CN103655501A - Nano ibuprofen dry powder, tablets and preparation method thereof - Google Patents
Nano ibuprofen dry powder, tablets and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a preparation method of nano ibuprofen dry powder and tablets thereof. The preparation method comprises the following steps of: firstly dissolving ibuprofen in an organic solvent, then dissolving multiple pharmaceutical adjuvants into water, carrying out spraying and drying on slurry formed by mixing the two types of solution under proper conditions at room temperature, successfully preparing nano ibuprofen powder with the water-soluble particle diameter being 20-200nm, and mixing and pressing the dry powder and proper adjuvants into the tablets. The tablets can be dispersed in water quickly, and the dissolving-out rate is obviously higher than that of a tablet mixed and pressed by crude drugs and same adjuvants. All the adjuvants in the invention conform to pharmacopeia standards, is biodegradable and is good in biocompatibility. The preparation method is simple in process, safe in operation, low in cost and easy in realizing industrial production of nano ibuprofen drugs.
Description
Technical field
The present invention relates to the preparation method of a kind of nanometer ibuprofen dry powder and dry powder tablet thereof
Technical background
Ibuprofen (Ibuprofen), chemical name 2-(4-isobutyl phenenyl) propanoic acid, its structural formula is as figure below
Ibuprofen is a kind of efficient nonsteroidal anti-inflammatory drug, there is stronger antipyretic, analgesia, antiinflammation, can be used for clinically inflammation and ailing treatment, ibuprofen has the preparation of 7 kinds of dosage forms at present using, and is respectively capsule, granule, tablet, suspension, suppository, ointment and syrup.It is oral adopting clinically maximum modes.But ibuprofen is poorly water soluble drugs, common Genpril drug bioavailability is low.
For poorly water soluble drugs, process in leaching is the key factor of its bioavailability of restriction.According to Ostwald Freundrich equation, drug-eluting speed and size of pharmaceutical particles are inversely proportional to, and reduce drug particles particle diameter and can increase substantially its dissolution rate, thereby significantly improve the bioavailability of medicine, reduce individual variation, reduce toxic and side effects.
For improving its dissolubility and improving its bioavailability, research mainly concentrates on novel form and new preparation developing, as make cyclodextrin clathrate (patent CN102258790A), spray (patent CN102204882A), but all there is the problem that preparation is complicated, production cost is high, drug particles is larger in these methods.The present invention is prepared into nanometer dry powder by ibuprofen, has not only improved dissolubility, has improved bioavailability, and greatly improved the stability of medicine.
Summary of the invention
The object of the invention is, overcomes the deficiencies in the prior art, for solving ibuprofen poorly water-soluble, the problem that oral absorption and bioavailability are low, provides a kind of degree of scatter good, good absorbing, the nanometer ibuprofen spray powder of good stability is prepared into dry powder the method for tablet simultaneously.By ibuprofen solution and adjuvant aqueous solution are made to nanosuspension, nanosuspension belongs to the submicron system of high degree of dispersion, and stability is not as good as dry powder.Under liquid condition, store, system is easily become sour and is gone mouldy, and nanoparticle is easily assembled, adhesion.For solving the problem of nanoemulsions stability, the present invention adopts spray-dired technology, and nanosuspension liquid is prepared into spray powder.Again it is mixed with into tablet with adjuvant.
First technical problem of the present invention is to provide a kind of ibuprofen nanometer spray powder, it is characterized in that can redispersion in water, particle diameter 20～100nm.Its nanometer spray powder is a kind of composite granule of take the nano-grade ibuprofen granule that hydrophilicity condiment is carrier, and the quality percentage composition of ibuprofen is 10-50%, and the quality percentage composition of hydrophilicity condiment is 50-90%; Hydrophilicity condiment is two or more in following material: polyvinylpyrrolidone, hydroxypropyl emthylcellulose, poloxamer, Polyethylene Glycol, polyvinyl alcohol, methylcellulose, lecithin, oleic acid, enuatrol, lauric acid and cholesterol.
Second technical problem of the present invention is to provide a kind of preparation method of ibuprofen nanometer dry powder, comprises the following steps:
A: ibuprofen crude drug is dissolved in and can be total in molten organic solvent with water, be configured to the raw material medicine solution that concentration is 1-3g/100ml; Hydrophilicity condiment is water-soluble, be configured to the aqueous solution that contains hydrophilicity condiment; Ibuprofen solution is 1/5～1/20 with the volume ratio that contains the aqueous solution of adjuvant;
B: at 20-30 ℃, under stirring condition, the adjuvant aqueous solution by the raw material medicine solution of A step and B step, obtains ibuprofen nanosuspension;
C: the ibuprofen nanosuspension spraying of B step is dry, obtain ibuprofen nano-powder.
The 3rd technical problem of the present invention is to provide a kind of ibuprofen nanometer dry powder and prepares method prepared by tablet.The method comprises the following steps:
A: ibuprofen crude drug is dissolved in and can be total in molten organic solvent with water, be configured to the raw material medicine solution that concentration is 1-3g/100ml; Hydrophilicity condiment is water-soluble, be configured to the aqueous solution that contains hydrophilicity condiment; Ibuprofen solution is 1/5～1/20 with the volume ratio that contains the aqueous solution of adjuvant;
B: at 20-30 ℃, under stirring condition, the adjuvant aqueous solution by the raw material medicine solution of A step and B step, obtains ibuprofen nanosuspension;
C: the ibuprofen nanosuspension spraying of B step is dry, obtain ibuprofen nano-powder;
D: take one or more in ibuprofen nano-powder that C step obtains and starch, micropowder silica gel, CMS-Na and mix, add starch slurry and make soft material, crossing 16 mesh sieves granulates, take out, be cooled to room temperature, cross 20 mesh sieve granulate, granule is dry in 60-65 ℃, add Pulvis Talci, magnesium stearate, in micropowder silica gel, one or more mix rear tabletting.It is qualified to detect, and obtains nanometer Genpril.
The 4th technical problem of the present invention is to provide the application of a kind of ibuprofen nanometer dry powder in other solid preparations.Nanometer spray powder provided by the invention, except being prepared into tablet, also can directly being filled and be prepared into capsule according to clinical needs; Add adjuvant to be processed into granule, pill.Based on nanometer ibuprofen, have larger surface area, the dissolubility after oral administration in gastrointestinal tract increases greatly, can significantly improve the absorption of medicine, increases bioavailability.
The advantage that the present invention has is:
Adopt spray drying technology to prepare nanometer dry powder, greatly improved the dissolubility of medicine, can be good at redispersion in water.
The ultra-small volume of nanometer ibuprofen and huge specific surface, Nano medication has higher drug loading, easily penetrates blood vessel and does not cause vascular endothelial injury; protection medicine is avoided enzymatic degradation; medicine in vivo local aggregate concentration is high, thereby can improve curative effect, can also reduce poisonous side effect of medicine simultaneously.
Ibuprofen nanometer dry powder tablet is had to good storage stability, and there is certain sustained release performance.
Tablet prepared by this method is high compared with conventional tablet dissolution, and bioavailability is high.And invented technology is simple, repeatability is strong, possesses industrialization prospect of production.
Accompanying drawing explanation
Fig. 1 is the scanning electron microscope (SEM) photograph of ibuprofen crude drug
Fig. 2 is the scanning electron microscope (SEM) photograph of ibuprofen nano powder redispersion in water
Fig. 3 is the stripping curve figure of ibuprofen crude drug and ibuprofen nano-powder of the present invention and tablet
The specific embodiment
Below in conjunction with accompanying drawing, the present invention is described in further detail, and following examples are explanation of the invention, and the present invention is not limited to following examples.
Embodiment 1:
A: take ibuprofen 10g and be dissolved in 50ml ethanol;
B: take 10g polyvinylpyrrolidone, 5g Polyethylene Glycol, 100g hydroxypropyl emthylcellulose, 3g poloxamer, 3g oleic acid and 3g enuatrol, be dissolved in 500ml distilled water;
C: the alcoholic solution of ibuprofen is slowly added dropwise in above-mentioned 500ml mixed solution; Under room temperature, high-speed stirred reaction obtains ibuprofen nanosuspension;
D: the drying dry powder that obtains of spray-dried instrument spray, inlet porting temperature is 120 ℃, and outlet temperature is 80 ℃, and feed rate is 5ml/min, and compressed air pressure is 0.6Mpa;
E: add appropriate amount of auxiliary materials and be pressed into tablet in dry powder.Getting ibuprofen nano-powder 1g and starch 0.6g, micropowder silica gel 0.18g, the CMS-Na0.1g that D step obtains mixes, add 15% starch slurry 1.2g and make soft material, cross 16 mesh sieves and granulate, take out, be cooled to room temperature, cross 20 mesh sieve granulate, granule in 60-65 ℃ dry, add magnesium stearate 0.08g, mix rear tabletting, it is qualified to detect, and obtains nanometer Genpril.
Embodiment 2:
A: take ibuprofen 10g and be dissolved in 50ml ethanol;
B: take 10g polyvinylpyrrolidone, 10g Polyethylene Glycol, 90g hydroxypropyl emthylcellulose, 5g poloxamer and 5g enuatrol, be dissolved in 500ml distilled water;
C: the alcoholic solution of ibuprofen is slowly added dropwise in above-mentioned 500ml mixed solution; Under room temperature, high-speed stirred reaction obtains ibuprofen nanosuspension;
D: the drying dry powder that obtains of spray-dried instrument spray, inlet porting temperature is 140 ℃, and outlet temperature is 80 ℃, and feed rate is 10ml/min, and compressed air pressure is 0.4Mpa;
E: add appropriate amount of auxiliary materials and be pressed into tablet in dry powder.Getting ibuprofen nano-powder 1g and starch 0.6g, micropowder silica gel 0.18g, the CMS-Na0.1g that D step obtains mixes, add 15% starch slurry 1.2g and make soft material, cross 16 mesh sieves and granulate, take out, be cooled to room temperature, cross 20 mesh sieve granulate, granule in 60-65 ℃ dry, add magnesium stearate 0.08g, mix rear tabletting, it is qualified to detect, and obtains nanometer Genpril.
Embodiment 3:
A: take ibuprofen 10g and be dissolved in 50ml ethanol;
B: take 20g polyvinylpyrrolidone, 10g Polyethylene Glycol, 80g hydroxypropyl emthylcellulose, 5g poloxamer, 3g lecithin and 3g enuatrol, be dissolved in 500ml distilled water;
C: the alcoholic solution of ibuprofen is slowly added dropwise in above-mentioned 500ml mixed solution; Under room temperature, high-speed stirred reaction obtains ibuprofen nanosuspension;
D: the drying dry powder that obtains of spray-dried instrument spray, inlet porting temperature is 120 ℃, and outlet temperature is 80 ℃, and feed rate is 10ml/min, and compressed air pressure is 0.6Mpa.
E: add appropriate amount of auxiliary materials and be pressed into tablet in dry powder.Getting ibuprofen nano-powder 1g and starch 0.6g, micropowder silica gel 0.18g, the CMS-Na0.1g that D step obtains mixes, add 15% starch slurry 1.2g and make soft material, cross 16 mesh sieves and granulate, take out, be cooled to room temperature, cross 20 mesh sieve granulate, granule in 60-65 ℃ dry, add magnesium stearate 0.08g, mix rear tabletting, it is qualified to detect, and obtains nanometer Genpril.
Embodiment 4:
A: take ibuprofen 10g and be dissolved in 50ml ethanol;
B: take 20g polyvinylpyrrolidone, 80g hydroxypropyl emthylcellulose, 5g poloxamer, 3g cholesterol and 3g enuatrol, be dissolved in 500ml distilled water;
C: the alcoholic solution of ibuprofen is slowly added dropwise in above-mentioned 500ml mixed solution; Under room temperature, high-speed stirred reaction obtains ibuprofen nanosuspension;
D: the drying dry powder that obtains of spray-dried instrument spray, inlet porting temperature is 120 ℃, and outlet temperature is 80 ℃, and feed rate is 5ml/min, and compressed air pressure is 0.4Mpa.
E: add appropriate amount of auxiliary materials and be pressed into tablet in dry powder.Getting ibuprofen nano-powder 1g and starch 0.6g, micropowder silica gel 0.18g, the CMS-Na0.1g that D step obtains mixes, add 15% starch slurry 1.2g and make soft material, cross 16 mesh sieves and granulate, take out, be cooled to room temperature, cross 20 mesh sieve granulate, granule in 60-65 ℃ dry, add Pulvis Talci 0.08g, mix rear tabletting, it is qualified to detect, and obtains nanometer Genpril.
Embodiment 5:
A: take ibuprofen 10g and be dissolved in 50ml ethanol;
B: take 2g polyvinylpyrrolidone, 8g hydroxypropyl emthylcellulose, 5g poloxamer, 3g cholesterol, 3g enuatrol, 0.5g polyvinyl alcohol and 1g Polyethylene Glycol, be dissolved in 500ml distilled water;
C: the alcoholic solution of ibuprofen is slowly added dropwise in above-mentioned 500ml mixed solution; Under room temperature, high-speed stirred reaction obtains ibuprofen nanosuspension;
D: the drying dry powder that obtains of spray-dried instrument spray, inlet porting temperature is 120 ℃, and outlet temperature is 80 ℃, and feed rate is 5ml/min, and compressed air pressure is 0.6Mpa.
E: add appropriate amount of auxiliary materials and be pressed into tablet in dry powder.Getting ibuprofen nano-powder 1g and starch 0.6g, micropowder silica gel 0.18g, the CMS-Na0.1g that D step obtains mixes, add 15% starch slurry 1.2g and make soft material, cross 16 mesh sieves and granulate, take out, be cooled to room temperature, cross 20 mesh sieve granulate, granule in 60-65 ℃ dry, add Pulvis Talci 0.08g, mix rear tabletting, it is qualified to detect, and obtains nanometer Genpril.
Claims (9)
1. an ibuprofen nano-powder, for a kind of composite granule of take the nano-grade ibuprofen granule that hydrophilicity condiment is carrier, is characterized in that, the quality percentage composition of ibuprofen is 10-50%, and the quality percentage composition of hydrophilicity condiment is 50-90%; The particle diameter of the amorphous ibuprofen granule that ibuprofen nano-powder obtains after redispersion in water is 20-200nm.
2. a nanometer Genpril, its composition comprises ibuprofen nano-powder and additive of tablet, wherein the mass ratio of nano-powder and additive of tablet is 1: 0-5.
3. ibuprofen nano-powder as claimed in claim 1, is characterized in that, the suspension that ibuprofen nano-powder redispersion obtains in water, and the mean diameter of ibuprofen granule is 20-200nm.
4. ibuprofen nano-powder as claimed in claim 1, it is characterized in that, hydrophilicity condiment is two or more in following material: polyvinylpyrrolidone, hydroxypropyl emthylcellulose, poloxamer, Polyethylene Glycol, polyvinyl alcohol, methylcellulose, lecithin, oleic acid, enuatrol, lauric acid and cholesterol.
5. ibuprofen nano-powder preparation method as claimed in claim 1, it is characterized in that: the drug solution of ibuprofen crude drug preparation, with the aqueous solution that contains water solublity pharmaceutic adjuvant, again that the ibuprofen suspension spraying being mixed to get is dry, obtain ibuprofen nano-powder, concrete step and method is:
A: ibuprofen crude drug is dissolved in and can be total in molten organic solvent with water, be configured to the raw material medicine solution that concentration is 1-3g/100ml; Hydrophilicity condiment is water-soluble, be configured to the aqueous solution of hydrophilicity condiment; Ibuprofen solution is 1/5～1/20 with the volume ratio that contains the aqueous solution of adjuvant;
B: at 20-30 ℃, under stirring condition, the adjuvant aqueous solution by the raw material medicine solution of A step and B step, obtains ibuprofen nanosuspension;
C: the ibuprofen nanosuspension spraying of B step is dry, obtain ibuprofen nano-powder.
6. according to the preparation method of claim 5, it is characterized in that, in A step, organic solvent is a kind of of methanol, ethanol, acetone, isopropyl alcohol, oxolane, chloroform, dimethyl sulfoxide or DMF or their mixture.
7. ibuprofen nano-powder preparation method as claimed in claim 1, it is characterized in that, in C step, spray-drying process control inlet temperature is 100-180 ℃, and outlet temperature is 60-80 ℃, feed rate is 5-25ml/min, and compressed air pressure is 0.4-0.8Mpa.
8. Genpril as claimed in claim 2, its preparation is characterised in that, additive of tablet used has: starch, CMS-Na, 15% starch slurry, micropowder silica gel, magnesium stearate, Pulvis Talci.
9. nanometer ibuprofen method for preparing tablet thereof as claimed in claim 2, is characterized in that, comprises the following steps:
A: ibuprofen crude drug is dissolved in and can be total in molten organic solvent with water, be configured to the raw material medicine solution that concentration is 1-3g/100ml; Hydrophilicity condiment is water-soluble, be configured to the aqueous solution that contains hydrophilicity condiment; Ibuprofen solution is 1/5～1/20 with the volume ratio that contains the aqueous solution of adjuvant;
B: at 20-30 ℃, under stirring condition, the adjuvant aqueous solution by the raw material medicine solution of A step and B step, obtains ibuprofen nanosuspension;
C: the ibuprofen nanosuspension spraying of B step is dry, obtain ibuprofen nano-powder;
D: take ibuprofen nano-powder and additive of tablet mix homogeneously that C step obtains, soft material processed, the granulate that sieves, granulates, dry, tabletting, it is qualified to detect, and obtains nanometer Genpril.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104224723A (en) * | 2014-10-14 | 2014-12-24 | 北京科莱博医药开发有限责任公司 | Pomalidomide nanoparticle and preparation and preparation method thereof |
| WO2018073632A1 (en) | 2016-10-20 | 2018-04-26 | Dukebox Sp. Z O.O. | A method of manufacturing a solution of nsaid nanoparticles |
| CN109394716A (en) * | 2019-01-07 | 2019-03-01 | 安徽东盛友邦制药有限公司 | A kind of novel nano Genpril and preparation method thereof |
| CN109512792A (en) * | 2019-01-11 | 2019-03-26 | 安徽东盛友邦制药有限公司 | A kind of process of the Genpril of granulation production twice |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101979091A (en) * | 2010-11-04 | 2011-02-23 | 中国科学院上海硅酸盐研究所 | Preparation method of calcium phosphate nano medicament-carrying systems |
| CN102256597A (en) * | 2008-11-10 | 2011-11-23 | 株式会社爱茉莉太平洋 | Method for producing powder containing nanoparticles of insoluble drug, powder produced thereby and pharmaceutical composition containing same |
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- 2013-12-26 CN CN201310750154.8A patent/CN103655501A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102256597A (en) * | 2008-11-10 | 2011-11-23 | 株式会社爱茉莉太平洋 | Method for producing powder containing nanoparticles of insoluble drug, powder produced thereby and pharmaceutical composition containing same |
| CN101979091A (en) * | 2010-11-04 | 2011-02-23 | 中国科学院上海硅酸盐研究所 | Preparation method of calcium phosphate nano medicament-carrying systems |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104224723A (en) * | 2014-10-14 | 2014-12-24 | 北京科莱博医药开发有限责任公司 | Pomalidomide nanoparticle and preparation and preparation method thereof |
| WO2018073632A1 (en) | 2016-10-20 | 2018-04-26 | Dukebox Sp. Z O.O. | A method of manufacturing a solution of nsaid nanoparticles |
| CN109394716A (en) * | 2019-01-07 | 2019-03-01 | 安徽东盛友邦制药有限公司 | A kind of novel nano Genpril and preparation method thereof |
| CN109512792A (en) * | 2019-01-11 | 2019-03-26 | 安徽东盛友邦制药有限公司 | A kind of process of the Genpril of granulation production twice |
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Application publication date: 20140326 |