CN102525989B - Loxoprofen sodium matrix sustained-release tablet - Google Patents
Loxoprofen sodium matrix sustained-release tablet Download PDFInfo
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- CN102525989B CN102525989B CN201110000292.5A CN201110000292A CN102525989B CN 102525989 B CN102525989 B CN 102525989B CN 201110000292 A CN201110000292 A CN 201110000292A CN 102525989 B CN102525989 B CN 102525989B
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Abstract
The present invention relates to a kind of Novel matrix sustained-release tablet containing loxoprofen sodium, relate in particular to a kind of Loxoprofen sodium matrix sustained-release tablet with regulation and control layer, can steadily discharge for 8 hours, releasing effect is desirable, and technique is simple, with low cost.
Description
Technical field
The present invention relates to a kind of Novel matrix sustained-release tablet containing loxoprofen sodium, relate in particular to a kind of Loxoprofen sodium matrix sustained-release tablet with regulation and control layer, can 8 hours long-acting slow-releases.
Background technology
Loxoprofen sodium belongs to phenylpropionic acid non-steroid antiinflammatory drug, be used for the treatment of rheumatoid arthritis, osteoarthritis, lumbago, scapulohumeral periarthritis, neck shoulder wrist syndrome, and Post operation, easing pain and diminishing inflammation after wound and after exodontia, the antipyretic-antalgic of acute upper respiratory tract inflammation.Belong to phenylpropionic acid non-steroid antiinflammatory drug.
The preparation applied clinically is at present common quick release preparation, specification is 60mg, daily 3 times, easily cause the fluctuation of blood drug level and increase the generation of untoward reaction, therefore be necessary to be made into slow releasing preparation, to reduce administration number of times, maintain stable blood drug level, reduce the generation of untoward reaction, improve the compliance of patient.
The rate of releasing drug of monolayer hydrogel matrix type slow releasing tablet is one-level or false first-order release, and its release feature is that release in early stage is very fast, and later stage release is comparatively slow, is unfavorable for steadily controlling blood drug level.For the medicine that water solublity is larger, simple gel skeleton is not enough to the control ability of rate of release, at the release initial stage, namely the medicine on surface discharged before hydrated gel layer is formed, and the initial stage of causing discharges very fast, generally can add excessive slow-release material to control initial release, this situation phase upon discharge, because drug diffusion concentration difference reduces, rate of release is declined, easily cause release not exclusively.
Summary of the invention
In order to overcome the defect of loxoprofen sodium slow releasing tablet in prior art, the present inventor is through studying for a long period of time, surprised discovery, as long as on the basis of the matrix sustained release tablet prepared in prior art, add a regulation and control layer, thus prepare the novel double-layer matrix sustained release tablet with regulation and control layer, within 8 hours, evenly can discharge medicine, overcome the defect of loxoprofen sodium slow releasing tablet in prior art, not only releasing effect is desirable, and technique is simple, with low cost.
Loxoprofen sodium very easily dissolves in water, easily molten in ethanol.Because loxoprofen sodium is very easily water-soluble, in order to control its release, when adopting conventional single layer hydrogel matrix type slow releasing tablet technology, adopting and strengthening skeleton slow-release material consumption, result of study shows that rate of release is qualified in earlier stage, but it is on the low side that end point 8h discharges numerical value, although also in limit, residual more serious, if skeleton slow-release material consumption is less, then discharge fast, especially early stage, release was obviously fast, did not reach desirable steady releasing effect.
Relative to common monolayer hydrogel matrix type slow releasing tablet, the present invention is by increasing one deck regulation and control layer, effectively reduce the direct release surface area close to 1/2, make it to transfer to by regulation and control layer diffusion release, thus add drug diffusion resistance, good control effects can be reached to release in early stage, simultaneously because regulation and control layer employs the less hydrophilic gel slow-release material hydroxypropyl emthylcellulose K100 of viscosity, its solubility property is as different in K4M from hydroxypropyl emthylcellulose high viscosity model, viscosity is less, easier gelation, dissolve faster, along with the prolongation of release time, it slowly dissolves, the unlocking resistance of medicine is reduced gradually, the speed that diffusional resistance remains unchanged and produces because drug diffusion concentration difference declines in effectively compensatory common simple gel skeleton release later stage declines, overall release rate is comparatively constant, and drug residue is very little.
Loxoprofen sodium matrix sustained-release tablet containing regulation and control layer of the present invention, is characterized in that the percetage by weight that medicine layer accounts for whole label is 70-80%, and regulation and control layer accounts for 20-30%.Wherein, medicine layer is made up of loxoprofen sodium, skeleton slow-release material and other adjuvants, and regulation and control layer is made up of skeleton slow-release material and other adjuvants.
Matrix sustained release tablet containing regulation and control layer of the present invention, the composition of described medicine layer has following weight percent:
Loxoprofen sodium 30% ~ 40%
Skeleton slow-release material+other adjuvant surplus
The composition of described regulation and control layer has following weight percent:
Skeleton slow-release material 45% ~ 60%
Other adjuvant surplus
Described skeleton slow-release material is selected from one or more in hydroxypropyl cellulose, hydroxypropyl emthylcellulose, carboxymethyl cellulose and sodium salt thereof, sodium alginate, methylcellulose, ethyl cellulose, polyacrylic resin class, polyvinyl acetate, carbomer, polyoxyethylene, stearic acid, glyceryl monostearate, castor oil hydrogenated, Cera Flava, paraffin, white beeswax, Brazil wax or microwax.Other adjuvants comprise one or more in wetting agent, lubricant, filler, porogen or binding agent.Medicine layer of the present invention preferably uses HPMC K4M and stearic acid that viscosity is larger as skeleton slow-release material, can control loxoprofen sodium in early stage with steadily discharge mid-term; The skeleton slow-release material of regulation and control layer preferably uses full-bodied HPMC K4M and low viscous hydroxypropyl emthylcellulose K100 to share, early stage can provide suitable diffusional resistance, control the rate of release of medicine, and can with the prolongation of release time, regulation and control layer slowly dissolves gradually, the unlocking resistance of loxoprofen sodium in medicine layer is reduced gradually, effectively compensatory medicine layer release later stage speed declines, thus ensure that rate of release is comparatively constant within the whole release cycle, and drug residue is very little.
Filler comprises micropowder silica gel, starch, lactose, pregelatinized Starch, microcrystalline Cellulose, calcium hydrogen phosphate, mannitol, starch milk sugar mixture, mannitol starch mixture.Loxoprofen sodium matrix sustained-release tablet of the present invention, when skeleton slow-release material adopts hydrophilic gel matrix material, preferred micropowder silica gel is as filler, and advantage is to play certain retardation simultaneously, jointly determines release behavior with skeleton slow-release material.
Binding agent comprises one or more in polyvinylpyrrolidone (having another name called polyvidone, PVP), methylcellulose, hydroxypropyl emthylcellulose; The alcoholic solution of preferred PVP K30, such as 8% PVP K30 alcoholic solution, can play wetting action simultaneously.
Lubricant comprises one or more in magnesium stearate, calcium stearate, zinc stearate, sodium stearyl fumarate, stearic acid, PEG, Pulvis Talci, starch, paraffin, preferred magnesium stearate.
Porogen comprise from sucrose, sorbitol, mannitol, glucose, lactose, fructose, sodium chloride, potassium chloride, magnesium sulfate, potassium sulfate, sodium sulfate one or more, preferred lactose.
As one preferred embodiment, the Loxoprofen sodium matrix sustained-release tablet containing regulation and control layer of the present invention, its prescription is as follows:
Medicine layer prescription:
Prescription forms 1000
Loxoprofen sodium 90g
HPMC K4M 45g-75g
Microcrystalline Cellulose 30g
Lactose 50g-60g
Stearic acid 5g-20g
Micropowder silica gel 20g
8% PVP K30 alcoholic solution is appropriate
Magnesium stearate 5g
Regulation and control layer prescription:
Prescription forms 1000
HPMC K4M 15g-20g
Hydroxypropyl emthylcellulose K100 25g-30g
Lactose 30g
Micropowder silica gel 10g
8% PVP K30 alcoholic solution is appropriate
Magnesium stearate 1g
As one of most preferred embodiment, the Loxoprofen sodium matrix sustained-release tablet containing regulation and control layer of the present invention, its prescription is as follows:
Medicine layer:
Prescription forms 1000
Loxoprofen sodium 90g
HPMC K4M 60g
Microcrystalline Cellulose 30g
Lactose 60g
Stearic acid 15g
Micropowder silica gel 20g
8% PVP K30 alcoholic solution is appropriate
Magnesium stearate 5g
Regulation and control layer:
Prescription forms 1000
HPMC K4M 15g
Hydroxypropyl emthylcellulose K100 30g
Lactose 30g
Micropowder silica gel 10g
8% PVP K30 alcoholic solution is appropriate
Magnesium stearate 1g
The preparation method of the matrix sustained release tablet containing regulation and control layer of the present invention, comprises the steps:
1) medicine layer: loxoprofen sodium is put into wet granulator with other component (except lubricant) of medicine layer and mixs homogeneously, add binding agent and make wet granular, dry, granulate, adds the lubricant of recipe quantity, mix homogeneously;
2) regulate and control layer: each component (except lubricant) is put into wet granulator mix homogeneously, adds binding agent and make wet granular, dry, granulate, adds the lubricant of recipe quantity, mix homogeneously;
3) drug layer granulation above-mentioned steps prepared is pressed into two synusia together with regulation and control layer granule, obtains the matrix sustained release tablet containing regulation and control layer of the present invention.
If needed, film coating can also be carried out.
Use of the present invention have regulation and control layer Novel matrix sustained-release tablet technology after, the basis of traditional matrix tablet adds regulation and control layer, overcome the defect of matrix sustained release tablet in prior art, the successful 8h long-acting slow-release preparation having prepared loxoprofen sodium, the release of the loxoprofen sodium slow releasing tablet obtained shows good effect astoundingly, suitable rate of release is all kept in whole dispose procedure, in addition technology is simple, general dual layer pressed-disc technique is only needed to realize, technological requirement is low, and also comparatively monolayer slow releasing tablet is low for the overall consumption of expensive slow-release material, thus with low cost.
Detailed description of the invention:
Subordinate's example is used for illustrating the detailed description of the invention of technical scheme of the present invention, but is not used in and limits the scope of the invention.
Comparative examples:
Comparative examples 1: the common monolayer slow releasing tablet of loxoprofen sodium
One, prescription composition:
Prescription forms 1000
Loxoprofen sodium 90g
HPMC K4M 95g
Hydroxypropyl emthylcellulose K100 60g
Microcrystalline Cellulose 30g
Lactose 60g
Stearic acid 15g
Micropowder silica gel 20g
8% PVP K30 alcoholic solution is appropriate
Magnesium stearate 5g
Two, preparation technology:
1, the loxoprofen sodium of recipe quantity, hydroxypropyl methylcellulose K4M, hydroxypropyl methylcellulose K100, microcrystalline Cellulose, lactose, micropowder silica gel and stearic acid mix homogeneously is got;
2,8% PVP K30 alcoholic solution soft material, crosses 24 mesh sieve wet granulars;
3,40 DEG C of oven dry, cross 24 mesh sieve granulate;
4, the magnesium stearate of recipe quantity is added, mixing.
5, by the above-mentioned particle rotation tablet machine prepared, tabletting, obtains the common monolayer slow releasing tablet of loxoprofen sodium.
Three, release detects:
Detection method: get this product, according to drug release determination method (China's coastal port two annex Ⅹ D first methods), adopt dissolution method first method device (China's coastal port two annex Ⅹ C), with water 900ml for solvent, rotating speed is 100 turns per minute, operates in accordance with the law, through 1,4,8 hour, get solution 10ml, filter, and in process container, supplement the water of identical temperature, same volume in time; Get subsequent filtrate 5ml, put in 25ml measuring bottle, be diluted with water to scale, as need testing solution.Drying under reduced pressure in 60 DEG C of phosphorus pentoxide desiccators of separately learning from else's experience is appropriate to the loxoprofen sodium reference substance of constant weight, accurately weighed, be dissolved in water and make the solution containing loxoprofen sodium about 20 μ g in every 1ml, product solution in contrast, according to ultraviolet visible spectrophotometry (China's coastal port two annex IV A), measure trap respectively at the wavelength place of 223nm; Calculate every burst size at different time respectively.This product every should should be 15%-45%, the 45%-75%, more than 80% of labelled amount respectively mutually the burst size of 1,4,8 hour.
Result is as shown in the table:
Comparative examples 1 release test result
*n=6, the i.e. meansigma methods of 6 samples
Result shows, because loxoprofen sodium dissolubility is larger, the common matrix sustained release tablet of loxoprofen sodium of the single layer structure prepared traditionally, employ relatively large skeleton slow-release material, better, it is on the low side that end point 8h discharges numerical value, although also in limit in result release in early stage, residual comparatively serious (about 15-20%), does not reach desirable releasing effect.
Comparative examples 2: the common monolayer slow releasing tablet of loxoprofen sodium
One, prescription composition:
Prescription forms 1000
Loxoprofen sodium 90g
HPMC K4M 90g
Hydroxypropyl emthylcellulose K100 50g
Microcrystalline Cellulose 30g
Lactose 60g
Stearic acid 15g
Micropowder silica gel 20g
8% PVP K30 alcoholic solution is appropriate
Magnesium stearate 5g
Two, preparation technology: with comparative examples 1.
Three, drug release determination: method is with comparative examples 1, and result is as shown in the table:
Comparative example 2 release test result
*n=6, the i.e. meansigma methods of 6 samples
Result shows, the common matrix sustained release tablet of loxoprofen sodium of the single layer structure prepared traditionally, in order to solve comparative example 1 end point residue problem, reduce the consumption of skeleton slow-release material HPMC K4M and hydroxypropyl emthylcellulose K100, its release is obviously fast, although end point noresidue, early stage discharges too fast, undesirable.
Employing embodiments of the invention are as follows:
Embodiment 1: containing the loxoprofen sodium double-layer tablet of regulation and control layer
One, prescription
Medicine layer prescription:
Prescription forms 1000
Loxoprofen sodium 90g
HPMC K4M 75g
Microcrystalline Cellulose 30g
Lactose 50g
Stearic acid 20g
Micropowder silica gel 20g
8% PVP K30 alcoholic solution is appropriate
Magnesium stearate 5g
Regulation and control layer prescription:
Prescription forms 1000
HPMC K4M 15g
Hydroxypropyl emthylcellulose K100 30g
Lactose 30g
Micropowder silica gel 10g
8% PVP K30 alcoholic solution is appropriate
Magnesium stearate 1g
Two, preparation technology
1, medicine layer preparation technology:
(1) loxoprofen sodium crosses 60 mesh sieves;
(2) take the loxoprofen sodium of recipe quantity, HPMC K4M, microcrystalline Cellulose, lactose, stearic acid, micropowder silica gel, put mix homogeneously in wet granulator;
(3) with 8% PVP K30 alcoholic solution soft material, cross 24 mesh sieves and granulate;
(4) fluid bed 40 DEG C of dry 2h;
(5) 24 mesh sieve granulate are crossed;
(6) the magnesium stearate mix homogeneously of recipe quantity is added.
Obtain drug layer granulation.
2, layer preparation technology is regulated and controled:
(1) take the HPMC K4M of recipe quantity, hydroxypropyl emthylcellulose K100, lactose, micropowder silica gel, put mix homogeneously in wet granulator;
(2) with 8% PVP K30 alcoholic solution soft material, cross 24 mesh sieves and granulate;
(3) fluid bed 40 DEG C of dry 2h;
(4) 24 mesh sieve granulate are crossed;
(5) the magnesium stearate mix homogeneously of recipe quantity is added.
Layer granule must be regulated and controled.
3, tabletting: circular for two parts granule 10mm scrobicula is struck out double-layer tablet, obtains loxoprofen sodium slow releasing tablet.
Three, release detects: method is with comparative examples 1, and result is as shown in the table::
Embodiment 1 release test result
*n=6, the i.e. meansigma methods of 6 samples
Result shows: relative to common monolayer hydrogel matrix type slow releasing tablet, by increasing one deck regulation and control layer, effectively reduce the direct release surface area close to 1/2, increase drug release resistance, good control effects can be reached to release in early stage, simultaneously because regulation and control layer employs the less hydrophilic gel slow-release material hydroxypropyl emthylcellulose K100 of viscosity, along with the prolongation of release time, it slowly dissolves, the unlocking resistance of medicine is reduced gradually, effectively compensatory simple gel skeleton release later stage speed declines, rate of release is comparatively constant, release result is all in limit, meet the requirements, and drug residue is very little.In addition, compared with comparative examples, also comparatively monolayer slow releasing tablet is low for the overall consumption of expensive slow-release material, thus with low cost.
Embodiment 2: containing the loxoprofen sodium double-layer tablet of regulation and control layer
One, prescription
Medicine layer:
Prescription forms 1000
Loxoprofen sodium 90g
HPMC K4M 60g
Microcrystalline Cellulose 30g
Lactose 60g
Stearic acid 15g
Micropowder silica gel 20g
8% PVP K30 alcoholic solution is appropriate
Magnesium stearate 5g
Regulation and control layer:
Prescription forms 1000
HPMC K4M 15g
Hydroxypropyl emthylcellulose K100 30g
Lactose 30g
Micropowder silica gel 10g
8% PVP K30 alcoholic solution is appropriate
Magnesium stearate 1g
Two, preparation technology: with embodiment 1
Three, release detects: method is with comparative examples 1, and result is as shown in the table::
Embodiment 2 release test result
*n=6, the i.e. meansigma methods of 6 samples
Result shows: discharge very desirable, meet the requirements.
Embodiment 3: containing the loxoprofen sodium double-layer tablet of regulation and control layer
One, prescription
Medicine layer:
Prescription forms 1000
Loxoprofen sodium 90g
HPMC K4M 45g
Microcrystalline Cellulose 30g
Lactose 60g
Stearic acid 5g
Micropowder silica gel 20g
8% PVP K30 alcoholic solution is appropriate
Magnesium stearate 5g
Regulation and control layer:
Prescription forms 1000
HPMC K4M 20g
Hydroxypropyl emthylcellulose K100 25g
Lactose 30g
Micropowder silica gel 10g
8% PVP K30 alcoholic solution is appropriate
Magnesium stearate 1g
Two, preparation technology: with embodiment 1.
Three, release detects: method is with comparative examples 1, and result is as shown in the table:
Embodiment 3 release test result
*n=6, the i.e. meansigma methods of 6 samples
Result shows: release, all in limit, meets the requirements.
Claims (2)
1. a Loxoprofen sodium matrix sustained-release tablet, it is characterized in that label forms double-deck matrix sustained release tablet by medicine layer and regulation and control layer, the prescription of described medicine layer and regulation and control layer is as follows:
Medicine layer prescription:
Regulation and control layer prescription:
2. Loxoprofen sodium matrix sustained-release tablet as claimed in claim 1, is characterized in that prescription is as follows: medicine layer:
Regulation and control layer:
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| CN201110000292.5A CN102525989B (en) | 2011-01-04 | 2011-01-04 | Loxoprofen sodium matrix sustained-release tablet |
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|---|---|---|---|
| CN201110000292.5A CN102525989B (en) | 2011-01-04 | 2011-01-04 | Loxoprofen sodium matrix sustained-release tablet |
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| CN105769773B (en) * | 2016-03-30 | 2021-05-14 | 中国药科大学 | Loxoprofen sodium sustained-release pellet |
| CN112438955A (en) * | 2019-08-30 | 2021-03-05 | 深圳翰宇药业股份有限公司 | Ranolazine sustained-release composition and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1628648A (en) * | 2004-08-26 | 2005-06-22 | 复旦大学 | Loxoprofen sodium sustained release preparation |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1628648A (en) * | 2004-08-26 | 2005-06-22 | 复旦大学 | Loxoprofen sodium sustained release preparation |
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