CN1762357A - Oral medicinal formulation of moxifloxacin and its preparation method - Google Patents
Oral medicinal formulation of moxifloxacin and its preparation method Download PDFInfo
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- CN1762357A CN1762357A CN 200510021736 CN200510021736A CN1762357A CN 1762357 A CN1762357 A CN 1762357A CN 200510021736 CN200510021736 CN 200510021736 CN 200510021736 A CN200510021736 A CN 200510021736A CN 1762357 A CN1762357 A CN 1762357A
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Abstract
The invention relates to an oral medicinal formulation of moxifloxacin and its preparation method, which comprises Moxifloxacin or its salt and/or its hydrate, and at least one film forming material for preparing intermediate particles of the preparation selected from hydroxy propyl methyl cellulose, hydroxy ethyl methyl cellulose, cellulose methyl, hydroxy propyl cellulose, hydroxy ethyl cellulose, sodium carboxymethyl cellulose, polyacrylic resins, polyethylene glycol, polyvinyl pyrrolidon-vinyl acetate copolymer, polyvinyl alcohol-polyethylene glycol grafted copolymer, carbopol, gelatine, poloxamer and polyvinyl pyrrolidon. The invention also discloses the process for preparing the pharmaceutical preparation.
Description
Technical field
The present invention relates to a kind of pharmaceutical preparation and preparation method thereof, special, the present invention relates to the stable oral drug preparation of a kind of Moxifloxacin (moxifloxacin) or its salt and/or its hydrate and the preparation method of this pharmaceutical preparation.
Background technology
Moxifloxacin is a fluoroquinolone antimicrobial drug of new generation, at present Moxifloxacin hydrochlorate approved is used for upper and lower respiratory tract infection due to the sensitive microbial, as the treatment of acute episode of chronic bronchitis, community acquired pneumonia, acute bacterial sinusitis and uncomplicated skin and soft tissue infection etc.
The moxifloxacin hydrochloride tablet is registered first in Mexico in February, 1999, in JIUYUE, 1999 is in German Initial Public Offering, infusion solution in calendar year 2001 December in the U.S. and German Initial Public Offering, at present should product go on the market in that Germany, Spain, Italy, Sweden, Switzerland, the U.S., Canada, Australia, Argentina, Brazil, Korea S, Malaysia etc. are national.
Chinese patent " pharmaceutical moxifloxacin preparation ", the preparation technology of the patent No. 99813124.5 report Moxifloxacin tablets is with medicine and at least a no aqueous adhesive and the granulation of lactose water, then with this granule and at least a disintegrating agent and at least a mix lubricant, and randomly tabletting and coating.This patent characteristic obtains outstanding releasing properties simultaneously owing to adopt 2.5～25% lactose to improve the hardness or the breaking load of previous patent (EP-A-0350733) tablet in prescription.
Chinese patent " pharmaceutical moxifloxacin preparation ", at least a no aqueous adhesive that the patent No. 99813124.5 is carried, former patent applicant has enumerated microcrystalline Cellulose, fibrous cellulose, calcium phosphate and has closed mannitol in description, and preferably microcrystalline cellulose, these adjuvants all do not possess film forming characteristics.
Chinese patent " pharmaceutical moxifloxacin preparation ", the patent No. 99813124.5 description are mentioned, the pharmaceutical preparation of its invention preferably exists with tablet form, can randomly carry out coating to this tablet, for coating, can use pharmaceutical field coated preparation commonly used, as based on various hydroxypropyl emthylcelluloses (HPMC) and/or Polyethylene Glycol, this coating can also contain pigment, for example titanium dioxide or the iron oxide red of routine in addition.Specifically mentioning the coating material that tablet is carried out among the embodiment 1,4,5,6 is HPMC.But in this patent documentation, described coating all refers to the coating that the plain sheet to tablet carries out, and does not mention and uses filmogen to prepare midbody particle or granule is carried out coating.
Applicant had before designed two kinds of test recipes voluntarily and had compared with the prescription of correlated Chinese patent " pharmaceutical moxifloxacin preparation " (patent No. 99813124.5).Tripartite all with reference to contrast patent (patent No. 99813124.5) technology of carrying, water pelletizing press sheet.Concrete prescription and investigating the results are shown in Table 1, table 2.
Table 1 moxifloxacin hydrochloride tablet formulation
| Contrast patent formulation * | From intending test recipe 1* | From intending test recipe 2* | |
| Moxifloxacin hydrochloride | 218.4 | 218.4 | 218.4 |
| Microcrystalline Cellulose | 68.0 | 57.6 | 124.6 |
| Lactose monohydrate | 34.0 | 104.0 | |
| Pregelatinized Starch | 37.0 | ||
| Carboxymethylstach sodium | 14.0 | 7.0 | |
| Cross-linking sodium carboxymethyl cellulose ** | 8 | 7.0 | |
| Magnesium stearate | 2.4 | 6.0 | 6.0 |
| Gross weight | 330.8 | 400 | 400 |
Remarks: *: the contrast patent formulation is Chinese patent 99813124.5 embodiment 4, contains lactose.Contain lactose from intending test recipe 1; Do not contain lactose from intending test recipe 2.
*: the contrast patent formulation is the Chinese patent (patent No. 99813124.5, publication number CN1325306A) the uncoated tablets core of embodiment 4 prescription in, but in the disclosure text, the * place is a sodium carboxymethyl cellulose, it is translated by croscarmellose soldium, see this former patent specification page 2, and this translation error in fact just should indeed be translated as cross-linking sodium carboxymethyl cellulose (disintegrating agent).
Table 2. three prescription label mass ratioes
| Contrast patent formulation * | From intending test recipe 1* | From intending test recipe 2* | |
| Hardness kg | 14 | 13 | 14 |
| Friability | ＜0.2％ | ＜0.2％ | ＜0.2％ |
| Disintegration | ＜5 minutes | ＜5 minutes | ＜5 minutes |
| Dissolution | 99.8％ | 100.1％ | 99.7％ |
Remarks: hardness adopts Meng Shandou (Mansanto) durometer to measure, friability, disintegration, dissolution are measured with reference to 2000 editions regulations of Chinese Pharmacopoeia, wherein dissolution determination method is pressed first method mensuration among two appendix XC of Chinese Pharmacopoeia version in 2000, dissolution medium is the 0.1M hydrochloric acid solution, rotating speed 100rpm measures 45 minutes stripping values.
Can see that from table 2 three prescriptions tablet hardness, friabilities, disintegration, dissolution determination result are suitable.
Yet obvious redness is showed by discovery tablet appearance or edge regular meeting in the tablet press process that above-mentioned three prescriptions make, and prompting produces new impurity.
Find in the moxifloxacin hydrochloride raw material stability study that these product should not contact with metallic iron, especially cause moxifloxacin hydrochloride variable color (red by xanthochromia) under the wet heat condition.Moxifloxacin hydrochloride and iron content container or rustless steel drift in the preparation process, punch die contacts or rub the back changeable colour, for this reason, the granulation of said preparation, drying should avoid using the iron content container, and the granule of hydrochloric Moxifloxacin but is inevitable with contacting of drift and punch die in the tabletting process usually.
At present do not have any document that pharmacology, the toxicological effect of moxifloxacin hydrochloride raw material or its red impurity that produces in the tabletting process are reported to some extent as yet, can not predict it is harmless to human body.
Summary of the invention
Purpose of the present invention is exactly in order to solve Moxifloxacin especially produces red impurity in the tabletting process in the preparation process problem, a kind of stable moxifloxacin oral pharmaceutical preparation, especially tablet are provided, and the preparation method of this pharmaceutical preparation, the tablet of preparation has good hardness and stripping character.
For achieving the above object, the present invention has adopted following technical scheme:
The invention discloses a kind of moxifloxacin oral pharmaceutical preparation; contain Moxifloxacin or its salt and/or its hydrate; described pharmaceutical preparation also contains at least a filmogen that is used to prepare the midbody particle of preparation or carries out powder or granule coating, and described filmogen comprises:
Hydroxypropyl emthylcellulose, hydroxyethylmethyl-cellulose, methylcellulose, hydroxypropyl cellulose, hydroxyethyl-cellulose, sodium carboxymethyl cellulose, polyacrylic resin class, Polyethylene Glycol, polyvinylpyrrolidone-vinyl acetate co-polymer, polyvinyl alcohol-polyethyleneglycol-graft copolymer, Ka Baibo (Carbopol), gelatin, poloxamer, polyvinylpyrrolidone.
Wherein, described polyacrylic resin class also often is called as poly-(methyl) crylic acid resin.
Described moxifloxacin oral pharmaceutical preparation preferably exists with tablet form, also can be oral formulations such as granule type.When preferred tablet, can be randomly the plain sheet of this tablet be carried out coating, coating for plain sheet, can use pharmaceutical field coated preparation commonly used, as based on various hydroxypropyl emthylcelluloses (HPMC) and/or Polyethylene Glycol, this coating can also contain conventional pigment, for example titanium dioxide or iron oxide red in addition.
The percentage by weight that described filmogen accounts for described pharmaceutical preparation is 0.2～20.0%.
Further, to account for the percentage by weight of described pharmaceutical preparation be 0.5～10.0% to described filmogen.
Described Moxifloxacin or its salt and/or its hydrate are meant moxifloxacin hydrochloride.
Described pharmaceutical preparation also contains the pharmaceutical excipient of pharmaceutically acceptable amount.
Described excipient comprises starch, dextrin, pregelatinized Starch, microcrystalline Cellulose, carboxymethylstach sodium, cross-linking sodium carboxymethyl cellulose, micropowder silica gel, magnesium stearate, lactose.Wherein, lactose is optional in the present invention.
In one group of preferred version of the present invention, described pharmaceutical preparation contains
Percentage by weight is 30～60% moxifloxacin hydrochloride;
Percentage by weight is 0.2～2.0% hydroxypropyl emthylcellulose;
Percentage by weight is 31～50% microcrystalline Cellulose;
Percentage by weight is 5～20% pregelatinized Starch;
Percentage by weight is 1～10% carboxymethylstach sodium;
Percentage by weight is 1～5% cross-linking sodium carboxymethyl cellulose;
Percentage by weight is 0.5～2.5% magnesium stearate.
In another group embodiment of the present invention, described pharmaceutical preparation contains
Percentage by weight is 50～76% moxifloxacin hydrochloride;
Percentage by weight is 0.2～10.0% filmogen hydroxypropyl emthylcellulose;
Percentage by weight is 0.2～10.0% filmogen Polyethylene Glycol;
Percentage by weight is 5～30% microcrystalline Cellulose;
Percentage by weight is 5～20% lactose;
Percentage by weight is 1～10% cross-linking sodium carboxymethyl cellulose;
Percentage by weight is 0.5～2.5% magnesium stearate.
The invention also discloses the preparation method of above-mentioned moxifloxacin oral pharmaceutical preparation, described method comprises step:
It is 0.5～10% aqueous solution or water dispersion solution or Diluted Alcohol solution that described filmogen is made into percentage by weight, mixes back preparation granule as binding agent and Moxifloxacin or its salt and/or its hydrate and pharmaceutical excipient; Perhaps
Part filmogen and Moxifloxacin or its salt and/or its hydrate and pharmaceutical excipient are mixed, the remainder filmogen is made into aqueous solution or the water dispersion solution or the Diluted Alcohol solution of percentage by weight 0.5～10%, mixes back preparation granule with said mixture as binding agent; Perhaps
After described filmogen and Moxifloxacin or its salt and/or its hydrate and pharmaceutical excipient mixed, water or Diluted Alcohol prepared granule after making soft material; Perhaps
It is 0.5～10% aqueous solution or water dispersion solution or Diluted Alcohol solution that described filmogen is made into percentage by weight, and the powder or the granule of Moxifloxacin or its salt and/or its hydrate and pharmaceutical excipient carried out coating.
Described method further comprises step, adds magnesium stearate behind granule of making or the particle drying behind the coating, and mixing tabletting is then made tablet.
The percentage by weight that used filmogen total amount accounts for described pharmaceutical preparation is 0.2～20.0%.
Further, to account for the percentage by weight of described pharmaceutical preparation be 0.5～10.0% to described filmogen total amount.
Described Moxifloxacin or its salt and/or its hydrate are meant moxifloxacin hydrochloride.
Described pharmaceutical excipient comprises starch, dextrin, pregelatinized Starch, microcrystalline Cellulose, carboxymethylstach sodium, cross-linking sodium carboxymethyl cellulose, micropowder silica gel, magnesium stearate, lactose.Wherein, lactose is optional in the present invention.
Because adopted above scheme, the beneficial effect that the present invention is possessed is:
Owing to used the listed filmogen of the present invention to be used to prepare intermediate particle, perhaps powder or granule are carried out coating, make moxifloxacin oral pharmaceutical preparation of the present invention, particularly tablet can retention properties be stablized in granulation and tabletting process, with iron content container or rustless steel drift, punch die contacts or rub after do not produce metachromatism, light, hardness is good, and the medicine stripping is rapid; And can ensure the quality of products after long-time the preservation yet, at room temperature place as label and can keep mass conservation in 2 years, hardness does not have remarkable change, color and luster and keeps yellow, dissolution all to remain on more than 90%.
The specific embodiment
But it is tabletting after adopting filmogen system granule or coating to granulate that the present invention obtains the method for stable Moxifloxacin or its salt and/or its hydrate tablet.The used film forming material can be that hydroxypropyl emthylcellulose (HPMC), hydroxyethylmethyl-cellulose, methylcellulose, hydroxypropyl cellulose, hydroxyethyl-cellulose, sodium carboxymethyl cellulose, poly-(methyl) crylic acid resin (stomach dissolution type or stomach decentralized), Polyethylene Glycol, polyvinylpyrrolidone-vinyl acetate co-polymer are (as Kollidon
VA64 or Plasdone
S-630), polyvinyl alcohol-polyethyleneglycol-graft copolymer is (as Kollicoat
IR), the mixing of one or more in Ka Baibo (Carbopol), gelatin, the poloxamer.It is 0.2～20.0% that filmogen accounts for total tablet weight percentage ratio.
The using method of filmogen is as follows: can be made into aqueous solution or Diluted Alcohol solution prepares granule, its concentration is 0.5～10.0%; Also available part filmogen wiring solution-forming (concentration is the same) is made binding agent, remainder filmogen and principal agent and the mixed granule of other adjuvants, the filmogen that is used for wiring solution-forming does not have special restriction in the ratio of used filmogen total amount, when only needing to satisfy the solution that uses as binding agent and being mixed with granule, make mixture keep the humidity of necessity with remainder filmogen, principal agent and other adjuvants; Whole filmogens can also be mixed with principal agent and other adjuvants, water or Diluted Alcohol are made granule after making suitable soft material; And can carry out coating to the powder or the granule of Moxifloxacin with filmogen solution.Described Diluted Alcohol is used 30%～50% ethanol always.
Granulation and drying can adopt conventional method.As the mixed at high speed granulation, or ebullated bed granulation seasoning.
Medicine is resolved by using filmogen and above-mentioned method of granulating with metal drift, the edge variable color of the fricative tablet of punch die in the tabletting process.
Pharmaceutical preparation of the present invention can also contain an amount of excipient, this excipient can be selected from following adjuvant, and they are starch, dextrin, pregelatinized Starch, microcrystalline Cellulose, carboxymethylstach sodium, cross-linking sodium carboxymethyl cellulose, micropowder silica gel, magnesium stearate, lactose.Also can not contain lactose.
The present invention is described in further detail below by specific embodiment.
Embodiment 1
Component: moxifloxacin hydrochloride 218.4mg
Microcrystalline Cellulose 124.6mg
Pregelatinized Starch 37.0mg
Carboxymethylstach sodium 7.0mg
Cross-linking sodium carboxymethyl cellulose 7.0mg
Magnesium stearate 4.7mg
HPMC(90SH 100) 1.3mg
Gross weight 400.0mg
Get fully mix homogeneously of said components Central Plains, adjuvant (except that magnesium stearate and HPMC), the HPMC aqueous solution system granule with 1.0%, dry back adds the magnesium stearate mixing, tabletting, promptly.Drift and punch die used during tabletting are stainless steel material.
The label of preparation can conventional coating, and also coating does not directly adopt lucifuge to pack.
After finishing respectively at firm preparation and investigate tablet quality after 2 years, the results are shown in Table shown in 6.
Embodiment 2
Component: moxifloxacin hydrochloride 218.4mg
Microcrystalline Cellulose 124.6mg
Pregelatinized Starch 34.3mg
Carboxymethylstach sodium 7.0mg
Cross-linking sodium carboxymethyl cellulose 7.0mg
Magnesium stearate 4.7mg
HPMC(90SH 100) 4.0mg
Gross weight 400.0mg
Get fully mix homogeneously of said components Central Plains, adjuvant (except that magnesium stearate and HPMC), the HPMC Diluted Alcohol solution with 3.0% (Diluted Alcohol is 50% ethanol) system granule, dry back adds the magnesium stearate mixing, tabletting, promptly.Drift and punch die used during tabletting are stainless steel material.
The label of preparation can be used the conventional method coating, and also coating does not directly adopt lucifuge to pack.
After finishing respectively at firm preparation and investigate tablet quality after 2 years, the results are shown in Table shown in 6
Embodiment 3
Component: moxifloxacin hydrochloride 218.4mg
Microcrystalline Cellulose 124.6mg
Pregelatinized Starch 31.5mg
Carboxymethylstach sodium 7.0mg
Cross-linking sodium carboxymethyl cellulose 7.0mg
Magnesium stearate 4.3mg
HPMC(90SH 100) 7.2mg
Gross weight 400.0mg
Get fully mix homogeneously of said components Central Plains, adjuvant (except that magnesium stearate and HPMC), the HPMC aqueous solution system granule with 4.5%, dry back adds the magnesium stearate mixing, tabletting, promptly.Drift that tabletting is used and punch die are stainless steel material.
The label of preparation can be used the conventional method coating, and also coating does not directly adopt lucifuge to pack.
After finishing respectively at firm preparation and investigate tablet quality after 2 years, the results are shown in Table shown in 6.
Embodiment 4
Component: moxifloxacin hydrochloride 436.8mg
Microcrystalline Cellulose 230.0mg
Pregelatinized Starch 60.2mg
Carboxymethylstach sodium 13.0mg
Cross-linking sodium carboxymethyl cellulose 9.0mg
Magnesium stearate 6.0mg
HPMC(90SH 100) 4.5mg
Ka Baibo (934 P) 0.5mg
Gross weight 760.0mg
Get fully mix homogeneously of said components Central Plains, adjuvant (except that magnesium stearate and HPMC, Ka Baibo), above-mentioned HPMC and Ka Baibo are made into percentage by weight in Diluted Alcohol (50%) be 3.0% solution, with this solution and the mixed granule of said mixture, dry back adds the magnesium stearate mixing, tabletting, promptly.Drift that tabletting is used and punch die are stainless steel material.
The label of preparation can be used the conventional method coating, and also coating does not directly adopt lucifuge to pack.
After finishing respectively at firm preparation and investigate tablet quality after 2 years, the results are shown in Table shown in 6.
Embodiment 5
Component: moxifloxacin hydrochloride 218.4mg
Microcrystalline Cellulose 124.6mg
Pregelatinized Starch 32.3mg
Carboxymethylstach sodium 7.0mg
Cross-linking sodium carboxymethyl cellulose 7.0mg
Magnesium stearate 4.7mg
Polyethylene Glycol (PEG) 6000 5.0mg
HPMC(90SH 100) 1.0mg
Gross weight 400.0mg
Getting fully mix homogeneously of said components Central Plains, adjuvant (except that magnesium stearate, PEG and HPMC), is 5.0% aqueous solution with PEG and HPMC mixed preparing concentration, with this aqueous solution system granule, and the dry magnesium stearate of adding afterwards mixing, tabletting, promptly.Drift and punch die used during tabletting are stainless steel material.
The label of preparation can be used the conventional method coating, and also coating does not directly adopt lucifuge to pack.
After finishing respectively at firm preparation and investigate tablet quality after 2 years, the results are shown in Table shown in 6.
Embodiment 6
Component: moxifloxacin hydrochloride 218.4mg
Microcrystalline Cellulose 129.6mg
Pregelatinized Starch 34.0mg
Carboxymethylstach sodium 7.0mg
Cross-linking sodium carboxymethyl cellulose 7.0mg
Magnesium stearate 4.0mg
Total amount 400.0mg
Get fully mix homogeneously of said components Central Plains, adjuvant (except that magnesium stearate), carry out powder coating with following solution; Or former, the abundant mixing dry granulation of adjuvant, the following solution of reuse carries out granule coating.Record former, adjuvant weightening finish 8% after the granule coating, promptly contain 0.8% Macrogol 4000 and 7.2% HPMC (90SH 100) after the granule coating in the preparation.Add the magnesium stearate mixing then, tabletting, promptly.Drift and punch die used during tabletting are stainless steel material.
HPMC(90SH 100) 7.2g
Macrogol 4000 0.8g
Water 92.0g
100.0g
The label of preparation can be used the conventional method coating, and also coating does not directly adopt lucifuge to pack.
After finishing respectively at firm preparation and investigate tablet quality after 2 years, the results are shown in Table shown in 6.
Embodiment 7-10
With each component (except that magnesium stearate) mixing of each Example formulations in the following table 3, add then and make granule after low amounts of water or Diluted Alcohol (30% ethanol) are made suitable soft material, dry back adds magnesium stearate mixing, tabletting.Equally, used drift and punch die is stainless steel material during tabletting.
Table 3. (unit of weight: mg)
| Former, adjuvant | Embodiment 7 | Embodiment 8 | Embodiment 9 | Embodiment 10 |
| Moxifloxacin hydrochloride | 218.4 | 218.4 | 218.4 | 218.4 |
| Microcrystalline Cellulose | 116.6 | 116.6 | 116.6 | 116.6 |
| Pregelatinized Starch | 32.0 | 32.0 | 32.0 | 32.0 |
| Carboxymethylstach sodium | 7.0 | 7.0 | 7.0 | 7.0 |
| Cross-linked carboxymethyl cellulose sodium | 7.0 | 7.0 | 7.0 | 7.0 |
| Methylcellulose | 5 | |||
| Hydroxyethyl-cellulose | 10 | |||
| Hydroxypropyl cellulose | 15 | |||
| Hymetellose | 10 | |||
| Gelatin | 5 | |||
| Carmethose | 15 | |||
| Magnesium stearate | 4.0 | 4.0 | 4.0 | 4.0 |
| System soft material solvent | Water | 30% ethanol | Water | Water |
| Total amount | 400 | 400 | 400 | 400 |
After finishing respectively at firm preparation and investigate tablet quality after 2 years, the results are shown in Table shown in 6.
Embodiment 11-12
With the abundant mix homogeneously of non-filmogen component except that magnesium stearate in the following table 4, the coating solution of coating solution component and described amount carries out powder coating in the table 4 with containing, add the magnesium stearate mixing then, tabletting, drift and punch die used during tabletting are stainless steel material.
Table 4 (unit of weight is mg)
| Former, adjuvant | Sample | ||
| Embodiment 11 | Embodiment 12 | ||
| Non-filmogen | Moxifloxacin hydrochloride | 218.4 | 218.4 |
| Microcrystalline Cellulose | 119.6 | 128.6 | |
| Pregelatinized Starch | 34.0 | 30.0 | |
| Carboxymethylstach sodium | 7.0 | 7.0 | |
| Cross-linked carboxymethyl cellulose sodium | 7.0 | 7.0 | |
| Magnesium stearate | 4.0 | 4.0 | |
| The coating solution group component | Youteqi RD100 | 20.0 | |
| Kollicoat IR | 20.0 | ||
| PEG 6000 | 10 | 5 | |
| Total amount | 420 | 420 | |
Wherein, Youteqi RD100 is a kind of poly-(methyl) crylic acid resin material, and Kollicoat IR is a kind of polyvinyl alcohol-polyethyleneglycol-graft copolymer.
After finishing respectively at firm preparation and investigate tablet quality after 2 years, the results are shown in Table shown in 6.
Embodiment 13,
| Former, adjuvant | Consumption (mg) |
| Moxifloxacin hydrochloride microcrystalline cellulose pregelatinized starch carboxyrnethyl starch sodium cross-linked carboxymethyl cellulose sodium polyvinylpyrrolidone-vinyl acetate co-polymer (S-630) poloxamer F-68 | 218.4 98.6 10.0 7.0 7.0 10.0 30.0 |
| PEG 6000 magnesium stearate | 35.0 4.0 |
| Total amount (mg) | 420 |
Get fully mix homogeneously of said components Central Plains, adjuvant (except that magnesium stearate), add suitable quantity of water and granulate, dry back adds the magnesium stearate mixing, with metal drift and punch die tabletting, promptly gets plain sheet, but coating, and also coating not directly adopts lucifuge to pack.
After finishing respectively at firm preparation and investigate tablet quality after 2 years, the results are shown in Table shown in 6.
Embodiment 14-19
With each component (except that magnesium stearate) mixing of each Example formulations in the following table 5, add then and make granule after suitable quantity of water is made suitable soft material, dry back adds the magnesium stearate mixing, with metal drift and punch die tabletting.
Table 5. (unit of weight: mg)
| Supplementary material | Embodiment 14 | Embodiment 15 | Embodiment 16 | Embodiment 17 | Embodiment 18 | Embodiment 19 |
| Moxifloxacin hydrochloride | 54.6 | 54.6 | 54.6 | 218.4 | 436.8 | 436.8 |
| Microcrystalline Cellulose | 17.0 | 7.1 | 12.8 | 88.0 | 136.0 | 136.0 |
| Lactose | 8.5 | 3.6 | 12.8 | 60.0 | 68.0 | 68.0 |
| Cross-linked carboxymethyl cellulose sodium | 2.0 | 2.7 | 3.4 | 8.0 | 16.0 | 32.0 |
| HPMC(90SH 100) | 2.5 | 4.0 | 5.0 | 11.0 | 44.0 | 30.0 |
| Macrogol 4000 | 0.4 | 1.0 | 3.0 | 9.0 | 15.0 | 8.0 |
| Magnesium stearate | 0.6 | 0.4 | 0.5 | 2.4 | 4.8 | 6.0 |
| Total amount | 85.6 | 73.4 | 92.1 | 396.8 | 720.6 | 716.8 |
After finishing respectively at firm preparation and investigate tablet quality after 2 years, the results are shown in Table shown in 6.
Embodiment 20
Component: moxifloxacin hydrochloride 218.4mg
Microcrystalline Cellulose 150.6mg
Carboxymethylstach sodium 14.0mg
Magnesium stearate 4.7mg
Polyvinylpyrrolidone 12.3mg
Gross weight 400.0mg
Get whole former, adjuvant mix homogeneously except that magnesium stearate in the said components, water system granule, dry back adds the magnesium stearate mixing, tabletting, promptly.Drift and punch die used during tabletting are stainless steel material.
The tablet of preparation can directly adopt lucifuge to pack.
After finishing respectively at firm preparation and investigate tablet quality after 2 years, the results are shown in Table shown in 6.
Each embodiment tablet quality of table 6. is investigated the result
| Quality index | Hardness (kg) | Color and luster | Dissolution (%) | |||
| 0 month | 24 months | 0 month | 24 months | 0 month | 24 months | |
| Embodiment 1 | 13 | 13 | Yellow | Yellow | 99.2 | 99.5 |
| Embodiment 2 | 14 | 14 | Yellow | Yellow | 98.1 | 97.8 |
| Embodiment 3 | 15 | 14 | Yellow | Yellow | 97.8 | 97.5 |
| Embodiment 4 | 14 | 14 | Yellow | Yellow | 99.0 | 99.1 |
| Embodiment 5 | 12 | 12 | Yellow | Yellow | 100.5 | 99.3 |
| Embodiment 6 | 12 | 12 | Yellow | Yellow | 99.0 | 99.3 |
| Embodiment 7 | 13 | 13 | Yellow | Yellow | 100.5 | 98.7 |
| Embodiment 8 | 14 | 14 | Yellow | Yellow | 98.6 | 99.9 |
| Embodiment 9 | 14 | 14 | Yellow | Yellow | 98.1 | 98.5 |
| Embodiment 10 | 14 | 14 | Yellow | Yellow | 98.2 | 97.1 |
| Embodiment 11 | 13 | 13 | Yellow | Yellow | 99.2 | 101.5 |
| Embodiment 12 | 14 | 15 | Yellow | Yellow | 98.3 | 96.1 |
| Embodiment 13 | 13 | 13 | Yellow | Yellow | 95.5 | 97.0 |
| Embodiment 14 | 14 | 14 | Yellow | Yellow | 99.1 | 102.5 |
| Embodiment 15 | 14 | 14 | Yellow | Yellow | 98.2 | 98.1 |
| Embodiment 16 | 13 | 13 | Yellow | Yellow | 99.2 | 99.5 |
| Embodiment 17 | 14 | 15 | Yellow | Yellow | 97.3 | 99.1 |
| Embodiment 18 | 13 | 13 | Yellow | Yellow | 99.5 | 101.0 |
| Embodiment 19 | 13 | 13 | Yellow | Yellow | 98.1 | 101.3 |
| Embodiment 20 | 14 | 14 | Yellow | Yellow | 99.5 | 100.8 |
Annotate: hardness adopts Meng Shandou (Mansanto) durometer to measure;
Dissolution is pressed first method mensuration in two appendix XC of Chinese Pharmacopoeia version in 2000 dissolution determination method, and dissolution medium is the 0.1M hydrochloric acid solution, and rotating speed 100rpm measures 45 minutes stripping values.
Claims (10)
1, a kind of moxifloxacin oral pharmaceutical preparation; contain Moxifloxacin or its salt and/or its hydrate; it is characterized in that: described pharmaceutical preparation also contains at least a filmogen; this filmogen is used to prepare the midbody particle of described moxifloxacin oral pharmaceutical preparation or carries out powder or granule coating, and described filmogen comprises:
Hydroxypropyl emthylcellulose, hydroxyethylmethyl-cellulose, methylcellulose, hydroxypropyl cellulose, hydroxyethyl-cellulose, sodium carboxymethyl cellulose, polyacrylic resin class, Polyethylene Glycol, polyvinylpyrrolidone-vinyl acetate co-polymer, polyvinyl alcohol-polyethyleneglycol-graft copolymer, Ka Baibo (Carbopol), gelatin, poloxamer, polyvinylpyrrolidone.
2, a kind of moxifloxacin oral pharmaceutical preparation according to claim 1, it is characterized in that: described moxifloxacin oral pharmaceutical preparation is tablet.
3, a kind of moxifloxacin oral pharmaceutical preparation according to claim 2 is characterized in that: the percentage by weight that described filmogen accounts for described pharmaceutical preparation is 0.2～20.0%.
4, a kind of moxifloxacin oral pharmaceutical preparation according to claim 3 is characterized in that: the percentage by weight that described filmogen accounts for described pharmaceutical preparation is 0.5～10.0%.
5, according to the arbitrary described a kind of moxifloxacin oral pharmaceutical preparation of claim 1～4, it is characterized in that: described Moxifloxacin or its salt and/or its hydrate are meant moxifloxacin hydrochloride.
6, according to the arbitrary described a kind of moxifloxacin oral pharmaceutical preparation of claim 1～4, it is characterized in that: described pharmaceutical preparation also contains the pharmaceutical excipient of pharmaceutically acceptable amount, and described excipient comprises starch, dextrin, pregelatinized Starch, microcrystalline Cellulose, carboxymethylstach sodium, cross-linking sodium carboxymethyl cellulose, micropowder silica gel, magnesium stearate, lactose.
7, a kind of moxifloxacin oral pharmaceutical preparation according to claim 6, it is characterized in that: described pharmaceutical preparation contains
Percentage by weight is 30～60% moxifloxacin hydrochloride;
Percentage by weight is 0.2～2.0% filmogen hydroxypropyl emthylcellulose;
Percentage by weight is 31～50% microcrystalline Cellulose;
Percentage by weight is 5～20% pregelatinized Starch;
Percentage by weight is 1～10% carboxymethylstach sodium;
Percentage by weight is 1～5% cross-linking sodium carboxymethyl cellulose;
Percentage by weight is 0.5～2.5% magnesium stearate.
8, a kind of moxifloxacin oral pharmaceutical preparation according to claim 6, it is characterized in that: described pharmaceutical preparation contains
Percentage by weight is 50～76% moxifloxacin hydrochloride;
Percentage by weight is 0.2～10.0% filmogen hydroxypropyl emthylcellulose;
Percentage by weight is 0.2～10.0% filmogen Polyethylene Glycol;
Percentage by weight is 5～30% microcrystalline Cellulose;
Percentage by weight is 5～20% lactose;
Percentage by weight is 1～10% cross-linking sodium carboxymethyl cellulose;
Percentage by weight is 0.5～2.5% magnesium stearate.
9, the preparation method of the arbitrary described a kind of moxifloxacin oral pharmaceutical preparation of claim 1～8, described method comprises step:
It is 0.5～10% aqueous solution or water dispersion solution or Diluted Alcohol solution that described filmogen is made into percentage by weight, mixes back preparation granule as binding agent and Moxifloxacin or its salt and/or its hydrate and pharmaceutical excipient; Perhaps
Part filmogen and Moxifloxacin or its salt and/or its hydrate and pharmaceutical excipient are mixed, it is 0.5～10% aqueous solution or water dispersion solution or Diluted Alcohol solution that the remainder filmogen is made into percentage by weight, mixes back preparation granule with said mixture as binding agent; Perhaps
After described filmogen and Moxifloxacin or its salt and/or its hydrate and pharmaceutical excipient mixed, water or Diluted Alcohol prepared granule after making soft material; Perhaps
It is 0.5～10% aqueous solution or water dispersion solution or Diluted Alcohol solution that described filmogen is made into percentage by weight, and the powder or the granule of Moxifloxacin or its salt and/or its hydrate and pharmaceutical excipient carried out coating.
10, the preparation method of a kind of moxifloxacin oral pharmaceutical preparation according to claim 9 is characterized in that: described method further comprises, will add magnesium stearate, compressed tablets behind the mixing behind granule that make or the particle drying behind the coating.
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| CN 200510021736 CN1762357B (en) | 2005-09-21 | 2005-09-21 | Oral medicinal formulation of moxifloxacin and its preparation method |
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| CN103169675A (en) * | 2011-12-22 | 2013-06-26 | 天津康鸿医药科技发展有限公司 | Moxifloxacin hydrochloride preparation and preparation method thereof |
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| DK1017392T3 (en) * | 1997-09-25 | 2002-10-21 | Bayer Ag | Medicines |
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| CN104414990A (en) * | 2013-09-11 | 2015-03-18 | 浙江海正药业股份有限公司 | Stable preparation containing everolimus or derivatives of everolimus and preparation method of stable preparation |
| CN105168164A (en) * | 2015-07-29 | 2015-12-23 | 董贵雨 | Solid medicine composition with moxifloxacin |
| CN105030717A (en) * | 2015-08-21 | 2015-11-11 | 哈尔滨珍宝制药有限公司 | Moxifloxacin hydrochloride film-coated tablet and preparation method thereof |
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| CN1762357B (en) | 2010-12-08 |
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Application publication date: 20060426 Assignee: Jiangsu Tianyishi Pharm Co., Ltd. Assignor: Tianyishi Sci-Tech Development Co., Ltd., Shenzhen Contract record no.: 2010320000719 Denomination of invention: Oral medicinal formulation of moxifloxacin and its preparation method License type: Exclusive License Record date: 20100602 |
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Assignee: Jiangsu Tianyishi Pharm Co., Ltd. Assignor: Tianyishi Sci-Tech Development Co., Ltd., Shenzhen Contract record no.: 2010320000719 Date of cancellation: 20170815 |
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Effective date of registration: 20170914 Address after: 225300, G08, 1 drug City Avenue, Jiangsu, Taizhou Patentee after: Jiangsu Tianyishi Pharm Co., Ltd. Address before: 518040 Guangdong city of Shenzhen province Futian District nongxuan Xiangxieli Garden Road 4-301 Patentee before: Tianyishi Sci-Tech Development Co., Ltd., Shenzhen |