CN109682939A - A kind of Mesalazine enema fluid dissolution determination method - Google Patents
A kind of Mesalazine enema fluid dissolution determination method Download PDFInfo
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Abstract
The present invention provides a kind of methods for measuring Mesalazine enema fluid dissolution rate, buffer salt, revolving speed, the screening of sample time, Detection wavelength, filter membrane, test sample concentration, sample measured quantity, the screening of sample loading alternative, the adding manner of sample is that exsolution goes out at the about 1cm of medium liquid level center to be slowly added to, the adding manner can obviously distinguish the dissolved corrosion between different product and prescription, with stronger separating capacity, the Conformance Assessment of formulation and technology exploitation and reference preparation can be instructed well.
Description
Technical field
The present invention relates to the technical field of measurement drug dissolution, in particular to a kind of Mesalazine enema fluid dissolution rate is surveyed
Determine the sample loading alternative of method.
Background technique
Ulcerative colitis is the disease that the whole world has, and in recent years, the disease incidence of ulcerative colitis is in China
Have and increase trend, salicylazosulfapyridine (SASP) is clinically mostly used to treat, although there is certain curative effect, its incidence of side effects
It is higher, and sulfanilamide (SN) allergy sufferers cannot be applied.Mesalazine is succeeded in developing and is launched by the German pharmaceutical factory Huo Ke great earliest, with
SASP is compared, and general chemical structure is to remain 5-aminosalicylic acid effective ingredient, eliminates sulfapryidine group, therefore
The shortcomings that overcoming SASP is a kind of new drug for treating ulcerative colitis, is widely applied in western countries.At present due to people
Living environment deteriorate and the factors such as living habit influence, pathogenesis of ulcerative colitis rate is increasing year by year, in U.S. salad
Before Qin Wenshi, without better drug for treating ulcerative colitis, after the advent of Mesalazine, with its good curative effect and not
It is good to react the advantages such as few, clinically constantly promote.
The main pharmacological of Mesalazine is directly to inhibit colon peroxidase, inhibits inflammatory mediator, including preceding
The synthesis and release of column parathyrine, leukotriene etc.；Inhibit the activity of platelet activating factor；Free radical is removed, intestinal mucosa is reduced
Damage and stimulation, and avoid the side effect of SASP, suitable for SASP, glucocorticoid is invalid or the patient that does not tolerate.From
Alleviate and change under symptom, Sigmoidoscope, effective percentage is apparently higher than SASP.In addition, also can obviously reduce in patients serum TNF- а and
IL-8 is horizontal, this may be its one of mechanism of action for treating ulcerative colitis.
The mechanisms of anti-inflammatory of Mesalazine is not fully understood.In vitro study shows Mesalazine to intestinal mucosa prostate
The content of element has certain influence, has the function of scavenging capacity oxygen radical, may play certain inhibition to lipoxygenase and make
With.After rectal administration Mesalazine enema fluid, Mesalazine mainly acts locally on intestinal mucosa and submucosa tissue.
The dissolution rate of drug is evaluated in one of drug quality in index, is a kind of simulation oral solid formulation in stomach and intestine
The in vitro test method of middle disintegration and dissolution, the purpose is to guarantee the validity of preparation, for the prediction of drug behavior in vivo
Also there is certain practical significance.The present invention grinds pharmaceutical preparation In Vitro Dissolution behavior with original to the imitated pharmaceutical preparation listed
It is no that a kind of detection method is unanimously provided, the consistent reference index of curative effect of medication is ground as imitated drug and original.
The various suspensions recorded in country's Extra Pharmacopoeia Martindale at present, it is desirable that measure the less of dissolution rate, generally oral administration solid
Preparation measures dissolution rate, while Mesalazine enema fluid records the measuring method of dissolution rate without standard both at home and abroad；The present invention
Provide that a kind of Mesalazine copies pharmaceutical preparation and original grinds the whether consistent detection method of pharmaceutical preparation In Vitro Dissolution behavior.
It is found in Mesalazine enema fluid dissolution study continuous mode, the adding manner of sample is to this product dissolution rate
It is affected, by studying screening verification, it is determined that the adding manner of this product when dissolution determination copies preparation and original to evaluating
It grinds that vitro Drug dissolved corrosion is consistent, there is great directive significance.
Summary of the invention
In order to solve the above technical problems, copying pharmaceutical preparation the present invention provides a kind of Mesalazine grinds pharmaceutical preparation with original
The whether consistent detection method of In Vitro Dissolution behavior can be applied to the quality control of Mesalazine enema fluid.
The present invention provides a kind of measuring method of Mesalazine enema fluid dissolution rate, and the leaching condition of the method includes:
This product is taken, according to dissolution rate and drug release determination method, using phosphate buffer (pH7.2) 900ml as dissolution medium, revolving speed is every point
50 turns of clock.
When the method was through 15 minutes, solution 10ml is taken, is filtered, precision measurement subsequent filtrate is appropriate, quantitative with dissolution medium
Dilution is made containing about the solution of 30 μ g of Mesalazine in every lml, as test solution；Another precision weighs Mesalazine reference substance
In right amount, add dissolution medium to dissolve and dilute and the solution that every 1ml contains 30 μ g is made, shake up, as reference substance solution.
The method takes this product are as follows: sample 60g (whole branch) is taken to measure dissolution rate.
The sample adding manner of the method are as follows: separate out and be slowly added at 1 ± 0.1cm of medium liquid level center.
It includes: to detect absorbance at 330nm wavelength according to Ultraviolet spectrophotometry that the method, which dissolves out quantity measuring method,.
The method in advance carries out the test solution using 0.45 μm of filter membrane before carrying out absorbance detection
Filtering.
For the method when dissolving out 15 minutes, the dissolution rate of the Mesalazine enema fluid is not less than the 75% of labelled amount.
Detailed description of the invention
Fig. 1 is to separate out to be slowly added to figure at the about 1cm of medium liquid level center using sample of the present invention；
Fig. 2 is to separate out medium liquid level using sample of the present invention to hit exactly middling speed addition figure at about 1cm；
Fig. 3 is to separate out to rapidly join figure at the about 1cm of medium liquid level center using sample of the present invention；
Fig. 4 is to separate out to be slowly added to figure at the about 5cm of medium liquid level center using sample of the present invention；
Fig. 5 is to separate out medium liquid level using sample of the present invention to hit exactly middling speed addition figure at about 5cm；
Fig. 6 is to separate out to rapidly join figure at the about 5cm of medium liquid level center using sample of the present invention；
Fig. 7 is to separate out medium liquid level using sample of the present invention to hit exactly addition process in leaching comparison diagram at about 1cm；
Fig. 8 is to separate out medium liquid level using sample of the present invention to hit exactly addition process in leaching comparison diagram at about 5cm；
Wherein, Fig. 7, in 8 be 1. quickly sample-adding, be 2. middling speed sample-adding, 3. to be loaded at a slow speed.
Specific embodiment
Since this product is that suspension finds the adding manner of sample to molten during this product dissolving-out method screening study
Test result is affected out.For the effect for confirming dissolution determination method of the present invention, inventor has carried out a large amount of experiment,
And the screening and verifying of science have been carried out to measuring method, screening verification experiment is as follows:
Different prescription sample preparations
Auxiliary material xanthan gum is the main component for increasing this product viscosity in reference preparation and own product prescription, and dosage difference is to this
Product dissolved corrosion has large effect, and dosage is bigger, and dissolution rate is lower；Therefore increase the use of xanthan gum in fixed prescription 1
Amount is prescription 2；The different prescription of proposed adoption goes the separating capacity of verifying dissolving-out method.
1 sample preparation of table
| Name of material | Own product 01 (prescription 1) | Own product 02 (prescription 2) |
| Mesalazine (g) | 2000 | 2000 |
| Natrium adetate (g) | 30 | 30 |
| Sodium pyrosulfite (g) | 120 | 120 |
| Sodium benzoate (g) | 30 | 30 |
| Xanthan gum (g) | 60 | 80 |
| Sodium acetate (g) | 90 | 90 |
The investigation of different sample loading alternatives
Consider that sample loading alternative influences the measurement result of dissolution rate, is taken respectively from product 01, own product 02 and reference preparation
(60s is added), middling speed addition are added at a slow speed being investigated respectively close to sample-adding at 1 ± 0.1cm of liquid level center and 5 ± 0.1cm
(30s is added) rapidly joins (10s is added) according to dissolution measuring method measurement, and calculates the sample-adding speed that content investigate sample
Influence of the rate to dissolution rate.Compare the amount of dissolution of different prescriptions and reference preparation.
Table 2 is loaded at a slow speed close to liquid level center 1cm
Table 3 is loaded close to liquid level center 1cm middling speed
Table 4 is quickly loaded close to liquid level center 1cm
5 chaotropic face center 5cm of table is loaded at a slow speed
6 chaotropic face center 5cm middling speed of table sample-adding
7 chaotropic face center 5cm of table is quickly loaded
It is slowly added at 1 ± 0.1cm of medium liquid level center to different prescriptions and production the results showed that (1) sample separates out
Separating capacity between product is most strong；The difference between different prescriptions and product can be distinguished well；The adding manner and reference system simultaneously
Application method (bottle tilts down, and then slowly squeezes) is closer in agent specification, can preferably embody this product in vivo and in vitro
The consistency of dissolved corrosion；(2) rapidly joining has part during sample-adding with the higher position adding manner in chaotropic face, sample
Sample has dispersed (especially quickly sample-adding, sample dispersion are more) in the medium, keeps dissolution data bigger than normal；It is thus determined that sample-adding side
Formula is to hit exactly slowly to squeeze at 1cm close to liquid level to be added, specifically as shown in Fig. 1,2,3,4,5,5,6,7,8.
Dissolve out homogeneity (in batch):
Take this product according to dissolution determination method, by the way of slowly squeezing addition close at the 1cm of liquid level center, measurement is inhaled
Luminosity investigates the dissolution homogeneity of Mesalazine enema fluid.Test result see the table below:
Table 8 dissolves out uniformity test result
Dissolve out reproducibility (between batch)
3 batches of this product are taken to survey by the way of slowly squeezing addition close at the 1cm of liquid level center according to dissolution determination method
Determine absorbance, investigates the dissolution reproducibility of Mesalazine enema fluid.Test result see the table below:
Table 9 dissolves out reproducible test results
Reproducibility meets the requirements between test result shows dissolution homogeneity in this method measurement sample batch and criticizes.
Claims (9)
1. a kind of Mesalazine enema fluid dissolution determination method, including buffer salt, revolving speed, sample time, Detection wavelength, filter
Film, screening of test sample concentration, sample measured quantity etc. operate, and are primarily characterized in that: in the screening of sample loading alternative, sample adds
Entering mode is that exsolution goes out at 1 ± 0.1cm of medium liquid level center to be added.
2. the method according to claim 1, it is characterised in that: the phosphate buffer are as follows: slow with pH7.2 phosphate
Fliud flushing 900ml is dissolution medium.
3. the method according to claim 1, it is characterised in that: the dissolution sample time is 15 minutes；The dissolution
It is carried out under the speed conditions of 50 turns/min.
4. the method according to claim 1, it is characterised in that: the absorbance detection is carried out at 330nm wavelength
's.
5. according to the method described in claim 1, it is characterized by: dissolve out 15 minutes when, the Mesalazine enema fluid
Dissolution rate is not less than the 75% of labelled amount.
6. the method according to claim 1, it is characterised in that: before carrying out the absorbance detection, use in advance
0.45 μm of filter membrane is filtered the test solution.
7. the method according to claim 1, it is characterised in that: the measurement concentration of test solution is 30 μ g/ml.
8. the method according to claim 1, it is characterised in that: the mode that sample is added be close to dissolution medium liquid level just
It is slowly added to or rapidly joins at middle about 1cm or 5cm, preferably hit exactly close to dissolution medium liquid level and be slowly added at about 1cm.
9. a kind of method for measuring Mesalazine enema fluid dissolution rate, it is characterised in that: the following steps are included:
1) it using the phosphate buffer 900ml of pH7.2 as dissolution medium, is injected separately into 6 stripping rotors, heating makes described molten
Medium temperature is maintained in 37 ± 0.5 DEG C out, and speed of agitator is 50 turns/min；
2) Mesalazine enema fluid 6 are taken, separates out be slowly added to 6 stripping rotors at the about 1cm of medium liquid level center respectively
It is interior, immediately begin to timing；
3) 6 stripping rotors are directed to, took solution 10ml at 15 minutes respectively, are filtered through 0.45 μm of filter membrane, using described molten
The solution for containing 20 μ g Mesalazines in every 1ml is made in the dilution of obtained filtrate by medium out, as test solution；
4) another precision weighs that Mesalazine reference substance is appropriate, adds dissolution medium dissolve and dilutes and every 1ml is made contains the molten of 30 μ g
Liquid shakes up, as reference substance solution；
5) test solution and control solution are taken respectively, according to UV-VIS spectrophotometry, respectively in 330nm wavelength
Place's measurement absorbance, and the amount of dissolution is calculated according to following equation:
Wherein, A is the absorbance of test solution；
W r is the amount of taking of reference substance, mg；
S r is the volume of dissolution and extension rate of reference substance；
A r is the absorbance of reference substance solution；
W is the compliance marker of test sample, mg；
S is the volume and extension rate of test sample dissolution medium.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110736813A (en) * | 2019-10-25 | 2020-01-31 | 广东嘉博制药有限公司 | Method for measuring in-vitro release rate of pharmaceutical preparations |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009080030A1 (en) * | 2007-12-21 | 2009-07-02 | Lifecycle Pharma A/S | Treatment of autoimmune hepatitis with a once daily oral dosage form comprising tacrolimus |
| CN101474148A (en) * | 2008-11-04 | 2009-07-08 | 深圳致君制药有限公司 | Oral liquid sustained-release preparation containing codeine and chlorphenamine and preparation method thereof |
| CN105372187A (en) * | 2014-08-29 | 2016-03-02 | 武汉光谷人福生物医药有限公司 | Method for determining dissolution rate of meisuoshuli tablets |
| CN105878177A (en) * | 2016-05-12 | 2016-08-24 | 中国人民解放军广州军区武汉总医院 | Mesalazine temperature-sensitive gel enema and preparation method thereof |
| CN108469400A (en) * | 2018-06-27 | 2018-08-31 | 北京市药品检验所 | The dissolution in vitro of enteric coated preparations detects and the method for evaluation |
-
2018
- 2018-12-26 CN CN201811603605.4A patent/CN109682939A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009080030A1 (en) * | 2007-12-21 | 2009-07-02 | Lifecycle Pharma A/S | Treatment of autoimmune hepatitis with a once daily oral dosage form comprising tacrolimus |
| CN101474148A (en) * | 2008-11-04 | 2009-07-08 | 深圳致君制药有限公司 | Oral liquid sustained-release preparation containing codeine and chlorphenamine and preparation method thereof |
| CN105372187A (en) * | 2014-08-29 | 2016-03-02 | 武汉光谷人福生物医药有限公司 | Method for determining dissolution rate of meisuoshuli tablets |
| CN105878177A (en) * | 2016-05-12 | 2016-08-24 | 中国人民解放军广州军区武汉总医院 | Mesalazine temperature-sensitive gel enema and preparation method thereof |
| CN108469400A (en) * | 2018-06-27 | 2018-08-31 | 北京市药品检验所 | The dissolution in vitro of enteric coated preparations detects and the method for evaluation |
Non-Patent Citations (3)
| Title |
|---|
| 刘阿兰: "美沙拉嗪灌肠液治疗溃疡性结肠炎的护理体会", 《实用临床护理学杂志》 * |
| 柳文媛 等: "《药物分析进展 （第二版）》", 30 September 2018 * |
| 沈丹丹等: "复方倍他米松注射混悬液溶出度方法的开发和验证", 《中国新药杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110736813A (en) * | 2019-10-25 | 2020-01-31 | 广东嘉博制药有限公司 | Method for measuring in-vitro release rate of pharmaceutical preparations |
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Application publication date: 20190426 |