CN103932998A - Orally disintegrating tablet of dry mifepristone emulsion, and preparation method thereof - Google Patents
Orally disintegrating tablet of dry mifepristone emulsion, and preparation method thereof Download PDFInfo
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Abstract
The invention discloses an orally disintegrating tablet of dry mifepristone emulsion, and a preparation method thereof. The method comprises the following steps: fully dissolving mifepristone in edible oil, adding an emulsifier and distilled water under certain conditions to prepare a mifepristone emulsion, adding a certain proportion of a propping agent, implementing a certain drying mode to prepare the dry emulsion, adding a disintegrating agent and other auxiliary materials, and tabletting to obtain the orally disintegrating tablet of dry mifepristone emulsion. Results of a series of drug quality detection tests of the orally disintegrating tablet of dry mifepristone emulsion shows that the disintegrating time of the orally disintegrating tablet of dry mifepristone emulsion does not exceed 15s, completely accords with the prescription in Draft and Discussion of Guidance of Orally Disintegrating Tablet published by American FDA, and is above 50% shorter than same products; the stability is greatly improved, and it is convenient for long time storage and transportation; and the dissolution rate is high, and the in vitro dissolution rate within 4min in dissolution rate test reaches 99.32+/-1012%. The orally disintegrating tablet has the advantages of high content uniformity, completeness, brightness, cleanness, uniform color, good mouthfeel, no gravel feeling and the like.
Description
Technical field
The present invention relates to pharmaceutical field, relate in particular to dry newborn oral cavity disintegration tablet of a kind of mifepristone and preparation method thereof.
Background technology
Oral cavity disintegration tablet, or title oral instant-dissolving tablet, refer to can be in oral cavity the preparation of disintegrate or dissolving rapidly, this type of preparation runs into saliva disintegrate most of dissolving rapidly in oral cavity, just can take without water, oral cavity disintegration tablet is mainly applicable to following situation: under the difficult variation of child, old man, bed position and hydropenia condition and patient's medication of dysphagia.
Mifepristone is novel anti-progesterone drug, there is at present bibliographical information mifepristone can alleviate woman soldier PTSD symptom, likely for the treatment of PTSD, but the gold treatment time of PTSD for experience important event after within 6 hours, this patient bad for function of deglutition or that drink water under the special environments such as inconvenience is a difficult problem, so mifepristone is made and can be solved this difficult problem by quickly disintegrated oral cavity disintegration tablet, especially facilitate under adverse circumstances or the patient of poor compliance use, can improve ageing, especially for using under the environment such as war or earthquake relief work.
But, because mifepristone is a kind of insoluble drug, adopt conventional formula to carry out direct compression process and prepare oral cavity disintegration tablet, there is many defects, such as disintegration time is long, be generally more than 30 seconds, dissolution is poor, and bioavailability is low, and there is sand type, the tablet content uniformity is unstable etc., does not meet the quality inspection standard that pharmacopeia specifies, therefore, how to realize disintegrate fast, and dissolution is high, bioavailability is high, and the good mifepristone oral cavity disintegration tablet without sand type of mouthfeel becomes the technical barrier of being badly in need of solution.
Summary of the invention
The object of this invention is to provide dry newborn oral cavity disintegration tablet of a kind of mifepristone and preparation method thereof, after the present invention is fully dissolved mifepristone in edible oil, add emulsifying agent to be prepared as mifepristone Emulsion under certain condition, and add and contain a certain proportion of microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, after other adjuvants such as lactose and disintegrating agent, carry out tabletting, obtain the dry newborn oral cavity disintegration tablet of mifepristone, detect test by a series of drug qualities, the present invention measures disintegration by static method, the disintegration time that obtains the dry newborn oral cavity disintegration tablet of described mifepristone is no more than 15 seconds, the disintegration time that comparison mifepristone carries out direct compression gained oral cavity disintegration tablet significantly shortens, disintegration rate improves more than 50%, no difference of science of statistics place 6 months in stability test time, stability is greatly improved, and is convenient to long-time storage and transport, dissolution is high, and in Dissolution Rate Testing, in 4min, dissolution in vitro reaches 99.32 ± 10.12%, in addition, have that uniformity of dosage units is high, tablet complete bright and clean, color and luster is even, mouthfeel good and without advantages such as sand types.
Technical scheme of the present invention is:
Dry newborn oral cavity disintegration tablet of a kind of mifepristone and preparation method thereof, is prepared from by crude drug and the adjuvant of weight components:
Mifepristone Emulsion 30-50
Proppant 50-70
Disintegrating agent 4-6
Wherein said mifepristone Emulsion is made up of according to following weight fraction mifepristone, edible oil and emulsifying agent:
Mifepristone 5-15
Edible oil 10-30
Emulsifying agent 4-8
Described proppant is selected from one or more in microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, lactose;
Described disintegrating agent is selected from one or more in carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone and dried starch.
Preferably, in the dry newborn oral cavity disintegration tablet of described mifepristone, the optimum prescription of the dry newborn oral cavity disintegration tablet of described mifepristone is:
Mifepristone 10
Edible oil 20
Emulsifying agent 6
Proppant 59
Disintegrating agent 4.8
Preferably, in the dry newborn oral cavity disintegration tablet of described mifepristone, described proppant is made up of the component of following weight portion:
Microcrystalline Cellulose 35-45
Low-substituted hydroxypropyl cellulose 10-20
Lactose 3-7
Preferably, in the dry newborn oral cavity disintegration tablet of described mifepristone, the optimum prescription of described proppant is:
Microcrystalline Cellulose 40
Low-substituted hydroxypropyl cellulose 14
Lactose 5
Preferably, in the dry newborn oral cavity disintegration tablet of described mifepristone, in described adjuvant, also contain the component of following weight portion:
Micropowder silica gel 0.1-0.2
Aspartame 0.1-0.2
Mannitol 0.1-0.2
Preferably, in the dry newborn oral cavity disintegration tablet of described mifepristone, described emulsifying agent is made up of Tween 80 and sorbester p17, and its mass ratio is 2:1.
Preferably, the preparation method of the dry newborn oral cavity disintegration tablet of described mifepristone, comprising following steps:
The preparation of step 1, mifepristone Emulsion, takes a certain amount of mifepristone and is dissolved in edible oil, obtains mifepristone solution, and emulsifying agent and distilled water are joined in described mifepristone solution, carries out emulsifying, homogenizing obtains mifepristone Emulsion;
Step 2, the dry newborn preparation of mifepristone, join proppant in described mifepristone Emulsion according to formula ratio, makes it to become moistening agglomerate, is dried approximately 8 hours in 60 DEG C of left and right, sieves, and obtains the dry breast of mifepristone;
Step 3, tabletting, mix dry gained mifepristone breast with disintegrating agent and other adjuvants, adjustment sheet heavily carries out tabletting, obtains the dry newborn oral cavity disintegration tablet of mifepristone.
Preferably, the preparation method of the described dry newborn oral cavity disintegration tablet of mifepristone, wherein, step 1 is prepared in mifepristone solution, the dehydrated alcohol of 3-5 weight portion is mixed with mifepristone and edible oil, and ultrasonic concussion is about 5 minutes.
Preferably, the preparation method of the described dry newborn oral cavity disintegration tablet of mifepristone, wherein, adds emulsifying agent and distilled water before mifepristone solution to be heated in step 1, and heating-up temperature is 60-80 DEG C, and institute's adding distil water is 5-15 weight portion.
Preferably, the preparation method of the described dry newborn oral cavity disintegration tablet of mifepristone, wherein, adopts boulton process to be dried in step 2, and gained desciccate is crossed and is not less than 200 mesh sieves, adopts direct compression process to carry out tabletting.
The present invention has following beneficial effect: after mifepristone is fully dissolved in edible oil, add emulsifying agent and distilled water to be prepared as mifepristone Emulsion under certain condition, and add and contain a certain proportion of microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, after other adjuvants such as lactose and disintegrating agent, carry out tabletting, obtain the dry newborn oral cavity disintegration tablet of mifepristone, detect test by a series of drug qualities, measure disintegration through adopting static method, the disintegration time of the dry newborn oral cavity disintegration tablet of mifepristone of the present invention is no more than 15 seconds, comparison mifepristone carry out direct compression obtain oral cavity disintegration tablet disintegration time shorten more than 50%, stability is greatly improved, and no difference of science of statistics place 6 months in stability test time is convenient to long-time storage and transport, dissolution is high, and in Dissolution Rate Testing, dissolution in vitro reaches 99.32 ± 10.12% in 4min, reaches the standard of pharmacopeia defined completely, and far away higher than the dissolution of general oral cavity disintegration tablet, in addition, have that uniformity of dosage units is high, tablet complete bright and clean, color and luster is even, mouthfeel good and without advantages such as sand types, solve how the mifepristone of slightly solubility is made can this difficult problem of quickly disintegrated oral cavity disintegration tablet completely, facilitate under adverse circumstances or the patient of poor compliance uses, and for using under the environment such as war or earthquake relief work.
Brief description of the drawings
The preparation method schematic diagram of the dry newborn oral cavity disintegration tablet of mifepristone described in Fig. 1;
The accumulation stripping curve figure of the dry newborn oral cavity disintegration tablet of mifepristone described in Fig. 2;
Described in Fig. 3, the dry breast of mifepristone and emulsion stability are investigated result of the test;
Formulation factors water-glass in orthogonal test described in Fig. 4;
Orthogonal test arrangement and analysis of results table described in Fig. 5;
SPSS16.0 analysis of variance table in orthogonal test described in Fig. 6;
Described in Fig. 7, the dry newborn oral cavity disintegration tablet uniformity of dosage units of mifepristone detects tables of data.
Detailed description of the invention
Below in conjunction with accompanying drawing, 1-7 elaborates to the present invention, after making those of ordinary skill in the art consult this description, can implement according to this.
As shown in Figure 1, dry newborn oral cavity disintegration tablet of a kind of mifepristone and preparation method thereof, is prepared from by crude drug and the adjuvant of weight components:
Mifepristone Emulsion 30-50
Proppant 50-70
Disintegrating agent 4-6
Wherein said mifepristone Emulsion is made up of according to following weight fraction mifepristone, edible oil and emulsifying agent:
Mifepristone 5-15
Edible oil 10-30
Emulsifying agent 4-8
Described proppant is selected from one or more in microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, lactose; Described disintegrating agent is selected from one or more in carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone and dried starch.
In the dry newborn oral cavity disintegration tablet of described mifepristone, the optimum prescription of the dry newborn oral cavity disintegration tablet of described mifepristone is: mifepristone 10; Edible oil 20; Emulsifying agent 6; Proppant 59; Disintegrating agent 4.8.
In the dry newborn oral cavity disintegration tablet of described mifepristone, described proppant comprises the component of following weight portion: microcrystalline Cellulose 35-45; Low-substituted hydroxypropyl cellulose 10-20; Lactose 3-7.
In the dry newborn oral cavity disintegration tablet of described mifepristone, the optimum prescription of described proppant is: microcrystalline Cellulose 40; Low-substituted hydroxypropyl cellulose 14; Lactose 5.In described adjuvant, also contain the component of following weight portion: disintegrating agent 4-6; Micropowder silica gel 0.1-0.2; Aspartame 0.1-0.2; Mannitol 0.1-0.2.The present invention is through repeatedly trial test, determine that these three factors of microcrystalline Cellulose, low-substituted hydroxypropyl cellulose and lactose have important impact to the quality of oral cavity disintegration tablet, through repeatedly orthogonal test, and measure disintegration by static method, the index such as disintegration time, outward appearance is investigated, the optimum of these three factors prescription in the present invention who obtains, external disintegration time is all in 15 seconds, gained tablet complete bright and clean, color and luster is even, hardness is moderate, for 23-29N, and taste is sweet, without sand type, mouthfeel is good.
In the dry newborn oral cavity disintegration tablet of described mifepristone, described emulsifying agent is made up of Tween 80 and sorbester p17, and its mass ratio is 2: 1.
The preparation method of the dry newborn oral cavity disintegration tablet of described mifepristone, comprising following steps:
The preparation of step 1, mifepristone Emulsion, takes a certain amount of mifepristone and is dissolved in edible oil, obtains mifepristone solution, wherein the preferred soybean oil of edible oil used; Emulsifying agent and distilled water are joined in described mifepristone solution, carry out emulsifying, homogenizing obtains mifepristone Emulsion; In the present invention, adopt high-shear emulsion machine to shear about 5 minutes, obtain mifepristone colostrum, gained mifepristone colostrum is carried out to homogenizing with high pressure homogenizer with 650kg/cm pressure, both uniform and stable mifepristone Emulsion;
Step 2, the dry newborn preparation of mifepristone, join proppant in described mifepristone Emulsion according to formula ratio, makes it to become moistening agglomerate, is dried approximately 8 hours in 60 DEG C of left and right, crosses and be not less than 200 mesh sieves, obtains the dry breast of mifepristone; The dry breast of gained mifepristone is the Powdered of good fluidity;
Step 3, tabletting, by dry gained mifepristone breast and disintegrating agent and other adjuvant mix homogeneously, adjustment sheet heavily carries out tabletting, obtains the dry newborn oral cavity disintegration tablet of mifepristone.The present invention adopts direct compression process to carry out tabletting.
The preparation method of the described dry newborn oral cavity disintegration tablet of mifepristone, wherein, step 1 is prepared in mifepristone solution, the dehydrated alcohol of 3-5 weight portion is mixed with mifepristone and edible oil, and ultrasonic concussion is about 5 minutes.Wherein, the optimal amount that adds dehydrated alcohol is 4 weight portions.
The preparation method of the described dry newborn oral cavity disintegration tablet of mifepristone, wherein, adds emulsifying agent and distilled water before mifepristone solution to be heated in step 1, heating-up temperature is 60-80 DEG C, and institute's adding distil water is 5-15 weight portion.Mode of heating is heating in water bath, and preferred bath temperature is 75 DEG C, and the optimal amount of institute's adding distil water is 10 weight portions.
The preparation method of the described dry newborn oral cavity disintegration tablet of mifepristone, wherein, adopts boulton process to be dried in step 2, gained desciccate is crossed and is not less than 200 mesh sieves, adopts direct compression process to carry out tabletting.
Specific embodiment:
Step 1, precision take mifepristone 25g, mix with 50g soybean oil, add dehydrated alcohol 10g, ultrasonic concussion 5min dissolves completely to mifepristone, in 75 DEG C of water-baths, adds emulsifying agent 15g, distilled water 25g, then shear 5min with high-shear emulsion machine, both obtained mifepristone colostrum, mifepristone colostrum is obtained to mifepristone Emulsion with 650kg/cm pressure with high pressure homogenizer homogenizing.Wherein emulsifying agent is made up of with mass ratio Tween 80 and sorbester p17 at 2: 1.
Step 2, take microcrystalline Cellulose 40g, low-substituted hydroxypropyl cellulose 14g and lactose 5g, add mifepristone Emulsion, mix homogeneously, obtain moistening agglomerate, in vacuum drying oven, dry 8h at 60 DEG C, crosses 200 mesh sieves, obtain the powder that dry, flowable is good, i.e. the dry breast of mifepristone.
Step 3, add the adjuvants such as disintegrating agent 4.8g, aspartame 0.1g, micropowder silica gel 0.1g and mannitol 0.1g to the dry Ruzhong of mifepristone, mix homogeneously, adjustment sheet is heavily 100mg, adopts direct compression process to make the tablet of diameter 6mm, and every containing mifepristone 10mg.
Be below the quality testing test of the dry newborn oral cavity disintegration tablet of mifepristone of the present invention, comprise:
Orthogonal test
The present invention determines its consumption by trial test repeatedly, and the consumption of wherein setting microcrystalline Cellulose is A, and the consumption of lactose is B, and the consumption of low-substituted hydroxypropyl cellulose is C, and described consumption is mass percent, and each factor is respectively got 3 levels, sees Fig. 4.
Adopt the test of L9 (34) orthogonal trial, taking disintegration time Y1, outward appearance Y2 as evaluation index, wherein, the score value of marking using the number of seconds of disintegration time as disintegrate, outward appearance is divided into 4 grades: fine, and both neat in edge, smooth in appearance, color and luster is even, glossy, and it is chosen as 15 points; Well, both neat in edge, appearance is substantially smooth, and color and luster is even, and it is chosen as 20 points; Generally, both edge crumblings, appearance injustice, has pit, and it is chosen as 25 points; Poor, both edge crumblings, sliver, it is chosen as 30 points.In addition, consider the importance of disintegration time in oral cavity disintegration tablet performance rating, the weight of this index is decided to be to 2, the weight of outward appearance is decided to be to 1, and by disintegrate 2 groups of data of score value and mouth feel score score value standardization respectively of marking, wherein, each numerical value obtained to standardized value divided by the maximum in this group data, comprehensive grading is Y=2Y1+Y2.In this test, total score value is lower, and Formulation is more reasonable.Fig. 5 is shown in orthogonal test arrangement and interpretation of result.Wherein, blank column D represents not arrange factor or interactive row, is used for reflecting test error, and using this as the whether reliably mark of effect of weighing experimental factor generation.
From Fig. 5 result, utilize Excel to carry out range analysis, each factor is followed successively by A>C>B to the size order that affects of disintegration time, and its optimal proportion be every containing microcrystalline Cellulose 40%, low-substituted hydroxypropyl cellulose 14%, lactose 5%.For checking range analysis result, utilize SPSS16.0 software to carry out variance analysis to orthogonal experiments, as shown in Figure 6, known B factor there is no significance impact to result of the test, and A, C factor all have appreciable impact to result of the test, this is identical with range analysis conclusion.Can obtain thus optimum prescription is microcrystalline Cellulose 40g; Low-substituted hydroxypropyl cellulose 14g; Lactose 5g; Mifepristone Emulsion 36g, wherein comprises according to mifepristone, emulsifying agent and the edible oil of formula ratio composition, and taking mifepristone as principal agent; Tablet tablet disintegrant 4.8g; Micropowder silica gel 0.1g; Aspartame 0.1g, makes 1000 altogether.
Mifepristone is done newborn stability test
The mifepristone Emulsion preparing and the dry newborn room temperature of mifepristone are placed 6 months, and since 0 month the 1st, 3, June, the particle diameter of the reconstruction Emulsion forming after sampling and measuring mifepristone Emulsion and dry milk powder end aquation respectively.The results are shown in Figure 3.From Fig. 3 statistical result, mifepristone Emulsion is placed 6 months, and particle diameter increases, 1,3, June particle diameter compared and all have significant difference with 0 month; The dry breast of mifepristone is placed 6 months, compared with the particle diameter of the reconstruction breast that when rebuilding newborn particle diameter and starting, dry breast forms, and P<0.01, no difference of science of statistics.This explanation mifepristone is made dry newborn rear stability and is improved greatly, and result of the test as shown in Figure 3.
The demonstration test of optimizing prescriptions:
According to above-mentioned optimizing prescriptions, use with a collection of supplementary material, adopt direct compression process, taking the dry breast of mifepristone as crude drug, prepare the dry newborn oral cavity disintegration tablet of 3 batches of mifepristones.Gained tablet complete bright and clean, color and luster is even, hardness 23～29N, external disintegration time is all in 15s, taste is sweet, without grittiness, mouthfeel is good.
The mensuration of external disintegration:
Get 6,10mL colorimetric test tube, the basket that built-in 26 eye mesh screens are made, adds 2mL distilled water, is placed in 37 ± 1 DEG C of waters bath with thermostatic control and is incubated 2min, makes in vitro outer hygral equilibrium.6 of sample thiefs, put into 1 in every test tube, adopt static method to measure disintegration.Start to clock with the tablet contact water surface, to all collapsing and fall apart for complete disintegrate, should be residual without bulky grain on screen cloth, record disintegration with stopwatch, average and be measurement result.As a result, the external disintegration time of 3 batch samples is respectively: 12.6 ± 2.4s, 10.2 ± 3.1s and 11.7 ± 3.8s.
Dissolution determination:
According to " Chinese Pharmacopoeia " version annex XC dissolution determination first method in 2010, measure the dissolution of the dry newborn oral cavity disintegration tablet of mifepristone, get 6 of the dry newborn oral cavity disintegration tablets of mifepristone, taking dilute hydrochloric acid liquid 1000ml as dissolution medium, turning basket rotating speed and be per minute 100 turns, 37 ± 1 DEG C of temperature, each sample repeats 3 times.Respectively 2,4,6,10,20min samples 5.0mL, 0.45 μ m membrane filtration supplements synthermal 5.0mL fresh medium simultaneously, gets subsequent filtrate and measures trap, substitution standard curve regression equation calculation content according to spectrophotography at 262nm wavelength place.Treated must accumulation stripping percentage rate, as shown in Figure 2, in 2min, dissolution in vitro is that in 94.65 ± 9.21%, 4min, dissolution in vitro is 99.32 ± 10.12% to result.
Content uniformity test
According to above-mentioned optimizing prescriptions, use with a collection of supplementary material, weigh, prepare dry breast, mixing, tabletting.Respectively at the tabletting time be 0min, 20min, 40min, tetra-time points of 60min are respectively got 10 of test samples, measure respectively the every relative amount X taking labelled amount as 100 according to Chinese Pharmacopoeia version annex XE Content uniformity test in 2010, ask its average
and standard deviation
and the absolute value of the difference of labelled amount and average
whether the value decision content uniformity according to A+1.8S conforms with the regulations.Result as shown in Figure 7, known by result of the test, through long-time tabletting, adopt spss16.0 to carry out statistical analysis to data, each time point does not have significant difference, and the uniformity of dosage units of tablet meets 2010 editions Chinese Pharmacopoeia regulations, illustrates that the tabletting time affects without significance uniformity of dosage units.
Detect determining of wavelength
Precision takes mifepristone reference substance 10mg and is placed in 10ml volumetric flask, adds dehydrated alcohol to be diluted to scale, to shake up.Precision measures above-mentioned solution 5ml and is placed in 100ml volumetric flask, is diluted to scale with dilute hydrochloric acid liquid (1 → 100), in contrast product solution (50.12 μ gmL-1).Meanwhile, take the dry newborn adjuvant of appropriate mifepristone add in ethanol and dissolve by recipe quantity, dilution in the same way, as negative control.Get respectively above-mentioned two kinds of solution and filter with 0.45um microporous filter membrane, in the interscan of wavelength 200～400nm scope, scanning result is as Fig. 2.Result shows that mifepristone reference substance solution 262nm place has absorption maximum and negative control solution nothing under this wavelength to absorb, therefore select 262nm for detecting wavelength.
The investigation of standard curve
The accurate mifepristone reference substance solution 25ml that draws puts in 50ml measuring bottle, be diluted to scale with dilute hydrochloric acid liquid (1 → 100), be configured to the solution of 25 μ gmL-1, respectively accurate absorption 1,2,4,10, in 20ml to 25ml volumetric flask, add dilute hydrochloric acid liquid (1 → 100) and be diluted to scale, jolting is even, measures absorbance at 262nm place.With absorbance A, concentration C is carried out to linear regression, A=0.0388x+0.0025r=0.9996. result shows: mifepristone is good in 1～20 μ gmL-1 scope internal linear relation.
Method determination of recovery rates
Accurately pipette 3ml, 5ml, 10ml mifepristone reference substance solution is put in 25ml volumetric flask, add respectively the dry emulsion adjuvant of removing mifepristone by recipe quantity, add dilute hydrochloric acid liquid (1 → 100) standardize solution, ultrasonic 15min, leave standstill cooling, with 0.45 μ m microporous filter membrane filtration, obtain the amount of the mifepristone of basic, normal, high (6,10,20 μ gmL-1) three kinds of concentration.Under 262nm, measure absorbance respectively, ask calculation measured concentration with standard curve, add concentration ratio with theory, result average recovery rate is respectively 98.5%, 99.2%, 98.9%, RSD and is respectively 0.59%, 0.81%, 0.72% (n=3).
Precision test
Get respectively the solution of above-mentioned 3 kinds of concentration, in the 1st day and continuously, in 5d, measure 5 times.The withinday precision and the day to day precision that calculate basic, normal, high concentration, result is respectively 1.83%, 1.37%, 1.52% and 1.13%, 0.87%, 0.98% (n=3)
Although embodiment of the present invention are open as above, but it is not restricted to listed utilization in description and embodiment, it can be applied to various applicable the field of the invention completely, for those skilled in the art, can easily realize other amendment, therefore do not deviating under the general concept that claim and equivalency range limit, the present invention is not limited to specific details and illustrates here and the legend of describing.
Claims (10)
1. the dry newborn oral cavity disintegration tablet of mifepristone, is characterized in that, is prepared from by crude drug and the adjuvant of weight components:
Mifepristone Emulsion 30-50
Proppant 50-70
Disintegrating agent 4-6
Wherein said mifepristone Emulsion is made up of according to following weight fraction mifepristone, edible oil and emulsifying agent:
Mifepristone 5-15
Edible oil 10-30
Emulsifying agent 4-8
Described proppant is selected from one or more in microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, lactose;
Described disintegrating agent is selected from one or more in carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone and dried starch.
2. the dry newborn oral cavity disintegration tablet of mifepristone as claimed in claim 1, is characterized in that, the optimum prescription of the dry newborn oral cavity disintegration tablet of described mifepristone is:
。
3. the dry newborn oral cavity disintegration tablet of mifepristone as claimed in claim 1 or 2, is characterized in that, described proppant is made up of the component of following weight portion:
Microcrystalline Cellulose 35-45
Low-substituted hydroxypropyl cellulose 10-20
Lactose 3-7.
4. the dry newborn oral cavity disintegration tablet of mifepristone as claimed in claim 3, is characterized in that, the optimum prescription of described proppant is:
Microcrystalline Cellulose 40
Low-substituted hydroxypropyl cellulose 14
Lactose 5.
5. the dry newborn oral cavity disintegration tablet of mifepristone as claimed in claim 1, is characterized in that, also contains the component of following weight portion in described adjuvant:
Micropowder silica gel 0.1-0.2
Aspartame 0.1-0.2
Mannitol 0.1-0.2.
6. the dry newborn oral cavity disintegration tablet of mifepristone as claimed in claim 1 or 2, is characterized in that, described emulsifying agent is made up of Tween 80 and sorbester p17, and its mass ratio is 2: 1.
7. the preparation method of the dry newborn oral cavity disintegration tablet of mifepristone as claimed in claim 1, is characterized in that, comprises the following steps:
The preparation of step 1, mifepristone Emulsion, takes a certain amount of mifepristone and is dissolved in edible oil, obtains mifepristone solution, and emulsifying agent and distilled water are joined in described mifepristone solution, carries out emulsifying, homogenizing obtains mifepristone Emulsion;
Step 2, the dry newborn preparation of mifepristone, join proppant in described mifepristone Emulsion according to formula ratio, makes it to become moistening agglomerate, is dried approximately 8 hours in 60 DEG C of left and right, sieves, and obtains the dry breast of mifepristone;
Step 3, tabletting, mix dry gained mifepristone breast with disintegrating agent and other adjuvants, adjustment sheet heavily carries out tabletting, obtains the dry newborn oral cavity disintegration tablet of mifepristone.
8. the preparation method of the dry newborn oral cavity disintegration tablet of mifepristone as claimed in claim 7, is characterized in that, step 1 is prepared in mifepristone solution, the dehydrated alcohol of 3-5 weight portion is mixed with mifepristone and edible oil, and ultrasonic concussion is about 5 minutes.
9. the preparation method of the dry newborn oral cavity disintegration tablet of mifepristone as claimed in claim 7 or 8, it is characterized in that, before adding emulsifying agent and distilled water in step 1, mifepristone solution is heated, heating-up temperature is 60-80 DEG C, and institute's adding distil water is 5-15 weight portion.
10. the preparation method of the dry newborn oral cavity disintegration tablet of mifepristone as claimed in claim 7, is characterized in that, in step 2, adopt boulton process to be dried, gained desciccate is crossed and is not less than 200 mesh sieves, adopts direct compression process to carry out tabletting.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1218665A (en) * | 1997-12-03 | 1999-06-09 | 上海市计划生育科学研究所 | High efficiency mifepristone preparation and its preparing method and use |
| CN1634078A (en) * | 2004-11-11 | 2005-07-06 | 上海现代药物制剂工程研究中心有限公司 | Combination of Mifepristone and Anordrin, Tablets |
| US20070213306A1 (en) * | 2006-03-08 | 2007-09-13 | Richard Hausknecht | Methods, dosing regimens & medications using anti-progestational agents for the treatment of disorders |
| CN101455671A (en) * | 2009-01-08 | 2009-06-17 | 湖北葛店人福药业有限责任公司 | Mifepristone medicinal preparation and preparation method thereof |
-
2014
- 2014-02-27 CN CN201410070301.1A patent/CN103932998B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1218665A (en) * | 1997-12-03 | 1999-06-09 | 上海市计划生育科学研究所 | High efficiency mifepristone preparation and its preparing method and use |
| CN1634078A (en) * | 2004-11-11 | 2005-07-06 | 上海现代药物制剂工程研究中心有限公司 | Combination of Mifepristone and Anordrin, Tablets |
| US20070213306A1 (en) * | 2006-03-08 | 2007-09-13 | Richard Hausknecht | Methods, dosing regimens & medications using anti-progestational agents for the treatment of disorders |
| CN101455671A (en) * | 2009-01-08 | 2009-06-17 | 湖北葛店人福药业有限责任公司 | Mifepristone medicinal preparation and preparation method thereof |
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| CN103932998B (en) | 2016-03-30 |
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