CN103463113A - Celecoxib amorphous condensate and preparation method thereof - Google Patents
Celecoxib amorphous condensate and preparation method thereof Download PDFInfo
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- CN103463113A CN103463113A CN2013103691401A CN201310369140A CN103463113A CN 103463113 A CN103463113 A CN 103463113A CN 2013103691401 A CN2013103691401 A CN 2013103691401A CN 201310369140 A CN201310369140 A CN 201310369140A CN 103463113 A CN103463113 A CN 103463113A
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Abstract
The invention provides a preparation method of a celecoxib amorphous condensate. The celecoxib amorphous condensate disclosed by the invention is powdered solid formed by dissolving celecoxib into a suitable solvent and then solidifying the mixture through a certain method, and at least 90% of the solid exists in an amorphous form through X-ray diffraction detection. The celecoxib amorphous condensate disclosed by the invention has the characteristics that the particle size D90 is less than 5 micrometers, the celecoxib amorphous condensate has an excellent flowing property and bulk density property, the production and the preparation of a composition containing celecoxib medicine are enabled to be relatively easy, the technological requirement of preparation can be satisfied without smashing operation, and the celecoxib amorphous condensate has sound bioavailability, and is suitable for industrialized production.
Description
Technical field
The present invention relates to the pharmaceutical chemistry field, be specifically related to amorphous solidfied material of a kind of celecoxib and preparation method thereof.
Background technology
Celecoxib (4-[5-(4-aminomethyl phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzsulfamide) be pyrazole compound, this compounds, widely as the Drug therapy material, comprises anti-inflammatory agent and antidiabetic.Celecoxib is first cox 2 inhibitor for osteoarthritis and rheumatismal treatment, and its structural formula is
Due to the physico-chemical property of celecoxib uniqueness, as reaching the factor relevant with crystal formation, low solubility comprises caking property, low bulk density and low compressibility, its effective oral Preparation just becomes complicated.
In order to address these problems, a kind of method for preparing the celecoxib preparation by pulverizing has been described in world patent WO 0032189, mention in patent the celecoxib crude drug is crushed to D90<200um, more preferably less than about 100um, further preferably lower than about 75um, more further preferably lower than about 40um, and most preferably lower than about 25um, make according to a conventional method preparation, can reach effective treatment blood concentration within a short period of time.But the celecoxib bulk density is low, and quality is light, easily stick on chamber wall during pulverizing or bond agglomeratingly, be difficult to pulverize, even if use jet mill to pulverize 7 times, D90 still is greater than 10um.Crushing process time consumption and energy consumption, complex operation, cost are higher, cause certain difficulty to the preparation of medicine.
Summary of the invention
Technical problem to be solved by this invention is to provide the amorphous solidfied material of a kind of celecoxib simple to operate, that be easy to get, makes it have good mobility and bulk density, is beneficial to manufacture and the preparation of pharmaceutical composition.
The amorphous solidfied material of celecoxib disclosed by the invention refers to celecoxib dissolving cured through certain method, forms pulverulent solids, and this solid is to exist with amorphous form through X-ray diffraction at least 90%, and its x-ray diffraction pattern is shown in Fig. 1.
Another technical problem to be solved by this invention is the preparation method that discloses the amorphous solidfied material of above-mentioned celecoxib.
The preparation method of the amorphous solidfied material of above-mentioned celecoxib disclosed by the invention comprises the following steps: to add 5-10 times of dissolution with solvents in the celecoxib solid, is cooled to 80 to-30
oc solidifies, and-100
oc-0
oc vacuum lyophilization 24-48 hour, then be warming up to-10
oc-0
othe C drying, obtain, and through X-ray diffraction at least 90%, is to exist with amorphous form.
A technical problem more to be solved by this invention is the application of open celecoxib in pharmaceutical compositions.
The amorphous solidfied material of celecoxib of the present invention can be mixed with various medically acceptable oral formulations with certain proportion with pharmaceutical excipient.Pharmaceutical excipient of the present invention comprises: diluent, disintegrating agent, binding agent and lubricant etc., as: lactose, microcrystalline Cellulose, starch, cross-linking sodium carboxymethyl cellulose, polyvinylpyrrolidone, sodium lauryl sulphate, magnesium stearate etc.
D90 is lower than 5um for the unformed solidfied material particle size distribution of celecoxib disclosed by the invention, there is good mobile performance and bulk density performance, without the process crushing operation, can meet the preparation process requirement, there is good bioavailability, make to become easier containing manufacture and the preparation of the compositions of celecoxib medicine, be applicable to suitability for industrialized production.
The accompanying drawing explanation: Fig. 1 is the amorphous solidfied material X ray diffracting spectrum of celecoxib.
Form is described in further detail content of the present invention more by the following examples, but should not be interpreted as in the above-mentioned subject area of the present invention at this point and only limit to following examples.Do not breaking away under the above-mentioned technology prerequisite of the present invention, the corresponding replacement of making according to ordinary skill knowledge and customary means or the modification of change, include within the scope of the invention
.
Embodiment 1
Celecoxib (5g) adds in the lyophilizing bottle, adds medicinal alcohol (30mL) in 25-30
oc dissolves, and then is cooled to-70
othe C rotation is solidified.Maintain-60 to-50
oc vacuum lyophilization, final stage can be warming up to-10 to 0
oc carries out drying.The amorphous solidfied material of gained celecoxib, wherein approximately 92% exist with unbodied form.
Embodiment 2
Replace ethanol (30 mL) with isopropyl alcohol (40mL), other are identical with embodiment 1.The amorphous solidfied material of gained celecoxib, wherein approximately 90% exist with unbodied form.
Embodiment 3
Celecoxib (5g) adds in the lyophilizing bottle, adds ethyl acetate (30mL) in 20-25
oc dissolves, and then is cooled to-20
othe C rotation is solidified.Maintain-10 to-0
oc vacuum lyophilization, final stage can be warming up to 0-5
oc carries out drying.The amorphous solidfied material of gained celecoxib, wherein approximately 95% exist with unbodied form.
Embodiment 4
With several pharmaceutical excipients, the amorphous solidfied material of celecoxib is made as follows to the celecoxib capsule of 100mg
| The supplementary material title | Supplementary material consumption (a g/1000 preparation unit) |
| Celecoxib | 100 |
| Lactose | 45 |
| Cross-linking sodium carboxymethyl cellulose | 2.8 |
| Polyvinylpyrrolidone | 6.9 |
| Sodium lauryl sulphate | 7.2 |
| Magnesium stearate | 3.0 |
Capsule manufacture method containing the amorphous solidfied material of celecoxib is that the amorphous solidfied material of celecoxib is mixed homogeneously with lactose, polyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, do the wetting agent wet granulation with the aqueous solution of sodium lauryl sulphate, after dry, granulate with encapsulated after magnesium stearate is mixed homogeneously and get final product.
Embodiment 5
With several pharmaceutical excipients, the amorphous solidfied material of celecoxib is made as follows to the celecoxib capsule of 200mg
| The supplementary material title | Supplementary material consumption (a g/1000 preparation unit) |
| Celecoxib | 200 |
| Lactose | 50 |
| Cross-linking sodium carboxymethyl cellulose | 2.8 |
| Polyvinylpyrrolidone | 6.9 |
| Sodium lauryl sulphate | 7.2 |
| Magnesium stearate | 3.0 |
Manufacture method is identical with embodiment 4.
Claims (4)
1. the unformed solidfied material of celecoxib, is characterized in that it is to exist with amorphous form that this solid detects at least 90% through X-ray diffraction.
2. the preparation method of the unformed solidfied material of celecoxib according to claim 1, is characterized in that the method comprises the following steps:
Add 5-10 times of dissolution with solvents in the celecoxib solid, be cooled to 80 to-30
oc solidifies, and-100
oc-0
oc vacuum lyophilization 24-48 hour, then be warming up to-10
oc-0
othe C drying, obtain.
3. according to the Preparation Method of the amorphous solidfied material of the described celecoxib of claim 2, its solvent for use includes but not limited to methanol, ethanol, isopropyl alcohol, n-butyl alcohol, ethyl acetate, dichloromethane, acetone, acetonitrile.
4. the application of the amorphous solidfied material of celecoxib according to claim 1 in pharmaceutical compositions.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013103691401A CN103463113A (en) | 2013-08-22 | 2013-08-22 | Celecoxib amorphous condensate and preparation method thereof |
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|---|---|---|---|
| CN2013103691401A CN103463113A (en) | 2013-08-22 | 2013-08-22 | Celecoxib amorphous condensate and preparation method thereof |
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| CN103463113A true CN103463113A (en) | 2013-12-25 |
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| CN2013103691401A Pending CN103463113A (en) | 2013-08-22 | 2013-08-22 | Celecoxib amorphous condensate and preparation method thereof |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120070469A1 (en) * | 2008-02-11 | 2012-03-22 | Technion Research And Development Foundation Ltd. | Beta-casein assemblies for mucosal delivery of therapeutic bioactive agents |
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2013
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120070469A1 (en) * | 2008-02-11 | 2012-03-22 | Technion Research And Development Foundation Ltd. | Beta-casein assemblies for mucosal delivery of therapeutic bioactive agents |
Non-Patent Citations (1)
| Title |
|---|
| 卡斯坦森（CARSTENSEN, J.T.）: "《现代药用粉体微粒学》", 31 October 2004 * |
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Application publication date: 20131225 |