CN103860520A - Moxifloxacin capsules, and preparation method thereof - Google Patents
Moxifloxacin capsules, and preparation method thereof Download PDFInfo
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- CN103860520A CN103860520A CN201210545256.1A CN201210545256A CN103860520A CN 103860520 A CN103860520 A CN 103860520A CN 201210545256 A CN201210545256 A CN 201210545256A CN 103860520 A CN103860520 A CN 103860520A
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- moxifloxacin
- magnesium stearate
- microcrystalline cellulose
- carboxymethyl starch
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Abstract
The invention belongs to the field of pharmaceutical industry, and relates to moxifloxacin capsules. A content of the moxifloxacin capsules comprises moxifloxacin hydrochloride, microcrystalline cellulose, sodium carboxymethyl starch, and magnesium stearate; the ingredients above are mixed, an obtained mixture is made into particles, and the particles are packaged by gelatin capsules so as to obtain the moxifloxacin capsules. Novel prescription and novel technology adopted by a preparation method of the moxifloxacin capsules are capable of avoiding reduction of dissolubility in storage processes, and ensuring f2 equivalence of the moxifloxacin capsules in four dissolution mediums with original grinded capsules.
Description
Technical field
The invention belongs to medical technical field, relate to the pharmaceutical preparation that contains moxifloxacin hydrochloride (moxifloxacin HCl), be specifically related to a kind of capsule of moxifloxacin hydrochloride and preparation method thereof.
Background technology
Moxifloxacin (moxiflaxacin) is fluoroquinolone antimicrobial drug of new generation, at present this kind with tablet and injection listing for upper and lower respiratory tract infection due to sensitive microbial, as the treatment of chronic bronchitis acute attack, community acquired pneumonia, acute bacterial sinusitis and uncomplicated skin and soft tissue infection etc.
The preparation patent that patent CN114993C studies for Beyer Co., Ltd of Yuan Yan producer, lays special stress on protecting tablet formulation.Prescription is described for Moxifloxacin, microcrystalline Cellulose, lactose, cross-linking sodium carboxymethyl cellulose, magnesium stearate, also contain the lactose of 2.5%-25%, the former sheet trade name of grinding of Gai Yuanyan producer listing is for visiing multiple pleasure (Avelox), adjuvant in preparation prescription comprises: microcrystalline Cellulose, lactose monohydrate, cross-linking sodium carboxymethyl cellulose, magnesium stearate, hypromellose, titanium dioxide, Polyethylene Glycol and iron sesquioxide.
Patent CN100363001C has described Moxifloxacin and has prepared after capsule cannedly in gelatine capsule shell, and finding capsule shells to occur swelling softgel shell, to be rubber lantern ring broken, and content cannot stripping; Meanwhile, strengthen disintegrating agent consumption, place for a long time stripping after 1 year and there will be defective.Adopt cellulose gum softgel shell can improve above phenomenon.
The inventor finds that the embodiment of patent CN100363001C has two defects: although a cellulose gum softgel shell can reach 90% by 45min in 0.1M hydrochloric acid, front 15min stripping is slower, and employing f2 factorization method and former grinding cannot be equivalent in sheet contrast; Two, drug act " oral solid formulation Dissolution Rate Testing guideline " requires imitation medicine and dosage changing form should carry out 4 stripping curves at present.As requested, while carrying out other three stripping curves contrast, far below the former tablet that grinds, and along with pH rising stripping is lower.
Summary of the invention
The invention provides a kind of moxifloxacin capsule that contains, contain moxifloxacin hydrochloride, microcrystalline Cellulose, carboxymethyl starch sodium, magnesium stearate in capsule 's content, the capsule shells of described capsule is gelatine capsule shell.
The percentage by weight that the microcrystalline Cellulose containing in capsule 's content accounts for capsule 's content total amount is 5-10%, is preferably 7-9%, most preferably is 8.5%
The percentage by weight that the carboxymethyl starch sodium containing in capsule 's content accounts for capsule 's content total amount is 11-17%, is preferably 14-15%, most preferably is 13.7%
The percentage by weight that the magnesium stearate containing in capsule 's content accounts for capsule 's content total amount is 1-3%.Be preferably 2-3%, most preferably be 2.6%
Described capsule, is characterized in that the moxifloxacin hydrochloride that said preparation contains 200-600mg take single dose as basis.
The preparation method of described capsule, comprises step: moxifloxacin hydrochloride and microcrystalline cellulose excipients, carboxymethyl starch sodium, magnesium stearate are fully mixed and made into granule, and fill is in gelatine capsule.Preferred step is: 1. by moxifloxacin hydrochloride and carboxymethyl starch sodium according to the equivalent method mix homogeneously that progressively increases, and then mix homogeneously with microcrystalline Cellulose, and get magnesium stearate mix homogeneously; 2. start dry granulating machine, adjusting roller spacing is 0.15-0.3mm, turn/min of feeding rotating speed 60-80, and pinch roller rotating speed is turn/min of 1-5, sieve number is 10-18 order, pours above-mentioned material into feeding hopper, from the discharging opening granulation granule that connects material to obtain; 3. by granulation granule filling in gelatine capsule.
The prepared gelatine capsule of the present invention attempts adopting other disintegrating agents such as cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose etc., and adopt different dosage, all can not make capsule grind simultaneously f2 equivalence of tablet with former in 4 dissolution mediums, especially can not equivalence in water and pH6.8 phosphate-buffered salt.
The present invention also attempts adopting carboxymethyl starch sodium and the magnesium stearate of low dosage, the percentage by weight that the carboxymethyl starch sodium for example containing in capsule 's content accounts for capsule 's content total amount is 5%, magnesium stearate is 1%, all can not make capsule grind simultaneously f2 equivalence of tablet with former in 4 dissolution mediums, especially can not equivalence in water and pH6.8 phosphate-buffered salt.
By the carboxymethyl starch sodium of high dose, (percentage by weight that the carboxymethyl starch sodium containing in capsule 's content accounts for capsule 's content total amount is that the capsule particle fill of 25% preparation is in cellulose capsule in the present invention, in 4 dissolution mediums, can not reach 15min stripping more than 85%, and cannot arrive f2 equivalence simultaneously with the former tablet that grinds, especially in water and pH6.8 phosphate-buffered salt, need the stripping of 1 hour ability more than 80%.
Formulation and technology of the present invention can be avoided and overcome the above problems, not only in 4 kinds of media, 15min all can reach more than 85%, and can grind tablet f2 equivalence simultaneously in 4 dissolution mediums with former, and acceleration result in June shows, stripping behavior does not change, and related substance does not also increase.
Accompanying drawing explanation
Fig. 1: embodiment 1, reference example and commercially available former tablet (trade name: the Avelox) stripping curve in the hydrochloric acid solution of 0.1mol/L that grinds.
Fig. 2: embodiment 1, reference example and commercially available former tablet (trade name: the Avelox) stripping curve in pH4.5 acetate buffer salt that grinds
Fig. 3: embodiment 1, reference example and commercially available former tablet (trade name: the Avelox) stripping curve in pH6.8 phosphate-buffered salt that grinds
Fig. 4: embodiment 1, reference example and commercially available former tablet (trade name: the Avelox) stripping curve in water that grinds
The specific embodiment
Further illustrate the present invention below by embodiment.Should correct understanding: embodiments of the invention are only used for the present invention is described and provide, rather than limitation of the present invention, so, under method prerequisite of the present invention, simple modifications of the present invention is all belonged to the scope of protection of present invention.
Reference example:
Adopt the embodiment 2 of patent CN200510021739.1 to prepare sample,
Prescription composition:
Preparation method: get former, adjuvant in said components, fully mix homogeneously, after dry method granule processed, fills hydroxypropyl cellulose capsule shell and get final product.
Embodiment 1
Prescription composition:
Preparation method:
1. by moxifloxacin hydrochloride and carboxymethyl starch sodium according to the equivalent method mix homogeneously that progressively increases, and then mix homogeneously with microcrystalline Cellulose, and in getting, add magnesium stearate mix homogeneously;
2. start dry granulating machine, adjusting roller spacing is 0.2mm, turn/min of feeding rotating speed 72, and pinch roller rotating speed is 2 turn/min, sieve number is 10-18 order, pours above-mentioned material into feeding hopper, connects material from discharging opening.
3. by dry granulation granule and additional magnesium stearate mix homogeneously, adopt capsule-filling agent fill in No. 0 gelatine capsule, to obtain final product.
Embodiment 2
Prescription composition:
Preparation method:
Moxifloxacin hydrochloride is fully mixed to dry method granulation with microcrystalline cellulose excipients, carboxymethyl starch sodium, magnesium stearate, and fill, in gelatine capsule, to obtain final product.
Embodiment 3
Prescription composition:
Preparation method:
Moxifloxacin hydrochloride is fully mixed to dry method granulation with microcrystalline cellulose excipients, carboxymethyl starch sodium, magnesium stearate, and fill, in gelatine capsule, to obtain final product.
Embodiment 4 sample dissolution determinations and the f2 factor are calculated
Stripping assay method:
Get this product, according to dissolution method (two appendix XC the second methods of Chinese Pharmacopoeia version in 2010), take the hydrochloric acid solution 900ml of 0.1mol/L as dissolution medium, rotating speed is 50 turn/min, operation in accordance with the law, the the the 5th, 10,15,30,45min gets solution and filters through 0.45 μ m filter membrane, gets subsequent filtrate as sample solution, adds the dissolution medium of respective volume simultaneously.According to determined by ultraviolet spectrophotometry, measure stripping data take 293nm as detecting wavelength.
Same method, is replaced by pH4.5 acetate buffer salt by dissolution medium, pH6.8 phosphate-buffered salt, the other three kinds of dissolution mediums of aquametry.
Embodiment 1, reference example and the commercially available former tablet (trade name: Avelox) that grinds are measured to stripping result according to dissolving-out method.Result is referring to Fig. 1, Fig. 2, Fig. 3 and Fig. 4, and visible formulation and technology of the present invention 15min in 4 kinds of media all can reach more than 85%.
The f2 factor is calculated Consult drug registration correlation technique guideline " oral solid formulation Dissolution Rate Testing guideline ".Similar factors (f
2) be the parameter of weighing two stripping curve similarities, computing formula is as follows:
f
2=50·log{[1+(1/n)∑
t=1 n(R
t-T
t)
2]
-0.5·100}
Wherein n is sampling time point number, R
tfor reference sample is at the dissolution value in t moment, T
tfor the test batch dissolution value in the t moment.
These rules and regulations: if the f2 value between the stripping curve of tested and reference preparation is not less than 50, think that both are similar, equivalence.
Calculate as stated above embodiment 1, embodiment 2 and the commercially available former f2 similarity of tablet (trade name: Avelox) in four kinds of dissolution mediums of grinding.The results are shown in Table 1:
Table 1
| Embodiment | Embodiment 1 | Embodiment 2 | Reference example |
| The hydrochloric acid solution of 0.1mol/L | 70 | 68 | 37 |
| PH4.5 acetate buffer salt | 78 | 75 | 21 |
| PH6.8 phosphate-buffered salt | 55 | 57 | 16 |
| Water | 63 | 64 | 16 |
Visible formulation and technology of the present invention can grind tablet simultaneously f2 equivalence in 4 dissolution mediums with former in 4 kinds of media, and accelerates June result and show, stripping behavior does not change, and related substance does not also increase.
Embodiment 5 stability result
Related substance adopts following methods to detect:
Measure according to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010).
Chromatographic condition and system suitability octadecylsilane chemically bonded silica are filler, chromatographic column is AglientSB-phenyl(4.6 × 250mm, 5 μ m), methanol-(4-butyl ammonium hydrogen sulfate solution of 0.5g/L, 1.0g/L potassium dihydrogen phosphate and 3.4g/L phosphoric acid solution) (28:72) be mobile phase, solvent is for getting 0.50g 4-butyl ammonium hydrogen sulfate and 1.0g potassium dihydrogen phosphate adds 500ml water dissolution, add again 2ml phosphoric acid and 0.05g anhydrous sodium sulfite, then thin up is to 1000ml, detection wavelength is 293nm, flow velocity is 1.3ml/min, column temperature is 45 ℃, detection wavelength is 293nm.
Algoscopy is got the fine powder appropriate (being approximately equivalent to moxifloxacin hydrochloride 10mg) of this product, accurately weighed, puts in 10ml measuring bottle, and solubilizer 6ml, makes to dissolve for ultrasonic 1 minute, lets cool, and solubilizer is diluted to scale, shakes up, and filters, and gets subsequent filtrate as need testing solution; Precision measures in right amount, and solubilizer is made the solution containing 1 μ g in every 1ml, solution in contrast.Get contrast solution 10 μ l, injection liquid chromatography, regulates detection sensitivity, makes the peak height of main constituent chromatographic peak be about 10%～25% of full scale.Get respectively the more each 10 μ l of need testing solution and contrast solution, injection liquid chromatography, records 2.5 times to main constituent peak retention time of chromatogram.In the chromatogram of need testing solution as show impurity peaks, desolventize and adjuvant peak outside, the peak area of single impurity must not be greater than 0.5 times (0.5%) of contrast solution main peak area, and each impurity peak area sum must not be greater than 1 times (1.0%) of contrast solution main peak area.
Dissolution adopts the method for embodiment 4.
Get the moxifloxacin hydrochloride capsule that embodiment 1 prepares and carry out the investigation of 6 months stability tests of accelerated test under 40 ℃ of high temperature, relative humidity 75% ± 5% condition, detect the variation of every quality index, the data obtained is as shown in table 2:
Table 2
Stability result shows, capsule of the present invention has better stability.
Claims (9)
1. a moxifloxacin capsule, contains moxifloxacin hydrochloride, microcrystalline Cellulose, carboxymethyl starch sodium, magnesium stearate in capsule 's content, the capsule shells of described capsule is gelatine capsule shell.
2. capsule claimed in claim 1, is characterized in that containing and accounts for the microcrystalline Cellulose that the percentage by weight of capsule 's content total amount is 5-10%, the carboxymethyl starch sodium of 11-17%, the magnesium stearate of 1-3%.
3. capsule claimed in claim 1, is characterized in that containing and accounts for the microcrystalline Cellulose that the percentage by weight of capsule 's content total amount is 7-9%.
4. capsule claimed in claim 1, is characterized in that containing and accounts for the carboxymethyl starch sodium that the percentage by weight of capsule 's content total amount is 14-15%.
5. capsule claimed in claim 1, is characterized in that containing and accounts for the magnesium stearate that the percentage by weight of capsule 's content total amount is 2-3%.
6. capsule claimed in claim 1, is characterized in that containing and accounts for the microcrystalline Cellulose that the percentage by weight of capsule 's content total amount is 8.5%, 13.7% carboxymethyl starch sodium, 2.6% magnesium stearate.
7. capsule claimed in claim 1, is characterized in that the moxifloxacin hydrochloride that said preparation contains 200-600mg take single dose as basis.
8. the preparation method of the capsule described in claim 1 ~ 7, comprises step: moxifloxacin hydrochloride and microcrystalline cellulose excipients, carboxymethyl starch sodium, magnesium stearate are fully mixed and made into granule, and fill is in gelatine capsule.
9. capsule claimed in claim 8, step is as follows:
1. by moxifloxacin hydrochloride and carboxymethyl starch sodium according to the equivalent method mix homogeneously that progressively increases, and then mix homogeneously with microcrystalline Cellulose, and get magnesium stearate mix homogeneously; 2. start dry granulating machine, adjusting roller spacing is 0.15-0.3mm, turn/min of feeding rotating speed 60-80, and pinch roller rotating speed is turn/min of 1-5, sieve number is 10-18 order, pours above-mentioned material into feeding hopper, from the discharging opening granulation granule that connects material to obtain; 3. by granulation granule filling in gelatine capsule.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210545256.1A CN103860520A (en) | 2012-12-14 | 2012-12-14 | Moxifloxacin capsules, and preparation method thereof |
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| CN201210545256.1A CN103860520A (en) | 2012-12-14 | 2012-12-14 | Moxifloxacin capsules, and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104807935A (en) * | 2015-04-30 | 2015-07-29 | 成都百裕科技制药有限公司 | Separation and detection method for moxifloxacin hydrochloride intermediate and enantiomer thereof |
| CN105287562A (en) * | 2015-10-27 | 2016-02-03 | 白强 | Moxifloxacin hydrochloride composition and application of same in preparing medicine for treating lung injury |
| CN114814067A (en) * | 2022-06-24 | 2022-07-29 | 珠海溪谷医疗科技有限公司 | Method for detecting content of heptasodium diethylenetriamine penta (methylene phosphonic acid) in hydrogen peroxide care solution by high performance liquid chromatography |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1672681A (en) * | 2004-03-23 | 2005-09-28 | 深圳市天一时科技开发有限公司 | Moxixacin capsule and its prepn process |
| CN1736379A (en) * | 2004-08-11 | 2006-02-22 | 深圳市天一时科技开发有限公司 | Moxifloxaci gelatin capsule and preparation process thereof |
| CN100363001C (en) * | 2005-09-21 | 2008-01-23 | 深圳市天一时科技开发有限公司 | Moxifloxacin capsule and its preparation method |
-
2012
- 2012-12-14 CN CN201210545256.1A patent/CN103860520A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1672681A (en) * | 2004-03-23 | 2005-09-28 | 深圳市天一时科技开发有限公司 | Moxixacin capsule and its prepn process |
| CN1736379A (en) * | 2004-08-11 | 2006-02-22 | 深圳市天一时科技开发有限公司 | Moxifloxaci gelatin capsule and preparation process thereof |
| CN100363001C (en) * | 2005-09-21 | 2008-01-23 | 深圳市天一时科技开发有限公司 | Moxifloxacin capsule and its preparation method |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104807935A (en) * | 2015-04-30 | 2015-07-29 | 成都百裕科技制药有限公司 | Separation and detection method for moxifloxacin hydrochloride intermediate and enantiomer thereof |
| CN105287562A (en) * | 2015-10-27 | 2016-02-03 | 白强 | Moxifloxacin hydrochloride composition and application of same in preparing medicine for treating lung injury |
| CN114814067A (en) * | 2022-06-24 | 2022-07-29 | 珠海溪谷医疗科技有限公司 | Method for detecting content of heptasodium diethylenetriamine penta (methylene phosphonic acid) in hydrogen peroxide care solution by high performance liquid chromatography |
| CN114814067B (en) * | 2022-06-24 | 2022-09-13 | 珠海溪谷医疗科技有限公司 | Method for detecting content of heptasodium diethylenetriamine penta (methylene phosphonic acid) by HPLC (high performance liquid chromatography) |
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Application publication date: 20140618 |