CN103768063A - Moxifloxacin hydrochloride pharmaceutical composition and preparation method thereof - Google Patents
Moxifloxacin hydrochloride pharmaceutical composition and preparation method thereof Download PDFInfo
- Publication number
- CN103768063A CN103768063A CN201210397924.0A CN201210397924A CN103768063A CN 103768063 A CN103768063 A CN 103768063A CN 201210397924 A CN201210397924 A CN 201210397924A CN 103768063 A CN103768063 A CN 103768063A
- Authority
- CN
- China
- Prior art keywords
- moxifloxacin hydrochloride
- hydroxypropyl methylcellulose
- coating
- label
- weight
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention provides a moxifloxacin hydrochloride pharmaceutical composition and preparation method thereof. The invention is characterized in that: tablet core is prepared by moxifloxacin hydrochloride, more than one excipient and a coating material, wherein, the weight of moxifloxacin hydrochloride is 60-70% of that of the tablet core, and the weight of excipients is 30-40% of that of the tablet core, and the weight of the coating material which is used for coating the tablet core and is composed of hypromellose with two or more than two viscosities is 1.0-4.0% of that of the pharmaceutical composition tablet core, and the weight ratio between hypromellose with viscosity of 40-120mPa.s and hypromellose with viscosity of 2.5-1.8mPa.s is 1:5-1:2. The pharmaceutical composition has the advantages of good stability, simple preparation technology and easy reproduction; the preparation method is suitable for industrial production.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition of medical technical field and preparation method thereof, particularly a kind of moxifloxacin hydrochloride medicinal composition and preparation method thereof.
Background technology
Moxifloxacin hydrochloride, English name: Moxifloxacin Hydrochloride, for faint yellow, to yellow crystalline powder, slightly water-soluble and methanol, is slightly soluble in ethanol, is dissolved in hardly acetone, and structural formula is shown below:
Moxifloxacin hydrochloride is the 4th generation wide spectrum 8-methoxy fluoroquinolone class antimicrobial drug, is the antibacterials more widely of clinical practice in recent years, is also the synthetic antibacterial drug that a class is newer.Moxifloxacin hydrochloride energy facedown streptococcus pneumoniae, hemophilus influenza and moraxelle catarrhalis, different from fluoroquinolones at present used.Moxifloxacin hydrochloride also can strengthen anti-rare G-bacterium: comprise that staphylococcus aureus, atypia pathogen are as mycoplasma, chlamydia and legionella.In addition, also effective to the antibacterial of beta-lactam and Macrolide drug resistance.
Moxifloxacin hydrochloride oral formulations taking convenience, medication every day once can prove effective, and has good toleration.This medicine is without phototoxicity regulating liver-QI toxicity, approximate with other quinolones, and its most obvious side effect is for feeling sick, suffering from diarrhoea.Another advantage of moxifloxacin hydrochloride is more much lower than the drug resistance degree of other Du-6859a deposits yields.
The invention of CN99813124.5 provides a kind of oral drug preparation that contains moxifloxacin hydrochloride, its salt and/or hydrate and lactose, and said preparation has good hardness and result of extraction.But the use of lactose has certain drawback, outstanding behaviours is that toleration is poor, is especially common in the crowd of intestinal lactase deficiency, can occur the untoward reaction such as abdominal cavity spasm, diarrhoea, abdominal distention and flatulence.
The invention of CN200510021736.8 provides a kind of moxifloxacin hydrochloride oral drug preparation; contain moxifloxacin hydrochloride or its salt and/or its hydrate; and at least one is for the preparation of the filmogen of preparation midbody particle: hydroxypropyl emthylcellulose (HPMC), Polyethylene Glycol, polyvinylpyrrolidone etc.; to tabletting after midbody particle or powder coating; said preparation is stable in properties in granulation and tabletting process; do not produce metachromatism; light, hardness is good; and drug-eluting is rapid; but complex process; wayward, poor reproducibility.
The invention of CN200510021739.1 provides a kind of moxifloxacin capsule, in capsule 's content, contain Moxifloxacin or its salt and/or its hydrate, in described capsule 's content, also contain at least one disintegrating agent and at least one lubricant, it is characterized in that: the capsule shells of described capsule is hydroxypropyl methylcellulose capsules shell.Though the hydroxypropyl methylcellulose capsules shell of this technical scheme uses gelatin softgel shell stable, price is relatively costly, and production cost is high.
The invention of CN200910212686.X provides the oral drug preparation that contains moxifloxacin hydrochloride, its salt and/or its hydrate and soluble starch and pregelatinized Starch, and said preparation contains 2.9%～14.5% soluble starch and 1.4%～6.5% pregelatinized Starch.The tablet hardness that this technical scheme makes is undesirable, and has selected the soluble starch that not yet has medicinal standard at present, and the industrialization of product is had to certain influence.
The invention of CN201110074564.6 provides pharmaceutical composition of a kind of moxifloxacin hydrochloride and preparation method thereof, said composition mainly comprises moxifloxacin hydrochloride, mannitol and other excipient, preparation method is to prepare drug particles by dry granulation technology, then make pharmaceutical preparation, preparation technology's relative complex, wayward.
The invention of CN201110074385.2 provides pharmaceutical composition of a kind of moxifloxacin hydrochloride and preparation method thereof, said composition mainly comprises: moxifloxacin hydrochloride, fusing agent polyethylene glycol 6000 and other excipient, preparation method is mainly prepared drug particles by hot melt granulation technique, then be pressed into tablet or incapsulate, preparation technology's relative complex, wayward.
The invention of CN201210039192.8 provides a kind of pharmaceutical composition of moxifloxacin hydrochloride, is made up of moxifloxacin hydrochloride, HYDROXYPROPYL BETA-CYCLODEXTRIN, mannitol, microcrystalline Cellulose 12, magnesium stearate, and this drug regimen amount is relatively stable.But microcrystalline Cellulose 12 prices are more expensive, the cost of preparing moxifloxacin oral preparation according to this technical scheme is higher.
Though a kind of oral solid formulation take Moxifloxacin as active component is mentioned in the invention of CN201110005690.6, coating materials main component is HPMC and the Polyethylene Glycol of low-viscosity, but in description, do not have the HPMC of coating materials low-viscosity and the concrete consumption of Polyethylene Glycol and ratio open, technical staff is difficult to the technical problem that realizes corresponding technical scheme and may solve.
CN201210105923.4, a kind of Moxifloxacin tablet is disclosed, comprise Moxifloxacin or its salt, waterless adhesive, disintegrating agent and lubricant, it is characterized in that, also comprise a kind of Hardening agent that mixes, described Hardening agent is to account in the part of the pregelatinized Starch of tablet formulation weight 10～25% and 2～8% to add the polyvidone additional with part, and wherein the weight ratio of Nei Jia and additional polyvidone is 3:7～7:3.
It is a kind of by the moxifloxacin hydrochloride medicinal composition of dry process that the invention of US2011293717 provides, coating materials adopts the mixture of hypromellose, titanium dioxide, Polyethylene Glycol and the ferrum oxide of low-viscosity, in practice, find, label adopts dry process, and technique relative complex is wayward, poor reproducibility, in coating materials, hypromellose adopts phamacoat 603 coatings, and coating membrane is imperfect, lack of homogeneity.
Though prior art discloses prescription composition and the preparation method of the multiple dosage form pharmaceutical composition of moxifloxacin hydrochloride, but find in practice, due to moxifloxacin hydrochloride poorly water-soluble and the part by weight in pharmaceutical composition larger, the particularly pharmaceutical composition of Tabules, adopt a kind of HPMC and Polyethylene Glycol of low-viscosity, or Opadry carries out coating, tend to exist coating membrane inhomogeneous, the coating time is long, the problem such as the not good or tablet medicine composition stable of result of extraction is poor.So, in order to provide Release Properties stable, the simple moxifloxacin chloride tablets agent medicine of technique compositions, this field still needs further research.
Summary of the invention
The inventor is through studying for a long period of time; unexpected discovery; exceed 60% moxifloxacin hydrochloride medicinal composition for containing raw material weight; except the composition requirement height to label; must strictly control composition and good hardness and the dissolution of use amount guarantee of adjuvant; more crucial is; adopt different coating materials to find its coating; coating membrane film property exists obviously different; adopt the coating materials of two kinds of different viscositys to combine by a certain percentage the stripping that not only can guarantee medicine, and can effectively protect the quality stability of pharmaceutical composition active component.
The first object of the present invention is to provide the moxifloxacin hydrochloride medicinal composition that a kind of hardness is good, stripping is fast, in this moxifloxacin hydrochloride medicinal composition prescription composition, do not contain lactose, there is better toleration, go for sugar part to take in the patient that must strictly control, as diabetics, have wider be applied to clinical.
The second object of the present invention is to provide a kind of coating material that is applicable to moxifloxacin hydrochloride medicinal composition of the present invention; during for coating; film forming speed is fast; good film-forming property; gained pharmaceutical composition not only can guarantee the stripping of medicine; and can effectively protect the quality stability of pharmaceutical composition active component, the method is simple.
The present invention adopts following technical scheme:
A kind of moxifloxacin hydrochloride medicinal composition, it contains to account for the moxifloxacin hydrochloride of label weight 60%～70% and account for more than one excipient of label weight 30%～40% makes label, and the coating materials of the coated hydroxypropyl methylcellulose that the contains two or more different viscositys composition that accounts for pharmaceutical composition label weight 1.0%～4.0%.
In above-mentioned a kind of moxifloxacin hydrochloride medicinal composition, moxifloxacin hydrochloride is counted 50mg～400mg with the weight of Moxifloxacin, preferably 50mg, 200mg or 400mg, particularly 400mg.
The hydroxypropyl methylcellulose of described different viscositys refers to that viscosity is the hydroxypropyl methylcellulose that 40mPa.s～120mPa.s and viscosity are 2.5mPa.s～18mPa.s, and the weight ratio of the hydroxypropyl methylcellulose that the hydroxypropyl methylcellulose that wherein viscosity is 40mPa.s～120mPa.s and viscosity are 2.5mPa.s～18mPa.s is 1:5～1:2.
The weight ratio of the hydroxypropyl methylcellulose that the hydroxypropyl methylcellulose that is 40mPa.s～120mPa.s when viscosity in this pharmaceutical composition coating materials and viscosity are 2.5mPa.s～18mPa.s is less than 1:5, or while only adopting viscosity to be the hydroxypropyl methylcellulose coating of 2.5mPa.s～18mPa.s, find that film property is not good, the film forming is imperfect, lack of homogeneity, can not can be complete as the coating of the hydroxypropyl methylcellulose of two kinds of different viscositys peel off with label.
When the weight ratio of the viscosity hydroxypropyl methylcellulose that is 40mPa.s～120mPa.s and the viscosity hydroxypropyl methylcellulose that is 2.5mPa.s～18mPa.s is greater than 1:2, or while only adopting viscosity to be the hydroxypropyl methylcellulose coating of 40mPa.s～120mPa.s, find that film forming is good but weightening finish is slow, the coating time is long, such as to 1000 these pharmaceutical composition coatings, the coating time adopts the long left and right that doubles of the mixing coating materials time of two kinds of viscositys, and the coating solution thickness of preparation, be unfavorable for being uniformly dispersed, prepare also more difficult.
In the present invention, the viscosity of hydroxypropyl methylcellulose is measured in accordance with the following methods: take this product 4.0g (by dry product), heating water 200ml, stir and within 40 minutes, make to dissolve with 400 revs/min, in lower than 10 ℃ of water-baths, continue to stir 20 minutes, water regulator solution weight, to 200g, is adjusted to 20 ± 0.5 ℃ by the temperature of solution, measures dynamic viscosity υ (mm according to viscosimetry (two appendix VI G first method capillary tube 2.0mm of Chinese Pharmacopoeia version in 2010)
2/ s); Measure the density p (g/cm of solution simultaneously
3), calculate dynamic viscosity η=ρ υ (mPa.s).In the present invention, indicate unless special, described " viscosity " all refers to " dynamic viscosity ".
Wherein, the hydroxypropyl methylcellulose commodity that the hydroxypropyl methylcellulose that viscosity is 2.5mPa.s～18mPa.s comprises commodity Pharmacoat603, Pharmacoat645 by name, Pharmacoat606, Methocel E5, Methocel E6, Methocel E15 etc.; Viscosity is the hydroxypropyl methylcellulose commodity that the hydroxypropyl methylcellulose of 40mPa.s～120mPa.s comprises commodity HPMC60RT50, HPMC60RT100 by name, Methocel E50, Methocel K100LV etc.
Adopt commercially available versicolor Opadry to carry out coating and find that film property is good and coating speed is moderate, but influence factor test under intense light irradiation (4500LX) condition 5 days less than, pharmaceutical composition surface color occurs obviously to change, and illustrates that the moxifloxacin hydrochloride medicinal composition quality stability of employing Opadry coating is poor.
The coating materials of described 1.0%～4.0% the hydroxypropyl methylcellulose that contains two or more different viscositys that accounts for pharmaceutical composition label weight, prepare coating after coating solution by the mixed solvent of water or water and ethanol, in coating solution, the weight ratio concentration of coating materials is 3.5%～15.0%.In the mixed solvent of described water and ethanol, the weight ratio of water and ethanol is 100:0～10:90.
In above-mentioned a kind of moxifloxacin hydrochloride medicinal composition, the excipient of composition label comprises the one, two or three in diluent, disintegrating agent, lubricant.
Wherein, more than one in described diluent preferably microcrystalline cellulose, calcium phosphate, mannitol; The weight of diluent is preferably and accounts for 10%～30% of pharmaceutical composition label weight.When the consumption of diluent is lower than 10% poor compressibility, be prone to the tabletting problems such as sliver, hardness be low; Can make stripping significantly slow down higher than 30%.
Wherein, more than one in the preferred pregelatinized Starch of described disintegrating agent, cross-linking sodium carboxymethyl cellulose, crospolyvinylpyrrolidone; The weight of disintegrating agent is preferably and accounts for 2%～20% of pharmaceutical composition label weight.When the consumption of disintegrating agent obviously slows down lower than the stripping of 2% medicine, and poor at the easy sucting wet stability of storage higher than 20% pharmaceutical composition.
Wherein, the preferred stearic acid of described lubricant or its salt, as magnesium stearate etc.; The weight of lubricant is preferably and accounts for 0.3%～2.0% of pharmaceutical composition label weight.Not obvious lower than 0.3% lubricant effect when the consumption of lubricant, and easily caused lubricating effect higher than 2.0%, the obvious step-down of pharmaceutical composition hardness, easy dry linting when coating, there is the situations such as pitted skin in surface.
When described moxifloxacin hydrochloride medicinal composition is made up of and when the active component of ratio and adjuvant form above-mentioned, prepared label does not contain lactose, can obviously improve the hardness of pharmaceutical composition, adopt tablet friability hardness analyzer to measure hardness and can reach 190N, in film-making process, be not prone to the problem such as sliver, bonding die, gained pharmaceutical composition tablet weight variation is little.
In order to increase the rate of dissolution of coating membrane, in coating materials, also can increase a certain amount of Polyethylene Glycol, preferably add that to account for coating solution weight ratio concentration be 0.75%～4.0% Polyethylene Glycol, coating membrane can dissolve completely in 5min.When containing Polyethylene Glycol in coating materials, its consumption can cause can not dissolving completely in coating membrane 5min lower than 0.75%, affects stripping.
In order to increase the light-proofness of coating membrane, in coating materials, also can increase a certain amount of titanium dioxide, preferably add and account for the titanium dioxide that coating solution weight ratio concentration is 1.0%～2.0%, can improve the light-proofness of pharmaceutical composition, and do not affect the tensile strength of coating membrane, the integrity that keeps coating membrane, does not change in preservation process.When containing titanium dioxide in coating materials, consumption is not obvious lower than 1.0% shaded effect, affect the integrity of coating membrane higher than 2.0% meeting.
In order to increase the color of coating membrane, in coating materials, also can increase a certain amount of red ferric oxide, preferably add and account for the red ferric oxide that coating solution weight ratio concentration is 0.2%～0.5%, pharmaceutical composition surface presents kermesinus, in preservation process, does not change.
It is the one, two or three that can also contain in described coating materials in Polyethylene Glycol, titanium dioxide and red ferric oxide.
In described coating materials, the weight ratio of hydroxypropyl methylcellulose, Polyethylene Glycol, titanium dioxide and red ferric oxide is 3.5～15.0:0～4.0:0～2.0:0～0.5.In the weight ratio of described hydroxypropyl methylcellulose, Polyethylene Glycol, titanium dioxide and red ferric oxide, Polyethylene Glycol is preferably 0.75～4.0, and titanium dioxide is preferably 1.0～2.0, and red ferric oxide is preferably 0.2～0.5.
Moxifloxacin hydrochloride medicinal composition of the present invention depends on its prescription composition and coating material composition, can be by the conventional preparation method preparation of tablet solid preparation, and preparation method includes but not limited to:
Label preparation: by even to moxifloxacin hydrochloride and mixed with excipients, add the mixed solvent wet granulation of a certain amount of water or water and ethanol, tabletting obtains label;
Coating: by the coating materials mix homogeneously of the hydroxypropyl methylcellulose composition that contains two or more different viscositys, joining and in the mixed solvent of water or water and ethanol, making coating materials weight ratio is 3.5%～15% coating solution, label is carried out to coating, label weightening finish 1.0%～4.0% after coating.
The amount of described wet granulation solvent for use can be determined according to formulation art common practise, 15%～70% of for example sheet core raw material and excipient weight; In the mixed solvent of described water and ethanol, the weight ratio of water and ethanol is 100:0～10:90.
Above-mentioned preparation method is simple, and cost is low, and favorable reproducibility is easy to industrialization and produces.
Beneficial effect with respect to prior art of the present invention is:
1, adopting coating to select viscosity is that two or more the hydroxypropyl methylcellulose mixture of 2.5mPa.s～18mPa.s and 40mPa.s～120mPa.s is as coating material, good film-forming property, coating membrane is complete, good uniformity, significantly shorten the coating time, saved use amount and the cost of coating material.
2, in label adjuvant, do not contain lactose, equally can improved hardness, adopt tablet friability hardness analyzer to measure hardness and can reach 190N, and there will not be the tabletting problems such as sliver, bonding die, tablet weight variation are large.
3, pharmaceutical composition has very outstanding Dissolution behaviours in dissolution medium, in pH4.0 medium stripping very fast, stripping can reach more than 90% in 5min.
4, influence factor's experiment condition is under high temperature, high humidity or intense light irradiation condition, to deposit pharmaceutical composition of the present invention after 10 days, does not detect impurity, and any variation does not occur dissolution substantially, illustrates that the quality stability of pharmaceutical composition is very good.
Accompanying drawing explanation
Fig. 1 is that embodiment 1 moxifloxacin hydrochloride medicinal composition coatings is peeled off figure.
The specific embodiment
Below in conjunction with embodiment and accompanying drawing, the present invention is described in further detail, but working of an invention mode is not limited to this.
Embodiment 1 moxifloxacin hydrochloride medicinal composition
Label preparation method: by moxifloxacin hydrochloride, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, pregelatinized Starch mix homogeneously, add the water of moxifloxacin hydrochloride, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, pregelatinized Starch gross weight 45%, carry out wet granulation, after dry granulate, dry granule is mixed homogeneously with magnesium stearate, obtain label according to granule content tabletting, every is equivalent to containing Moxifloxacin 400mg;
Coating: by two kinds of hydroxypropyl methylcellulose, polyethylene glycol 6000, titanium dioxide and red ferric oxide mix homogeneously, be added in dehydrated alcohol and be uniformly dispersed, under stirring condition, add purified water again, make coating solution, label is placed in coating pan, control 40 ℃ of coatings of temperature of charge, coating weightening finish 2%, stop coating, dry, obtain moxifloxacin chloride tablets.
Embodiment 2 moxifloxacin hydrochloride medicinal compositions
Label preparation method: by moxifloxacin hydrochloride, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, pregelatinized Starch mix homogeneously, add the water of moxifloxacin hydrochloride, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, pregelatinized Starch gross weight 50%, carry out wet granulation, after dry granulate, dry granule is mixed homogeneously with magnesium stearate, obtain label according to granule content tabletting, every is equivalent to containing Moxifloxacin 400mg;
Coating: by two kinds of hydroxypropyl methylcellulose, polyethylene glycol 6000, titanium dioxide and red ferric oxide mix homogeneously, be added in dehydrated alcohol and purified water mixed solvent and be uniformly dispersed, stir, make coating solution, label is placed in coating pan, control 50 ℃ of coatings of temperature of charge, coating weightening finish 3%, stop coating, dry, obtain moxifloxacin chloride tablets.
Embodiment 3 moxifloxacin hydrochloride medicinal compositions
Label preparation method: by moxifloxacin hydrochloride, calcium phosphate, crospolyvinylpyrrolidone mix homogeneously, add the water of moxifloxacin hydrochloride, calcium phosphate, crospolyvinylpyrrolidone gross weight 40% to carry out wet granulation, after dry granulate, dry granule is mixed homogeneously with stearic acid, obtain label according to granule content tabletting, every is equivalent to containing Moxifloxacin 400mg;
Coating: by two kinds of hydroxypropyl methylcellulose, polyethylene glycol 6000, titanium dioxide and red ferric oxide mix homogeneously, be added in purified water and be uniformly dispersed, stir, make coating solution, label is placed in coating pan, control 50 ℃ of coatings of temperature of charge, coating weightening finish 1.0%, stop coating, dry, obtain moxifloxacin chloride tablets.
Embodiment 4 moxifloxacin hydrochloride medicinal compositions
Label preparation method: by moxifloxacin hydrochloride, mannitol, pregelatinized Starch mix homogeneously, add the water of moxifloxacin hydrochloride, mannitol, pregelatinized Starch gross weight 40%, carry out wet granulation, after dry granulate, dry granule is mixed homogeneously with magnesium stearate, obtain label according to granule content tabletting, every is equivalent to containing Moxifloxacin 400mg;
Coating: by two kinds of hydroxypropyl methylcellulose, polyethylene glycol 6000, titanium dioxide and red ferric oxide mix homogeneously, be added in dehydrated alcohol and be uniformly dispersed, add purified water, stir, make coating solution, label is placed in coating pan, control 40 ℃ of coatings of temperature of charge, coating weightening finish 4.0%, stops coating, dry, obtain moxifloxacin chloride tablets.
Comparing embodiment 1 and comparing embodiment 2
Label and coating preparation thereof are with embodiment 1.
Embodiment 5 embodiment 1 and comparing embodiment 1, comparing embodiment 2 coating situations and dissolution comparison
Coating duration to embodiment 1, comparing embodiment 1 and comparing embodiment 2, coating membrane all even integrity situation, the coating membrane situation of peeling off compare, and result is as follows:
In addition, embodiment 2, embodiment 3 and embodiment 4 have coating situation substantially the same manner as Example 1; And be less than 1:5 when the weight ratio of hydroxypropyl methylcellulose that in coating materials, viscosity is 40mPa.s～120mPa.s and the viscosity hydroxypropyl methylcellulose that is 2.5mPa.s～18mPa.s, have and the essentially identical coating situation of comparing embodiment 1, when the weight ratio of the hydroxypropyl methylcellulose that is 40mPa.s～120mPa.s of viscosity in coating materials and the viscosity hydroxypropyl methylcellulose that is 2.5mPa.s～18mPa.s is greater than 1:2, have and the essentially identical coating situation of comparing embodiment 2.
From above experimental result, the weight ratio of the hydroxypropyl methylcellulose that the hydroxypropyl methylcellulose that is 40mPa.s～120mPa.s when viscosity in this pharmaceutical composition coating materials and viscosity are 2.5mPa.s～18mPa.s is less than 1:5, or while only adopting viscosity to be the hydroxypropyl methylcellulose coating of 2.5mPa.s～18mPa.s, film property is not good, the film forming is imperfect, lack of homogeneity, coating not can completely and label is peeled off; And be greater than 1:2 when the weight ratio of the viscosity hydroxypropyl methylcellulose that is 40mPa.s～120mPa.s and the viscosity hydroxypropyl methylcellulose that is 2.5mPa.s～18mPa.s, or while only adopting viscosity to be the hydroxypropyl methylcellulose coating of 40mPa.s～120mPa.s, find that film forming is good but weightening finish is slow, the coating time is long, such as to 1000 these pharmaceutical composition coatings, the coating time adopts the long left and right that doubles of the mixing coating materials time of two kinds of viscositys, coating membrane is inhomogeneous, and can completely and label are not peeled off.
The uniformity of coating membrane and integrity will further directly affect the stability in drug-eluting effect and preservation process.Follow-up contrast experiment's confirmation, inhomogeneous because of the coating membrane of comparative example, integrity is poor, and its result of extraction and quality stability are also obviously poor.
Embodiment 1, comparing embodiment 1 and comparing embodiment 2 gained moxifloxacin hydrochloride medicinal compositions are carried out to dissolution determination, and result is as follows:
Dissolution determination method: measure according to two appendix XC dissolution determinations of Chinese Pharmacopoeia version in 2010 the second method oar method, get 12 of moxifloxacin hydrochloride medicinal compositions, take pH4.0 citric acid-sodium hydrogen phosphate buffer 900mL as dissolution medium, rotating speed is 50rpm, temperature is 37 ℃ ± 0.5 ℃, add pH4.0 citric acid-sodium hydrogen phosphate buffer of 10mL uniform temp respectively at 5min, 10min, 15min, 30min sampling 10mL() simultaneously, ultraviolet 293nm measures, and calculates average accumulated stripping percentage rate % as follows:
| Sample time (min) | Embodiment 1 | Comparing embodiment 1 | Comparing embodiment 2 |
| 5 | 92.86% | 82.64% | 85.38% |
| 10 | 99.02% | 92.32% | 95.90% |
| 15 | 100.01% | 94.23% | 98.02% |
| 30 | 100.09% | 98.02% | 98.87% |
From measurement result, embodiment 1 has stripping result faster in comparative example 1 and comparative example 2 are in 5min.
In addition, embodiment 2, embodiment 3 and embodiment 4 and embodiment 1 dissolution basic identical in pH4.0 medium, dissolution rate is very fast; And be less than 1:5 when the weight ratio of hydroxypropyl methylcellulose that in coating materials, viscosity is 40mPa.s～120mPa.s and the viscosity hydroxypropyl methylcellulose that is 2.5mPa.s～18mPa.s, have and the essentially identical dissolution situation of comparing embodiment 1, when the weight ratio of the hydroxypropyl methylcellulose that is 40mPa.s～120mPa.s of viscosity in coating materials and the viscosity hydroxypropyl methylcellulose that is 2.5mPa.s～18mPa.s is greater than 1:2, have and the essentially identical dissolution situation of comparing embodiment 2.
Because embodiment 1, embodiment 2, embodiment 3 and embodiment 4 have result of extraction faster, can better guarantee Fast Stripping and the stripping completely of pharmaceutical composition use procedure Chinese medicine, obviously improve the effectiveness of medication.
Because prior art discloses more moxifloxacin hydrochloride medicinal composition prescription and preparation method, write out a prescription separately and preparation method according to prior art, the prior art that select the close and preparation method of prescription to be easy to reproductions, gained pharmaceutical composition good stability, to cover 50mg, 200mg and 400mg specification and two kinds of solid preparations of Tablet and Capsula agent contrasts, and specifically comparing embodiment is as follows:
Comparing embodiment 3
Patent CN201210039192.8 embodiment 1
Moxifloxacin hydrochloride medicinal composition described in every 1000, its formula consists of:
Preparation technology:
1) moxifloxacin hydrochloride spray-dried powders preparation: the HYDROXYPROPYL BETA-CYCLODEXTRIN of recipe quantity is dissolved in to stirring and dissolving in 80% alcoholic solution, the moxifloxacin hydrochloride stirring and dissolving that adds again recipe quantity completely after, dry the granularity of spraying is at the single-size of 80 ± 10 μ m, for subsequent use;
2) by 1) mix homogeneously with mannitol, microcrystalline Cellulose 12, the magnesium stearate of recipe quantity;
3) tabletting: regulate suitable hardness and sheet weight, carry out tabletting;
4) packing: adopt aluminum aluminum blister packaging machine to pack;
5) warehouse-in.
Comparing embodiment 4
Patent ZL99813124.5 embodiment 1
Contain the tablet of 50mg Moxifloxacin as micronized reactive compound, the content of reactive compound is about 66% (take uncoated tablets as basic calculation):
Comparing embodiment 5
Patent CN200510021739.1 embodiment 1
Preparation method: get former, adjuvant in said components, fully mix homogeneously, fills in hydroxypropyl methylcellulose capsules shell and get final product.
The Moxifloxacin sheet influence factor study on the stability of embodiment 6 embodiment 2 and comparing embodiment 3, comparing embodiment 4 and comparing embodiment 5
Comparing embodiment 3, comparing embodiment 4 and comparing embodiment 5 and embodiment 2 are placed in respectively to the illumination of 4500LX ± 500LX, 60 ℃ ± 2 ℃ high temperature, 92.5% ± 5% high humidity calorstat 10 days, respectively at 0 day, 10 days, its character, related substance, content are checked.The results are shown in following table:
Content assaying method: get 20 moxifloxacin hydrochloride medicinal composition pulverizes, mix; Precision takes the sample powder being equivalent to containing Moxifloxacin 200mg, put in 200mL volumetric flask, add the diluent (containing 4-butyl ammonium hydrogen sulfate 0.5g/L, potassium dihydrogen phosphate 1.0g/L and volume ratio 0.2% phosphorus aqueous acid) of 150mL, ultrasonic 15min, be cooled to room temperature, be settled to scale with diluent and make stock solution, then become containing 0.1mg/mL Moxifloxacin sample solution by diluted, measure in 293nm wavelength HPLC with reference to moxifloxacin hydrochloride American Pharmacopeia content assaying method.
Determination of related substances method: the preparation of sample stock solution is with containing quantifier, stock solution is mixed with to the solution containing American Pharmacopeia moxifloxacin hydrochloride 2.2 μ g/mL with diluent, measures in the 293nm wavelength HPLC of place with reference to the assay method of moxifloxacin hydrochloride American Pharmacopeia related substance.
Dissolution determination adopts the corresponding dissolution determination method of embodiment 5.
| 0 day | Embodiment 2 | Comparing embodiment 3 | Comparing embodiment 4 | Comparing embodiment 5 |
| Character | Dark red color chips | White tablets | White tablets | White tablets |
| Single largest impurity (%) | Do not detect | 0.02 | 0.05 | 0.05 |
| Total impurities (%) | Do not detect | 0.03 | 0.07 | 0.07 |
| Dissolution (%) | 99.8 | 99.7 | 99.0 | 99.1 |
| Content (%) | 99.9 | 99.9 | 99.5 | 99.6 |
| Illumination in 10 days | Embodiment 2 | Comparing embodiment 3 | Comparing embodiment 4 | Comparing embodiment 5 |
| Character | Dark red color chips | White tablets | White tablets | White tablets |
| Single largest impurity (%) | Do not detect | 0.03 | 0.08 | 0.09 |
| Total impurities (%) | Do not detect | 0.04 | 0.12 | 0.15 |
| Dissolution (%) | 99.7 | 99.5 | 95.8 | 96.1 |
| Content (%) | 99.8 | 99.8 | 99.5 | 99.6 |
| 10 days high temperature | Embodiment 2 | Comparing embodiment 3 | Comparing embodiment 4 | Comparing embodiment 5 |
| Character | Dark red color chips | White tablets | White tablets | White tablets |
| Single largest impurity (%) | Do not detect | 0.04 | 0.11 | 0.12 |
| Total impurities (%) | Do not detect | 0.05 | 0.16 | 0.17 |
| Dissolution (%) | 99.5 | 99.1 | 90.1 | 90.5 |
| Content (%) | 99.6 | 99.7 | 99.1 | 99.0 |
| 10 days high humiditys | Embodiment 2 | Comparing embodiment 3 | Comparing embodiment 4 | Comparing embodiment 5 |
| Character | Dark red color chips | White tablets | White tablets | White tablets |
| Single largest impurity (%) | Do not detect | 0.04 | 0.14 | 0.16 |
| Total impurities (%) | Do not detect | 0.05 | 0.18 | 0.21 |
| Dissolution (%) | 99.5 | 99.1 | 90.1 | 90.5 |
| Content (%) | 99.7 | 99.7 | 99.1 | 99.0 |
Known according to upper watch test result, embodiment 2 and comparing embodiment 3, comparing embodiment 4 and comparing embodiment 5 are placed 10 days in the calorstat of the illumination of 4500LX ± 500LX, 60 ℃ ± 2 ℃ high temperature, 92.5% ± 5% high humidity, embodiment 2 is under different condition, single largest impurity and total impurities all do not detect, character, dissolution and the each check item of content have no significant change, and stability is obviously better than comparing embodiment 3, comparing embodiment 4 and comparing embodiment 5.
In addition, under same experiment and condition determination, embodiment 1, embodiment 3 and embodiment 4 have stability substantially the same manner as Example 2, have good stability, and are obviously better than comparing embodiment 3, comparing embodiment 4 and comparing embodiment 5.
Because embodiment 1, embodiment 2, embodiment 3 and embodiment 4 have better quality stability, there is better product quality, more can guarantee effectiveness and safety in pharmaceutical composition use procedure.
Above-described embodiment is preferably embodiment of the present invention; but embodiments of the present invention are not restricted to the described embodiments; other any do not deviate from change, the modification done under spirit of the present invention and principle, substitutes, combination, simplify; all should be equivalent substitute mode, within being included in protection scope of the present invention.
Claims (10)
1. a moxifloxacin hydrochloride medicinal composition, it is characterized in that: it makes label by accounting for the moxifloxacin hydrochloride of pharmaceutical composition label weight 60%～70% and accounting for more than one excipient of label weight 30%～40%, and the coating materials of the hydroxypropyl methylcellulose of the coated two or more different viscositys that account for pharmaceutical composition label weight 1.0%～4.0% composition, the hydroxypropyl methylcellulose of described different viscositys refers to that viscosity is the hydroxypropyl methylcellulose that 40mPa.s～120mPa.s and viscosity are 2.5mPa.s～18mPa.s, the weight ratio of the hydroxypropyl methylcellulose that the hydroxypropyl methylcellulose that wherein viscosity is 40mPa.s～120mPa.s and viscosity are 2.5mPa.s～18mPa.s is 1:5～1:2.
2. a kind of moxifloxacin hydrochloride medicinal composition as claimed in claim 1, is characterized in that: the excipient of composition label comprises the one, two or three in diluent, disintegrating agent, lubricant; Described diluent is more than one in microcrystalline Cellulose, calcium phosphate, mannitol; Described disintegrating agent is more than one in pregelatinized Starch, cross-linking sodium carboxymethyl cellulose, crospolyvinylpyrrolidone; Described lubricant is stearic acid or its salt.
3. a kind of moxifloxacin hydrochloride medicinal composition as claimed in claim 2, is characterized in that: the weight of described diluent is to account for 10%～30% of pharmaceutical composition label weight; The weight of disintegrating agent is to account for 2%～20% of pharmaceutical composition label weight; The weight of lubricant is to account for 0.3%～2.0% of pharmaceutical composition label weight.
4. a kind of moxifloxacin hydrochloride medicinal composition as described in claim as arbitrary in claims 1 to 3, it is characterized in that: in described coating materials, also contain the one, two or three in Polyethylene Glycol, titanium dioxide and red ferric oxide, the weight ratio of hydroxypropyl methylcellulose, Polyethylene Glycol, titanium dioxide and red ferric oxide is 3.5～15.0:0～4.0:0～2.0:0～0.5.
5. a kind of moxifloxacin hydrochloride medicinal composition as claimed in claim 4, is characterized in that: in the weight ratio of described hydroxypropyl methylcellulose, Polyethylene Glycol, titanium dioxide and red ferric oxide, Polyethylene Glycol is 0.75～4.0.
6. a kind of moxifloxacin hydrochloride medicinal composition as claimed in claim 4, is characterized in that: in the weight ratio of described hydroxypropyl methylcellulose, Polyethylene Glycol, titanium dioxide and red ferric oxide, titanium dioxide is 1.0～2.0.
7. a kind of moxifloxacin hydrochloride medicinal composition as claimed in claim 5, is characterized in that: in the weight ratio of described hydroxypropyl methylcellulose, Polyethylene Glycol, titanium dioxide and red ferric oxide, titanium dioxide is 1.0～2.0.
8. a kind of moxifloxacin hydrochloride medicinal composition as claimed in claim 4, is characterized in that: in the weight ratio of described hydroxypropyl methylcellulose, Polyethylene Glycol, titanium dioxide and red ferric oxide, red ferric oxide is 0.2～0.5.
9. a kind of moxifloxacin hydrochloride medicinal composition as described in claim 5,6 or 7 arbitrary claim, is characterized in that: in the weight ratio of described hydroxypropyl methylcellulose, Polyethylene Glycol, titanium dioxide and red ferric oxide, red ferric oxide is 0.2～0.5.
10. a method of preparing a kind of moxifloxacin hydrochloride medicinal composition as described in claim as arbitrary in claim 1 to 9, is characterized in that: by even to moxifloxacin hydrochloride and mixed with excipients, and wet granulation, tabletting obtains label; By the coating materials mix homogeneously of the hydroxypropyl methylcellulose composition that contains two or more different viscositys, joining and in the mixed solvent of water or water and ethanol, making coating materials weight ratio is 3.5%～15.0% coating solution, label is carried out to coating, label weightening finish 1.0%～4.0% after coating.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210397924.0A CN103768063B (en) | 2012-10-19 | 2012-10-19 | A kind of moxifloxacin hydrochloride medicinal composition and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210397924.0A CN103768063B (en) | 2012-10-19 | 2012-10-19 | A kind of moxifloxacin hydrochloride medicinal composition and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103768063A true CN103768063A (en) | 2014-05-07 |
| CN103768063B CN103768063B (en) | 2016-04-20 |
Family
ID=50561127
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210397924.0A Expired - Fee Related CN103768063B (en) | 2012-10-19 | 2012-10-19 | A kind of moxifloxacin hydrochloride medicinal composition and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103768063B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105168166A (en) * | 2015-09-08 | 2015-12-23 | 深圳信立泰药业股份有限公司 | Coating technique of solid preparation for treating cardiovascular diseases |
| CN105769799A (en) * | 2014-12-23 | 2016-07-20 | 北大方正集团有限公司 | Moxixacin tablet and preparation method thereof |
| CN105769783A (en) * | 2014-12-23 | 2016-07-20 | 北大方正集团有限公司 | Moxifloxacin hydrochloride tablet and preparation method thereof |
| CN105769801A (en) * | 2014-12-23 | 2016-07-20 | 北大方正集团有限公司 | Moxifloxacin tablet |
| CN109045034A (en) * | 2018-09-29 | 2018-12-21 | 哈尔滨珍宝制药有限公司 | A kind of moxifloxacin hydrochloride medicinal composition and its preparation method and application |
| CN113181125A (en) * | 2021-04-27 | 2021-07-30 | 海南通用三洋药业有限公司 | Sitafloxacin hydrate tablet and preparation method thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1325306A (en) * | 1998-11-10 | 2001-12-05 | 拜尔公司 | Pharmaceutical moxifloxacin preparation |
| CN1762357A (en) * | 2005-09-21 | 2006-04-26 | 深圳市天一时科技开发有限公司 | Oral medicinal formulation of moxifloxacin and its preparation method |
| CN102247313A (en) * | 2010-06-11 | 2011-11-23 | 北京润德康医药技术有限公司 | Oral-administration slow release solid preparation by taking Moxifloxacin as active ingredient |
| CN102247314A (en) * | 2011-01-12 | 2011-11-23 | 北京润德康医药技术有限公司 | Oral solid preparation using moxifloxacin as active component |
| US20110293717A1 (en) * | 2008-12-08 | 2011-12-01 | Ratiopharm Gmbh | Compacted moxifloxacin |
-
2012
- 2012-10-19 CN CN201210397924.0A patent/CN103768063B/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1325306A (en) * | 1998-11-10 | 2001-12-05 | 拜尔公司 | Pharmaceutical moxifloxacin preparation |
| CN1762357A (en) * | 2005-09-21 | 2006-04-26 | 深圳市天一时科技开发有限公司 | Oral medicinal formulation of moxifloxacin and its preparation method |
| US20110293717A1 (en) * | 2008-12-08 | 2011-12-01 | Ratiopharm Gmbh | Compacted moxifloxacin |
| CN102247313A (en) * | 2010-06-11 | 2011-11-23 | 北京润德康医药技术有限公司 | Oral-administration slow release solid preparation by taking Moxifloxacin as active ingredient |
| CN102247314A (en) * | 2011-01-12 | 2011-11-23 | 北京润德康医药技术有限公司 | Oral solid preparation using moxifloxacin as active component |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105769799A (en) * | 2014-12-23 | 2016-07-20 | 北大方正集团有限公司 | Moxixacin tablet and preparation method thereof |
| CN105769783A (en) * | 2014-12-23 | 2016-07-20 | 北大方正集团有限公司 | Moxifloxacin hydrochloride tablet and preparation method thereof |
| CN105769801A (en) * | 2014-12-23 | 2016-07-20 | 北大方正集团有限公司 | Moxifloxacin tablet |
| CN105168166A (en) * | 2015-09-08 | 2015-12-23 | 深圳信立泰药业股份有限公司 | Coating technique of solid preparation for treating cardiovascular diseases |
| WO2016161990A3 (en) * | 2015-09-08 | 2016-11-24 | 深圳信立泰药业股份有限公司 | Solid preparation used for treating cardiovascular disease |
| CN107213131A (en) * | 2015-09-08 | 2017-09-29 | 深圳信立泰药业股份有限公司 | Packaging technique for treating angiocardiopathy solid pharmaceutical preparation |
| CN109045034A (en) * | 2018-09-29 | 2018-12-21 | 哈尔滨珍宝制药有限公司 | A kind of moxifloxacin hydrochloride medicinal composition and its preparation method and application |
| CN109045034B (en) * | 2018-09-29 | 2021-04-13 | 哈尔滨珍宝制药有限公司 | Moxifloxacin hydrochloride pharmaceutical composition and preparation method and application thereof |
| CN113181125A (en) * | 2021-04-27 | 2021-07-30 | 海南通用三洋药业有限公司 | Sitafloxacin hydrate tablet and preparation method thereof |
| CN113181125B (en) * | 2021-04-27 | 2022-07-19 | 海南通用三洋药业有限公司 | Sitafloxacin hydrate tablet and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103768063B (en) | 2016-04-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103768063B (en) | A kind of moxifloxacin hydrochloride medicinal composition and preparation method thereof | |
| US20220249491A1 (en) | Oral solid tablet comprising bruton's tyrosine kinase inhibitor and preparation method therefor | |
| US20240082275A1 (en) | Pharmaceutical formulations comprising 5-Chloro-N4-[2-(dimethylphosphoryl)phenyl]-N2-{2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}pyrimidine-2,4-diamine | |
| CN103520128B (en) | A kind of sustained-release tablet of Pramipexole, preparation method and its usage | |
| CN106913529B (en) | Preparation method of pharmaceutical composition of neratinib or pharmaceutically acceptable salt thereof | |
| CN103610658B (en) | Immunomodulator slow-release preparation and preparation method thereof | |
| CN107753458A (en) | Nimodipine tablet pharmaceutical composition and preparation method | |
| CN103191114A (en) | Moxifloxacin-containing oral drug solid preparation and preparation method thereof | |
| WO2018095403A1 (en) | Pyridone derivative pharmaceutical composition and preparation method thereof | |
| CN105343028A (en) | Medicine composition with norfloxacin and method for preparing medicine composition | |
| JP2022544167A (en) | Pharmaceutical composition containing nitroxoline, nitroxoline oral solid tablet, method of preparation thereof, and use thereof | |
| WO2019080830A1 (en) | Pharmaceutical composition containing quinoline derivative | |
| CN105030717A (en) | Moxifloxacin hydrochloride film-coated tablet and preparation method thereof | |
| CN106994121A (en) | A kind of pharmaceutical composition for treating cancer | |
| CN113616613A (en) | Metformin-glipizide compound tablet for treating diabetes and preparation method thereof | |
| CN103908435B (en) | A kind of Flutamide sustained release preparation and preparation method thereof | |
| CN102370629B (en) | Entecavir liquid capsule and preparation method thereof | |
| EP3052086A1 (en) | Pharmaceutical composition comprising low dose active pharmaceutical ingredient and preparation thereof | |
| TW202038918A (en) | Pharmaceutical composition | |
| CN105534980B (en) | The pharmaceutical composition and its preparation process of Repaglinide Metformin hydrochloride | |
| WO2007033515A1 (en) | Oral formulation containing moxifloxacin and its preparation method | |
| CN114727965B (en) | JAK kinase inhibitor pharmaceutical composition | |
| CN106974892A (en) | A kind of pharmaceutical composition containing 4 amino-pyrroles and triazine derivatives species kinase inhibitor and preparation method thereof | |
| JPH04368330A (en) | Sustained release preparation of pemirolast potassium | |
| CN113116840B (en) | Preparation method of hydroxychloroquine sulfate tablet |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20160420 Termination date: 20201019 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |