CN105878201A - Topiroxostat extended-release preparation - Google Patents
Topiroxostat extended-release preparation Download PDFInfo
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- CN105878201A CN105878201A CN201410659692.0A CN201410659692A CN105878201A CN 105878201 A CN105878201 A CN 105878201A CN 201410659692 A CN201410659692 A CN 201410659692A CN 105878201 A CN105878201 A CN 105878201A
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- topiroxostat
- release
- matrix material
- hydrophilic gel
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Abstract
The invention provides a sustained-release preparation pharmaceutical composition which is capable of regulating a blood uric acid level and a preparation method of the pharmaceutical composition. The composition is characterized by consisting of topiroxostat, hydrophilic gel sustained-release matrix material and pharmaceutically acceptable excipients. The composition, within a time period of 24h, is capable of offering an extended and therapeutically effective plasma level and is capable of reducing the occurrence rate of adverse reactions by eliminating a peak-valley phenomenon of drug concentration in plasma. The finished product (the pharmaceutical composition) of the invention is prepared by virtue of wet granulation, dry granulation or direct compression.
Description
Technical field:
The invention belongs to field of pharmaceutical preparations.It is the slow of active component it is more particularly related to a kind of containing Topiroxostat
Release formulation pharmaceutical composition and preparation method thereof.
Background technology:
Use the preparation of high viscosity hydrophilic polymer to extend release or controlled release drug compositions is well known in the art.Once make
Agent contacts with surrounding medium, and medium just causes polymer hydration, Drug controlled release.By producing active component Constant plasma
Level and reduction use frequency, thus improve patient's compliance to dosage regimen, thus control rate of release useful to treatment.
The present invention provides the Topiroxostat being applicable to be administered to once a day human subjects to extend the pharmaceutical composition of release.‘
Topiroxostat chemical name is 5-(2-cyano group-4-pyridine radicals)-3-(4-pyridine radicals)-1, and 2,4-triazoles, molecular formula is C13H8N6,
Molecular weight is 248.24.Topiroxostat is white to light yellow crystalline powder, is slightly soluble in DMF, is slightly soluble in
0.1mol/L hydrochloric acid solution, soluble,very slightly is in methanol and dehydrated alcohol, insoluble or the most insoluble in water.
Topiroxostat is applicable to ventilate and the treatment of high hematuria, for selectivity xanthin oxidoreductase inhibitors (X O R).
Suppress the generation of endogenic uric acid.Pharmacokinetic study results shows, after this product is oral, gastrointestinal absorption is good.Oral
Latter about 0.6～1.5 hour blood drug level peaking.Oral administration biaavailability about 80%, food does not affect the absorption of Topiroxostat
Degree, but make CmaxReduce by 20% and make TmaxPostpone 1.5 hours.The pharmacokinetics of Topiroxostat is at 20mg to 180mg
In the range of linearly, the most twice daily be administered after within 3rd～4, reach stability kinetics.The medicine of 97.5%～98.8% and blood plasma
Protein binding.Topiroxostat plasma elimination half life is 7 ± 1 hours.
At present, Topiroxostat is administered to adult as conventional fast-release tablet.Existing dosage regimen is for take twice daily.Torr
His fast-release tablet of department is in Japan's list marketing, trade nameSpecification is 20,40,60mg.Every day is given for 2 times
The fast-release tablet side effect of medicine is liver function injury and erythema multiforme.Incidence of side effects is proportional to drug blood plasma level.Therefore it is
Raising therapeutic effect, reduces adverse events incidence rate and also improves patient compliance, and the present invention have studied prolongation release once a day
Dosage regimen.
Goal of the invention:
It is an object of the invention to provide the prolongation release of pharmaceutical compositions of levetiracetam, it caused having through picked-up within the extended period
The blood plasma level of platform effect.
Another object of the present invention is the pharmaceutical composition prepared and discharge levetiracetam in a predefined manner.
It is an object of the present invention to provide the levetiracetam for dosage regimen once a day and extend release of pharmaceutical compositions.
Summary of the invention:
The present invention relates to prepare the method that Topiroxostat extends release of pharmaceutical compositions, described compositions comprises Topiroxostat, optionally
Binding agent, hydrophilic gel sustained-release matrix material and conventional pharmaceutical can accept excipient.Described compositions can be further with polymerization
Thing carries out non-functional coatings.
The present invention relates to extend delivery formulations, it is characterised in that in percentage by weight, its comprise 10%～50% hydrophilic solidifying
Glue-type sustained-release matrix material, preferably comprises 20%～40% hydrophilic gel sustained-release matrix material.Coated tablet described further is given
The non-functional coatings of composition total weight 1%～3%.
Described hydrophilic gel sustained-release matrix material includes hypromellose, sodium carboxymethyl cellulose, alginate, card ripple
One or more in nurse, polyoxyethylene, acrylate resins.
Diluent that described pharmaceutically acceptable excipient includes pharmaceutically commonly using, binding agent, lubricant.
Described diluent includes microcrystalline Cellulose, lactose, each kind of starch, sucrose, mannitol, calcium hydrogen phosphate etc. therein
Kind or several mixture.Described diluent may also comprise the material of scalable drug release, such as porogen etc., selected from chlorine
Change sodium, fructose, sorbitol, Polyethylene Glycol, polyvidone, water soluble surfactant active etc..
Described binding agent includes wetting agent water or alcohol and the mixed solution of the arbitrary proportion of the two, and adds or be not added on moistening
Polyvidone in agent, hypromellose, hydroxypropyl cellulose etc..
Described lubricant choosing thief magnesium stearate, Pulvis Talci, micropowder silica gel etc..
According to the present invention, preparing prolongation delivery formulations by compressed tablets, described method has steps of:
1) Topiroxostat, slow-release material, other excipient are mixed.
2) carry out pelletizing or dry granulation by mixture binding agent.
3) dry granule is carried out tabletting.
4) it is coated described tablet with the aqueous dispersion of non-functional coatings polymer.
Accompanying drawing illustrates:
Fig. 1 is left in 4 kinds of different components in display Ch.p. device 1 (turning basket), 100rpm, 0.1mol/L hydrochloric acid solution
The figure of etiracetam drug release characteristics in substrate.
Detailed description of the invention:
Below will by embodiment, the invention will be further described, these describe not is to make present invention further
Limit.It should be understood by those skilled in the art that the equivalent that present invention is made, or be correspondingly improved, still fall within this
Within the protection domain of invention.
Embodiment 1
Preparation method: by Topiroxostat, hydroxypropyl cellulose K4M, lactose mix homogeneously, adds 80% ethanol and prepares soft material,
Granulation, dry, granulate, add magnesium stearate mix homogeneously, tabletting, use gastric solubleness Opadry coating, to obtain final product.
Embodiment 2
Preparation method: by Topiroxostat, hydroxypropyl cellulose K15M, lactose mix homogeneously, adds 80% ethanol and prepares soft material,
Granulation, dry, granulate, add magnesium stearate mix homogeneously, tabletting, use gastric solubleness Opadry coating, to obtain final product.
Embodiment 3
Using direct compression method to prepare embodiment 2, preparation method is: by Topiroxostat, hydroxypropyl cellulose K15M,
Lactose mix homogeneously, adds magnesium stearate mix homogeneously, tabletting, uses gastric solubleness Opadry coating, to obtain final product.
Embodiment 4
Preparation method: by Topiroxostat, polyoxyethylene, lactose, microcrystalline Cellulose, mix homogeneously, adds 80% ethanol and prepares
Soft material, pelletizes, is dried, granulate, adds magnesium stearate mix homogeneously, tabletting, uses gastric solubleness Opadry coating, to obtain final product.
Embodiment 5
Preparation method: by Topiroxostat, polyoxyethylene, lactose, microcrystalline Cellulose, mix homogeneously, adds 80% ethanol and prepares
Soft material, pelletizes, is dried, granulate, adds magnesium stearate mix homogeneously, tabletting, uses gastric solubleness Opadry coating, to obtain final product.
Embodiment 6
Preparation method: by Topiroxostat, hydroxypropyl cellulose K4M, hypromellose K100LV, lactose mix homogeneously, add
Enter 80% ethanol and prepare soft material, pelletize, be dried, granulate, add magnesium stearate mix homogeneously, tabletting, use gastric solubleness Opadry
Coating, to obtain final product.
Embodiment 7
Preparation method: by Topiroxostat, hydroxypropyl cellulose K15M, carbomer, lactose, microcrystalline Cellulose, magnesium stearate
Mix homogeneously, adds 80% ethanol and prepares soft material, pelletizes, is dried, granulate, adds magnesium stearate mix homogeneously, tabletting, makes
With gastric solubleness Opadry coating, to obtain final product.
Take Topiroxostat slow releasing tablet prepared by above-described embodiment, survey with reference to Chinese Pharmacopoeia two annex X D releases of version in 2010
Determine method the first method, use the device of dissolution method (annex X C) the first method, 100 turns per minute of rotating speed, use 0.1mol/L
Hydrochloric acid solution 900ml is release medium, operates in accordance with the law, respectively with 1,2,4,6,8,10,12 hours sampling and measuring.No
Accumulative dissolution rate in vitro (%) data such as following table with the time.
Claims (7)
1. the prolongation release of pharmaceutical compositions of a blood uric acid levels of readjusting prices.It is characterized in that said composition comprises Topiroxostat, hydrophilic gel sustained-release matrix material and pharmaceutically acceptable excipient.
2. compositions as claimed in claim 1, it is characterised in that one or more in hypromellose, sodium carboxymethyl cellulose, alginate, carbomer, polyoxyethylene, acrylate resins of described hydrophilic gel sustained-release matrix material.
3. compositions as claimed in claim 1 or 2, it is characterised in that containing the hydrophilic gel sustained-release matrix material of 10%～50%.
4. compositions as claimed in claim 3, it is characterised in that containing the hydrophilic gel sustained-release matrix material of 20%～40%.
5. compositions as claimed in claim 1, it is characterised in that diluent that described pharmaceutically acceptable excipient includes pharmaceutically commonly using, binding agent, lubricant.
6. compositions as claimed in claim 1, it is characterised in that be prepared by wet granulation, dry granulation or direct compression process.
7. the compositions as described in claim 1～6, it is characterised in that in Ch.p. device 1 (turning basket) 100rpm, there is in 0.1mol/L hydrochloric acid solution following dissolution feature:
。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410659692.0A CN105878201A (en) | 2014-11-18 | 2014-11-18 | Topiroxostat extended-release preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410659692.0A CN105878201A (en) | 2014-11-18 | 2014-11-18 | Topiroxostat extended-release preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105878201A true CN105878201A (en) | 2016-08-24 |
Family
ID=56698478
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410659692.0A Pending CN105878201A (en) | 2014-11-18 | 2014-11-18 | Topiroxostat extended-release preparation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105878201A (en) |
-
2014
- 2014-11-18 CN CN201410659692.0A patent/CN105878201A/en active Pending
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| DD01 | Delivery of document by public notice |
Addressee: SHANDONG RUIHE PHARMACEUTICAL R&D CO., LTD. Document name: Notification of before Expiration of Request of Examination as to Substance |
|
| DD01 | Delivery of document by public notice | ||
| DD01 | Delivery of document by public notice |
Addressee: SHANDONG RUIHE PHARMACEUTICAL R&D CO., LTD. Document name: Notification that Application Deemed to be Withdrawn |
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| DD01 | Delivery of document by public notice | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20160824 |
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| WD01 | Invention patent application deemed withdrawn after publication |