CN103893138B - A kind of tablet containing linezolid form III - Google Patents
A kind of tablet containing linezolid form III Download PDFInfo
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- CN103893138B CN103893138B CN201210581947.7A CN201210581947A CN103893138B CN 103893138 B CN103893138 B CN 103893138B CN 201210581947 A CN201210581947 A CN 201210581947A CN 103893138 B CN103893138 B CN 103893138B
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Abstract
The present invention relates to a kind of tablet containing linezolid form III, the tablet contains other pharmaceutically useful excipient such as 67.0wt% ~ 75.0wt% Linezolids, 2.0wt% ~ 4.8wt% lactose, 9.0wt% ~ 18.0wt% microcrystalline celluloses and disintegrant, adhesive, lubricant, and tablet composition preferably is：Linezolid 67.0wt% ~ 75.0wt%, lactose 2.0wt% ~ 4.8wt%, microcrystalline cellulose 9.0wt% ~ 18.0wt%, disintegrant 2.0wt% ~ 10.0wt%, adhesive 1.2wt% ~ 4.0wt%, lubricant 0.3wt% ~ 2.0wt%.The tablet of the linezolid form III for the above-mentioned prescription that the present invention is provided, under extremely limited auxiliary material addition scope, it is ensured that tablet has that compressibility is good, mouldability is good and Fast Stripping feature.
Description
Technical field
The present invention relates to pharmaceutical preparation, and in particular to a kind of tablet containing linezolid form III.
Background technology
Linezolid（LINEZOLID, (S)-N- { [oxazoline of 3- (3- fluorine 4- (4- morpholinyls) benzene) 2- oxygen -5] methyl }-second
Acid amides）Also known as linezolid, Linezolid, it is a kind of artificial synthesized novel oxazolidinone class antibiotic, acts on bacterium 50S
Ribosomal subunit, and closest to site of action.Different from other medicines, Linezolid does not influence peptidyl transferase activity,
The initial period of translation system is simply acted on, suppresses mRNA and is connected with ribosomes, prevent the formation of 70S initiation complexes, from
And inhibit the synthesis of bacterioprotein.
Linezolid is researched and developed by Pharmacia＆Upjohn companies of the U.S., is approved listing by U.S. FDA within 2000,
For treating Grain-positive (G+) coccigenic infection, including as caused by MRSA it is doubtful or make a definite diagnosis nosocomial pneumonia
(HAP), community acquired pneumonia (CAP), complexity skin or skin soft-tissue infection (SSTI) and vancomycin resistance intestines ball
Bacterium (VRE) infects.2006, Linezolid injection and tablet in Discussion on Chinese Listed, trade name this irrigate（ZYVOX）.
Compared with other formulations, Linezolid tabletting properties are more stablized；And oral absorption is utilized, its tolerance and safety
Property is more preferable；Have simultaneously dosage it is accurate, using the advantage such as mechanization degree that is convenient, with low cost, producing is higher.However, piece
Agent need to be by medicine and auxiliary material compression forming, after being taken through patient, and the medicine in tablet is again through disintegration, dissolving（That is dissolution）Afterwards and then
It is absorbed by the body, therefore, selects suitable auxiliary material to meet the dissolution of tablet after the compressibility of material and tabletting before tabletting（At 15 points
Clock dissolution rate is more than 85% tablet, it is believed that medicine is before by gastric emptying to small intestine, and its form has been similar to solution, with this
Form enters small intestine, is more beneficial for intestinal absorption）It is that ensure drug quality excellent and curative effect is rapidly crucial.
Because the content of Linezolid in Linezolid tablet is higher, therefore, crystal formation the pressing to tablet of Linezolid
Property and dissolution have considerable influence.There are a variety of crystal formations in known Linezolid, the crystalline substance as disclosed in US6444813 and US6559305
Crystal formation III disclosed in type II and WO2005035530（The 2 of the X-ray powder diffraction of crystal formation III disclosed in WO2005035530
θ values be 7.6,9.6,13.6,14.9,18.2,18.9,21.2,22.3,25.6,26.9,27.9 and 29.9 degree, the present invention below
Signified linezolid form III is the crystal formation III defined in WO2005035530）.Compared with crystal formation II, Linezolid is brilliant
Type III have electrostatic is small, thermodynamics is more stable, crystal formation is closer, the advantages of mobility is more preferable, these advantages advantageously ensure that piece
The stability of the mixing uniformity of material and finished product after preparation when prepared by agent.But because crystal formation III and crystal formation II are in engineering properties side
The difference that face has, especially crystal formation III are prism form（Crystal formation II is needle）, its compressibility is not as crystal formation II, the present patent application
People is according to prescription disclosed in the patent CN1208058C of Linezolid tablet Yuan Yan companies, respectively with linezolid form II or crystalline substance
Type III（71.43wt%）, starch（7.14wt%）And microcrystalline cellulose（14.0wt%）And described adhesive, disintegrant, lubricant system
During standby tablet, find with disclosed in Yuan Yan house journals CN1221547C and the linezolid form II protected prepared for main ingredient
Tablet, compressibility and mouldability are preferable, but the tablet strength prepared with linezolid form III is relatively low, and friability is high, rear
Easily fragment, therefore the prescription that the original is ground disclosed in patent is only capable of meeting linezolid form II for main ingredient system in continuous coating process
The compressibility of standby tablet, it is impossible to meet the mouldability requirement for the tablet that linezolid form III is prepared for main ingredient.
WO2007102082 discloses a kind of solid pharmaceutical preparation of high medicament contg, and it contains 50mg ~ 800mg oxazolidones
Class or its pharmaceutically acceptable salt, hydrate or crystal and the water soluble adjuvant based on lactose, wherein the water based on lactose
Soluble auxiliary materials content is 5wt% ~ 25wt%.Present invention applicant is according to its disclosed prescription with linezolid form III for main ingredient system
Standby tablet, it is found that tablet stripping property is poor, dissolution test result shows, above-mentioned tablet can not in dissolution more than 85% in 15 minutes,
Can not reach the purpose of quick acting, and for nosocomial pneumonia and Patients with Simple Community Acquired Pneumonia, often can with heating,
The symptom such as expectoration and expiratory dyspnea, it is extremely important to carry out anti-infective therapy to it in time, therefore, the profit with Fast Stripping feature
How azoles amine piece is very necessary for the patients with pneumonia of above-mentioned nonessential use injection for treating.
WO2010026597 embodiment 1 discloses one kind with Linezolid（68.03wt%）, microcrystalline cellulose
（25.49wt%）, sodium carboxymethyl starch（4.57wt%）, sodium carboxymethylcellulose（0.71wt%）, lauryl sodium sulfate
（0.25wt%）And magnesium stearate（0.95wt%）The piller prepared for formulation ingredients, present invention applicant is according to the extrusion described in it
Spheronization prepares the tablet that other available ordinary preparation methods in piller and tabletting, or production prepare linezolid form III,
It was found that its 15 minutes dissolution rates are only 58.6% ~ 68.6%, 85% still is below.
In view of the poor compressibility of linezolid form III, Linezolid monolithic main ingredient dosage is high, therefore every Linezolid piece
The auxiliary material amount that can be added in agent is extremely limited, and prior art do not provide it is any in extremely limited auxiliary material addition cause
Linezolid form III has the tablet formulation of good compressibility and Fast Stripping feature simultaneously, therefore exploitation one kind is applied to
The tablet formulation of linezolid form III so that its compressibility is good, mouldability is good and dissolution in 15 minutes can reach more than 85%,
Quick acting is very necessary.
The content of the invention
In order to overcome the deficiencies in the prior art, the invention provides the prescription technical side of following suitable linezolid form III
Case so that compressibility, mouldability that the tablet of linezolid form III prepared by following prescription had both had, while can also obtain
15 minutes dissolution rates reach more than 85% Fast Stripping and action.
A kind of tablet containing linezolid form III, the tablet contain 67.0wt% ~ 75.0wt% Linezolids,
Other are pharmaceutically acceptable for 2.0wt% ~ 4.8wt% lactose, 9.0wt% ~ 18.0wt% microcrystalline celluloses and disintegrant, adhesive, lubricant etc.
Excipient.
The invention provides a kind of tablet composition containing linezolid form III：
Linezolid 67.0wt% ~ 75.0wt%
Lactose 2.0wt% ~ 4.8wt%
Microcrystalline cellulose 9.0wt% ~ 18.0wt%
Disintegrant 2.0wt% ~ 10.0wt%
Adhesive 1.2wt% ~ 4.0wt%
Lubricant 0.3wt% ~ 2.0wt%.
It is fine that the disintegrant is selected from sodium carboxymethyl starch, PVPP, low-substituted hydroxypropyl cellulose, cross-linked carboxymethyl
The one or more of the plain sodium of dimension, preferably sodium carboxymethyl starch.
The one kind of described adhesive in Hydroxypropylcelliloxe, hydroxypropyl methylcellulose, polyvinylpyrrolidone
Or a variety of, preferably Hydroxypropylcelliloxe.
The one kind of the lubricant in magnesium stearate, talcum powder, superfine silica gel powder, preferably magnesium stearate.
The tablet can be thin membrane coated tablet.
The invention provides a kind of specific tablet containing linezolid form III, consisting of：
Linezolid 70.0wt% ~ 74.5wt%
Lactose 2.0wt% ~ 4.8wt%
Microcrystalline cellulose 11.0wt% ~ 16.0wt%
Sodium carboxymethyl starch 7.5wt% ~ 9.5wt%
Hydroxypropylcelliloxe 1.5wt% ~ 2.2wt%
Magnesium stearate 0.3wt% ~ 1.5wt%.
Present invention also offers a kind of tablet more specifically containing linezolid form III, consisting of：
Linezolid 73.26wt%
Lactose 2.44wt%
Microcrystalline cellulose 13.43wt%
Sodium carboxymethyl starch 8.55wt%
Hydroxypropylcelliloxe 1.83wt%
Magnesium stearate 0.49wt%.
Present invention applicant prepares the tablet of linezolid form III according to the prescription disclosed in Yuan Yan companies CN1208058C
Shi Faxian, different from the needle form of crystal formation II, the prism structure of crystal formation III makes drug crystallization be difficult queueing discipline in tabletting,
Compressibility and coherency are substantially reduced compared with crystal formation II, because every unit dose of Linezolid tablet is larger, therefore not
Influence of the same main ingredient crystal formation to preparation process thereof is larger.To improve the compressibility of crystal formation III, present invention applicant tastes first
Linezolid bulk drug is crushed and crosses the screen cloth of different meshes by examination, to the size and form by changing particle, Jin Ergai
The compressibility and mouldability of kind raw material.When will with prior art synthesize obtain Linezolid bulk drug mechanical crushing after and mistake
150 mesh sieves, are prepared after tablet according to prescription disclosed in Yuan Yan house journals CN1208058C, and present invention applicant has found tablet
Compressibility and mouldability have clear improvement, and the tablet strength of compacting is suitable, and friability is low, meet follow-up coating, transport will
Ask, but particle diameter is less than the Linezolid bulk drug of 150 mesh with very high adhesiveness, the substantial amounts of powder produced in crushing process
Dirt pole influences operating environment, and especially Linezolid is new antibiotic medicine, therefore is crushed in process of production to use
The method of sieve, the then labour protection to operating personnel requires high, the safeguard of higher level need to be equipped with, so as to greatly increase
Production cost.
Present invention applicant attempts not mechanical crushing bulk drug, only changes the method for other auxiliary materials in prescription to improve tablet
Compact property.Use PVPP, Ac-Di-Sol or the more preferable low substituted hydroxy-propyl fiber of compressibility
Element is as disintegrant, but the tablet prepared is still loosely, vibrated rear easily shedding or broken；Present invention applicant further tastes
Compressive strength and time during examination increase tabletting, to increase intergranular cohesive force, but will obtain the suitable tablet of hardness, press
The pressure of piece machine requires more than the rated pressure of equipment and close to maximum pressure, produced for a long time under the compressive strength, holds
Punch die bending or the edge breakage of tablet are easily caused, shortens the service life of punch die；Also, present invention applicant prepares this method
Tablet carry out Dissolution experiments, dissolution rate when finding its 15 minutes is less than 85%.
The present inventor attempts not against mechanical crushing bulk drug, and by increasing the consumption of adhesive, using stickiness more again
Strong adhesive is to increase the cohesiveness of storeroom, though now the mouldability of tablet makes moderate progress, hardness is greatly improved,
Dissolution Rate Testing shows that dissolution rate during above-mentioned tablet 15 minutes is below 85%, it is impossible to reach the requirement of Fast Stripping.
Because the content of Linezolid tablet medicine is larger, to control the volume size of tablet to ensure that it is suitable that patient takes
Ying Xing, present invention applicant attempts to adjust the consumption and proportioning of each filler in extremely limited spatial dimension again, to obtain
Obtain the tablet that compressibility is good, dissolution rate is high.General, could be to granulation and tabletting when the consumption of filler is more than 5.0wt%
Process produces influence, causes the obvious change in terms of particle, unilateral, disintegration and dissolution, but adjust and sieve in substantial amounts of prescription
During choosing, present invention applicant chances on, when the consumption using lactose and lactose is in 2.0wt% ~ 4.8wt%, with
9.0wt% ~ 18.0wt% microcrystalline celluloses coordinate as filler, and now the compressibility of tablet is good, and moderate strength, friability is low；
Further, when disintegrant consumption is 2.0wt% ~ 10.0wt%, binder dosage is 1.2wt% ~ 4.0wt%, and lubricant quantity
During for 0.3wt% ~ 2.0wt%, tablet can be in dissolution more than 85% in 15 minutes；It is preferred that, when 70.0wt% containing Linezolid ~
74.5wt%, lactose 2.0wt% ~ 4.8wt%, microcrystalline cellulose 11.0wt% ~ 16.0wt%, sodium carboxymethyl starch 7.5wt% ~
9.5wt%, Hydroxypropylcelliloxe 1.5wt% ~ 2.2wt%, can be by supplementary product consumption during magnesium stearate 0.3wt% ~ 1.5wt%
Control is in below 30wt%, and by taking the tablet of the Linezolid containing 600mg as an example, tablet weight can be controlled within 857mg；Especially
When the composition and percentage by weight of the tablet are：Linezolid 73.26wt%, lactose 2.44wt%, microcrystalline cellulose
It is auxiliary when 13.43wt%, sodium carboxymethyl starch 8.55wt%, Hydroxypropylcelliloxe 1.83wt%, magnesium stearate 0.49wt%
Material consumption accounts for the 26.7wt% of tablet total amount, and by taking the tablet of the Linezolid containing 600mg as an example, tablet weight is 819mg, further
Improve the compliance of patient.
Friability test of the present invention, be according to《Chinese Pharmacopoeia》（2010 editions）The inspection of the lower non-packet garment piece of annex XG
Method is implemented, and " the average less loss weight of tablet must not cross 1%, and must not detect fracture, cracking and powder with reference to its test stone
Broken piece ", and practical condition is combined, to ensure that complete, attractive in appearance, dosage is accurate after tablet coating, it is desirable to the piece before coating
Situations such as tablet is broken, unilateral and corner is worn and torn must not occur in addition to above-mentioned standard is met, also in agent, judge whether tablet accords with this
Close to be coated and require.Satisfactory tablet is coated, and carries out dissolution test.
Dissolution Rate Testing of the present invention, is that the dissolution described in Dissolution of Tablet quality standard is ground with reference to Linezolid original
Condition, according to《Chinese Pharmacopoeia》（2010 editions）Lower second method of annex XC（Paddle method）, setting speed is 50r/min, 37 ± 0.5
At DEG C, 900ml pH6.8 phosphate buffers determine dissolution rate at its 15 minutes.
It is part Experiment result of study below
Good in order to obtain compressibility, tablet strength is moderate, it is not necessary to which mechanical crushing is capable of the Linezolid piece of Fast Stripping,
Present invention applicant carries out substantial amounts of experimental study, below the part Experiment content only during enumerative study.
First, influence of the particle diameter to Linezolid piece compressibility and dissolution rate
The screen cloth of different meshes will be crossed after the mechanical crushing of linezolid form III（The mesh of 80 mesh ~ 200）, obtain varigrained
Linezolid, prepares Linezolid piece by the table 1-1 prescriptions provided, determines its friability, and the tablet that requirement is coated to meeting exists
It is coated（Material opatry white ys-1-18202-A）After determine its dissolution rate, the results are shown in Table 1-2.
Influence of the table 1-1 particle diameters to Linezolid piece compressibility and dissolution rate（1）
| Composition | Weight（Mg/ pieces） | Percentage |
| Linezolid | 600.0 | 71.43% |
| Cornstarch | 60.0 | 7.14% |
| Microcrystalline cellulose | 117.6 | 14.00% |
| Sodium carboxymethyl starch | 42.0 | 5.00% |
| Hydroxypropylcelliloxe | 12.0 | 1.43% |
| Magnesium stearate | 8.4 | 1.00% |
| Total amount | 840.0 | 100% |
Influence of the table 1-2 particle diameters to Linezolid piece compressibility and dissolution rate（2）
| Prescription | 1 | 2 | 3 | 4 | 5 |
| Sieve mesh number | 80 | 100 | 120 | 150 | 200 |
| Friability | 1.02% | 0.97% | 0.87% | 0.82% | 0.71% |
| Tablet situation | Cracking | Abrasion | Abrasion | Completely | Completely |
| Dissolution rate（15min） | — | — | — | 87.6% | 89.4% |
As a result show, with the reduction of particle diameter, the compressibility of tablet be improved significantly, friability reduction, when profit how azoles
Amine is crossed after 150 mesh sieves, and the tablet strength of compacting is suitable, and friability meets coating and required, and 15 minutes dissolution rates are more than 85%, but
Now the adhesiveness of material is high, it is necessary to which larger labour protection dynamics is to ensure that personnel's is healthy unaffected.
2nd, influence of the disintegrant to Linezolid piece compressibility and dissolution rate
The prescription provided by table 2 prepares the tablet of linezolid form III, determines its friability, is coated what is required to meeting
Tablet is being coated（Material opatry white ys-1-18202-A）After determine its dissolution rate, the results are shown in Table 2.
Influence of the disintegrant of table 2 to Linezolid piece compressibility and dissolution rate
| Prescription（Mg/ pieces） | 6 | 7 | 8 | 9 |
| Linezolid | 600.0 | 600.0 | 600.0 | 600.0 |
| Cornstarch | 60.0 | 60.0 | 60.0 | 60.0 |
| Microcrystalline cellulose | 117.6 | 117.6 | 117.6 | 117.6 |
| PVPP | 42.0 | — | — | 21.0 |
| Low-substituted hydroxypropyl cellulose | — | 42.0 | — | 21.0 |
| Ac-Di-Sol | — | — | 42.0 | — |
| Hydroxypropylcelliloxe | 12.0 | 12.0 | 12.0 | 12.0 |
| Magnesium stearate | 8.4 | 8.4 | 8.4 | 8.4 |
| Total amount | 840.0 | 840.0 | 840.0 | 840.0 |
| Friability | 1.05% | 0.98% | 0.84% | 0.82% |
| Tablet situation | Abrasion | Abrasion | Abrasion | Abrasion |
| Dissolution rate（15min） | — | — | — | — |
Above-mentioned experiment shows, replaces the preferable disintegrant of compressibility, such as PVPP, low-substituted hydroxypropyl cellulose
Deng, the compressibility of tablet can not be obviously improved, friability test is found, above-mentioned tablet in a certain degree of extruding, overturn it
Tablet corner is easy to abrasion afterwards, it is impossible to the need for meeting coating process.
3rd, influence of the adhesive to Linezolid piece compressibility and dissolution rate
The prescription provided by table 3 prepares the tablet of linezolid form III, determines its friability, is coated what is required to meeting
Tablet is being coated（Material opatry white ys-1-18202-A）After determine its dissolution rate, the results are shown in Table 3.
Influence of the adhesive of table 3 to Linezolid piece compressibility and dissolution rate
| Prescription（Mg/ pieces） | 10 | 11 | 12 | 13 |
| Linezolid | 600.0 | 600.0 | 600.0 | 600.0 |
| Cornstarch | 60.0 | 60.0 | 60.0 | 60.0 |
| Microcrystalline cellulose | 117.6 | 117.6 | 117.6 | 117.6 |
| Sodium carboxymethyl starch | 42.0 | 42.0 | 42.0 | 42.0 |
| Hydroxypropylcelliloxe | 16.0 | 20.0 | — | — |
| Hydroxypropyl methylcellulose | — | — | 16.0 | 10.0 |
| Polyvinylpyrrolidone | — | — | — | 10.0 |
| Magnesium stearate | 8.4 | 8.4 | 8.4 | 8.4 |
| Total amount | 844.0 | 848.0 | 844.0 | 848.0 |
| Friability | 0.83% | 0.74% | 0.77% | 0.68% |
| Tablet situation | Abrasion | Completely | Completely | Completely |
| Dissolution rate（15min） | — | 72.8% | 75.6% | 69.4% |
Using the different adhesive of stickiness, or by the consumption increase of adhesive, the cohesiveness of storeroom can be effectively improved,
The compressibility of tablet is improved, but disintegration of tablet and dissolution is slowed down simultaneously, so as to influence the bioavilability of tablet.
4th, influence of the filler to Linezolid piece compressibility and dissolution rate
The tablet of linezolid form III is prepared by table 4-1 to table 4-3 prescription, its friability is determined, to meeting coating
It is required that tablet be coated（Material opatry white ys-1-18202-A）After determine its dissolution rate, the results are shown in Table 4-1 to table
4-3。
Influence of the table 4-1 fillers to Linezolid piece compressibility and dissolution rate（1）
| Prescription（Mg/ pieces） | 14 | 15 | 16 | 17 | 18 |
| Linezolid | 600.0 | 600.0 | 600.0 | 600.0 | 600.0 |
| Lactose | — | 60.0 | — | — | — |
| Mannitol | — | — | 60.0 | — | — |
| Sorbierite | — | — | — | 60.0 | — |
| Pregelatinized starch | — | — | — | — | 60.0 |
| Microcrystalline cellulose | 117.6 | 117.6 | 117.6 | 117.6 | 117.6 |
| Sodium carboxymethyl starch | 42.0 | 42.0 | 42.0 | 42.0 | 42.0 |
| Hydroxypropylcelliloxe | 12.0 | 12.0 | 12.0 | 12.0 | 12.0 |
| Magnesium stearate | 8.4 | 8.4 | 8.4 | 8.4 | 8.4 |
| Total amount | 780.0 | 840.0 | 840.0 | 840.0 | 840.0 |
| Friability | 0.81% | 0.72% | 0.80% | 0.73% | 0.79% |
| Tablet situation | Abrasion | Abrasion | Abrasion | Abrasion | Abrasion |
| Dissolution rate（15min） | — | — | — | — | — |
Influence of the table 4-2 fillers to Linezolid piece compressibility and dissolution rate（2）
| Prescription (mg/ pieces) | 19 | 20 | 21 | 22 | 23 |
| Linezolid | 600.0(75.00%) | 600.0(73.89%) | 600.0(74.07%) | 600.0(70.75%) | 600.0(75.00%) |
| Lactose | 40.0(5.00%) | — | 15.0(1.85%) | 20.0(2.36%) | 38.0(4.75%) |
| Mannitol | — | 32.0(3.94%) | — | — | — |
| Microcrystalline cellulose | 102.0(12.75%) | 116.0(14.29%) | 113.0(13.95%) | 156.0(18.40%) | 70.0(8.75%) |
| Sodium carboxymethyl starch | 40.0(5.00%) | 50.0(6.16%) | 60.0(7.41%) | 52.0(6.13%) | 68.0(8.50%) |
| Hydroxypropylcelliloxe | 10.0(1.25%) | 10.0(1.23%) | 14.0(1.73%) | 12.0(1.41%) | 18.0(2.25%) |
| Magnesium stearate | 8.0(1.00%) | 4.0(0.49%) | 8.0(0.99%) | 8.0(0.94%) | 6.0(0.75%) |
| Total amount | 800.0 | 812.0 | 810.0 | 848.0 | 800.0 |
| Friability | 0.77% | 0.85% | 0.87% | 0.92% | 0.88% |
| Tablet situation | Abrasion | Abrasion | Abrasion | Abrasion | Abrasion |
| Dissolution rate（15min） | — | — | — | — | — |
Present invention applicant is attempted without cornstarch in prescription, or uses lactose, mannitol, pregelatinized starch etc.
As one of filler, and attempt to increase the consumption of lactose etc., but result shows that the compressibility of tablet is still not improved.
Influence of the table 4-3 fillers to Linezolid piece compressibility and dissolution rate（3）
| Prescription（Mg/ pieces） | 24 | 25 | 26 | 27 |
| Linezolid | 600.0(69.44%) | 600.0(71.43%) | 600.0(69.77%) | 600.0(73.26%) |
| Lactose | 36.0(4.17%) | 30.0(3.57%) | 37.0(4.30%) | 20.0(2.44%) |
| Microcrystalline cellulose | 150.0(17.36%) | 120.0(14.29%) | 136.0(15.81%) | 110.0(13.43%) |
| Sodium carboxymethyl starch | 60.0(6.94%) | 70.0(8.33%) | 62.0(7.21%) | 70.0(8.55%) |
| Hydroxypropylcelliloxe | 12.0(1.39%) | 14.0(1.67%) | 20.0(2.33%) | 15.0(1.83%) |
| Magnesium stearate | 6.0(0.69%) | 6.0(0.71%) | 5.0(0.58%) | 4.0(0.49%) |
| Total amount | 864.0 | 840.0 | 860.0 | 819.0 |
| Friability | 0.52% | 0.42% | 0.40% | 0.45% |
| Tablet situation | Completely | Completely | Completely | Completely |
| Dissolution rate（15min） | 89.6% | 88.1% | 87.9% | 89.3% |
Research is found, micro- with 9.0wt% ~ 18.0wt% when the consumption using lactose and lactose is in 2.0wt% ~ 4.8wt%
Crystalline cellulose coordinates as filler, and now the compressibility of tablet is good, and moderate strength, friability is low；Further, when containing disintegration
Agent 2.0wt% ~ 10.0wt%, adhesive 1.2wt% ~ 4.0wt%, during lubricant 0.3wt% ~ 2.0wt%, tablet can be molten at 15 minutes
Go out more than 85%；It is preferred that, as 70.0wt% containing Linezolid ~ 74.5wt%, lactose 2.0wt% ~ 4.8wt%, microcrystalline cellulose 11.0
Wt% ~ 16.0wt%, sodium carboxymethyl starch 7.5wt% ~ 9.5wt%, Hydroxypropylcelliloxe 1.5wt% ~ 2.2wt%, stearic acid
During magnesium 0.3wt% ~ 1.5wt%, supplementary product consumption can be controlled in below 30wt%, by taking the tablet of the Linezolid containing 600mg as an example,
Tablet weight can be controlled within 857mg；Especially when the composition and percentage by weight of the tablet are：Linezolid
73.26wt%, lactose 2.44wt%, microcrystalline cellulose 13.43wt%, sodium carboxymethyl starch 8.55wt%, high substitution hydroxy propyl cellulose
When plain 1.83wt%, 0.49 wt% of magnesium stearate, supplementary product consumption is 26.7wt%, by taking the tablet of the Linezolid containing 600mg as an example,
Tablet weight is 819mg, improves the compliance of patient.
Embodiment
With reference to specific embodiment, the present invention is expanded on further.But these embodiments be only limitted to explanation the present invention without
It is for limiting the scope of the present invention.
Embodiment 1
Prescription recipe quantity percentage by weight
The 300.0mg 75.00% of linezolid form III
Lactose 19.2mg 4.80%
Microcrystalline cellulose 36.0mg 9.00%
PVPP 33.6mg 8.40%
Hydroxypropyl methylcellulose 10.0mg 2.50%
Magnesium stearate 1.2mg 0.30%
Total 400.0mg.
Embodiment 2
Prescription recipe quantity percentage by weight
The 400.0mg 67.00% of linezolid form III
Lactose 15.0mg 2.51%
Microcrystalline cellulose 107.5mg 18.01%
Low-substituted hydroxypropyl cellulose 59.7mg 10.00%
Polyvinylpyrrolidone 11.6mg 1.94%
Superfine silica gel powder 3.2mg 0.54%
Total 597.0mg.
Embodiment 3
Prescription recipe quantity percentage by weight
The 400.0mg 72.73% of linezolid form III
Lactose 11.0mg 2.00%
Microcrystalline cellulose 88.4mg 16.07%
Sodium carboxymethyl starch 33mg 6.00%
Polyvinylpyrrolidone 3.3mg 0.60%
Hydroxypropylcelliloxe 3.3mg 0.60%
Talcum powder 11.0mg 2.00%
Total 550.0mg.
Embodiment 4
Prescription recipe quantity percentage by weight
The 600.0mg 69.77% of linezolid form III
Lactose 40.6mg 4.72%
Microcrystalline cellulose 151.4mg 17.60%
PVPP 17.2mg 2.00%
Hydroxypropyl methylcellulose（E3） 34.4mg 4.00%
Talcum powder 16.4mg 1.91%
Total 860.0mg.
Embodiment 5
Prescription recipe quantity percentage by weight
The 600.0mg 69.61% of linezolid form III
Lactose 20.0mg 2.32%
Microcrystalline cellulose 140.0mg 16.24%
Sodium carboxymethyl starch 45.0mg 5.22%
Ac-Di-Sol 40.0mg 4.64%
Hydroxypropylcelliloxe 11.0mg 1.28%
Magnesium stearate 6.0mg 0.70%
Total 862.0mg.
Embodiment 6
Prescription recipe quantity percentage by weight
The 600.0mg 70.01% of linezolid form III
Lactose 38.7mg 4.52%
Microcrystalline cellulose 137.1mg 16.00%
Sodium carboxymethyl starch 64.3mg 7.50%
Hydroxypropylcelliloxe 12.9mg 1.50%
Magnesium stearate 4.0mg 0.47%
Total 857.0mg.
Embodiment 7
Prescription recipe quantity percentage by weight
The 400.0mg 74.50% of linezolid form III
Lactose 10.8mg 2.01%
Microcrystalline cellulose 59.1mg 11.00%
Sodium carboxymethyl starch 51.0mg 9.50%
Hydroxypropylcelliloxe 11.5mg 2.14%
Magnesium stearate 4.5mg 0.84%
Total 536.9mg.
Embodiment 8
Prescription recipe quantity percentage by weight
The 600.0mg 70.78% of linezolid form III
The mg 4.13% of lactose 35.0
Microcrystalline cellulose 110.0mg 12.98%
Sodium carboxymethyl starch 71.3mg 8.41%
Hydroxypropylcelliloxe 18.7mg 2.20%
Magnesium stearate 12.7mg 1.50%
Total 847.7mg.
Embodiment 9
Prescription recipe quantity percentage by weight
The 600.0mg 71.86% of linezolid form III
Lactose 23.8mg 2.85%
Microcrystalline cellulose 133.6mg 16.00%
Sodium carboxymethyl starch 62.6mg 7.50%
Hydroxypropylcelliloxe 12.5mg 1.50%
Magnesium stearate 2.5mg 0.30%
Total 835.0mg.
Embodiment 10
Prescription recipe quantity percentage by weight
The 600.0mg 70.01% of linezolid form III
Lactose 36.5mg 4.26%
Microcrystalline cellulose 133.5mg 15.58%
Sodium carboxymethyl starch 67.3mg 7.85%
Hydroxypropylcelliloxe 14.7mg 1.72%
Magnesium stearate 5.0mg 0.58%
Total 857.0mg.
Embodiment 11
Prescription recipe quantity percentage by weight
The 600.0mg 73.26% of linezolid form III
Lactose 20.0mg 2.44%
Microcrystalline cellulose 110.0mg 13.43%
Sodium carboxymethyl starch 70.0mg 8.55%
Hydroxypropylcelliloxe 15.0mg 1.83%
Magnesium stearate 4.0mg 0.49%
Total 819.0mg.
By above-described embodiment, Linezolid, lactose, microcrystalline cellulose, disintegrant, adhesive and lubricant are weighed, will be viscous
Mixture adds stirring and dissolving in purified water and completely, granulation liquid is made, Linezolid, lactose, microcrystalline cellulose and disintegrant are mixed
Close uniform, granulation liquid added in mixed powder, softwood is made, 24 mesh granulation, 60 ± 5 DEG C of dryings control moisture 2.0%~4.0%,
By the mesh whole grain of dry particl 30, hard mix lubricant is added uniformly, tabletting determines friability, opatry white ys-1-
18202-A coating powders, which are added to the water, is configured to coating solution, and 15 minutes dissolution rates are determined after coating, 5 are the results are shown in Table.
The embodiment friability of table 5 and dissolution test result
| Embodiment | Friability | Dissolution rate (15min) |
| 1 | 0.42% tablet is complete | 87.5% |
| 2 | 0.39% tablet is complete | 88.6% |
| 3 | 0.44% tablet is complete | 86.9% |
| 4 | 0.51% tablet is complete | 88.7% |
| 5 | 0.49% tablet is complete | 87.9% |
| 6 | 0.47% tablet is complete | 89.0% |
| 7 | 0.36% tablet is complete | 90.4% |
| 8 | 0.48% tablet is complete | 89.2% |
| 9 | 0.31% tablet is complete | 89.4% |
| 10 | 0.44% tablet is complete | 88.6% |
| 11 | 0.35% tablet is complete | 90.2% |
Claims (7)
1. a kind of troche medical composition containing Linezolid, be characterised by the troche medical composition comprising below into
Point：
Linezolid 67.0wt% ~ 75.0wt%
Lactose 2.0wt% ~ 4.8wt%
Microcrystalline cellulose 9.0wt% ~ 18.0wt%
Disintegrant 2.0wt% ~ 10.0wt%
Adhesive 1.2wt% ~ 4.0wt%
Lubricant 0.3wt% ~ 2.0wt%,
The Linezolid is crystal formation III；It is fine that the disintegrant is selected from sodium carboxymethyl starch, PVPP, low substituted hydroxy-propyl
One or more in dimension element, Ac-Di-Sol；Described adhesive is selected from Hydroxypropylcelliloxe, hydroxypropyl first
One or more in cellulose, polyvinylpyrrolidone；The lubricant is in magnesium stearate, talcum powder, superfine silica gel powder
One kind.
2. Linezolid troche medical composition according to claim 1, it is characterised in that the disintegrant is carboxymethyl
Sodium starch.
3. Linezolid troche medical composition according to claim 1, it is characterised in that described adhesive replaces to be high
Hydroxypropyl cellulose.
4. Linezolid troche medical composition according to claim 1, it is characterised in that the lubricant is stearic acid
Magnesium.
5. Linezolid troche medical composition according to claim 1, it is characterised in that the troche medical composition
For thin membrane coated tablet.
6. Linezolid troche medical composition according to claim 1, it is characterised in that the troche medical composition
Consist of the following composition：
Linezolid 70.0wt% ~ 74.5wt%
Lactose 2.0wt% ~ 4.8wt%
Microcrystalline cellulose 11.0wt% ~ 16.0wt%
Sodium carboxymethyl starch 7.5wt% ~ 9.5wt%
Hydroxypropylcelliloxe 1.5wt% ~ 2.2wt%
Magnesium stearate 0.3wt% ~ 1.5wt%.
7. Linezolid troche medical composition according to claim 1, it is characterised in that the troche medical composition
Consist of the following composition：
Linezolid 73.26wt%
Lactose 2.44wt%
Microcrystalline cellulose 13.43wt%
Sodium carboxymethyl starch 8.55wt%
Hydroxypropylcelliloxe 1.83wt%
Magnesium stearate 0.49wt%.
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| Application Number | Priority Date | Filing Date | Title |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210581947.7A CN103893138B (en) | 2012-12-28 | 2012-12-28 | A kind of tablet containing linezolid form III |
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| CN103893138B true CN103893138B (en) | 2017-09-29 |
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| CN104173303B (en) * | 2014-08-14 | 2017-01-11 | 杭州华东医药集团新药研究院有限公司 | Linezolid-containing composition and preparation method thereof |
| CN105055354B (en) * | 2015-09-08 | 2017-11-21 | 深圳万乐药业有限公司 | A kind of Linezolid piece and preparation method thereof |
| RU2690491C2 (en) * | 2017-07-19 | 2019-06-04 | Общество с ограниченной ответственностью "МБА-групп" | Solid-phase linezolid-containing preparation |
| CN109481412A (en) * | 2018-08-17 | 2019-03-19 | 扬子江药业集团北京海燕药业有限公司 | A kind of II crystal linezolid piece and its preparation process |
| CN115998890A (en) * | 2023-02-01 | 2023-04-25 | 晨光生物科技集团股份有限公司 | Auxiliary material of traditional Chinese medicine extract tablet, traditional Chinese medicine extract tablet and preparation method thereof |
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| EP1749517B8 (en) * | 2005-07-20 | 2008-10-22 | Teva Pharmaceutical Industries Ltd. | Stable pharmaceutical composition comprising linezolid form IV |
| US20070104785A1 (en) * | 2005-07-29 | 2007-05-10 | Navale Suryakant V | Tablets of linezolid form iii and processes for their preparation |
| WO2011050826A1 (en) * | 2009-10-28 | 2011-05-05 | Synthon B.V. | Process for making crystalline form a of linezolid |
| WO2011080570A2 (en) * | 2009-12-29 | 2011-07-07 | Micro Labs Limited | Extended release pharmaceutical composition comprising linezolid and process for preparing the same |
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