CN103156819A - Benzoic acid alogliptin composition troche and preparation method thereof - Google Patents
Benzoic acid alogliptin composition troche and preparation method thereof Download PDFInfo
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- CN103156819A CN103156819A CN2013101058594A CN201310105859A CN103156819A CN 103156819 A CN103156819 A CN 103156819A CN 2013101058594 A CN2013101058594 A CN 2013101058594A CN 201310105859 A CN201310105859 A CN 201310105859A CN 103156819 A CN103156819 A CN 103156819A
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Abstract
The invention relates to the field of pharmacy, and discloses a benzoic acid alogliptin composition troche and a preparation method thereof. The effective components of the benzoic acid alogliptin composition troche comprise benzoic acid alogliptin, mannitol, microcrystalline cellulose, croscarmellose sodium, magnesium stearate and 5% hydroxy propyl cellulose aqueous liquor. The synthetic materials are easy to obtain and low in cost. The troche is quick in disintegration speed, high in dissolution rate, good in stability, accurate in dosage and convenient to take and carry. The benzoic acid alogliptin composition troche is simple in step, short in production period, low in production cost and suitable for industrialized application, and the technical process is easy to control,.
Description
Technical field
The present invention relates to medical domain, disclose a kind of SYR-322 composition tablet and preparation method thereof.
Background technology
Type 2 diabetes mellitus is a kind of due to multiple dysbolismus, comprises that insulin secretion is complete, liver is replied and insulin peripheral tissue is impaired, the gradual disappearance of β cell, glucagon secretion disorder and incretin hinder a kind of glycemic control that causes disorderly.This sick sickness rate worldwide increases year by year, expectation will from 2000 2.8% be increased to 4.4% of the year two thousand thirty.Ill total number of persons from 2000 17,100 ten thousand rise to 36,600 ten thousand of the year two thousand thirty.
In type 2 diabetes mellitus, a part of patient is take insulin resistant as main, and how fat patient is, and because of insulin resistant, insulin sensitivity descends, and in blood, insulin increases to compensate its insulin resistant, but relative patient's hyperglycemia, insulin secretion is relative deficiency still.This type of patient's early symptom is not obvious, but just macrovascular and the microvascular complication of clarifying a diagnosis before of being everlasting.How Diet Therapy and the oral polysaccharide medicine that falls can be effective.Another part patient needs the supplemented with exogenous insulin clinically take defect of insulin secretion as main.
Egelieting is the DPP-4 activity inhibitor of highly selecting, and can promote by the plasma concentration that improves GLP-1 in body the secretion with sugared concentration dependent insulin.Therefore, promote that when hypoglycemia insulin secretion can not increase the weight of the hypoglycemia symptom.
SYR-322 sheet, chinesization formal name used at school are 2-(6-((3R)-3-amino piperidine-1-yl)-3-methyl-2,4-dioxy-3, the base of 4-dihydro-pyrimidin-1(2H)) methyl) benzonitrile list benzoate, chemical formula C
18H
21N
5O
2C
7H
6O
2, molecular weight 461.5, chemical structural formula is as follows:
Produced by Japanese Takeda company the earliest, disintegration rate is slow, dissolution rate is low and the shortcoming of inconvenient use but have.
Summary of the invention
The first purpose of the present invention is to provide a kind of SYR-322 composition tablet, the effective ingredient of described SYR-322 composition tablet is SYR-322, mannitol, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, magnesium stearate and 5% hydroxypropyl cellulose aqueous solution, have that synthesis material is easy to get, cost is low, and disintegration rate is fast, dissolution rate is high, good stability, dosage accurately, taking convenience, the characteristics such as be easy to carry.
In order to reach above technique effect, technical scheme of the present invention is as follows:
Produce the SYR-322 composition tablet of 25mg specification, in parts by weight, the effective ingredient of described SYR-322 composition tablet is 15 parts of 34 parts of SYR-322s, 45 parts, mannitol, 68 parts of microcrystalline Cellulose, 1.5 parts of cross-linking sodium carboxymethyl celluloses, 0.8 part of magnesium stearate and 5% hydroxypropyl cellulose aqueous solutions.
Produce the SYR-322 composition tablet of 12.5mg specification, in parts by weight, the effective ingredient of described SYR-322 composition tablet is 15 parts of 17 parts of SYR-322s, 62 parts, mannitol, 68 parts of microcrystalline Cellulose, 1.5 parts of cross-linking sodium carboxymethyl celluloses, 0.8 part of magnesium stearate and 5% hydroxypropyl cellulose aqueous solutions.
SYR-322 composition tablet of the present invention is take SYR-322 as active constituents of medicine, and the hydroxypropyl cellulose aqueous solution that is equipped with certain mannitol, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, magnesium stearate and 5% is made.
Because SYR-322 itself is poorly soluble, for increasing disintegration time and the dissolution of tablet, add cross-linking sodium carboxymethyl cellulose as disintegrating agent, add hydroxypropyl cellulose aqueous solution as binding agent, add mannitol and microcrystalline Cellulose as filler, add magnesium stearate as lubricant.
Cross-linking sodium carboxymethyl cellulose is the ether of water-soluble cellulose, and it is sodium-salt type that 70% carboxyl is approximately arranged, have larger draw moist, existence due to cross-bond, water insoluble, the water that can absorb the several times amount in water expands and insoluble, has disintegration preferably and compressibility.
Hydroxypropyl cellulose is water-soluble and multiple organic solvent at normal temperatures, as: absolute methanol, ethanol, isopropyl alcohol, propylene glycol, dichloromethane, also dissolve in acetone, chloroform, toluene and cellosolve, solution is all transparent, be good thermoplastic, have good film property, institute's film forming is very tough and tensile, glossiness is good, and elasticity is abundant; Ash is extremely low, makes this product have good caking property, and is very stable as emulsion tackify use, and good dispersion.
Mannitol (Mannitol) claim again D-mannital, is the hexahydroxylic alcohols that a kind of people are familiar with, with sorbitol be isomers.It is a kind of non-hygroscopic, odorless, white or colourless crystalline powder.Mannitol has pleasant sweet taste, and its sugariness is 0.55-0.65 times of sucrose, has the general character of multi-sugar alcohol.Mannitol is a kind of functional Sugar Alcohol that enters the earliest people's life.In functional Sugar Alcohol, mannitol is unique a kind of hexabasic alcohol that is difficult for the moisture absorption, has simultaneously the characteristics such as sugariness is suitable, heat is low, have no side effect.In the human physiological metabolism, it is the same with other functional sugar alcohol, has with insulin to have nothing to do, and does not improve the characteristics such as blood glucose value, unlikely dental caries, can be used as the sweeting agent of diabetes patient, adiposis patient.
Microcrystalline Cellulose is a kind of tasteless, imperceptible white corynebacterium cellular granule, and it does not have fibroid and mobility is extremely strong, has higher reactivity worth in carboxymethyl acidylate, acetylation, esterification process, and is very favourable to chemical modification.Owing to having hydrogen bond between the microcrystalline Cellulose molecule, hydrogen bond association during pressurized, admittedly have the compressibility of height, simultaneously, after the tablet of compacting ran into liquid, it is inner that moisture enters rapidly the tablet that contains microcrystalline Cellulose, hydrogen bond ruptures at once.Microcrystalline Cellulose in Dimemorfan phosphate tablet composition of the present invention has improved hardness, disintegrative and the compressibility of tablet greatly.
Magnesium stearate is hydrophobic lubricant, and its quality is very soft, and is therefore main as lubricant; play and fill and lead up the recessed effect in particle surface hole, the packing interaction after using between granule dies down, and is easy to each other slide; easily and the granule mixing, after tabletting, unilateral smooth and beautiful appearance, most widely used.
The invention also discloses a kind of preparation method of SYR-322 composition tablet, comprise the following steps:
(1) sieve: SYR-322 is crossed the 90-110 mesh sieve, with mannitol, microcrystalline Cellulose and the cross-linking sodium carboxymethyl cellulose 70-95 mesh sieve that sieves respectively;
(2) mix: it is standby that the SYR-322 that weighs up according to quantity after sieving, mannitol, microcrystalline Cellulose and cross-linking sodium carboxymethyl cellulose mix homogeneously get the first mixture;
(3) granulate: 5% the hydroxypropyl cellulose aqueous solution that will weigh up adds soft material processed in the first mixture, granulates after crossing the 20-25 mesh sieve;
(4) granule of step (3) is dried to moisture at 60 ℃ and is not more than 3.5%, cross granulate after the 15-25 mesh sieve, then add the magnesium stearate mix homogeneously that weighs up, measure intermediate content after tabletting namely get the SYR-322 tablet composition.
Preferably, the SYR-322 described in step (1) is crossed 100 mesh sieves, and described mannitol, microcrystalline Cellulose and cross-linking sodium carboxymethyl cellulose are crossed respectively 80 mesh sieves.
Preferably, sieving as crossing 24 mesh sieves in step (3).
Preferably, sieving as crossing 20 mesh sieves in step (4).
Preferably, the tabletting process tablet hardness in step (4) is controlled and is not less than 8Kg/mm2.
Adopt the effect that above-mentioned preparation method has to be: step is simple, and technical process is easily controlled, and is with short production cycle, and production cost is low, is fit to industrial applications.
In order to reach better technique effect, the invention also discloses a kind of SYR-322 composition film garment piece, in parts by weight, adopt above-described SYR-322 composition tablet and stomach dissolved film coating pre-mix dose to make;
150 parts of described SYR-322 composition tablets;
Described stomach dissolved film coating pre-mix dose is made by the Opadry coating powder of 16.0-16.5 part and the water of 84 parts.
In order to reach better technique effect, the present invention also provides the preparation method of above-mentioned SYR-322 composition film garment piece, comprises the following steps:
(1) weigh up Opadry coating powder and water, be mixed and made into coating solution, standby, preferably adopt purified water;
(2) weighing up the SYR-322 composition tablet puts in coating pan, adjusting the coating pan rotating speed is 5-10 rev/min, controlling inlet temperature is that 55-65 ℃ of blowing hot-air makes plain sheet temperature reach 35-45 ℃, spray into the described coating solution of step (1) until coating weightening finish 2.0%～4.0%, the stop-spraying coating solution, determine whether be rotated further coating pan depending on unilateral adhesion degree, then advance drying, namely get SYR-322 composition film garment piece.
Use technical scheme of the present invention, have following technique effect: the effective ingredient of (1) SYR-322 composition tablet of the present invention is SYR-322, mannitol, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, magnesium stearate and 5% hydroxypropyl cellulose aqueous solution, have that synthesis material is easy to get, cost is low, and disintegration rate is fast, dissolution rate is high, good stability, dosage accurately, taking convenience, the characteristics such as be easy to carry; (2) to prepare the method step of SYR-322 composition tablet simple in the present invention, and technical process is easily controlled, and is with short production cycle, and production cost is low, is fit to industrial applications; (3) SYR-322 composition film garment piece provided by the invention has increased the stability of tablet, and tablet increases weight little, little on the disintegration rate impact; (4) preparation method of SYR-322 composition film garment piece provided by the invention is simple to operate, with short production cycle, and production cost is low, is fit to suitability for industrialized production.
The specific embodiment
Describe below in conjunction with specific embodiments technical scheme of the present invention in detail, be used for explaining technical scheme of the present invention in this illustrative examples of the present invention and explanation, but not as a limitation of the invention.
In the present invention program, the source of each raw material and quality standard are as shown in table 1 below:
The source of table 1 raw material and quality standard table
Embodiment 1:
Produce 1000 SYR-322 composition tablets that specification is 25mg, the effective ingredient of described SYR-322 composition tablet is SYR-322, mannitol, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, magnesium stearate and 5% hydroxypropyl cellulose aqueous solution, and the consumption of each raw material is as shown in table 2.
Concrete preparation process is as follows:
The first step: sieve, SYR-322 is crossed 100 mesh sieves, mannitol, microcrystalline Cellulose and cross-linking sodium carboxymethyl cellulose are crossed respectively 80 mesh sieves;
Second step: mix, the SYR-322 that weighs up according to quantity after sieving, mannitol, microcrystalline Cellulose and cross-linking sodium carboxymethyl cellulose mix homogeneously are obtained the first mixture, standby;
The 3rd step: granulate, 5% the hydroxypropyl cellulose aqueous solution that weighs up is added soft material processed in the first mixture, granulate after crossing 24 mesh sieves;
The 4th step: the granule of step (3) is dried to moisture at 60 ℃ is not more than 3.5%, cross 20 mesh sieve granulate, add the magnesium stearate mix homogeneously that weighs up, tabletting namely gets the SYR-322 tablet composition again, shown in tabletting process tablet hardness control and to be not less than 8Kg/mm
2
Table 2 raw material use scale
| The supplementary material title | Consumption (g) |
| SYR-322 (g) | 34 |
| Mannitol (g) | 45 |
| Microcrystalline Cellulose (g) | 68 |
| Cross-linking sodium carboxymethyl cellulose (g) | 1.5 |
| Magnesium stearate (g) | 0.8 |
| Hyprolose (g) | 15 |
The indices of the SYR-322 composition tablet that obtains according to this formula and this method is as shown in table 3:
The indices tables of data of table 3 SYR-322 composition tablet
SYR-322 composition tablet synthesis material is easy to get, cost is low, and disintegration rate is fast, dissolution rate is high, good stability, dosage accurately, taking convenience, be easy to carry; Above-mentioned preparation method step is simple, technical process is easily controlled, with short production cycle, production cost is low, be fit to industrial applications.
Embodiment 2:
Produce 1000 SYR-322 composition tablets that specification is 12.5mg, the effective ingredient of described SYR-322 composition tablet is SYR-322, mannitol, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, magnesium stearate and 5% hydroxypropyl cellulose aqueous solution, and the consumption of each raw material is as shown in table 4.
Concrete preparation process is as follows:
The first step: sieve, the active constituents of medicine SYR-322 is crossed 100 mesh sieves, mannitol, microcrystalline Cellulose and cross-linking sodium carboxymethyl cellulose are crossed respectively 80 mesh sieves;
Second step: mix, the SYR-322 that weighs up according to quantity after sieving, mannitol, microcrystalline Cellulose and cross-linking sodium carboxymethyl cellulose mix homogeneously are obtained the first mixture, standby;
The 3rd step: granulate, 5% the hydroxypropyl cellulose aqueous solution that weighs up is added soft material processed in the first mixture, granulate after crossing 24 mesh sieves;
The 4th step: the granule of step (3) is dried to moisture at 60 ℃ is not more than 3.5%, cross 20 mesh sieve granulate, add again the magnesium stearate mix homogeneously that weighs up, measure intermediate content after tabletting namely get the SYR-322 tablet composition, shown in tabletting process tablet hardness control and be not less than 8Kg/mm
2Table 4 raw material use scale
| The supplementary material title | Consumption (g) |
| SYR-322 (g) | 17 |
| Mannitol (g) | 62 |
| Microcrystalline Cellulose (g) | 68 |
| Cross-linking sodium carboxymethyl cellulose (g) | 1.5 |
| Magnesium stearate (g) | 0.8 |
| Hyprolose (g) | 15 |
The indices of the SYR-322 composition tablet that obtains according to this formula and this method is as shown in table 5:
The indices tables of data of table 5 SYR-322 composition tablet
SYR-322 composition tablet synthesis material is easy to get, cost is low, and disintegration rate is fast, dissolution rate is high, good stability, dosage accurately, taking convenience, be easy to carry; Above-mentioned preparation method step is simple, technical process is easily controlled, with short production cycle, production cost is low, be fit to industrial applications.
Embodiment 3:
Adopt the SYR-322 composition tablet of embodiment 1 to make the SYR-322 composition film garment piece that specification is 25mg, fill a prescription as follows:
Preparation method is as follows:
The first step: weigh up Opadry coating powder and water, be mixed and made into coating solution, standby;
Second step: weigh up the SYR-322 composition tablet and put in coating pan, adjusting the coating pan rotating speed is 5-10 rev/min, controlling inlet temperature is that 55-65 ℃ of blowing hot-air makes plain sheet temperature reach 35-45 ℃, spray into the described coating solution of step (1) until coating weightening finish 2.0%～4.0%, the stop-spraying coating solution, determine whether be rotated further coating pan depending on unilateral adhesion degree, then advance drying, namely get SYR-322 composition film garment piece.
Carry out influence factor's test under high temperature (40 ℃, 60 ℃), high humidity (75%RH, 92.5%RH) and illumination (4500lx) condition, emphasis is investigated appearance character, content and the related substance of tablet and be the results are shown in Table shown in 6:
Table 6 SYR-322 composition film garment piece influence factor test
Annotate: this film is moisture absorption weightening finish moisture absorption weightening finish 8.02% after 2.29%, 10 day after 92.5%RH places 5 days; Moisture absorption weightening finish moisture absorption weightening finish 2.95% after 0.83%, 10 day after 75%RH places 5 days.
Experimental result shows, this preparation was placed 5,10 days under high humidity, illumination (4500lx) condition, and every investigation index was compared with 0 day and had no significant change, and related substance slightly increases under 60 ℃ of conditions, related substance is without significant change, so suggestion this product room temperature is preserved under 40 ℃ of conditions
SYR-322 composition film garment piece provided by the invention has increased the stability of tablet, and tablet increases weight little, little on the disintegration rate impact; The preparation method of SYR-322 composition film garment piece provided by the invention is simple to operate, with short production cycle, and production cost is low, is fit to suitability for industrialized production.
Embodiment 4:
Adopt the SYR-322 composition tablet of embodiment 2 to make the SYR-322 composition film garment piece that specification is 12.5mg, fill a prescription as follows:
Preparation method is as follows:
The first step: weigh up Opadry coating powder and water, be mixed and made into coating solution, standby;
Second step: weigh up the SYR-322 composition tablet and put in coating pan, adjusting the coating pan rotating speed is 5-10 rev/min, controlling inlet temperature is that 55-65 ℃ of blowing hot-air makes plain sheet temperature reach 35-45 ℃, spray into the described coating solution of step (1) until coating weightening finish 2.0%～4.0%, the stop-spraying coating solution, determine whether be rotated further coating pan depending on unilateral adhesion degree, then advance drying, namely get SYR-322 composition film garment piece.
Carry out influence factor's test under high temperature (40 ℃, 60 ℃), high humidity (75%RH, 92.5%RH) and illumination (4500lx) condition, emphasis is investigated appearance character, content and the related substance of tablet, the results are shown in Table shown in 7:
Table 7 SYR-322 composition film garment piece influence factor tests (specification 12.5mg)
Annotate: this film is moisture absorption weightening finish moisture absorption weightening finish 8.31% after 1.58%, 10 day after 92.5%RH places 5 days; Moisture absorption weightening finish moisture absorption weightening finish 2.52% after 1.02%, 10 day after 75%RH places 5 days.
Experimental result shows, this preparation was placed under high humidity, illumination condition 5,10 days, and every investigation index was compared with 0 day and had no significant change, and related substance slightly increases under 60 ℃ of conditions, related substance is without significant change, so suggestion this product room temperature is preserved under 40 ℃ of conditions.
SYR-322 composition film garment piece provided by the invention has increased the stability of tablet, and tablet increases weight little, little on the disintegration rate impact; The preparation method of SYR-322 composition film garment piece provided by the invention is simple to operate, with short production cycle, and production cost is low, is fit to suitability for industrialized production.
Embodiment 5:
Adopt the formula of embodiment 3 to carry out scale-up, the concrete consumption of raw material is as shown in table 8 below:
Table 8 specification is the SYR-322 composition film garment piece scale-up raw material consumption of 25mg
Control parameter in concrete technology as shown in table 9:
The control table of table 9 key process parameter
The result demonstration, in amplification process, the equal practical of the formulation and technology of this specification preparation, process stabilizing.Sample to preparation carries out the index investigation with reference to embodiment 3, and indices all meets the clinical research quality standard.
Embodiment 6:
Adopt the formula of embodiment 4 to carry out scale-up, lot number is WA110517, WA110519, WA110521, and the concrete consumption of raw material is as shown in table 10 below:
Table 10 specification is the SYR-322 composition film garment piece scale-up raw material consumption of 12.5mg
Control parameter in concrete technology as shown in table 11:
The control table of table 11 key process parameter
The result demonstration, in amplification process, the equal practical of the formulation and technology of this specification preparation, process stabilizing.Sample to preparation carries out the index investigation with reference to embodiment 4, and indices all meets the clinical research quality standard.
Detecting instrument and the detection method thereof used in above embodiment 1, embodiment 2, embodiment 3, embodiment 4, embodiment 5 and embodiment 6 techniques are summed up as follows:
1, pellet moisture: adopt the Ka Shi micro-water analyzer, with reference to " two appendix VIII M first method A of Chinese pharmacopoeia version in 2010 measure pellet moisture.
2, the tablet friability checks: adopt the tablet friabilator, with reference to " two appendix XG of Chinese pharmacopoeia version in 2010 check.
3, check tablet hardness and disintegration: adopt tablet four-function analyzer, with reference to " two appendix XA of Chinese pharmacopoeia version in 2010 check.
4, dissolution test: with reference to " Chinese pharmacopoeia version (two ones) dissolution method (appendix X C the second method) in 2010, specific as follows:
Take water 900ml as dissolution medium, rotating speed is per minute 50 to turn, operation in accordance with the law, through 30 minutes, getting solution filters in right amount, get subsequent filtrate (sample concentration 12.5 μ g/ml) as need testing solution, it is appropriate that another precision takes the SYR-322 reference substance, is diluted to Egelieting that every 1ml approximately contains 12.5 μ g product solution in contrast with dissolution medium; Get respectively above-mentioned two kinds of solution and measure trap in 275nm wavelength place, calculate the stripping quantity of every.
5, related substance inspection: with reference to SYR-322 raw material detection method, the photograph high performance liquid chromatography (" two appendix V D of Chinese pharmacopoeia version in 2010) measure.
(1) chromatographic condition: the detection wavelength is 224nm, and column temperature is 30 ℃, and flow velocity is 1.0ml/min, and number of theoretical plate is not less than 3000 by SYR-322.
(2) mobile phase A be 0.1% high chloro acid solution (containing 0.3% triethylamine) (pH=3.0), Mobile phase B is acetonitrile, shown in table 12 specific as follows:
The mapping table of table 12 mobile phase A and Mobile phase B and time
| Time (minute) | Mobile phase A (%) | Mobile phase B (%) |
| 0 | 80 | 20 |
| 10 | 80 | 20 |
| 20 | 55 | 45 |
| 30 | 55 | 45 |
| 31 | 80 | 20 |
| 40 | 80 | 20 |
(3) system suitability: get SYR-322 and impurity F 1008 each approximately 5mg put respectively in 10ml and 1000ml measuring bottle, adding the initial flow mutual-assistance dissolves and is diluted to scale, shake up, get respectively above-mentioned two kinds of solution 2ml mixings, precision measures mixed solution 20 μ l injection liquid chromatographies, record chromatogram (peak sequence is followed successively by Egelieting, benzoic acid and impurity F 1008), number of theoretical plate is not less than 3000 by Egelieting peak calculating.
(4) algoscopy: get this product, porphyrize, precision takes fine powder appropriate (approximately being equivalent to SYR-322 10mg) and puts in the 20ml volumetric flask, add the initial flow phased soln and dilute and put scale, filter, make the solution that every 1ml approximately contains 0.5mg, as need testing solution; Precision measures need testing solution 20 μ l, and injection liquid chromatography respectively records chromatogram to 5 times of main constituent peak retention time.After the deduction solvent peak, if any impurity peaks, detect single maximum contaminant and total impurities content in the need testing solution chromatogram.
6, assay: with reference to SYR-322 raw material detection method, measure according to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010).
Chromatographic condition is as follows with reference to the chromatographic condition that related substance checks:
Chromatographic column: YMC C18 post;
Mobile phase: (pH=3.0)=20:80 of acetonitrile-0.1% perchloric acid (containing 0.3% triethylamine);
Survey wavelength: 224nm;
Column temperature: 30 ℃;
Sample size: 20 μ l;
Method: get this product, porphyrize, precision takes fine powder appropriate (approximately being equivalent to SYR-322 12.5mg), puts in the 25ml volumetric flask, adds mobile phase and dissolves and dilute and put scale, shakes up filtration; Precision measures 1ml and puts in the 10ml volumetric flask, adds mobile phase and is diluted to scale, shakes up, and gets need testing solution.It is appropriate that another precision takes reference substance, is made in the same way of every 1ml and approximately contains 50 μ g SYR-322 solution, product solution in contrast.Precision measures need testing solution and reference substance solution 20 μ l injection liquid chromatographies, records chromatogram, presses external standard method with calculated by peak area this product content.
7, enantiomer inspection: with reference to SYR-322 raw material detection method, measure according to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010).
Get this product appropriate, add mobile phase and dissolve and dilute and make the solution that every 1ml approximately contains 25 μ g SYR-322s, shake up, as need testing solution; Separately get the SYR-322 raceme appropriate, add mobile phase and dissolve and dilute and make the solution that every 1ml approximately contains 25 μ g, as system test solution.Be chromatographic column with the CBH chiral column, with water (disodiumedetate of the Ammoniom-Acetate of 10mM and 50 μ M is transferred PH to 6.0 with glacial acetic acid): methanol=95:5 is mobile phase, and flow velocity is 0.2ml/ minute, and the detection wavelength is 224nm.Get system test solution 20 μ l injection liquid chromatographies, record chromatogram, the separating degree between each composition should be less than 1.5.Precision measures need testing solution and each 20 μ l of contrast solution, and the injection liquid chromatography, record chromatogram respectively.
The above is the preferred embodiment of the present invention; should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the principle of the invention; can also make some improvements and modifications, these improvements and modifications also are considered as protection scope of the present invention.
Claims (10)
1. SYR-322 composition tablet, it is characterized in that: in parts by weight, the effective ingredient of described SYR-322 composition tablet is 15 parts of 34 parts of SYR-322s, 45 parts, mannitol, 68 parts of microcrystalline Cellulose, 1.5 parts of cross-linking sodium carboxymethyl celluloses, 0.8 part of magnesium stearate and 5% hydroxypropyl cellulose aqueous solutions.
2. SYR-322 composition tablet, it is characterized in that: in parts by weight, the effective ingredient of described SYR-322 composition tablet is 15 parts of 17 parts of SYR-322s, 62 parts, mannitol, 68 parts of microcrystalline Cellulose, 1.5 parts of cross-linking sodium carboxymethyl celluloses, 0.8 part of magnesium stearate and 5% hydroxypropyl cellulose aqueous solutions.
3. the preparation method of a SYR-322 composition tablet as claimed in claim 1 is characterized in that: in parts by weight, comprise the following steps:
(1) sieve: SYR-322 is crossed the 90-110 mesh sieve, with mannitol, microcrystalline Cellulose and the cross-linking sodium carboxymethyl cellulose 70-95 mesh sieve that sieves respectively;
(2) mix: take the SYR-322 of 34 parts after step (1) is sieved, the mannitol of 45 parts, the microcrystalline Cellulose of 68 parts and the cross-linking sodium carboxymethyl cellulose mix homogeneously of 1.5 parts and obtain the first mixture, standby;
(3) granulate: 5% hydroxypropyl cellulose aqueous solutions of 15 parts are added soft material processed in described the first mixture, excessively granulate after the 20-25 mesh sieve;
(4) granule of step (3) is dried to moisture at 60 ℃ and is not more than 3.5%, cross granulate after the 15-25 mesh sieve, then add the magnesium stearate mix homogeneously of 0.8 part, measure intermediate content after tabletting namely get the SYR-322 tablet composition.
4. the preparation method of a SYR-322 composition tablet as claimed in claim 2 is characterized in that: in parts by weight, comprise the following steps:
(1) sieve: SYR-322 is crossed the 90-110 mesh sieve, with mannitol, microcrystalline Cellulose and the cross-linking sodium carboxymethyl cellulose 70-95 mesh sieve that sieves respectively;
(2) mix: take the SYR-322 of 17 parts after step (1) is sieved, the mannitol of 62 parts, the microcrystalline Cellulose of 68 parts and the cross-linking sodium carboxymethyl cellulose mix homogeneously of 1.5 parts and obtain the first mixture, standby;
(3) granulate: 5% the hydroxypropyl cellulose aqueous solution of 15 parts is added soft material processed in the first mixture, granulate after crossing the 20-25 mesh sieve;
(4) granule of step (3) is dried to moisture at 60 ℃ and is not more than 3.5%, cross granulate after the 15-25 mesh sieve, then add the magnesium stearate mix homogeneously of 0.8 part, measure intermediate content after tabletting namely get the SYR-322 tablet composition.
5. the preparation method of according to claim 3 or 4 described SYR-322 composition tablets, it is characterized in that: the SYR-322 described in step (1) is crossed 100 mesh sieves, and described mannitol, microcrystalline Cellulose and cross-linking sodium carboxymethyl cellulose are crossed respectively 80 mesh sieves.
6. the preparation method of according to claim 3 or 4 described SYR-322 composition tablets, is characterized in that: sieving as crossing 24 mesh sieves in step (3).
7. the preparation method of according to claim 3 or 4 described SYR-322 composition tablets, is characterized in that: sieving as crossing 20 mesh sieves in step (4).
8. the preparation method of according to claim 3 or 4 described SYR-322 composition tablets is characterized in that: in step (4) in the tabletting process tablet hardness control and be not less than 8Kg/mm
2
9. SYR-322 composition film garment piece is characterized in that: in parts by weight, made by claim 1 or 2 described SYR-322 composition tablets and stomach dissolved film coating pre-mix dose;
150 parts of described SYR-322 composition tablets;
Described stomach dissolved film coating pre-mix dose is made by the Opadry coating powder of 16.0-16.5 part and the water of 84 parts.
10. preparation method of SYR-322 composition film garment piece as claimed in claim 9 is characterized in that: comprise the following steps:
(1) weigh up Opadry coating powder and water, be mixed and made into coating solution, standby;
(2) weighing up the SYR-322 composition tablet puts in coating pan, adjusting the coating pan rotating speed is 5-10 rev/min, controlling inlet temperature is that 55-65 ℃ of blowing hot-air makes plain sheet temperature reach 35-45 ℃, spray into the described coating solution of step (1) until coating weightening finish 2.0%～4.0%, the stop-spraying coating solution, determine whether be rotated further coating pan depending on unilateral adhesion degree, then advance drying, namely get SYR-322 composition film garment piece.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103353491A (en) * | 2013-06-29 | 2013-10-16 | 北京万全德众医药生物技术有限公司 | Method for separating and determining alogliptin benzoate raw material and preparation thereof by liquid chromatography |
| CN103610661A (en) * | 2013-11-22 | 2014-03-05 | 迪沙药业集团有限公司 | Composition |
| CN104569172A (en) * | 2014-11-05 | 2015-04-29 | 广东东阳光药业有限公司 | Method for detecting dissolution rate of alogliptin benzoate tablets by using liquid chromatography |
| CN104721188A (en) * | 2013-12-20 | 2015-06-24 | 中美华世通生物医药科技（武汉）有限公司 | Stable composition containing Alogliptin benzoate |
| CN105203678A (en) * | 2015-07-10 | 2015-12-30 | 迪沙药业集团有限公司 | Method for measuring optical purity of R-alogliptin benzoate |
| CN105527348A (en) * | 2014-09-28 | 2016-04-27 | 中美华世通生物医药科技（武汉）有限公司 | Method for separating and analyzing alogliptin benzoate and its related substance |
| CN105796514A (en) * | 2014-12-31 | 2016-07-27 | 江苏万邦生化医药股份有限公司 | Alogliptin benzoate oral disintegrating tablet and preparation method thereof |
| CN106913555A (en) * | 2017-02-04 | 2017-07-04 | 辰欣药业股份有限公司 | A kind of preparation method of the SYR-322 piece of high bioavilability |
| CN107744499A (en) * | 2017-11-30 | 2018-03-02 | 常州市阳光药业有限公司 | SYR-322 oral administration solution and preparation method thereof |
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| CN101646420A (en) * | 2007-02-01 | 2010-02-10 | 武田药品工业株式会社 | Solid preparation comprising alogliptin and pioglitazone |
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Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103353491A (en) * | 2013-06-29 | 2013-10-16 | 北京万全德众医药生物技术有限公司 | Method for separating and determining alogliptin benzoate raw material and preparation thereof by liquid chromatography |
| CN103353491B (en) * | 2013-06-29 | 2018-11-16 | 北京万全德众医药生物技术有限公司 | A method of with liquid chromatography for separating and determining alogliptin benzoate raw material and its preparation |
| CN103610661A (en) * | 2013-11-22 | 2014-03-05 | 迪沙药业集团有限公司 | Composition |
| CN103610661B (en) * | 2013-11-22 | 2017-09-12 | 威海迪素制药有限公司 | A kind of composition |
| CN104721188A (en) * | 2013-12-20 | 2015-06-24 | 中美华世通生物医药科技（武汉）有限公司 | Stable composition containing Alogliptin benzoate |
| CN105527348A (en) * | 2014-09-28 | 2016-04-27 | 中美华世通生物医药科技（武汉）有限公司 | Method for separating and analyzing alogliptin benzoate and its related substance |
| CN105527348B (en) * | 2014-09-28 | 2018-07-24 | 中美华世通生物医药科技（武汉）有限公司 | Separation analysis alogliptin benzoate preparation and its method in relation to substance |
| CN104569172A (en) * | 2014-11-05 | 2015-04-29 | 广东东阳光药业有限公司 | Method for detecting dissolution rate of alogliptin benzoate tablets by using liquid chromatography |
| CN105796514A (en) * | 2014-12-31 | 2016-07-27 | 江苏万邦生化医药股份有限公司 | Alogliptin benzoate oral disintegrating tablet and preparation method thereof |
| CN105203678A (en) * | 2015-07-10 | 2015-12-30 | 迪沙药业集团有限公司 | Method for measuring optical purity of R-alogliptin benzoate |
| CN106913555A (en) * | 2017-02-04 | 2017-07-04 | 辰欣药业股份有限公司 | A kind of preparation method of the SYR-322 piece of high bioavilability |
| CN107744499A (en) * | 2017-11-30 | 2018-03-02 | 常州市阳光药业有限公司 | SYR-322 oral administration solution and preparation method thereof |
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