains described composite auxiliary material after sieving, and described composite auxiliary material carries out by mannitol and polyvinylpolypyrrolidone the spherical or spherical particle that cocrystallization obtains.
Described composite auxiliary material is spherical or that class is spherical granular particles rounding, and sphericity is better, can improve the mobility of described composite auxiliary material.
Preferably, described mannitol saturated solution be placed in ice-water bath and be stirred to when starting there is crystallization, adding described polyvinylpolypyrrolidone suspension, continuing to stir, make described mannitol and described polyvinylpolypyrrolidone carry out cocrystallization.
Preferably, described mannitol and described polyvinylpolypyrrolidone are that cocrystallization is carried out in 98 ~ 40:2 ~ 60 in mass ratio.
More preferably, described mannitol and described polyvinylpolypyrrolidone are that cocrystallization is carried out in 98 ~ 75:2 ~ 25 in mass ratio.
Further preferably, described mannitol and described polyvinylpolypyrrolidone are that cocrystallization is carried out in 90 ~ 75:10 ~ 25 in mass ratio.
Preferably, one or more being dispersed in by described polyvinylpolypyrrolidone in water, ethanol and ethyl acetate obtain described polyvinylpolypyrrolidone suspension.
More preferably, described polyvinylpolypyrrolidone is dispersed in water and obtains described polyvinylpolypyrrolidone suspension.
Preferably, in described polyvinylpolypyrrolidone suspension, the concentration of described polyvinylpolypyrrolidone is 0.4g/mL ~ 0.8g/mL.
Preferably, one or more being dissolved in by described mannitol in water, ethanol and ethyl acetate obtain described mannitol saturated solution.
More preferably, described mannitol is joined in the hot water of 80 ~ 90 DEG C and stir, make it dissolve completely and obtain described mannitol saturated solution.
Preferably, described baking temperature is 65 DEG C.
Preferably, employing 65 mesh sieve that sieves described in sieves.
The preparation method of the composite auxiliary material that second aspect present invention provides, only need the method for cocrystallization be adopted can to obtain described composite auxiliary material described mannitol and described polyvinylpolypyrrolidone, the composite auxiliary material mobility obtained and compressibility better, the tablet adopting described composite auxiliary material to prepare has certain hardness, any surface finish, the cohesive between composite auxiliary material is better, and the tablet that tabletting obtains comes off without sheet powder, the oral cavity disintegration tablet disintegrate utilizing described composite auxiliary material to prepare is fast, and mouthfeel is good.Preparation method provided by the invention is simple to operation, does not need large-scale instrument and equipment, and cost is low, is conducive to suitability for industrialized production.Solve prior art and adopt the problem that spray drying method prepares composite auxiliary material method complexity, adjuvant exists waste, cost is higher.
Third aspect present invention provides a kind of purposes of composite auxiliary material, and described composite auxiliary material is for the preparation of oral cavity disintegration tablet.
The obtained composite auxiliary material that third aspect present invention provides may be used for preparing oral cavity disintegration tablet, and the disintegration time of obtained oral cavity disintegration tablet is all within 1min, and disintegrate is very fast, good mouthfeel, without grains of sand sense, and have suitable hardness, be suitable for transport and deposit, tablet weight variation is less.
To sum up, the beneficial effect of a kind of composite auxiliary material provided by the invention and its production and use comprises the following aspects:
(1), the character such as mobility, compressibility of described composite auxiliary material all can reach the requirement of direct compression technique;
(2), the preparation method technique of described composite auxiliary material is simple, and cost is low, is conducive to industrialized production;
(3), adopt described composite auxiliary material to prepare oral cavity disintegration tablet, the disintegration time of obtained oral cavity disintegration tablet is all within 1min.
Accompanying drawing explanation
Fig. 1 is the electronic scanner microscope figure of the obtained composite auxiliary material of the product of comparative example 1 ~ 3 and embodiment 1;
Fig. 2 is differential scanning calorimetry (DSC) collection of illustrative plates of the obtained composite auxiliary material of the product of comparative example 1 ~ 3 and embodiment 1;
Fig. 3 is X-ray powder diffraction (XRD) curve of the obtained composite auxiliary material of the product of comparative example 1 ~ 3 and embodiment 1;
Fig. 4 is infrared spectrum (FT-IR) spectrogram of the obtained composite auxiliary material of the product of comparative example 1 ~ 3 and embodiment 1.
Detailed description of the invention
The following stated is the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the premise without departing from the principles of the invention; can also make some improvements and modifications, these improvements and modifications are also considered as protection scope of the present invention.
Embodiment 1:
A preparation method for composite auxiliary material, comprises the following steps:
Take polyvinylpolypyrrolidone 20g and be placed in beaker, add water and make the polyvinylpolypyrrolidone suspension that concentration is 0.8g/mL; Take mannitol 80g and be placed in beaker, add 80 DEG C of hot water stirs and make it dissolve completely, make mannitol saturated solution, mannitol saturated solution is placed in ice-water bath lower the temperature and be stirred to beaker when starting there is crystallization, add polyvinylpolypyrrolidone suspension, under low temperature stirring, make mannitol and polyvinylpolypyrrolidone carry out cocrystallization, after crystallization of mannitol completes, material in beaker is carried out sucking filtration, 65 DEG C of oven dry, grinding, cross 65 mesh sieves to sieve, obtain composite auxiliary material.
Embodiment 2:
A preparation method for composite auxiliary material, comprises the following steps:
Take polyvinylpolypyrrolidone 15g and be placed in beaker, add water and make the polyvinylpolypyrrolidone suspension that concentration is 0.6g/mL; Take mannitol 85g and be placed in beaker, add 90 DEG C of hot water stirs and make it dissolve completely, make mannitol saturated solution, mannitol saturated solution is placed in ice-water bath lower the temperature and be stirred to beaker when starting there is crystallization, add polyvinylpolypyrrolidone suspension, under low temperature stirring, make mannitol and polyvinylpolypyrrolidone carry out cocrystallization, after crystallization of mannitol completes, material in beaker is carried out sucking filtration, 65 DEG C of oven dry, grinding, cross 65 mesh sieves to sieve, obtain composite auxiliary material.
Embodiment 3:
A preparation method for composite auxiliary material, comprises the following steps:
Take polyvinylpolypyrrolidone 10g and be placed in beaker, add water and make the polyvinylpolypyrrolidone suspension that concentration is 0.4g/mL; Take mannitol 90g and be placed in beaker, add 80 DEG C of hot water stirs and make it dissolve completely, make mannitol saturated solution, mannitol saturated solution is placed in ice-water bath lower the temperature and be stirred to beaker when starting there is crystallization, add polyvinylpolypyrrolidone suspension, under low temperature stirring, make mannitol and polyvinylpolypyrrolidone carry out cocrystallization, after crystallization of mannitol completes, material in beaker is carried out sucking filtration, 65 DEG C of oven dry, grinding, cross 65 mesh sieves to sieve, obtain composite auxiliary material.
Embodiment 4:
A preparation method for composite auxiliary material, comprises the following steps:
Take polyvinylpolypyrrolidone 2g and be placed in beaker, add water and make the polyvinylpolypyrrolidone suspension that concentration is 0.4g/mL; Take mannitol 98g and be placed in beaker, add 80 DEG C of hot water stirs and make it dissolve completely, make mannitol saturated solution, mannitol saturated solution is placed in ice-water bath lower the temperature and be stirred to beaker when starting there is crystallization, add polyvinylpolypyrrolidone suspension, under low temperature stirring, make mannitol and polyvinylpolypyrrolidone carry out cocrystallization, after crystallization of mannitol completes, material in beaker is carried out sucking filtration, 65 DEG C of oven dry, grinding, cross 65 mesh sieves to sieve, obtain composite auxiliary material.
Embodiment 5:
A preparation method for composite auxiliary material, comprises the following steps:
Take polyvinylpolypyrrolidone 40g and be placed in beaker, add water and make the polyvinylpolypyrrolidone suspension that concentration is 0.8g/mL; Take mannitol 60g and be placed in beaker, add 80 DEG C of hot water stirs and make it dissolve completely, make mannitol saturated solution, mannitol saturated solution is placed in ice-water bath lower the temperature and be stirred to beaker when starting there is crystallization, add polyvinylpolypyrrolidone suspension, under low temperature stirring, make mannitol and polyvinylpolypyrrolidone carry out cocrystallization, after crystallization of mannitol completes, material in beaker is carried out sucking filtration, 65 DEG C of oven dry, grinding, cross 65 mesh sieves to sieve, obtain composite auxiliary material.
Embodiment 6:
A preparation method for composite auxiliary material, comprises the following steps:
Take polyvinylpolypyrrolidone 25g and be placed in beaker, add water and make the polyvinylpolypyrrolidone suspension that concentration is 0.6g/mL; Take mannitol 75g and be placed in beaker, add 80 DEG C of hot water stirs and make it dissolve completely, make mannitol saturated solution, mannitol saturated solution is placed in ice-water bath lower the temperature and be stirred to beaker when starting there is crystallization, add polyvinylpolypyrrolidone suspension, under low temperature stirring, make mannitol and polyvinylpolypyrrolidone carry out cocrystallization, after crystallization of mannitol completes, material in beaker is carried out sucking filtration, 65 DEG C of oven dry, grinding, cross 65 mesh sieves to sieve, obtain composite auxiliary material.
Embodiment 7:
Point out in the article of the relevant composite auxiliary material that American Pharmacopeia committee expert delivers in American Pharmacopeia forum, one-component for the preparation of adjuvant is clear and legible under physical mixed state, and in the process of common processing, chemical reaction can not be there is, so carry out bonding mechanism for the composite auxiliary material prepared by the present invention and sign state carries out studying and explaining between single adjuvant.
Comparative example 1: take single mannitol (representing with A) and test.
Comparative example 2: take single polyvinylpolypyrrolidone (representing with B) and test.
Comparative example 3: take mannitol 80g and polyvinylpolypyrrolidone 20g, mix homogeneously, makes physics mixed accessories (representing with C), tests.
The composite auxiliary material (representing with D) that the product of comparative example 1 ~ 3 and embodiment 1 obtain is analyzed.Make a concrete analysis of as described below.
1, electronic scanner microscope analysis
Get the product of comparative example 1 ~ 3 and the obtained composite auxiliary material of embodiment 1 carries out bonding mechanism and characterization research between adjuvant:
Metal spraying method is adopted to observe surface texture, sample (being respectively the composite auxiliary material (D) that mannitol (A), polyvinylpolypyrrolidone (B), mannitol and above-mentioned polyvinylpolypyrrolidone physical mixture (C), embodiment 1 are obtained) is placed in glass dish, observe sample surfaces structure with SEM after ion sputtering, accelerating potential is 25.0kV.
Fig. 1 is the electronic scanner microscope figure of the obtained composite auxiliary material of the product of comparative example 1 ~ 3 and embodiment 1.From Figure 1A, comparative example 1 has the obvious crystal formation of the single adjuvant of mannitol; Figure 1B is the structure of the polyvinylpolypyrrolidone of comparative example 2; Fig. 1 C is the physical mixed adjuvant that comparative example 3 obtains, and can observe the independent feature of mannitol and polyvinylpolypyrrolidone.Fig. 1 D is the composite auxiliary material that embodiment 1 obtains, the composite auxiliary material that mannitol and polyvinylpolypyrrolidone obtain after cocrystallization is an integral particle, outward appearance is spherical or class is spherical, and do not observe out the independent feature of the obvious crystal formation of the single adjuvant of mannitol and single polyvinylpolypyrrolidone, both combine well.And physical mixed adjuvant can observe the independent feature of mannitol and polyvinylpolypyrrolidone, both can not combine well.Illustrating that mannitol and polyvinylpolypyrrolidone can combine by preparation method of the present invention well, is not simple mixing, the reason that the advantage further illustrating composite auxiliary material physical property improves.
2, differential calorimetric scan (DSC) is analyzed
The mannitol appropriate mannitol (A), polyvinylpolypyrrolidone (B), mannitol and polyvinylpolypyrrolidone physical mixture (C), embodiment 1 obtained respectively and polyvinylpolypyrrolidone composite auxiliary material (D) are placed in an aluminum pot, with empty aluminum crucible for reference substance, heating rate: 10.00 DEG C of min
-1; Temperature elevating range: 0 ~ 500 DEG C, records the differential calorimetric scan curve of sample respectively, and Fig. 2 is differential scanning calorimetry (DSC) collection of illustrative plates of the obtained composite auxiliary material of the product of comparative example 1 ~ 3 and embodiment 1.
As can be seen from Figure 2, the DSC spectral line of contrast mixed accessories (C) and composite auxiliary material (D), in known composite auxiliary material, mannitol and polyvinylpolypyrrolidone do not produce new endothermic peak, illustrate that in composite auxiliary material, the two does not have the change in chemical constituent.
3, x-ray powder diffraction (XRD) is analyzed
Respectively appropriate mannitol (A), polyvinylpolypyrrolidone (B), mannitol and polyvinylpolypyrrolidone physical mixture (C), mannitol and polyvinylpolypyrrolidone composite auxiliary material (D) are carried out X-ray powder diffraction analysis.Test condition is Cu target (40kV, 40mV); Step-scan: 0.02 °/step; Sweep limits: 5 ° ~ 60 °; Scanning speed: 0.02 ° of min
-1.Record the X-ray powder diffraction curve of sample respectively, see accompanying drawing 3.
Fig. 3 is X-ray powder diffraction (XRD) curve of the obtained composite auxiliary material of the product of comparative example 1 ~ 3 and embodiment 1; As can be seen from Figure 3, mannitol has multiple strong crystalline characteristics diffraction maximum within the scope of 10 ° ~ 50 °; Polyvinylpolypyrrolidone is amorphization compound, does not have obvious diffraction maximum; In the spectral line of mixed accessories, mannitol still has crystal diffraction peak to exist, strength reduction, and illustrate that mannitol crystal formation does not change, chemical constituent does not change yet; And crystallization of mannitol diffraction maximum part exists in the spectral line of composite auxiliary material, may be because part mannitol is dispersed in composite auxiliary material with amorphous state or molecularity in the technical process of crystallization.
4, infrared spectrum (FT-IR) is analyzed
After the mannitol appropriate mannitol (A), polyvinylpolypyrrolidone (B), mannitol and polyvinylpolypyrrolidone physical mixture (C), embodiment 1 obtained respectively and polyvinylpolypyrrolidone composite auxiliary material (D) mix film-making in dry environments with KBr, at 400 ~ 4000cm
-1carry out infrared spectrum measurement in scope, obtain accompanying drawing 4.
Fig. 4 is infrared spectrum (FT-IR) spectrogram of the obtained composite auxiliary material of the product of comparative example 1 ~ 3 and embodiment 1.As can be seen from Figure 4, the characteristic peak of mixed accessories spectral line is the simple superposition of mannitol and polyvinylpolypyrrolidone.The spectral line of composite auxiliary material contrasts with mixed accessories, has no new absworption peak in the spectral line of composite auxiliary material, infers and does not generate new chemical bond between mannitol and polyvinylpolypyrrolidone.
To sum up, by by mannitol and polyvinylpolypyrrolidone cocrystallization, the composite auxiliary material obtained is an integral particle, particle size distribution is even, outward appearance is spherical or class is spherical, do not observe out the independent feature of mannitol and polyvinylpolypyrrolidone, composite auxiliary material chemical constituent does not change relative to simple physical mixed accessories yet, does not generate new chemical bond between mannitol and polyvinylpolypyrrolidone.
Effect example 1
Pharmaceutic adjuvant obtained in embodiment 1 ~ 3 is carried out the performance test of the aspect such as powder fluidity, compressibility.
Powder fluidity: the weight differential impact of mobility on preparations such as granule, capsule, tablets of powder body is comparatively large, is the important step ensureing product quality.And direct compression process is prepared the mobility of tablet to powder body and is had specific requirement.Referring to the maximum angular that the free inclined-plane of powder body accumulation horizon and horizontal plane are formed angle of repose (Angle of Repose), is the index being commonly used to represent powder fluidity.It is generally acknowledged that angle of repose is less, the frictional force between particle is less, and mobility is better.When angle of repose≤35 ° time can meet the demand of mobility in production process.The fixing conical bottom method of the composite auxiliary material obtained in embodiment 1 ~ 3 is measured angle of repose, and result is as shown in table 1.
Bulk density, tap density, carr's index: the compressibility of carr's index reaction powder and filling capacity.The powder compressibility that carr's index is large is good, but poor fluidity; The powder fillibility that carr's index is little and good fluidity,
But poor compressibility.Generally, when carr's index is between 15% ~ 25% time, the mobility of powder and compressibility all can reach the requirement of rotary tablet machine direct powder compression.Measure bulk density, tap density, the carr index of the composite auxiliary material obtained in embodiment 1 ~ 3, result is as shown in table 1.
The dry jet mixing pile of table 1 composite auxiliary material
The result of table 1 shows, the angle of repose of the composite auxiliary material that the present invention obtains and carr index all meet the requirement of direct compression process to adjuvant.
Composite auxiliary material obtained in embodiment 2 is carried out comparing of mobility with the product of comparative example 1 ~ 3, and result is as shown in table 2.
The single adjuvant of table 2, physical mixed and composite auxiliary material dry jet mixing pile
The result of table 2 shows, the composite auxiliary material dry jet mixing pile that the present invention obtains is better than the adjuvant that its single adjuvant and simple physical are mixed to get, illustrate the performance of the composite auxiliary material that the present invention obtains be not the performance of two kinds of single adjuvants simply adding and, composite auxiliary material dry jet mixing pile of the present invention is advantageously.
Effect example 2
Make blank oral cavity disintegration tablet with the composite auxiliary material of embodiment 1 ~ 3 gained when separately not adding adjuvant, and measure the hardness of blank oral cavity disintegration tablet, disintegration, mouthfeel, surface smoothness and friability, every point three groups measure.Result is as shown in table 3:
Disintegration time: oral cavity disintegration tablet is as a kind of special dosage form, and one of its technical essential controls the disintegration time of tablet in oral cavity.Adopt huge sky to send out KB-1 Orally disintegrating instrument to measure.Concrete mensuration process is as follows: add the distilled water of 900mL 37 DEG C in stripping rotor, oral cavity disintegration tablet drops in disintegrate basket, click and start, disintegrate basket teetertotters, and record from dropping into tablet is the disintegration time of oral cavity disintegration tablet during this period of time to noresidue basic screen cloth.
Mouthfeel: compare mouthfeel with volunteer's experiment.Select 6 healthy volunteers, wherein 3 male 3 female, the age, between 18 ~ 36 years old, adopts three opinion ratings, A: good; B: general; C: poor.
Lustrous surface: visualization.
Friability: measure by " Chinese Pharmacopoeia " friability algoscopy.
The blank oral cavity disintegration tablet characteristic research that table 3 composite auxiliary material is obtained
Result: the blank oral cavity disintegration tablet any surface finish that this composite auxiliary material is obtained, good mouthfeel, without grains of sand sense, disintegration time all within 1min, and has certain hardness, is suitable for transporting and depositing.
Application Example 1
Prepare ibuprofen oral disintegrating tablets with the composite auxiliary material that embodiment 2 is obtained, preparation method is as follows:
Get ibuprofen 18g, add above embodiment 2 gained composite auxiliary material 27g, finally add appropriate magnesium stearate, mixing, adopts direct powder compression preparation, compressing with 8mm punch die, every sheet 0.2g, Hardness Control, at 70 ~ 80N, obtains ibuprofen oral disintegrating tablets 200.
Above-mentioned obtained ibuprofen oral disintegrating tablets is tested: test result shows complete bright and clean, the uniform color of obtained sheet agent, tablet hardness 70 ~ 80N, and disintegration time is within 40s, and taste is micro-sweet, without grains of sand sense, good mouthfeel.Tablet weight variation controls within 0.75%.
Application Example 2
Prepare vitamin C oral disintegration tablet with the composite auxiliary material that embodiment 3 is obtained, preparation method is as follows:
Get vitamin C 6g, add above embodiment 3 gained composite auxiliary material 56g, finally add appropriate magnesium stearate, mixing, adopts direct powder compression preparation, compressing with 8mm punch die, every sheet 0.2g, Hardness Control, at 70 ~ 80N, obtains vitamin C oral disintegration tablet 260.
Above-mentioned obtained vitamin C oral disintegration tablet is tested: test result shows complete bright and clean, the uniform color of obtained sheet agent, tablet hardness 70 ~ 80N, and disintegration time is within 40s, and taste is micro-sweet, without grains of sand sense, good mouthfeel.Tablet weight variation controls within 0.75%.
To sum up, the adjuvant performance that the simple physical of Performance Ratio two kinds of adjuvants of the composite auxiliary material that the embodiment of the present invention is obtained by simple cocrystallization method is mixed to get is more excellent, and its character such as mobility, compressibility all can reach the requirement of direct compression technique; The disintegration time of the oral cavity disintegration tablet adopting composite auxiliary material of the present invention to obtain is all within 1min.This composite auxiliary material can with other adjuvants and principal agent mix homogeneously, after direct compression, the tablet weight difference obtained is little, and in addition, any surface finish of oral cavity disintegration tablet, good mouthfeel, without grains of sand sense, and have certain hardness, is suitable for transport and deposits.
The above embodiment only have expressed several embodiment of the present invention, and it describes comparatively concrete and detailed, but therefore can not be interpreted as the restriction to the scope of the claims of the present invention.It should be pointed out that for the person of ordinary skill of the art, without departing from the inventive concept of the premise, can also make some distortion and improvement, these all belong to protection scope of the present invention.Therefore, the protection domain of patent of the present invention should be as the criterion with claims.
Claims (10)
1. a composite auxiliary material, is characterized in that, described composite auxiliary material carries out by mannitol and polyvinylpolypyrrolidone the spherical or spherical particle that cocrystallization obtains.
2. composite auxiliary material as claimed in claim 1, it is characterized in that, described mannitol and described polyvinylpolypyrrolidone are that cocrystallization is carried out in 98 ~ 40:2 ~ 60 in mass ratio.
3. a preparation method for composite auxiliary material, is characterized in that, comprises the following steps:
Polyvinylpolypyrrolidone suspension is added in mannitol saturated solution, under ice-water bath and stirring, described mannitol and described polyvinylpolypyrrolidone is made to carry out cocrystallization, after crystallization of mannitol completes, sucking filtration, dry, grinding obtains described composite auxiliary material after sieving, and described composite auxiliary material carries out by mannitol and polyvinylpolypyrrolidone the spherical or spherical particle that cocrystallization obtains.
4. the preparation method of composite auxiliary material as claimed in claim 3, it is characterized in that, described mannitol and described polyvinylpolypyrrolidone are that cocrystallization is carried out in 98 ~ 40:2 ~ 60 in mass ratio.
5. the preparation method of composite auxiliary material as claimed in claim 4, it is characterized in that, described mannitol and described polyvinylpolypyrrolidone are that cocrystallization is carried out in 98 ~ 75:2 ~ 25 in mass ratio.
6. the preparation method of composite auxiliary material as claimed in claim 5, it is characterized in that, described mannitol and described polyvinylpolypyrrolidone are that cocrystallization is carried out in 90 ~ 75:10 ~ 25 in mass ratio.
7. the preparation method of composite auxiliary material as claimed in claim 3, it is characterized in that, described mannitol saturated solution is placed in ice-water bath and is stirred to when starting there is crystallization, add described polyvinylpolypyrrolidone suspension, continue to stir, make described mannitol and described polyvinylpolypyrrolidone carry out cocrystallization.
8. the preparation method of composite auxiliary material as claimed in claim 3, is characterized in that, one or more being dispersed in by described polyvinylpolypyrrolidone in water, ethanol and ethyl acetate obtain described polyvinylpolypyrrolidone suspension.
9. the preparation method of composite auxiliary material as claimed in claim 3, is characterized in that, one or more being dissolved in by described mannitol in water, ethanol and ethyl acetate obtain described mannitol saturated solution.
10. a purposes for composite auxiliary material, is characterized in that, the composite auxiliary material that preparation method is obtained as described in any one of claim 4-9 is for the preparation of oral cavity disintegration tablet.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111166891A (en) * | 2018-11-13 | 2020-05-19 | 中国药科大学 | Mannitol eutectic auxiliary material and preparation method and application thereof |
| WO2020150930A1 (en) * | 2019-01-23 | 2020-07-30 | 谭淞文 | Novel microcrystalline mannitol medicinal auxiliary agent |
| CN114504559A (en) * | 2022-03-01 | 2022-05-17 | 安徽山河药用辅料股份有限公司 | Preparation method of lactose cellulose co-processed product serving as pharmaceutical adjuvant |
| CN116459347A (en) * | 2023-06-07 | 2023-07-21 | 江苏西典药用辅料有限公司 | Mannitol and microcrystalline cellulose-based composite auxiliary material and preparation method thereof |
Citations (3)
| 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 |
| WO2007043538A1 (en) * | 2005-10-05 | 2007-04-19 | Kyoto Pharmaceutical Industries, Ltd. | Composition for oral administration |
| WO2009006516A1 (en) * | 2007-07-02 | 2009-01-08 | Eurand, Inc. | Orally disintegrating tablet compositions of lamotrigine |
-
2015
- 2015-01-04 CN CN201510003814.5A patent/CN104645336B/en active Active
Patent Citations (3)
| 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 |
| WO2007043538A1 (en) * | 2005-10-05 | 2007-04-19 | Kyoto Pharmaceutical Industries, Ltd. | Composition for oral administration |
| WO2009006516A1 (en) * | 2007-07-02 | 2009-01-08 | Eurand, Inc. | Orally disintegrating tablet compositions of lamotrigine |
Non-Patent Citations (1)
| Title |
|---|
| TOSHIFUSA SHU ET AL.: "Studies of Rapidly Disintegrating Tablets in the Oral Cavity Using Co-ground Mixtures of Mannitol with Crospovidone", 《CHEM. PHARM. BULL.》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111166891A (en) * | 2018-11-13 | 2020-05-19 | 中国药科大学 | Mannitol eutectic auxiliary material and preparation method and application thereof |
| CN111166891B (en) * | 2018-11-13 | 2022-04-05 | 中国药科大学 | Mannitol eutectic auxiliary material and preparation method and application thereof |
| WO2020150930A1 (en) * | 2019-01-23 | 2020-07-30 | 谭淞文 | Novel microcrystalline mannitol medicinal auxiliary agent |
| CN114504559A (en) * | 2022-03-01 | 2022-05-17 | 安徽山河药用辅料股份有限公司 | Preparation method of lactose cellulose co-processed product serving as pharmaceutical adjuvant |
| CN116459347A (en) * | 2023-06-07 | 2023-07-21 | 江苏西典药用辅料有限公司 | Mannitol and microcrystalline cellulose-based composite auxiliary material and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104645336B (en) | 2017-08-29 |
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