CN103417507B - Budesonide pharmaceutical composition - Google Patents
Budesonide pharmaceutical composition Download PDFInfo
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- CN103417507B CN103417507B CN201310370132.9A CN201310370132A CN103417507B CN 103417507 B CN103417507 B CN 103417507B CN 201310370132 A CN201310370132 A CN 201310370132A CN 103417507 B CN103417507 B CN 103417507B
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- alcohol
- budesonide
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- RCMAZTKFCJZDGC-FNKKQHHVSA-N CCC[C@H](O[C@@H]1CC([C@H](CC2)[C@H]3[C@@](C)(C=CC4)C2=C4C=O)[C@@]2(C)C[C@@H]3O)OC12C(CO)=O Chemical compound CCC[C@H](O[C@@H]1CC([C@H](CC2)[C@H]3[C@@](C)(C=CC4)C2=C4C=O)[C@@]2(C)C[C@@H]3O)OC12C(CO)=O RCMAZTKFCJZDGC-FNKKQHHVSA-N 0.000 description 1
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Abstract
The invention belongs to field of pharmaceutical preparations, relate to the Budesonide pharmaceutical composition that a kind of release is stable, it is characterized in that comprising (a) C
21-C
30fatty alcohol or the lipotropy substrate of ester that formed of fatty acid or fatty acid and alcohol; B () can form the hydrophilic matrix of hydrophilic gel; (c) amphiphilic compound; The coating of (d) outside coating one deck acid resisting material.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, relate to the Budesonide pharmaceutical composition that a kind of release is stable, it is characterized in that comprising
(a) C
21-C
30fatty alcohol or the lipotropy substrate of ester that formed of fatty acid or fatty acid and alcohol;
B () can form the hydrophilic matrix of hydrophilic gel;
(c) amphiphilic compound;
The coating of (d) outside coating one deck acid resisting material.
Background of invention
Budesonide is a kind of glucocorticoid with efficient local anti-inflammatory effect.It can strengthen the stability of endotheliocyte, smooth muscle cell and lysosome membrane, Immunosuppression reaction and the synthesis of reduction antibody, thus the release of the activity media such as histamine is reduced and active reduction, and can alleviate antigen-antibody in conjunction with time the enzymatic processes that excites, suppress the synthesis of bronchoconstriction material and release and alleviate the contractile response of smooth muscle.Meanwhile, budesonide can also be used for the treatment of cloning grace disease and inflamed colon inflammation.The structural formula of budesonide is as follows:
Chinese patent CN1355693 relates to a kind of pharmaceutical composition of Co ntrolled release, has wherein related to the preparation of budesonide Co ntrolled release sheet, but it adopts lipotropy substrate to be stearic acid and Brazil wax.
US Patent No. 2006134208 discloses the pharmaceutical composition of budesonide, also relates to the preparation method of budesonide simultaneously, and its lipotropy substrate adopted remains stearic acid or stearic acid and Brazil wax equally.
Medicine secondary more than a day is all passed through controlled-release material by general sustained-release preparation, make medicine once a day, therefore, dosage is often high than ordinary preparation, if drug release rate instability can cause drug release rate to increase or dash forward and release, therefore, the stability of the release of sustained-release preparation is the prerequisite ensureing Drug safety.The selection of slow-release material may play an important role to the stability of drug release.
The lipophilic materials that Chinese patent CN1355693 and US Patent No. 2006134208 disclose the compositions of budesonide is all the lipotropy substrate of below employing 20 carbon atoms is stearic acid and Brazil wax.The inventor of this patent is by research, and compositions prepared by the stearic acid below discovery employing 20 carbon atoms and Brazil wax is placed 6 months under accelerated test (temperature: 40 DEG C, relative humidity 75%) condition, and release has the trend of increase.And adopt the fatty acid of more than 20 carbon, fatty alcohol or fatty glyceride, under acceleration conditions, release is basicly stable, achieves beyond thought effect, thus completes the present invention.
Summary of the invention
The invention belongs to field of pharmaceutical preparations, relate to the pharmaceutical composition of the stable budesonide Co ntrolled release of a kind of release, it is characterized in that comprising
(a) C
21-C
30fatty alcohol or the lipotropy substrate of ester that formed of fatty acid or fatty acid and alcohol;
B () can form the hydrophilic matrix of hydrophilic gel;
(c) amphiphilic compound;
The coating of (d) outside coating one deck acid resisting material.
Pharmaceutical composition of the present invention, wherein C
21-C
30fatty alcohol is behenyl alcohol.
Pharmaceutical composition of the present invention, wherein C
21-C
30fatty alcohol is Cera Flava.
Pharmaceutical composition of the present invention, wherein C
21-C
30fatty acid is behenic acid.
Pharmaceutical composition of the present invention, wherein C
21-C
30the ester that fatty acid and alcohol are formed is Glyceryl Behenate.
Pharmaceutical composition of the present invention, wherein C
21-C
30the ester that fatty acid and alcohol are formed is Glyceryl Behenate is behenic acid monoglyceride, the sweet ester of behenic acid two or behenic acid Triglycerides.Or their mixture.
C of the present invention
21-C
30fatty alcohol is the fatty alcohol with 20-30 carbon atom, and this is that the general researcher of this area is to understand.
Equally, C of the present invention
21-C
30fatty acid is the fatty acid with 20-30 carbon atom, C of the present invention
21-C
30the ester that fatty acid and alcohol are formed, wherein alcohol comprises monohydric alcohol, dihydroxylic alcohols, trihydroxylic alcohol and polyhydric alcohol, wherein preferred trihydroxylic alcohol, further preferably glycerine.
Pharmaceutical composition of the present invention, wherein hydrophilic matrix is selected from one or more of following compounds: the polymer of acrylic acid or methacrylic acid or copolymer, alkyl vinyl polymers, hydroxy alkyl cellulose, carboxyalkyl cellulose, poly-polyvinylpyrrolidone, dextrin, pectin starch and derivant, alginic acid, carbomer.Wherein said hydroxy alkyl cellulose is hypromellose or hydroxypropyl cellulose, and carboxyalkyl class is spread out as sodium carboxymethyl cellulose, starch based derivant are carboxymethyl starch sodium.Preferred hypromellose or hydroxypropyl cellulose.
Amphiphilic compound of the present invention is selected from I type, the polar lipid of II type, nonionic surfactant, glycol ether, anion surfactant, or their mixture.
Described I type, the polar lipid of II type comprise phospholipid, phosphatidylcholine, PHOSPHATIDYL ETHANOLAMINE, neural choline.
Nonionic surfactant is selected from Polyethylene Glycol sorbate, polyethylene glycol fatty ester, and anion surfactant selects alkylsulfonate or alkyl sulfate
The coating of compositions of the present invention outside coating one deck acid resisting material.
Acidproof material of the present invention is acroleic acid polymerization or copolymer or cellulose derivative.
Acroleic acid polymerization of the present invention is methacrylic acid and methylmethacrylate copolymer.
Methacrylic acid of the present invention and methyl methacrylate polymerization or copolymer are the polyacrylic resin II described in " Chinese Pharmacopoeia ", polyacrylic resin III or their mixture.
Methacrylic acid of the present invention and methyl methacrylate polymerization or copolymer are the polyacrylic resin A described in " American Pharmacopeia ", polyacrylic resin B or their mixture.
Polyacrylic resin of the present invention is especially strange L100 or especially strange S100, or their mixture.
Embodiment
Be below specific embodiments of the invention, but do not represent that the present invention is only limitted to following examples.
Embodiment 1
| Label | |
| Budesonide | 90g |
| Behenic acid | 100g |
| Soybean phospholipid | 100g |
| Hypromellose | 600g |
| Microcrystalline Cellulose | 1560g |
| Lactose | 500g |
| Silicon dioxide | 20g |
| Magnesium stearate | 30g |
| Every 10000 |
Preparation technology: prepared by referenced patent US2006134208 embodiment 1-3.By budesonide 90g, soybean phospholipid 100g, behenic acid 100g mix homogeneously; add 130g microcrystalline Cellulose and 300g hypromellose mix homogeneously; add appropriate distilled water soft material, rotating pelletizer 40 eye mesh screens are granulated, and adopt fluid bed drying to be less than 3% to moisture.Add remaining microcrystalline Cellulose, lactose 500g, hypromellose 300g, silicon dioxide 20g mix homogeneously, then add magnesium stearate 30g, mix homogeneously, tabletting, heavy about the 300mg of sheet.
Embodiment 2
| Label | |
| Budesonide | 90g |
| Glyceryl Behenate | 100g |
| Soybean phospholipid | 100g |
| Hydroxypropyl cellulose | 600g |
| Microcrystalline Cellulose | 1560g |
| Lactose | 500g |
| Silicon dioxide | 20g |
| Magnesium stearate | 30g |
| Every 10000 |
Preparation technology: prepared by referenced patent US2006134208 embodiment 1-3.By budesonide 90g, soybean phospholipid 100g, mountain Yu glyceride 100g mix homogeneously; add 130g microcrystalline Cellulose and 300g hydroxypropyl cellulose mix homogeneously; add appropriate distilled water soft material, rotating pelletizer 40 eye mesh screens are granulated, and adopt fluid bed drying to be less than 3% to moisture.Add remaining microcrystalline Cellulose, lactose 500g, hydroxypropyl cellulose 300g, silicon dioxide 20g mix homogeneously, then add magnesium stearate 30g, mix homogeneously, tabletting, heavy about the 300mg of sheet.
| Coating | |
| Eudragit L 100 | 140g |
| Eudragit S 100 | 120g |
| Pulvis Talci | 79g |
| Titanium dioxide | 45g |
| Triethyl citrate | 16g |
| Ethanol | In right amount |
Adopt high-efficiency coating machine or other packaging technique, above coating material wiring solution-forming is carried out coating, and coating rear panel is heavily 315mg-340mg.
Embodiment 3
| Label | |
| Budesonide | 90g |
| Glyceryl Behenate | 100g |
| Soybean phospholipid | 100g |
| Hydroxypropyl cellulose | 600g |
| Microcrystalline Cellulose | 1560g |
| Lactose | 500g |
| Silicon dioxide | 20g |
| Magnesium stearate | 30g |
| Every 10000 |
Preparation technology: prepared by referenced patent US2006134208 embodiment 1-3.By budesonide 90g, soybean phospholipid 100g, mountain Yu glyceride 100g mix homogeneously; add 130g microcrystalline Cellulose and 300g hydroxypropyl cellulose mix homogeneously; add appropriate distilled water soft material, rotating pelletizer 40 eye mesh screens are granulated, and adopt fluid bed drying to be less than 3% to moisture.Add remaining microcrystalline Cellulose, lactose 500g, hydroxypropyl cellulose 300g, silicon dioxide 20g mix homogeneously, then add magnesium stearate 30g, mix homogeneously, tabletting, heavy about the 200mg of sheet.
Adopt high-efficiency coating machine or other packaging technique, the coating material wiring solution-forming with embodiment 2 carries out coating, and coating rear panel is heavily 215mg-230mg.
Embodiment 4
| Label | |
| Budesonide | 90g |
| Behenyl alcohol | 100g |
| Tween 80 | 20g |
| Sodium carboxymethyl cellulose | 400g |
| Microcrystalline Cellulose | 1560g |
| Lactose | 780g |
| Silicon dioxide | 20g |
| Magnesium stearate | 30g |
| 10000 |
Preparation technology: prepared by referenced patent US2006134208 embodiment 1-3.By budesonide 90g, tween 80 20g, behenyl alcohol 100g mix homogeneously; add 130g microcrystalline Cellulose and 200g sodium carboxymethyl cellulose mix homogeneously; add appropriate distilled water soft material, rotating pelletizer 40 eye mesh screens are granulated, and adopt fluid bed drying to be less than 3% to moisture.Add remaining microcrystalline Cellulose, lactose 780g, sodium carboxymethyl cellulose 200g, silicon dioxide 20g mix homogeneously, then add magnesium stearate 30g, mix homogeneously, tabletting, heavy about the 300mg of sheet.
Adopt high-efficiency coating machine or other packaging technique, with the coating material of embodiment 2, wiring solution-forming carries out coating, and coating rear panel is heavily 315mg-330mg.
Embodiment 5
| Label | |
| Budesonide | 100g |
| Cera Flava | 40g |
| Diethylene glycol monomethyl ether | 10g |
| Hypromellose | 300g |
| Carbomer | 100g |
| Microcrystalline Cellulose | 590g |
| Lactose | 80g |
| Silicon dioxide | 20g |
| Magnesium stearate | 10g |
| 5000 |
Preparation technology: prepare with reference to patent US2006134208 embodiment 4.Change Brazil wax and stearic acid into Cera Flava, heavy about the 250mg of sheet.
| Coating | |
| Eudragit L 100 | 70g |
| Eudragit S 100 | 60g |
| Pulvis Talci | 40g |
| Titanium dioxide | 20g |
| Triethyl citrate | 8g |
| Ethanol | In right amount |
Adopt high-efficiency coating machine or other packaging technique, above coating material wiring solution-forming is carried out coating, and coating rear panel is heavily 265mg-280mg.
Comparative example
Comparative example 1-4 of the present invention is prepared with reference to US2006134208 embodiment 1-4.
Embodiment of the present invention 1-5 and comparative example 1-4 is carried out study on the stability at 40 DEG C/RH75%, and carries out the mensuration of release.Drug release determination method:
Slurry processes, rotating speed: 75rpm,
| Medium | Sample time | Volume |
| PH1.0 hydrochloric acid solution | 2 hours | 1000ml |
| PH6.4 phosphate solution | 1 hour | 1000ml |
| PH7.2 phosphate solution | 2,4,8 hours | 1000ml |
Embodiment 1, owing to not adopting enteric coating, does not carry out the tolerance test of pH1.0 and pH6.4.Adopt ultraviolet spectrophotometer 242nm to measure absorption value, calculate dissolution, result is as shown in the table.
Show from above embodiment dissolution determination result, of the present inventionly be combined in acceleration (40 DEG C, RH75%) in the process tested, in the phosphate buffer of pH7.2,2 hours, 4 hours and 8 hours at 0 month, March and June release stablize basicly stable, without the trend increased, the release had in the phosphate solution buffer of accelerated test process at pH7.2 with comparative example has the trend of increase.Therefore, there is better quality stability, better can ensure safety.Achieve beyond thought result, thus complete the present invention.
Although describe spirit of the present invention with embodiment above, only for illustration of object instead of restriction the present invention, the change of embodiment for the general technical staff in this area, after reading technology path of the present invention or become apparent after embodiment.Therefore, without departing from the scope and spirit of the present invention, can adjust embodiments of the invention and change, these adjustment and change all belong to equivalent replacement of the present invention.
Claims (8)
1. what release was stable contains a budesonide controlled release pharmaceutical compositions, it is characterized in that comprising
The lipotropy substrate of a ester that () behenyl alcohol or behenic acid or behenic acid and alcohol are formed;
B () can form the hydrophilic matrix of hydrophilic gel;
(c) amphiphilic compound;
The coating of (d) outside coating one deck acid resisting material.
2. pharmaceutical composition as claimed in claim 1, the ester that behenic acid and alcohol are formed is Glyceryl Behenate.
3. pharmaceutical composition as claimed in claim 2, Glyceryl Behenate is behenic acid monoglyceride.
4. pharmaceutical composition as claimed in claim 1, wherein hydrophilic matrix is selected from one or more of following compounds: acrylate copolymer, methacrylate polymer, acrylic arid methacrylic acid copolymer, alkyl vinyl polymers, hydroxy alkyl cellulose, carboxyalkyl cellulose, polyvinylpyrrolidone, dextrin, alginic acid, carbomer.
5. pharmaceutical composition as claimed in claim 4, wherein said hydroxy alkyl cellulose is hypromellose or hydroxypropyl cellulose, and carboxyalkyl cellulose is sodium carboxymethyl cellulose.
6. pharmaceutical composition as claimed in claim 1, described acid resisting material is acrylate copolymer or methacrylate polymer or acrylic arid methacrylic acid copolymer.
7. pharmaceutical composition as claimed in claim 1, described acid resisting material is the copolymer of methacrylic acid and methyl methacrylate.
8. compositions as claimed in claim 1, amphiphilic compound is selected from I type, the polar lipid of II type, nonionic surfactant, glycol ether, anion surfactant or their mixture.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310370132.9A CN103417507B (en) | 2013-08-23 | 2013-08-23 | Budesonide pharmaceutical composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310370132.9A CN103417507B (en) | 2013-08-23 | 2013-08-23 | Budesonide pharmaceutical composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103417507A CN103417507A (en) | 2013-12-04 |
| CN103417507B true CN103417507B (en) | 2015-12-02 |
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ID=49643253
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310370132.9A Active CN103417507B (en) | 2013-08-23 | 2013-08-23 | Budesonide pharmaceutical composition |
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| Country | Link |
|---|---|
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101961320A (en) * | 2010-09-29 | 2011-02-02 | 山东欣博药物研究有限公司 | Budesonide nano crystallizing preparation and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MY118354A (en) * | 1995-05-01 | 2004-10-30 | Scarista Ltd | 1,3-propane diol derivatives as bioactive compounds |
| ATE251449T1 (en) * | 1999-06-14 | 2003-10-15 | Cosmo Spa | FLAVOR-MASKED ORAL PHARMACEUTICAL COMPOSITIONS WITH CONTROLLED DELIVERY |
| GB0525254D0 (en) * | 2005-12-12 | 2006-01-18 | Jagotec Ag | Powder compositions for inhalation |
| KR20140031227A (en) * | 2011-03-24 | 2014-03-12 | 레오 파마 에이/에스 | A composition comprising lipid nanoparticles and a corticosteroid or vitamin d derivative |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101961320A (en) * | 2010-09-29 | 2011-02-02 | 山东欣博药物研究有限公司 | Budesonide nano crystallizing preparation and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| REVERSIBLE FATTY ACID CONJUGATION OF BUDESONIDE Novel Mechanism for Prolonged Retention of Topically Applied Steroid in Airway Tissue;A. MILLER-LARSSON.et al;《DRUG METABOLISM & DISPOSITION》;19981231;第26卷(第7期);第623-630页 * |
| The Role of Intracellular Esterification in Budesonide Once-Daily Dosing and Airway Selectivity;Ralph Brattsand,et al;《CLINICAL THERAPECTICS》;20031231;第25卷;C28-C41 * |
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|---|---|
| CN103417507A (en) | 2013-12-04 |
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Effective date of registration: 20220712 Address after: 401329 No. 1-1, building 2, No. 28, Gaoxin Avenue, Jinfeng Town, Jiulongpo District, Chongqing Patentee after: Chongqing yaoguiren Biomedical Technology Co.,Ltd. Address before: 402260 room 11-7, building D, Xingyun Manting, Dingshan street, Jiangjin District, Chongqing Patentee before: Wang Xianzhu |