A kind of flupentixol and melitracen pharmaceutical composition and preparation method thereof
Technical field
The invention belongs to technical field of medicine, and in particular, to a kind of flupentixol and melitracen pharmaceutical composition
And preparation method thereof, and the Flupentixol and Melitracen Tablets made of the composition.
Background technique
Flupentixol (flupentixol) belongs to thioxanthene class atypical antipsychotic, by blocking midbrain-edge system
System and midbrain-cortex system dopamine receptor work, chemical name are as follows: α-trifluoromethyl -9- { 3- [4- (2- ethoxy) -1-
Diethylene diamines]-propane }-thioxanthene, structure is as shown in formula I:
Melitracen (melitracen) belongs to tricyclic (heterocycle) class antidepressant, by inhibiting norepinephrine and 5-
The reuptake of hydroxytryptamine increases the concentration of both mediators of synaptic cleft and plays antidepressant effect, chemical name are as follows: 3- [10,
10- dimethyl -9 (10H)-anthracene subunit]-N, N- dimethyl -1- propylamine, structure is as shown in formula II:
Since there may be the side effects of extrapyramidal system for Flupentixol, and melitracen has the side effect of cholinolytic, because
On the one hand synaptic cleft dopamine, norepinephrine and 5- can be improved in Flupentixol and melitracen use in conjunction by this
The concentration of the neurotransmitters such as hydroxytryptamine generates synergistic effect, enhances its antidepression, antianxiety and firing properties;On the other hand, fluorine
Piperazine thioxanthene can weaken melitracen cholinolytic effect, and melitracen can fight the issuable extrapyramidal system of Flupentixol
Side effect.So both Flupentixol, melitracen are combined, collaboration, synergy, attenuation are haved the function that.
Have more documents at present and discloses flupentixol and melitracen compound preparation and preparation method thereof.
CN1732940A discloses a kind of compound melitracen Flupentixol capsule and preparation method thereof: by hydrochloric acid U.S. benefit
Qu Xin, diluent, disintegrating agent mix well, and powder is made;After the Flupenthixol Hydrochloride solvent dissolution pharmacologically allowed,
It is uniformly added in above-mentioned powder, it is dry;Again with adhesive wet granulation, drying, whole grain, addition lubricant total mix, dress after drying
Enter capsule to obtain the final product;The weight ratio range of melitracen and Flupentixol is 40~8: 1;Diluent, disintegrating agent and Flupentixol
Weight ratio is 850~60: 150~5: 1.
CN101125131A discloses a kind of preparation method of flupentixol and melitracen capsule, it is characterised in that takes ball
The Flupentixol of recipe quantity/U.S. benefit Qu Xin and diluent are carried out the mode of mixed grinding by grinding machine, and preparation method includes weighing, ball
Grinding machine ball milling mixing 22-26 hours, River Bank Stability, granulation, drying, total mix, capsule charge.
CN104288153A discloses a kind of flupentixol and melitracen pharmaceutical composition and preparation method thereof, open to make
The pharmaceutical composition is prepared with the method for equal increments, specifically, the equal increments hybrid mode is as follows: taking recipe quantity fluorine
Piperazine thioxanthene is added the melitracen of equivalent, sieving, stirring or movement mixing, then takes and continue with the melitracen of mixture equivalent
Mixing, continuously adds after mixing and mixes with the melitracen of mixture equivalent, until by the melitracen of whole recipe quantities
It mixes and finishes with Flupentixol.Although this method improves the stability of product, but equal increments method preparation contains fluorine
The uniformity of the capsule of piperazine thioxanthene melitracen pharmaceutical composition is very low, the dosage phase of Flupentixol and melitracen in prescription
Difference is very big, brings difficulty to the mixing of supplementary material, so that the uniformity of product is very low, affects the curative effect of the drug.
To solve the above-mentioned problems, be badly in need of developing it is a kind of it is at low cost, operating method is simple and can effectively improve fluorine piperazine thiophene
The preparation method of the ton melitracen pharmaceutical composition uniformity.
Summary of the invention
It is an object of that present invention to provide a kind of preparation methods of flupentixol and melitracen pharmaceutical composition, mainly solve existing
There is the uniform of the flupentixol and melitracen pharmaceutical composition of the preparation method preparation of flupentixol and melitracen pharmaceutical composition
Spend the problem of difference.
The first aspect of the present invention provides a kind of preparation method of flupentixol and melitracen pharmaceutical composition, including fluorine
Piperazine thioxanthene and melitracen mix the step of gained mixture is mixed with the filler and/or disintegrating agent being optionally present again,
Wherein the Flupentixol and melitracen are mixed as follows: under the air-flow crushing that liquidates, melitracen is equal
It is added in Flupentixol and is mixed in batches evenly.
Preferably, it melitracen is evenly divided into 2-5 batch is added in Flupentixol and mix.
In order to further increase the uniformity of flupentixol and melitracen pharmaceutical composition, the preferably described Flupentixol and beauty
Litracen, filler and disintegrating agent cross 40-100 mesh before mixing, preferably cross 60-100 mesh.
Preferably, Flupentixol is 1-3 parts by weight, and melitracen is 7-75 parts by weight, and filler is 150-300 weight
Part, disintegrating agent is 8-20 parts by weight.
Preferably, the amount ratio of the Flupentixol and the melitracen is 1:10-25;Further preferably 1:18-
25。
In the present invention, the selection of the filler is not particularly limited, the preferably described filler is selected from crystallite
One of cellulose, lactose, starch, calcium monohydrogen phosphate, calcium sulfate, calcium carbonate, magnesium carbonate, mannitol and sorbierite are a variety of.
In addition, to the selection of the disintegrating agent, also there is no particular limitation, and the preferably described disintegrating agent is selected from sodium carboxymethyl starch, carboxymethyl
One of sodium cellulosate, crosslinked polyethylene pyrrole network alkanone and hydroxypropylcellulose are a variety of.
The second aspect of the present invention provides a kind of flupentixol and melitracen pharmaceutical composition prepared by the above method
Object.
The third aspect of the present invention provides a kind of Flupentixol and Melitracen Tablets, which contains
Above-mentioned flupentixol and melitracen pharmaceutical composition and the following auxiliary material being optionally present: adhesive, disintegrating agent or lubricant.
Preferably, it calculates by weight, in the Flupentixol and Melitracen Tablets, flupentixol and melitracen medicine group
Close object 8-78 parts, 1-10 parts of adhesive, 8-20 parts of disintegrating agent, 1-10 parts of lubricant.
Described adhesive is preferably selected from polyvinylpyrrolidone, hydroxypropylcellulose, starch, hydroxypropyl methylcellulose, carboxymethyl
One of sodium cellulosate and gelatin are a variety of;
The disintegrating agent is preferably selected from sodium carboxymethyl starch, sodium carboxymethylcellulose, crosslinked polyethylene pyrrole network alkanone and hydroxyl
One of third cellulose is a variety of;
The lubricant is preferably selected from talcum powder, magnesium stearate, calcium stearate, sodium stearyl fumarate, silica and hard
One of resin acid is a variety of.
The fourth aspect of the present invention provides a kind of preparation method of above-mentioned Flupentixol and Melitracen Tablets, this method packet
Include following steps:
(1) described adhesive is configured to binder solution, then with the flupentixol and melitracen pharmaceutical composition
Carry out mixing softwood processed;
(2) softwood that step (1) obtains is pelletized using 24-18 mesh, it is then dry under conditions of 40-70 DEG C
0.5-3h;
(3) dry particl that step (2) obtains is subjected to dry whole grain using 20-14 mesh;Then by obtained dry particl with
Disintegrating agent and mix lubricant uniformly rear tabletting.
According to the fourth aspect of the invention, in step (1), prepare adhesive used in solvent be preferably selected from water, ethyl alcohol,
At least one of isopropanol;It is further preferred that the weight of the flupentixol and melitracen pharmaceutical composition and adhesive
Amount ratio is 20:1-5:1.
In step (3), the disintegrating agent is preferably selected from sodium carboxymethyl starch, sodium carboxymethylcellulose, crosslinked polyethylene
One of pyrrole network alkanone and hydroxypropylcellulose are a variety of, and the lubricant is preferably selected from talcum powder, magnesium stearate, stearic rich horse
One of sour sodium, silica and stearic acid are a variety of.
The present inventor has found by in-depth study, and melitracen bulk pharmaceutical chemicals equably (are preferably divided in batches
Be 2-5 crowd) be added in Flupentixol bulk pharmaceutical chemicals, and the mode for the air-flow crushing that liquidates is combined to be mixed, using this kind of spy
Fixed preparation method can obtain the uniformity more tablet, ensure that drug effect.And disclosed in patent of invention CN104288153A
Equal increments mode be mainly a small amount of component raw material and a large amount of component raw materials and auxiliary material according to prescription weight from as little as more sequences by
A equal increments mixing, operating process is complicated, cumbersome, and compared with the above method of the application, prepares resulting fluorine piperazine
The uniformity of thioxanthene melitracen pharmaceutical composition is lower, influences the curative effect of medication.
Detailed description of the invention
Fig. 1 is the Dissolution profiles figure of melitracen in embodiment 1 and commercially available Flupentixol and Melitracen Tablets.
Fig. 2 is the Dissolution profiles figure of melitracen in embodiment 2 and commercially available Flupentixol and Melitracen Tablets.
Fig. 3 is the Dissolution profiles figure of melitracen in embodiment 3 and commercially available Flupentixol and Melitracen Tablets.
Fig. 4 is the Dissolution profiles figure of melitracen in comparative example 3 and commercially available Flupentixol and Melitracen Tablets.
Fig. 5 is the Dissolution profiles figure of Flupentixol in embodiment 1 and commercially available Flupentixol and Melitracen Tablets.
Fig. 6 is the Dissolution profiles figure of Flupentixol in embodiment 2 and commercially available Flupentixol and Melitracen Tablets.
Fig. 7 is the Dissolution profiles figure of Flupentixol in embodiment 3 and commercially available Flupentixol and Melitracen Tablets.
Fig. 8 is the Dissolution profiles figure of Flupentixol in comparative example 3 and commercially available Flupentixol and Melitracen Tablets.
Specific embodiment
The present invention is described in detail by the following examples.It should be understood that embodiments herein is given for example only
The present invention will be described for property, is not used to limit the invention.
Embodiment 1
Prescription:
Title |
Dosage |
Flupenthixol Hydrochloride |
0.1168g |
Melitracen hydrochloride |
2.25g |
Lactose |
195.71g |
Starch |
5.68g |
Croscarmellose sodium |
1.48g |
Hydroxypropyl methylcellulose |
0.1800g |
Talcum powder |
0.3455g |
Magnesium stearate |
0.1745g |
It amounts to |
205.94g |
Preparation method:
(1) premixing prepares flupentixol and melitracen pharmaceutical composition: by the Flupentixol and melitracen of recipe quantity
80 meshes are crossed, then under the air-flow crushing that liquidates, the melitracen of recipe quantity is uniformly divided into 5 parts, Flupentixol is added portionwise
In mixed, obtained mixture is uniformly mixed with filler, the disintegrating agent of 80 mesh of mistake of recipe quantity then, obtains fluorine
Piperazine thioxanthene melitracen pharmaceutical composition.
(2) softwood processed: being configured to binder solution for the solvent of the adhesive of recipe quantity and 29 parts by weight, then with it is above-mentioned
Flupentixol and melitracen pharmaceutical composition carries out mixing softwood processed;
(3) it pelletizes, is dry: the softwood that step (2) obtains is crossed into the granulation of 24 meshes, dry 1h in baking oven;
(4) whole grain: the dry particl that step (3) obtains is crossed into 18 meshes and carries out dry whole grain;
(5) total mix, tabletting: the dry particl and disintegrating agent, mix lubricant that step (4) is obtained uniformly rear tabletting.
Embodiment 2
Prescription:
Title |
Dosage |
Flupenthixol Hydrochloride |
0.1168g |
Melitracen hydrochloride |
2.25g |
Lactose |
115.14g |
Starch |
25.87g |
Croscarmellose sodium |
0.95g |
Hydroxypropyl methylcellulose |
0.1254g |
Talcum powder |
0.2641g |
Silica |
0.0897g |
It amounts to |
144.81g |
Preparation method:
(1) premixing prepares flupentixol and melitracen pharmaceutical composition: by the Flupentixol and melitracen of recipe quantity
60 meshes are crossed, then under the air-flow crushing that liquidates, the melitracen of recipe quantity is uniformly divided into 2 parts, Flupentixol is added portionwise
In, obtained mixture is uniformly mixed with filler, the disintegrating agent of 80 mesh of mistake of recipe quantity then, obtains Flupentixol beauty
Litracen pharmaceutical composition.
(2) softwood processed: being configured to binder solution for the solvent of the adhesive of recipe quantity and 36 parts by weight, then with it is above-mentioned
Flupentixol and melitracen pharmaceutical composition carries out mixing softwood processed;
(3) it pelletizes, is dry: the softwood that step (2) obtains is crossed into the granulation of 20 meshes, dry 1h in baking oven;
(4) whole grain: the dry particl that step (3) obtains is crossed into 18 meshes and carries out dry whole grain;
(5) total mix, tabletting: the dry particl and disintegrating agent, mix lubricant that step (4) is obtained uniformly rear tabletting.
Embodiment 3
Prescription:
Title |
Dosage |
Flupenthixol Hydrochloride |
0.2554g |
Melitracen hydrochloride |
1.7541g |
Microcrystalline cellulose |
200g |
Mannitol |
43.4g |
Sodium carboxymethyl starch |
0.8669g |
Polyvinylpyrrolidone |
0.2354g |
Talcum powder |
0.3061g |
Magnesium stearate |
0.1497g |
It amounts to |
246.97g |
Preparation method:
(1) premixing prepares flupentixol and melitracen pharmaceutical composition: by the Flupentixol and melitracen of recipe quantity
It is sieved with 100 mesh sieve in prescription ratio, then under the air-flow crushing that liquidates, the melitracen of recipe quantity is uniformly divided into 3 parts in batches
It is added in Flupentixol, then mixes obtained mixture with the filler sieved with 100 mesh sieve, the disintegrating agent of recipe quantity
It is even, obtain flupentixol and melitracen pharmaceutical composition.
(2) softwood processed: being configured to binder solution for the solvent of the adhesive of recipe quantity and 50 parts by weight, then with it is above-mentioned
Flupentixol and melitracen pharmaceutical composition carries out mixing softwood processed;
(3) it pelletizes, is dry: the softwood that step (2) obtains is crossed into the granulation of 24 meshes, dry 1h in baking oven;
(4) whole grain: the dry particl that step (3) obtains is crossed into 20 meshes and carries out dry whole grain;
(5) total mix, tabletting: the dry particl and disintegrating agent, mix lubricant that step (4) is obtained uniformly rear tabletting.
Comparative example 1
Prescription:
Preparation method:
(1) premixing prepares flupentixol and melitracen pharmaceutical composition: by the Flupentixol and melitracen of recipe quantity
80 meshes are crossed, then under the grinding of ball mill, the melitracen of recipe quantity is uniformly divided into 5 parts, fluorine piperazine is added portionwise
It is mixed in thioxanthene, obtained mixture is uniformly mixed with filler, the disintegrating agent of 80 mesh of mistake of recipe quantity then, is obtained
To flupentixol and melitracen pharmaceutical composition.
(2) softwood processed: being configured to binder solution for the solvent of the adhesive of recipe quantity and 29 parts by weight, then with it is above-mentioned
Flupentixol and melitracen pharmaceutical composition carries out mixing softwood processed;
(3) it pelletizes, is dry: the softwood that step (2) obtains is crossed into the granulation of 24 meshes, dry 1h in baking oven;
(4) whole grain: the dry particl that step (3) obtains is crossed into 18 meshes and carries out dry whole grain;
(5) total mix, tabletting: the dry particl and disintegrating agent, mix lubricant that step (4) is obtained uniformly rear tabletting.
Comparative example 2
Prescription:
Preparation method:
(1) premixing prepares flupentixol and melitracen pharmaceutical composition: by the Flupentixol of recipe quantity and recipe quantity beauty
Litracen crosses 80 meshes, is then mixed under the air-flow crushing that liquidates, then by the mistake 80 of obtained mixture and recipe quantity
Filler, the disintegrating agent of mesh are uniformly mixed, and obtain flupentixol and melitracen pharmaceutical composition.
(2) softwood processed: being configured to binder solution for the solvent of the adhesive of recipe quantity and 29 parts by weight, then with it is above-mentioned
Flupentixol and melitracen pharmaceutical composition carries out mixing softwood processed;
(3) it pelletizes, is dry: the softwood that step (2) obtains is crossed into the granulation of 24 meshes, dry 1h in baking oven;
(4) whole grain: the dry particl that step (3) obtains is crossed into 18 meshes and carries out dry whole grain;
(5) total mix, tabletting: the dry particl and disintegrating agent, mix lubricant that step (4) is obtained uniformly rear tabletting.
Comparative example 3
Prescription:
Preparation method:
(1) Flupentixol of recipe quantity and croscarmellose sodium are carried out four equivalent to progressively increase mixing, 80 mesh of mistake
1. sieve, obtains mixture;
(2) 1. with the secondary equivalent of melitracen hydrochloride progress and is mixed, crossed 80 meshes, obtain mixture 2.;
(3) 2. with the secondary equivalent of starch progress and is mixed, crossed 80 meshes, obtain mixture 3.;
(4) 3. with the secondary equivalent of lactose progress and is mixed, crossed 80 meshes, obtain mixture 4.;
(5) 4. mixture is put into three-dimensional motion mixer with remaining lactose, crosses 40 meshes, obtains mixture 5.;
(6) softwood processed: being configured to binder solution for the solvent of the adhesive of recipe quantity and 29 parts by weight, then with mix
5. object carries out mixing softwood processed;
(7) it pelletizes, is dry: the softwood that step (6) obtains is crossed into the granulation of 24 meshes, dry 1h in baking oven;
(8) whole grain: the dry particl that step (7) obtains is crossed into 18 meshes and carries out dry whole grain;
(9) total mix, tabletting: the dry particl and disintegrating agent, mix lubricant that step (8) is obtained uniformly rear tabletting.
The test of 1 uniformity of dosage units of test example
Method: prepare each 1, tablet of Example 1-3 and comparative example 1 and 2 sets in 25mL measuring bottle respectively, adds water suitable
Amount adds methanol to make to dissolve in right amount after shaking makes disintegration of tablet, and ultrasound 40 minutes with methanol dilution to scale, shakes up, and filters, and shines
High performance liquid chromatography (four chromatographies 0512 of Chinese Pharmacopoeia version in 2015) measurement.It is filler with phenyl silane bonded silica gel
(chromatographic column of phenyl, 4.6 × 150mm, 5 μm of XBridge TM or same efficiency);With 0.04mol/L Ammonium formate buffer
(ammonium formate 2.52g is taken, appropriate amount of water is added to make to dissolve, adds triethylamine 10mL, mixes, adds water to 1000mL, extremely with formic acid tune pH
7.5)-methanol (20: 80) is mobile phase, and column temperature is 35 DEG C, Detection wavelength 270nm, flow velocity 1.0mL/min.Take hydrochloric acid U.S. benefit
Bent pungent reference substance adds methanol to dissolve and quantifies the solution for diluting and being made in every 1mL containing about 0.6mg, takes 10 μ L, inject liquid chromatogram
Instrument records chromatogram, and theoretical cam curve is calculated by melitracen peak is not less than 2000, and tailing factor meets the requirements.Precision measures
10 μ L of test solution injects liquid chromatograph, records chromatogram;Separately take melitracen hydrochloride reference substance and Flupenthixol Hydrochloride
Appropriate reference substance, it is accurately weighed, add methanol to dissolve and dilute and is made in every 1mL containing about melitracen 0.6mg and Flupentixol
The solution of 0.03mg, is measured in the same method, by external standard method with calculated by peak area to get.
1 air blending method of table (embodiment 1,2,3) and equal increments method (comparative example 3) product uniformity effect
2 Comparative Examples 1 and 2 product uniformity effect of table
Remarks: S: standard deviation, A: every with relative amount that labelled amount is 100 for x, mean value X, A=| 100-X |,
" Chinese Pharmacopoeia " (version in 2015) regulation:
If A+2.2S≤L, the uniformity of dosage units of test sample meets regulation;
It is against regulation if A+S > L;
If A+2.2S > L, and A+S < L then should separately take 20 retrials of test sample.
L is specified value in above-mentioned formula.Unless otherwise specified, L=15.0.
From the results shown in Table 1, melitracen bulk pharmaceutical chemicals equably (are preferably divided into 2 batches, 3 batches, 5 batches) in batches
Ground is added in Flupentixol bulk pharmaceutical chemicals, and the mode for the air-flow crushing that liquidates is combined to be mixed, Flupentixol beauty obtained
The uniformity of litracen tablet is superior to the fluorine that equal increments mixing method is prepared described in patent of invention CN104288153A
The uniformity of piperazine thioxanthene melitracen tablet.Under the air-flow that liquidates, melitracen bulk pharmaceutical chemicals are added to equably dividing 5 batches
In Flupentixol bulk pharmaceutical chemicals, the uniformity effect of the Flupentixol and Melitracen Tablets agent of acquisition has more apparent raising.In addition, grinding
Mixing method and disposable mixture content uniformity effect are unable to reach pharmacopoeial requirements.
2 dissolution rate of test example is investigated
Method: prepare each 1, tablet of Example 1-3 and comparative example 3, according to high performance liquid chromatography (middle traditional Chinese medicines
Four chromatographies 0512 of allusion quotation version in 2015) measurement.According to dissolution method (four general rules of Chinese Pharmacopoeia version in 2015 0931 second
Method) using 1.2 hydrochloric acid solution 900mL of pH as solvent, revolving speed is 50 turns per minute, is operated according to methods, and takes solution suitable when through 30 minutes
Amount, filtration, takes subsequent filtrate as test solution;With phenyl silane bonded silica gel be filler (XBridge TM phenyl,
4.6 × 150mm, the chromatographic column of 5 μm or same efficiency);With 0.04mol/L Ammonium formate buffer (ammonium formate 2.52g is taken, water is added
Make to dissolve in right amount, add triethylamine 10mL, mix, add water to 1000mL, is flowing with formic acid tune pH to 7.5)-methanol (20: 80)
Phase, column temperature are 35 DEG C, Detection wavelength 270nm, flow velocity 1.0mL/min.Melitracen hydrochloride reference substance is taken, adds methanol dissolution simultaneously
The solution in every 1mL containing about 0.6mg is made in quantitative dilution, takes 10 μ L, injects liquid chromatograph, records chromatogram, theoretical tray
Number is calculated by melitracen peak is not less than 2000, and tailing factor meets the requirements.Precision measures 10 μ L of test solution and injects liquid phase
Chromatograph records chromatogram;Separately take melitracen hydrochloride (conversion factor of melitracen and melitracen hydrochloride is 0.8887)
Reference substance about 11.3mg, it is accurately weighed, it sets in 25mL volumetric flask, precision measures 5mL, sets in 10mL volumetric flask, adds methanol dilution
It to scale, shakes up, as melitracen hydrochloride reference substance mother liquor;Take Flupenthixol Hydrochloride (Flupentixol and Flupenthixol Hydrochloride
Conversion factor be 0.8562) reference substance about 11.8mg, it is accurately weighed, set in 25mL measuring bottle, add methanol to dissolve and be diluted to quarter
Degree, shakes up, and precision measures 5mL, sets in 200mL volumetric flask, adds methanol dilution to scale, shake up, as Flupenthixol Hydrochloride pair
According to product mother liquor solution;It is accurate respectively to measure melitracen hydrochloride reference substance mother liquor and each 1mL of Flupenthixol Hydrochloride reference substance mother liquor,
It sets in 20mL volumetric flask, solubilization goes out medium to scale, shakes up, as reference substance solution.It is measured in the same method, calculates every middle fluorine
The amount of dissolution of piperazine thioxanthene and melitracen.Limit is the 80% of labelled amount, should meet regulation.
1 embodiment 1 of table is compared with the dissolution rate of melitracen in commercially available Flupentixol and Melitracen Tablets
2 embodiment 2 of table is compared with the dissolution rate of melitracen in commercially available Flupentixol and Melitracen Tablets
3 embodiment 3 of table is compared with the dissolution rate of melitracen in commercially available Flupentixol and Melitracen Tablets
4 comparative example 3 of table is compared with the dissolution rate of melitracen in commercially available Flupentixol and Melitracen Tablets
Time min |
Piece 1 |
Piece 2 |
Piece 3 |
Piece 4 |
Piece 5 |
Piece 6 |
It is average |
RSD% |
Commercially available product |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
5 |
52.41 |
44.64 |
58.74 |
62.56 |
59.77 |
60.78 |
56.48 |
11.96 |
39.65 |
10 |
74.18 |
82.53 |
86.37 |
90.67 |
84.51 |
87.97 |
84.37 |
6.79 |
78.92 |
15 |
93.17 |
91.68 |
92.11 |
95.48 |
94.03 |
96.75 |
93.87 |
2.09 |
90.29 |
20 |
94.53 |
96.47 |
92.54 |
95.18 |
95.65 |
96.23 |
95.10 |
1.51 |
95.08 |
30 |
94.15 |
96.12 |
92.20 |
95.39 |
95.74 |
96.42 |
95.00 |
1.67 |
94.17 |
45 |
93.82 |
95.43 |
92.09 |
95.74 |
95.23 |
96.15 |
94.74 |
1.61 |
94.34 |
5 embodiment 1 of table is compared with Flupentixol dissolution rate in commercially available Flupentixol and Melitracen Tablets
6 embodiment 2 of table is compared with Flupentixol dissolution rate in commercially available Flupentixol and Melitracen Tablets
Time min |
Piece 1 |
Piece 2 |
Piece 3 |
Piece 4 |
Piece 5 |
Piece 6 |
It is average |
RSD% |
Commercially available product |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
5 |
80.16 |
76.57 |
84.48 |
78.76 |
83.62 |
67.69 |
78.55 |
7.75 |
38.04 |
10 |
96.49 |
99.11 |
95.93 |
96.51 |
101.72 |
89.87 |
96.61 |
4.10 |
69.68 |
15 |
97.56 |
98.68 |
96.12 |
95.27 |
101.53 |
98.55 |
97.95 |
2.25 |
85.87 |
20 |
97.45 |
98.84 |
95.73 |
96.13 |
101.68 |
98.54 |
98.06 |
2.21 |
94.36 |
30 |
97.60 |
98.59 |
95.98 |
96.21 |
101.17 |
98.29 |
97.97 |
1.93 |
96.93 |
45 |
97.33 |
98.16 |
96.29 |
95.58 |
101.39 |
98.35 |
97.85 |
2.08 |
97.42 |
7 embodiment 3 of table is compared with Flupentixol dissolution rate in commercially available Flupentixol and Melitracen Tablets
Time min |
Piece 1 |
Piece 2 |
Piece 3 |
Piece 4 |
Piece 5 |
Piece 6 |
It is average |
RSD% |
Commercially available product |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
5 |
76.69 |
73.04 |
83.48 |
86.41 |
70.14 |
82.42 |
78.70 |
8.15 |
38.04 |
10 |
95.47 |
96.33 |
93.89 |
99.04 |
102.04 |
97.05 |
97.30 |
2.96 |
69.68 |
15 |
95.14 |
96.81 |
94.34 |
99.73 |
101.69 |
97.06 |
97.46 |
2.86 |
85.87 |
20 |
95.37 |
96.74 |
94.06 |
99.52 |
101.86 |
96.46 |
97.34 |
2.94 |
94.36 |
30 |
95.48 |
96.35 |
94.52 |
99.64 |
101.71 |
96.97 |
97.45 |
2.79 |
96.93 |
45 |
95.68 |
96.58 |
94.20 |
99.69 |
101.65 |
96.58 |
97.40 |
2.82 |
97.42 |
8 comparative example 3 of table is compared with Flupentixol dissolution rate in commercially available Flupentixol and Melitracen Tablets
Time min |
Piece 1 |
Piece 2 |
Piece 3 |
Piece 4 |
Piece 5 |
Piece 6 |
It is average |
RSD% |
Commercially available product |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
5 |
52.14 |
48.69 |
63.91 |
65.48 |
46.36 |
58.41 |
55.83 |
14.31 |
38.04 |
10 |
86.00 |
87.05 |
76.47 |
78.15 |
68.69 |
82.24 |
79.77 |
8.58 |
69.68 |
15 |
92.45 |
90.38 |
83.59 |
88.85 |
81.39 |
96.79 |
88.91 |
6.40 |
85.87 |
20 |
92.73 |
92.41 |
92.45 |
92.46 |
94.01 |
99.40 |
93.91 |
2.94 |
94.36 |
30 |
93.15 |
95.29 |
94.63 |
93.15 |
93.76 |
100.69 |
95.11 |
3.01 |
96.93 |
45 |
93.40 |
95.10 |
94.16 |
92.66 |
93.51 |
100.46 |
94.88 |
3.01 |
97.42 |
Flupentixol and Melitracen Tablets and comparative example provided by the invention it can be seen from the result of table 1-8 and Fig. 1-8
The Flupentixol and Melitracen Tablets that 3 (using CN104288153A the method) obtain are compared, the former Flupentixol and Mei Li
Difference is small between the dissolution rate piece of Qu Xin, it is rapider to dissolve out.Compared with commercially available Flupentixol and melitracen piece, dissolution rate
More rapidly.To sum up, the method for the present invention can effectively improve the uniformity of products material medicine and auxiliary material, increase the dissolution effect of drug
Rate, obtains that rapid-action, effect is good, stable and reliable quality Flupentixol and Melitracen Tablets.