CN104606139A - Preparation and application of drug powder - Google Patents
Preparation and application of drug powder Download PDFInfo
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- CN104606139A CN104606139A CN201410206962.2A CN201410206962A CN104606139A CN 104606139 A CN104606139 A CN 104606139A CN 201410206962 A CN201410206962 A CN 201410206962A CN 104606139 A CN104606139 A CN 104606139A
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- 229940079593 drug Drugs 0.000 title claims abstract description 61
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- Medicinal Preparation (AREA)
Abstract
Belonging to the field of pharmaceutical preparations, the invention provides a preparation method for a drug A (formula 1) powder and its application in oral solid preparations. The method includes: dispersing the crude drugs of drug A in a hydrophilic suspending aid solution, employing wet grinding to reduce the particle size to less than 5 micrometers, adding a spray-drying support agent, and combining spray drying, thus obtaining the drug A powder with an average particle size of less than 20 micrometers. The drug A powder prepared by the invention has high surface hydrophilicity, small particle size and good redispersibility in water. Compared with the crude drugs, the oral solid preparations prepared from the drug A powder and suitable auxiliary materials can significantly improve the dissolution rate. The preparation method for the drug A powder provided by the invention is suitable for industrial production and has high application value. (formula I).
Description
Technical field
The invention belongs to field of pharmaceutical preparations, relate to a kind of medicine A (2-ethyoxyl-1-[[2'-(4,5-dihydro-5-oxo-1,2,4-oxadiazoles-3-base) biphenyl-4-base] methyl]-1H-benzimidazole-7-carboxylic acid) powder and Synthesis and applications thereof, particular by wet grinding in conjunction with spraying dry, a kind of surface of preparation is covered by hydrophilic suspending agent, water soluble adjuvant is had to support medicine A powder between powder, and the application in oral solid formulation.
Background technology
Hypertension is modal chronic disease, is also one of topmost risk factor of cardiovascular and cerebrovascular disease.The whole world has tens of millions of people to cause the complication such as coronary heart disease, cerebral infarction, chronic renal failure and heart disease because of hypertension every year, and serious meeting causes the death of people.
Medicine A is novel hypertension II receptor antagonist medicine, selectivity antagonism A II type 1 receptor.Hindered the strong boosting of the end-product A II of renin-angiotensin system by acceptor levels and reach antihypertensive effect.At present, most depressor has the shortcomings such as obvious drug withdrawal rebounds, and fluctuation of blood pressure is large, and medicine A after 2 weeks, does not occur drug withdrawal rebound phenomena at successive administration, and blood pressure is normally steady.
Medicine A indissoluble in water, and the absorption window of medicine is at jejunum and duodenum.At present, existing people adopts solid dispersions technique (CN102793680A), airflow pulverization (CN102580097A), or use the methods such as low viscosity adhesive (CN101528262A) to improve the dissolution of medicine A, promote the absorption of medicine A.
But all there is obvious deficiency in the method for the dissolution of above-mentioned raising medicine A: in CN102793680A, because medicine A is strong dose thing, make solid dispersion and need use a large amount of hydrophilic carriers (medicine: carrier=1:4-1:10), obtained solid preparation quality is larger, be difficult to swallow, patient's compliance is poor.In addition, the easy moisture absorption of solid dispersion is aging and dissolution is reduced, but also there is the problems such as organic solvent residual.
In CN102580097A, although medicine mean diameter can be reduced within 5 μm by comminution by gas stream, but compared with the medicine A powder of same particle size obtained by the present invention, at the dissolution lower (Fig. 1, Fig. 2) of its absorption window pH scope (pH5.4-6.0).Because compared with comminution by gas stream; Chinese medicine A of the present invention and hydrophilic suspending agent are through wet grinding; again after spraying dry; hydrophilic suspending agent defines one deck hydrophilic protective films on medicine A surface; both the hydrophilic of the rear medicine of grinding had been added; prevent again the gathering of drug powder when tabletting, thus facilitate the stripping of medicine.
In CN101528262A, relative to trowel adhesive, tabletting after adopting low viscosity adhesive to granulate, increase, but low viscosity adhesive can not reduce the particle diameter of medicine A, the gathering of hydrophobic drug A when being also difficult to avoid tabletting to the dissolution rate of medicine A.So compared with the medicine A powder obtained by the present invention, still there is significant difference at absorption window pH scope place in its stripping, dissolution is obviously lower.
Those skilled in the art employ large metering method, but still can not overcome the defect of prior art.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of medicine A powder.
The present invention is realized by following technical proposal:
The present invention, by hydrophilic suspending agent and medicine A co-ground, adopts wet grinding to combine with spraying dry, prepares medicine A powder.Wet grinding is adopted to be reduced within 5 μm by the mean diameter of the medicine A be scattered in hydrophilic suspending agent aqueous solution, obtain medicine A suspension, in said medicine A suspension, add the dry proppant of appropriate spray again, prepare by spray drying method the medicine A powder that mean diameter is less than 20 μm.
Hydrophilic suspending agent is selected from the one in hydroxypropyl emthylcellulose, hydroxypropyl cellulose, polyvinylpyrrolidone and polyvinyl alcohol, preferred hydroxypropyl cellulose.
The concentration of hydrophilic suspending agent is 0.5-5%, preferred 1-3%.
The mass ratio of hydrophilic suspending agent and medicine A is 1:1-1:40, preferred 1:2-1:20.
Wet grinding device is selected from colloid mill, high pressure homogenizer, supertension homogenizer, the one in sand mill and ball mill, preferred sand mill.
After grinding, the mean diameter of medicine A in suspending liquid is less than 5 μm, is preferably less than 3 μm.。
Spray dry proppant and be selected from water soluble adjuvant, as the one or two or more in glucose, mannitol, sucrose, maltose and lactose, preferred lactose.
The mass ratio spraying dry proppant and medicine A is 1:4-4:1, preferred 1:2-2:1.
The technological parameter of spray drying method is as follows: the blow rate required: 60L/h, inlet temperature: 80-120 DEG C, leaving air temp: 40-75 DEG C, cleansing pin frequency: 1 time/3s, material flow: 4-15ml/min.
The mean diameter that medicine A powder after spray is dry is dispersed in water again is less than 20 μm.
Medicine A powder obtained by the present invention can prepare oral solid formulation with pharmaceutically acceptable adjuvant.Pharmaceutically acceptable adjuvant of the present invention comprises: filler is as microcrystalline Cellulose, pregelatinized Starch, corn starch, lactose, mannitol, sorbitol, calcium sulfate; Disintegrating agent is as dried starch, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, gas-producing disintegrant; Lubricant is as Polyethylene Glycol, magnesium stearate, magnesium laurylsulfate, sodium stearyl fumarate, micropowder silica gel; Binding agent is as hydroxypropyl emthylcellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, polyvinyl alcohol, starch slurry.Oral solid formulation kind prepared by medicine A powder and above-mentioned adjuvant comprises tablet, granule, hard capsule etc.
Medicine A is scattered in hydrophilic suspending agent aqueous solution, while utilizing grinding to reduce medicine A particle diameter, because suspending agent has certain viscosity, not only increase the effective grinding of sand mill to medicine, further suppress again the gathering of rear small particle diameter (mean diameter is less than 1 μm) the medicine A of grinding.But nanosuspension exists Ostwald ripening phenomenon, the particle diameter of medicine A is made to become large.For avoiding the generation of above-mentioned phenomenon, add the dry proppant of spray in suspension after, adopt spray drying method by moisture removing in nanosuspension, to obtain the stable medicine A powder of particle diameter.In spray-drying process, due to the rapid evaporation of moisture, hydrophilic suspending agent and spray dry proppant medicine A microparticle surfaces or between separate out, greatly improve the hydrophilic on medicine A surface, be conducive to the redispersion of medicine A.Meanwhile, owing to spraying adding of dry proppant, increase the inventory that spray is dry, decrease the loss of medicine.Wet grinding noise is little, and grinding temperature is low, and mean diameter is little, can continuous circulation grinding.It is even that spray drying method has particle dispersion, the features such as dry rate is fast.Wet grinding and spraying dry all can continuous operations, and easy and simple to handle, are applicable to suitability for industrialized production.
The present invention adopts wet grinding technology, utilizes sand mill will be dispersed in suspending agent drug in solution A porphyrize, reduces its mean diameter; In conjunction with spray drying technology, by adding, the drug suspension spray of spraying dry proppant is dry, prevents Ostwald ripening.Medicine can better disperse by suspending agent, improves grinding efficiency, suppresses the gathering of the rear medicine of grinding, and can after spray be dry, be wrapped in medicine A surface and increase its hydrophilic.Before spraying dry, add the dry proppant lactose of spray, can improve and spray dry inventory, reduce the loss of spraying dry rear medicine, also enhance the redispersibility of the dry rear medicine A powder of spray simultaneously.Because during spraying dry, along with the evaporation of moisture, the lactose of precipitation is isolated between drug powder, inhibits the gathering of drug powder, and the water solublity that lactose is good facilitates the redispersion of powder.In medicine A spray powder end, suspending agent is to the improvement of medicine A surface hydrophilicity and lactose to the buffer action of drug powder, avoids the impact of preparation process on its dissolution.During as tabletting, both made pressure excessive, drug powder is also not easily assembled, and causes dissolution to reduce.
After medicine A powder prepared by the present invention mixes with the acceptable proper auxiliary materials of pharmacy, the oral solid formulation of preparation all can reach good dissolved corrosion in different pH medium in vitro.In addition, preparation method of the present invention is simple to operate, can continuous seepage, and having can suitability for industrialized production advantage.Compared with the preparation method of inventing with other, after the medicine A powder prepared by preparation method of the present invention mixes with the acceptable proper auxiliary materials of pharmacy, more can improve the dissolution of medicine A.
Accompanying drawing explanation
Fig. 1 from film-making 1 (sand milling spray is dry), from film-making 2 (comminution by gas stream) with from film-making 3 (unprocessed crude drug) stripping curve figure in pH5.4 phosphate buffer.
Fig. 2 from film-making 1 (sand milling spray is dry), from film-making 2 (comminution by gas stream) with from film-making 3 (unprocessed crude drug) stripping curve figure in pH6.0 phosphate buffer.
Detailed description of the invention
Following examples only for illustration of the present invention, but are not used for limiting the scope of the invention.
Embodiment 1: prepare medicine A suspension with different hydrophilic suspending agent
Medicine A suspension prescription:
Medicine A 20g
Hydrophilic suspending agent 4g
distilled water 200ml
Sand mill grinding suitable time obtains suspension
Preparation technology: after 4g hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, polyvinyl alcohol are dissolved in 200ml distilled water respectively, adds 20g medicine A and makes it abundant suspendible under stirring.Utilize ESW-750 type laboratory sand mill (dynamo-electric company limited is easily strangled in Shanghai) to grind suitable time and obtain suspension, adopt LS-230 type particle size analyzer (Beckman company) to record drug particle distribution in table 1.
Table 1 different hydrophilic suspending agent is on the impact of diameter of aspirin particle after grinding
Result shows, with hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone or polyvinyl alcohol for suspensoid, all can effectively reduce the mean diameter of medicine A.But be suspending agent with hydroxy propyl cellulose, the bubble produced in process of lapping is less, improve effective grinding of sand mill, in same time, more can reduce the mean diameter of drug particle.
Embodiment 2: variable concentrations hydroxypropyl cellulose is that suspending agent prepares medicine A suspension
Medicine A suspension prescription:
Medicine A 20g
Hydroxypropyl cellulose is appropriate
distilled water 200ml
Sand mill grinding suitable time obtains suspension
Preparation technology: by 1,2,4,6, after 10g hydroxy propyl cellulose is dissolved in 200ml distilled water respectively, under stirring, adds 20g medicine A respectively make it abundant suspendible.Utilize ESW-750 type laboratory sand mill (dynamo-electric company limited is easily strangled in Shanghai) to grind suitable time and obtain suspension, adopt LS-230 type particle size analyzer (Beckman company) to record drug particle distribution in table 2.
Table 2 variable concentrations hydroxypropyl cellulose is on the impact of diameter of aspirin particle after grinding
Result shows, different hydroxypropyl cellulose concentration is less on the impact of diameter of aspirin particle after grinding, but when hydroxypropyl cellulose concentration is too low (C≤0.5%), suspending agent is difficult to maintain the suspendible of drug microparticles after sand milling, microgranule easily sinks to the bottom gathering, is difficult to dispersion when spraying dry.When hydroxypropyl cellulose excessive concentration (C >=5%), after spray is dry, because suspending agent consumption is large, the tablet made is difficult to disintegrate, affects the stripping of preparation.Therefore during grinding, suspending agent hydroxypropyl cellulose concentration elects 1-3% as, preferably 2%.
The mass ratio of embodiment 3 medicine and hydroxypropyl cellulose is on the impact of grinding effect
Medicine A suspension prescription:
Medicine A is appropriate
Hydroxypropyl cellulose 4g
distilled water 200ml
Sand mill grinding suitable time obtains suspension
After 4g hydroxy propyl cellulose is dissolved in 200ml distilled water respectively, under stirring, add 4 respectively, 10,20,40,80,120,160g medicine A makes it abundant suspendible.Utilize ESW-750 type laboratory sand mill (dynamo-electric company limited is easily strangled in Shanghai) to grind suitable time and obtain suspension, adopt LS-230 type particle size analyzer (Beckman company) to record drug particle distribution in table 3.
Impact on diameter of aspirin particle after table 3 hydroxypropyl cellulose and different proportion medicine co-ground
Result shows, along with the increase of drug ratios, grind the decreased effectiveness to reducing diameter of aspirin particle, but drug ratios is very few, produces productive rate low, being unfavorable for large-scale production.Therefore the mass ratio of hydroxypropyl cellulose and medicine is 1:2-1:20, preferred 1:5.
Embodiment 4: different milling apparatus prepares suspension
Medicine A suspension prescription:
Medicine A 20g
Hydroxypropyl cellulose 4g
distilled water 200ml
Grinding suitable time obtains suspension
Preparation technology: after 4g hydroxypropyl cellulose is dissolved in 200ml distilled water, adds 20g medicine A and makes it abundant suspendible under stirring.Adopt ESW-750 type laboratory sand mill (dynamo-electric company limited is easily strangled in Shanghai), QM-DK2 type low temp planetary ball mill (Nanjing Univ. Instrument Factory), AH110D type high pressure homogenizer (ATS industrial system company limited) to grind suitable time and obtain suspension respectively, adopt LS-230 type particle size analyzer (Beckman company) to record drug particle distribution in table 4.
The different milling apparatus of table 4 is on the impact of diameter of aspirin particle after grinding
Result shows, sand mill and high pressure homogenizer all can effectively reduce the particle diameter of medicine A, but sand mill grinding chamber is comparatively large, and can operate continuously, equipment loss is little, and production efficiency is high, is applicable to industrialized great production.
Embodiment 5 sprays the selection of dry proppant
Medicine A suspension prescription:
Medicine A 20g
Hydroxypropyl cellulose 4g
distilled water 200ml
Sand mill grinding suitable time obtains suspension
Spraying dry prescription:
Medicine A suspension 200ml
spray dry proppant 10g
Be suitable for spraying trepang numeral system and obtain medicine A powder
Preparation technology: after 6g hydroxypropyl cellulose is dissolved in 300ml distilled water, adds 30g medicine A and makes it abundant suspendible under stirring.Utilize ESW-750 type laboratory sand mill (dynamo-electric company limited is easily strangled in Shanghai) to grind suitable time and obtain suspension, adopting LS-230 type particle size analyzer (Beckman company) to record drug particle mean diameter is 0.489 μm, D90=0.873 μm.3 parts will be divided into above-mentioned suspension, add 10g lactose, mannitol and sucrose respectively, as the dry proppant of spray, slowly stir, spraying dry after it dissolves completely.After the spray powder of gained is dispersed in water again, record its particle size distribution in table 5.
The impact of diameter of aspirin particle after the dry proppant of table 5 difference spray is dry on spray
Result shows, when lactose can better suppress suspension to spray dry, aggregation of particles becomes large, and lactose hygroscopicity is less, is good solid preparation adjuvant.
Embodiment 6 suspension Chinese medicine amount and galactose ratio are on the impact of spraying dry rear diameter of aspirin particle
Medicine A suspension prescription:
Medicine A 50g
Hydroxypropyl cellulose 10g
distilled water 500ml
Sand mill grinding suitable time obtains suspension
Spraying dry prescription:
Medicine A suspension 100ml
lactose is appropriate
Be suitable for spraying trepang numeral system and obtain medicine A powder
Preparation technology: after 10g hydroxypropyl cellulose is dissolved in 500ml distilled water, adds 50g medicine A and makes it abundant suspendible under stirring.Utilize ESW-750 type laboratory sand mill (dynamo-electric company limited is easily strangled in Shanghai) to grind suitable time and obtain suspension, adopting LS-230 type particle size analyzer (Beckman company) to record drug particle mean diameter is 0.517 μm, D90=0.954 μm.Above-mentioned suspension is divided equally 5 parts, every part of 100ml, in medicine: the ratio of lactose (10:1,4:1,2:1,1:1,1:2), add 1 respectively, 2.5,5,10,20g lactose is as the dry proppant of spray, slow stirring, spraying dry after it dissolves completely.After the spray powder of gained is dispersed in water again, record its particle size distribution in table 6.
The impact of diameter of aspirin particle after table 6 different proportion lactose is dry on spray
Result shows, when medicine: when galactose ratio is less than 2:1, sprays aggregation of particles when dry proppant can better suppress suspension to spray dry and becomes large.Consider that the membership that adds of too much lactose increases sheet weight simultaneously, therefore medicine: lactose (w/w) ratio is 1:2-2:1, preferred 2:1.
The selection of embodiment 7 spray drying parameters
Medicine A suspension prescription:
Medicine A 50g
Hydroxypropyl cellulose 10g
distilled water
500ml
Sand mill grinding suitable time obtains suspension
Spraying dry prescription:
Medicine A suspension 500ml
lactose 25g
Be suitable for spraying trepang numeral system and obtain medicine A powder
Preparation technology: after 10g hydroxypropyl cellulose is dissolved in 500ml distilled water, adds 50g medicine A and makes it abundant suspendible under stirring.Utilize ESW-750 type laboratory sand mill (dynamo-electric company limited is easily strangled in Shanghai) to grind suitable time and obtain suspension, adopting LS-230 type particle size analyzer (Beckman company) to record drug particle mean diameter is 0.801 μm, D90=2.133 μm.By above-mentioned 500ml medicine A suspension, in medicine: the ratio of lactose (2:1), add 25g lactose as the dry proppant of spray, slowly stir, after it dissolves completely, carry out spraying dry.The spray powder particle diameter of spray drying parameters and gained is in table 7.
Table 7 spray drying parameters is on the impact of medicine A spray powder particle diameter, moisture
Consider spray-dired speed, medicine A spray powder particle diameter, moisture, select drying process with atomizing as follows: the blow rate required: 60L/h, inlet temperature: 120 DEG C, leaving air temp: 65 DEG C, cleansing pin frequency: 1 time/3s, material flow: 9ml/min.
The preparation of embodiment 8 medicine A powder
Medicine A suspension prescription:
Medicine A 50g
Hydroxypropyl cellulose 10g
distilled water 500ml
Sand mill grinding suitable time obtains suspension
Spraying dry prescription:
Medicine A suspension 500ml
lactose 25g
Be suitable for spraying trepang numeral system and obtain medicine A powder
Preparation technology: after 10g hydroxypropyl cellulose is dissolved in 500ml distilled water, adds 50g medicine A and makes it abundant suspendible under stirring.Utilize ESW-750 type laboratory sand mill (dynamo-electric company limited is easily strangled in Shanghai) to grind suitable time and obtain suspension, adopt LS-230 type particle size analyzer (Beckman company) to record drug particle mean diameter and be less than 1 μm.By above-mentioned 500ml medicine A suspension, in medicine: the ratio of lactose (2:1), add 25g lactose as the dry proppant of spray, slowly stir, after it dissolves completely, carry out spraying dry.Spray drying parameters is as follows: the blow rate required: 60L/h, inlet temperature: 120 DEG C, leaving air temp: 65 DEG C, cleansing pin frequency: 1 time/3s, material flow: 9ml/min.Obtained medicine A powder average particle size≤5 μm, content of dispersion is 53.33%.
Embodiment 9-11 prescription Chinese medicine A powder is prepared by embodiment 8.
Embodiment 9 adopts wet granulation to prepare tablet
Core formulation:
Coating fluid prescription:
Opadry (stomach dissolution type) 20g
distilled water 200ml
The obtained coating solution containing 10% solid content
Preparation technology: the lactose of medicine A powder and recipe quantity, starch, microcrystalline Cellulose and polyethylene glycol 6000 are mixed by the equivalent method of progressively increasing, after mixing, with appropriate distilled water soft material, cross 30 mesh sieves and granulate, after 40 DEG C of dry 1h, cross 20 mesh sieve granulate, add recipe quantity low-substituted hydroxypropyl cellulose and magnesium stearate, tabletting after mixing, No. 7 punchings, sheet heavy 130mg, hardness 5-7kg.Adopt the Opadry coating solution coating (coating weight gain 2%) of above-mentioned preparation, to obtain final product.
Embodiment 10 adopts dry granulation to prepare tablet
Core formulation:
Coating fluid prescription:
Opadry (stomach dissolution type) 20g
distilled water 200ml
The obtained coating solution containing 10% solid content
Preparation technology: the lactose of medicine A powder and recipe quantity, starch, microcrystalline Cellulose, polyethylene glycol 6000, interior dosage low-substituted hydroxypropyl cellulose and magnesium stearate are mixed by the equivalent method of progressively increasing, after mixing, dry granulation, take a certain amount of dry granule (30-80 order) and fine powder (being less than 80 orders), granule: fine powder (2:1), low-substituted hydroxypropyl cellulose and the magnesium stearate of outer dosage is added in prescription ratio, tabletting after mixing, No. 7 punchings, sheet heavy 130mg, hardness 6-8kg.Adopt the Opadry coating solution coating (coating weight gain 2%) of above-mentioned preparation, to obtain final product.
Embodiment 11 adopts technique of direct powder compression to prepare tablet
Core formulation:
Coating fluid prescription:
Opadry (stomach dissolution type) 20g
distilled water 200ml
The obtained coating solution containing 10% solid content
Preparation technology: the lactose of medicine A powder and recipe quantity, starch, microcrystalline Cellulose, polyethylene glycol 6000, polyvinylpolypyrrolidone, magnesium stearate are mixed by the equivalent method of progressively increasing, direct compression after mixing, No. 7 punchings, sheet weight 130mg, hardness 8-10kg.Adopt the Opadry coating solution coating (coating weight gain 2%) of above-mentioned preparation, to obtain final product.
Embodiment 12 In Vitro Dissolution is tested
Get it filled thing A from film-making 1 (tablet obtained by embodiment 9), from film-making 2 (except medicine A powder being replaced with except the medicine A (particle diameter is identical) after comminution by gas stream, other adjuvants are all with embodiment 9), (replace with except medicine A crude drug (unprocessed) except by medicine A powder from film-making 3, other adjuvants are all with embodiment 9) according to dissolution determination method (Chinese Pharmacopoeia 2010 editions two annex XC second methods), respectively with pH6.0, pH5.4 phosphate buffer 900ml is dissolution medium, rotating speed 50r/min, operate in accordance with the law, respectively 5, 10, 15, 20, 30, 45, solution 10ml is taken out from stripping rotor during 60min, supplement same volume dissolution medium simultaneously, 0.45 μm of filtering with microporous membrane, take out subsequent filtrate dilution suitable multiple, according to Ultraviolet spectrophotometry (Chinese Pharmacopoeia 2010 editions second annex IVA), absorbance is measured at 249nm wavelength place, calculate accumulation dissolution, its stripping curve figure is shown in Fig. 1 and Fig. 2.
Conclusion:
From Fig. 1 and Fig. 2, with prepared by undressed crude drug from film-making 3 and comparing from film-making 2 of preparing by method described in CN102580097A, the medicine A powder prepared by the present invention and proper auxiliary materials prepare from film-making 1 its absorption window place pH value phosphate buffer (pH5.4 and pH6.0) in dissolution have significantly improved.This is to promoting that the body absorption of 2-ethyoxyl-1-[[2'-(4,5-dihydro-5-oxo-1,2,4-oxadiazoles-3-base) biphenyl-4-base] methyl]-1H-benzimidazole-7-carboxylic acid is significant with its bioavailability of raising.
Claims (10)
1. the preparation method of a medicine A powder, it is characterized in that: adopt hydrophilic suspending agent and medicine A co-ground, utilize wet grinding device that the mean diameter of medicine is reduced to less than 5 μm, and in suspension after grinding, add the dry proppant of spray, spray drying method is adopted to obtain mean diameter 1-20 μm of medicine A powder, described medicine A is 2-ethyoxyl-1-[[2'-(4,5-dihydro-5-oxo-1,2,4-oxadiazoles-3-base) biphenyl-4-base] methyl]-1H-benzimidazole-7-carboxylic acid.
2. preparation method as claimed in claim 1, it is characterized in that: described suspending agent is the aqueous solution of hydrophilicity condiment, hydrophilicity condiment is selected from methylcellulose, hydroxypropyl emthylcellulose, carmethose, hydroxypropyl cellulose, polyvinylpyrrolidone, polyvinyl alcohol, starch or dextrin, preferred hydroxypropyl cellulose.
3. preparation method as claimed in claim 1 or 2, is characterized in that: the concentration of described suspending agent is 0.5-5%, preferred 1-3%.
4. the preparation method as described in claim 1 or 2 or 3, is characterized in that: the mass ratio of described suspending agent and medicine A is 1:1-1:40, preferred 1:2-1:20.
5. preparation method as claimed in claim 1, is characterized in that: wet grinding device is selected from high speed shear dispersion machine, mixer grinder, colloid mill, high pressure homogenizer, supertension homogenizer, the one in sand mill and ball mill, preferred sand mill.
6. preparation method as claimed in claim 1, is characterized in that: after grinding, the mean diameter of medicine A is less than 5 μm, is preferably less than 3 μm.
7. preparation method as claimed in claim 1, is characterized in that: the dry proppant of described spray is water soluble adjuvant, is selected from one or more in water soluble starch, dextrin, glucose, mannitol, sorbitol, sucrose, maltose and lactose, preferred lactose.
8. the preparation method as described in claim 1 or 7, is characterized in that: the mass ratio spraying dry proppant and medicine is 1:4-4:1, preferred 1:2-2:1.
9. preparation method according to claim 1, is characterized in that: the technological parameter of spray drying method is as follows: the blow rate required: 60L/h, inlet temperature: 80-120 DEG C, leaving air temp: 40-75 DEG C, cleansing pin frequency: 1 time/3s, material flow: 4-15ml/min.
10. preparation method according to claim 9, it is characterized in that: the mean diameter that the drug powder after spray is dry is dispersed in water again is less than 20 μm, preferably be less than 10 μm, obtained drug powder and pharmaceutically acceptable adjuvant, prepare tablet, granule or hard capsule by routine techniques means.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106214637A (en) * | 2016-07-28 | 2016-12-14 | 北京万全德众医药生物技术有限公司 | A kind of Aripiprazole is co-mulled and made into thing and Preparative Technology of Dispersible Tablets |
| CN111514111A (en) * | 2020-05-07 | 2020-08-11 | 福建海西新药创制有限公司 | Pharmaceutical composition containing mosapride citrate and preparation method thereof |
| CN114272842A (en) * | 2022-01-13 | 2022-04-05 | 南昌百济制药有限公司 | Preparation method of nasal spray |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040121003A1 (en) * | 2002-12-19 | 2004-06-24 | Acusphere, Inc. | Methods for making pharmaceutical formulations comprising deagglomerated microparticles |
| 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 |
| CN102920654A (en) * | 2012-11-14 | 2013-02-13 | 沈阳药科大学 | Valsartan spray-dried nanosuspension and preparation method of valsartan spray-dried nanosuspension |
| CN103705510A (en) * | 2013-12-27 | 2014-04-09 | 华润赛科药业有限责任公司 | Method for preparing azilsartan solid composition |
-
2014
- 2014-05-16 CN CN201410206962.2A patent/CN104606139B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040121003A1 (en) * | 2002-12-19 | 2004-06-24 | Acusphere, Inc. | Methods for making pharmaceutical formulations comprising deagglomerated microparticles |
| 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 |
| CN102920654A (en) * | 2012-11-14 | 2013-02-13 | 沈阳药科大学 | Valsartan spray-dried nanosuspension and preparation method of valsartan spray-dried nanosuspension |
| CN103705510A (en) * | 2013-12-27 | 2014-04-09 | 华润赛科药业有限责任公司 | Method for preparing azilsartan solid composition |
Non-Patent Citations (2)
| Title |
|---|
| ANUJ KUMAR ETAL: "REVIEW ON SOLUBILITY ENHANCEMENT TECHNIQUES FOR HYDROPHOBIC DRUGS", 《PHARMACIE GLOBALE INTERNATIONAL JOURNAL OF COMPREHENSIVE PHARMACY》 * |
| 冯镇 主编: "《乳剂机械与设备》", 30 September 2013, 中国轻工业出版社 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106214637A (en) * | 2016-07-28 | 2016-12-14 | 北京万全德众医药生物技术有限公司 | A kind of Aripiprazole is co-mulled and made into thing and Preparative Technology of Dispersible Tablets |
| CN111514111A (en) * | 2020-05-07 | 2020-08-11 | 福建海西新药创制有限公司 | Pharmaceutical composition containing mosapride citrate and preparation method thereof |
| CN114272842A (en) * | 2022-01-13 | 2022-04-05 | 南昌百济制药有限公司 | Preparation method of nasal spray |
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