CN104606139B - A kind of preparation and application of drug powder - Google Patents
A kind of preparation and application of drug powder Download PDFInfo
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- CN104606139B CN104606139B CN201410206962.2A CN201410206962A CN104606139B CN 104606139 B CN104606139 B CN 104606139B CN 201410206962 A CN201410206962 A CN 201410206962A CN 104606139 B CN104606139 B CN 104606139B
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- 239000000843 powder Substances 0.000 title claims abstract description 57
- 238000002360 preparation method Methods 0.000 title claims abstract description 33
- 238000001694 spray drying Methods 0.000 claims abstract description 59
- 239000002245 particle Substances 0.000 claims abstract description 49
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- Medicinal Preparation (AREA)
Abstract
The present invention provides a kind of medicine A（Formula 1）The preparation method of powder, and its application in oral solid formulation, belong to field of pharmaceutical preparations.The drug powder of the present invention is by the way that medicine A bulk drugs are dispersed in hydrophily suspending agent solution, and its particle diameter is reduced into less than 5 μm using wet grinding, adds spray drying supporting agent, and with reference to spray drying, the medicine A powder that average grain diameter is less than 20 μm is made.Medicine A powder produced by the present invention, its surface hydrophilicity is high, particle diameter is small, redispersibility is good in water.Compared with its bulk drug, medicine A powder and oral solid formulation made from suitable auxiliary material, its dissolution rate can be significantly improved.Medicine A powder preparation methods provided by the invention, it is adapted to industrialized production, there is higher application value.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, is related to a kind of medicine A (2- ethyoxyls -1- [[2'- (4,5- dihydro -5- oxygen
- 1,2,4- oxadiazoles -3- bases of generation) biphenyl -4- bases] methyl] -1H- benzimidazole -7- carboxylic acids) powder and its preparation and application, tool
Body is to combine to be spray-dried by wet grinding, prepares a kind of surface and is covered by hydrophily suspending agent, there is water solubility between powder
Auxiliary material supports medicine A powder, and its application in oral solid formulation.
Background technology
Hypertension is most common chronic disease, and one of most important risk factor of cardiovascular and cerebrovascular diseases.The whole world has every year
Tens of millions of people causes the complication such as coronary heart disease, cerebral infarction, chronic renal failure and heart disease because of hypertension, and serious meeting is made
The death of adult.
Medicine A is novel hypertension II receptor antagonist medicine, the selective acceptor of II types of antagonism A 1.Pass through acceptor levels
Hinder the end-product A II of renin-angiotensin system strong boosting and reach antihypertensive effect.At present, most drop
The shortcomings of pressing has obvious bounce-back of being discontinued, and fluctuation of blood pressure is big, and there is not bounce-back of being discontinued after successive administration 2 weeks in medicine A
Phenomenon, and blood pressure is normally steady.
Medicine A indissolubles in water, and the absorption window of medicine is in jejunum and duodenum.At present, someone is divided using solid
Granular media technology (CN102793680A), airflow pulverization (CN102580097A), or use low viscosity adhesive
(CN101528262A) the methods of, improves medicine A dissolution rate, promotes medicine A absorption.
But there is obvious deficiency in the method for above-mentioned raising medicine A dissolution rate：In CN102793680A, due to medicine A
It is strong dose thing, solid dispersions, which are made, need to use substantial amounts of hydrophilic carrier (medicine：Carrier=1:4-1:10) it is, made
The solid pharmaceutical preparation quality obtained is larger, it is difficult to swallows, patient's compliance is poor.In addition, the easy moisture absorption aging of solid dispersions and make molten
Out-degree reduces, but also the problems such as organic solvent residual be present.
In CN102580097A, although medicine average grain diameter can be reduced within 5 μm by air-flow crushing, with institute of the present invention
The medicine A powder that same particle size is made is compared, relatively low (Fig. 1, Fig. 2) in the dissolution rate of its absorption window pH scopes (pH5.4-6.0).
Because compared with air-flow crushing, in the present invention medicine A with hydrophily suspending agent through wet grinding, then after being spray-dried, hydrophily
Suspending agent forms one layer of hydrophilic protective films on medicine A surfaces, both adds the hydrophily of medicine after grinding, prevents medicine again
Aggregation of the thing powder in tabletting, so as to promote the dissolution of medicine.
In CN101528262A, relative to trowel adhesive, tabletting after being pelletized using low viscosity adhesive, to medicine A
Dissolution rate increase, but low viscosity adhesive can not reduce medicine A particle diameter, it is also difficult to hydrophobicity medicine when avoiding tabletting
Thing A aggregation.So compared with the medicine A powder obtained by the present invention, its dissolution still exists aobvious at absorption window pH scopes
Difference is write, dissolution rate is significant lower.
Those skilled in the art have used a large amount of methods, but still the defects of prior art can not be overcome.
The content of the invention
It is an object of the invention to provide a kind of preparation method of medicine A powder.
The present invention is realized by following technical proposal：
Hydrophily suspending agent and medicine A co-grounds are combined by the present invention using wet grinding with spray drying, preparation
Medicine A powder.The average grain diameter for the medicine A being scattered in the hydrophily suspending agent aqueous solution is reduced to 5 μm using wet grinding
Within, medicine A suspensions are obtained, then appropriate spray drying supporting agent is added into said medicine A suspensions, by being spray-dried legal system
Standby average grain diameter is less than 20 μm of medicine A powder.
Hydrophily suspending agent is selected from hydroxypropyl methyl cellulose, hydroxypropyl cellulose, polyvinylpyrrolidone and polyethylene
One kind in alcohol, preferably hydroxypropyl cellulose.
The concentration of hydrophily suspending agent is 0.5-5%, preferably 1-3%.
Hydrophily suspending agent and medicine A mass ratio are 1:1-1:40, preferably 1:2-1:20.
Wet grinding device is selected from colloid mill, high pressure homogenizer, super-pressure homogenizer, and one in sand mill and ball mill
Kind, preferably sand mill.
Average grain diameters of the medicine A in suspending liquid is less than 5 μm, preferably smaller than 3 μm after grinding..
Spray drying supporting agent is selected from water soluble adjuvant, such as one kind in glucose, mannitol, sucrose, maltose and lactose or
Two or more, preferred lactose.
Spray drying supporting agent and medicine A mass ratio are 1:4-4:1, preferably 1:2-2:1.
The technological parameter of spray drying process is as follows：The blow rate required：60L/h, EAT：80-120 DEG C, leaving air temp：40-
75 DEG C, cleansing pin frequency：1 time/3s, material flow:4-15ml/min.
The average grain diameter that medicine A powder after spray drying 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 auxiliary material.The present invention
The pharmaceutically acceptable auxiliary material includes：Filler such as microcrystalline cellulose, pregelatinized starch, cornstarch, lactose, sweet dew
Alcohol, sorbierite, calcium sulfate；Disintegrant such as dried starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, crosslinked polyethylene pyrrole
Pyrrolidone, Ac-Di-Sol, gas-producing disintegrant；Lubricant for example polyethylene glycol, magnesium stearate, magnesium laurylsulfate,
Sodium stearyl fumarate, superfine silica gel powder；Adhesive such as hydroxypropyl methyl cellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, poly-
Vinyl alcohol, starch slurry.Medicine A powder includes tablet, granule, hard shell capsules with oral solid formulation species prepared by above-mentioned auxiliary material
Deng.
Medicine A is scattered in the hydrophily suspending agent aqueous solution, while reducing medicine A particle diameters using grinding, due to suspending
Agent has certain viscosity, not only increases effective grinding of the sand mill to medicine, further inhibits small particle after grinding
(average grain diameter is less than 1 μm) medicine A aggregation.But there is Ostwald ripening phenomenon in nanosuspension so that medicine A particle diameter becomes
Greatly.To avoid the generation of above-mentioned phenomenon, after adding spray drying supporting agent in suspension, using spray drying process by nanosuspension
Middle moisture removes, to obtain the stable medicine A powder of particle diameter.In spray-drying process, due to the rapid evaporation of moisture, hydrophily
Suspending agent and spray drying supporting agent medicine A microparticle surfaces or between separate out, greatly improve the hydrophily on medicine A surfaces, favorably
In medicine A redisperse.Simultaneously as the addition of spray drying supporting agent, the inventory of spray drying is increased, reduces the damage of medicine
Lose.Wet grinding noise is small, and grinding temperature is low, and average grain diameter is small, can continuous circular grinding.Spray drying process has particle point
Dissipate uniform, the features such as rate of drying is fast.Wet grinding can continuously work with spray drying, and easy to operate, be adapted to industrialization
Production.
The present invention uses wet grinding technology, and it is finely ground to will be dispersed in suspending agent drug in solution A using sand mill, reduces it
Average grain diameter；With reference to spray drying technology, the drug suspension spray drying of spray drying supporting agent will be added, prevent Ostwald ripening.Suspending
Agent can preferably disperse medicine, improve grinding efficiency, suppress the aggregation of medicine after grinding, and medicine can be wrapped in after spray drying
A surfaces and increase its hydrophily.Before spray drying, spray drying supporting agent lactose is added, the inventory of spray drying can be improved, reduces spray drying
The loss of medicine afterwards, while also enhance the redispersibility of medicine A powder after spray drying.Because during spray drying, with moisture
Evaporation, the lactose of precipitation are isolated between drug powder, it is suppressed that the aggregation of drug powder, the good water solubility of lactose promote
The redisperse of powder.In medicine A spray drying powder improvement of the suspending agent to medicine A surface hydrophilicities and lactose to drug powder every
From effect, influence of the preparation process to its dissolution rate is avoided.During such as tabletting, both made pressure excessive, drug powder is not easy to gather
Collection, causes dissolution rate to reduce.
After medicine A powder prepared by the present invention mixes with pharmaceutically acceptable proper auxiliary materials, the oral administration solid system of preparation
Agent can reach good dissolved corrosion in different pH medium in vitro.In addition, the preparation method of the present invention is simple to operate, can connect
Continuous production, having can industrialized production advantage.Compared with the preparation method of other inventions, prepared by preparation method of the invention
After medicine A powder mixes with pharmaceutically acceptable proper auxiliary materials, medicine A dissolution rate can be more improved.
Brief description of the drawings
Fig. 1 exists from film-making 1 (sand milling spray drying) from film-making 2 (air-flow crushing) and from film-making 3 (unprocessed bulk drug)
Stripping curve figure in pH5.4 phosphate buffers.
Fig. 2 exists from film-making 1 (sand milling spray drying) from film-making 2 (air-flow crushing) and from film-making 3 (unprocessed bulk drug)
Stripping curve figure in pH6.0 phosphate buffers.
Embodiment
Following examples are merely to illustrate the present invention, but are not limited to the scope of the present invention.
Embodiment 1：Medicine A suspensions are prepared with different hydrophilic suspending agent
Medicine A suspension prescriptions：
Medicine A 20g
Hydrophily suspending agent 4g
Distilled water 200ml
Sand mill grinding suitable time obtains suspension
Preparation technology：By 4g hydroxypropyl celluloses, HPMC, polyvinylpyrrolidone, polyvinyl alcohol difference
After being dissolved in 200ml distilled water, addition 20g medicines A is allowed to fully be suspended under stirring.Utilize ESW-750 types laboratory
Sand mill (easily strangling electromechanical Co., Ltd in Shanghai) grinding suitable time obtains suspension, using LS-230 type particle size analyzers
(Beckman companies) measures drug particle distribution and is shown in Table 1.
Influence of the different hydrophilic suspending agent of table 1 to diameter of aspirin particle after grinding
As a result show, using hydroxypropyl cellulose, HPMC, polyvinylpyrrolidone or polyvinyl alcohol as suspension
Agent, it can effectively reduce medicine A average grain diameter.But using hydroxy propyl cellulose as suspending agent, the caused bubble in process of lapping
It is less, effective grinding of sand mill is improved, in same time, can more reduce the average grain diameter of drug particle.
Embodiment 2：Various concentrations hydroxypropyl cellulose is that suspending agent prepares medicine A suspensions
Medicine A suspension prescriptions：
Medicine A 20g
Appropriate hydroxypropyl cellulose
Distilled water 200ml
Sand mill grinding suitable time obtains suspension
Preparation technology：After 1,2,4,6,10g hydroxy propyl celluloses are dissolved separately in into 200ml distilled water, under stirring
20g medicines A is separately added into be allowed to fully be suspended.Utilize ESW-750 types laboratory sand mill (easily strangling electromechanical Co., Ltd in Shanghai)
Grinding suitable time obtains suspension, and measuring drug particle distribution using LS-230 types particle size analyzer (Beckman companies) is shown in Table
2。
Influence of the various concentrations hydroxypropyl cellulose of table 2 to diameter of aspirin particle after grinding
As a result show, influence of the different hydroxypropyl cellulose concentration to diameter of aspirin particle after grinding is smaller, but hydroxypropyl is fine
Tie up plain concentration it is too low when (C≤0.5%), suspending agent is difficult to the suspension of drug microparticles after maintaining to be sanded, and particulate easily sinks to the bottom aggregation,
It is difficult to disperse during spray drying.When hydroxypropyl cellulose excessive concentration (C >=5%), after spray drying, because suspending agent dosage is big, it is made
Tablet be difficult to be disintegrated, influence the dissolution of preparation.Therefore when grinding, suspending agent hydroxypropyl cellulose concentration elects 1-3% as, preferably
2%.
Influence of the mass ratio of the medicine of embodiment 3 and hydroxypropyl cellulose to grinding effect
Medicine A suspension prescriptions：
Medicine A is appropriate
Hydroxypropyl cellulose 4g
Distilled water 200ml
Sand mill grinding suitable time obtains suspension
After 4g hydroxy propyl celluloses are dissolved separately in into 200ml distilled water, be separately added into 4 under stirring, 10,20,40,
80th, 120,160g medicines A is allowed to fully be suspended.Utilize ESW-750 types laboratory sand mill (easily strangling electromechanical Co., Ltd in Shanghai)
Grinding suitable time obtains suspension, and measuring drug particle distribution using LS-230 types particle size analyzer (Beckman companies) is shown in Table
3。
The hydroxypropyl cellulose of table 3 and the influence after different proportion medicine co-ground to diameter of aspirin particle
As a result show, with the increase of drug ratios, grind the decreased effectiveness to reducing diameter of aspirin particle, but drug ratios mistake
It is few, low yield is produced, is unfavorable for mass producing.Therefore the mass ratio of hydroxypropyl cellulose and medicine is 1:2-1:20, preferably 1:
5。
Embodiment 4：Different milling apparatus prepare suspension
Medicine A suspension prescriptions：
Medicine A 20g
Hydroxypropyl cellulose 4g
Distilled water 200ml
Grinding suitable time obtains suspension
Preparation technology：After 4g hydroxypropyl celluloses are dissolved in into 200ml distilled water, 20g medicines A is added under stirring
It is allowed to fully be suspended.ESW-750 types laboratory sand mill (easily strangling electromechanical Co., Ltd in Shanghai), QM-DK2 type low temperature is respectively adopted
Planetary ball mill (Nanjing Univ. Instrument Factory), AH110D types high pressure homogenizer (ATS industrial systems Co., Ltd) grinding are suitable
Time obtains suspension, and measuring drug particle distribution using LS-230 types particle size analyzer (Beckman companies) is shown in Table 4.
Influence of the 4 different milling apparatus of table to diameter of aspirin particle after grinding
As a result show, sand mill and high pressure homogenizer can effectively reduce medicine A particle diameter, but sand mill grinding chamber compared with
Greatly, can continuously run, equipment loss is small, and production efficiency is high, is adapted to industrialized production.
The selection of the spray drying supporting agent of embodiment 5
Medicine A suspension prescriptions：
Medicine A 20g
Hydroxypropyl cellulose 4g
Distilled water 200ml
Sand mill grinding suitable time obtains suspension
It is spray-dried prescription：
Medicine A suspensions 200ml
Spray drying supporting agent 10g
Medicine A powder is made in suitable spray drying parameter
Preparation technology：After 6g hydroxypropyl celluloses are dissolved in into 300ml distilled water, 30g medicines A is added under stirring
It is allowed to fully be suspended.It must be mixed using ESW-750 types laboratory sand mill (easily strangling electromechanical Co., Ltd in Shanghai) grinding suitable time
Suspension, LS-230 types particle size analyzer (Beckman companies) is used to measure drug particle average grain diameter as 0.489 μm, D90=
0.873μm.3 parts will be divided into above-mentioned suspension, and be separately added into 10g lactose, mannitol and sucrose, as spray drying supporting agent,
It is slowly stirred, is spray-dried after it is completely dissolved.After the spray powder of gained is dispersed in water again, measures its particle diameter distribution and see
Table 5.
Influence of the different spray drying supporting agents of table 5 to diameter of aspirin particle after spray drying
As a result showing, the aggregation that lactose can preferably suppress particle during suspension spray drying becomes big, and lactose hygroscopicity is smaller,
It is good solid pharmaceutical preparation auxiliary material.
Medication amount and influence of the galactose ratio to diameter of aspirin particle after spray drying in the suspension of embodiment 6
Medicine A suspension prescriptions：
Medicine A 50g
Hydroxypropyl cellulose 10g
Distilled water 500ml
Sand mill grinding suitable time obtains suspension
It is spray-dried prescription：
Medicine A suspensions 100ml
Appropriate lactose
Medicine A powder is made in suitable spray drying parameter
Preparation technology：After 10g hydroxypropyl celluloses are dissolved in into 500ml distilled water, 50g medicines are added under stirring
A is allowed to fully be suspended.It must be mixed using ESW-750 types laboratory sand mill (easily strangling electromechanical Co., Ltd in Shanghai) grinding suitable time
Suspension, LS-230 types particle size analyzer (Beckman companies) is used to measure drug particle average grain diameter as 0.517 μm, D90=
0.954μm.Above-mentioned suspension is divided equally 5 parts, every part of 100ml, by medicine：Lactose (10:1、4:1、2:1、1:1、1:2) ratio
Example, be separately added into 1,2.5,5,10,20g lactose as spray drying supporting agent, be slowly stirred, be spray-dried after it is completely dissolved.
After the spray powder of gained is dispersed in water again, measures its particle diameter distribution and be shown in Table 6.
Influence of the different proportion lactose of table 6 to diameter of aspirin particle after spray drying
As a result show, work as medicine：Galactose ratio is less than 2:When 1, when spray drying supporting agent can preferably suppress suspension spray drying
The aggregation of particle becomes big.The addition in view of excessive lactose can increase piece weight simultaneously, therefore medicine：Lactose (w/w) ratio is 1:2-
2:1, preferably 2:1.
The selection of the spray drying parameters of embodiment 7
Medicine A suspension prescriptions：
Medicine A 50g
Hydroxypropyl cellulose 10g
Distilled water
500ml
Sand mill grinding suitable time obtains suspension
It is spray-dried prescription：
Medicine A suspensions 500ml
Lactose 25g
Medicine A powder is made in suitable spray drying parameter
Preparation technology：After 10g hydroxypropyl celluloses are dissolved in into 500ml distilled water, 50g medicines are added under stirring
A is allowed to fully be suspended.It must be mixed using ESW-750 types laboratory sand mill (easily strangling electromechanical Co., Ltd in Shanghai) grinding suitable time
Suspension, LS-230 types particle size analyzer (Beckman companies) is used to measure drug particle average grain diameter as 0.801 μm, D90=
2.133μm.By above-mentioned 500ml medicines A suspensions, by medicine：Lactose (2:1) ratio, add 25g lactose and supported as spray drying
Agent, it is slowly stirred, after it is completely dissolved, is spray-dried.The spray powder particle diameter of spray drying parameters and gained is shown in Table 7.
Influence of the spray drying parameters of table 7 to medicine A spray powders particle diameter, moisture
Consider the speed of spray drying, medicine A spray powders particle diameter, moisture, select drying process with atomizing as follows：Air blast
Amount：60L/h, EAT：120 DEG C, leaving air temp：65 DEG C, cleansing pin frequency：1 time/3s, material flow：9ml/min.
The preparation of the medicine A powder of embodiment 8
Medicine A suspension prescriptions：
Medicine A 50g
Hydroxypropyl cellulose 10g
Distilled water 500ml
Sand mill grinding suitable time obtains suspension
It is spray-dried prescription：
Medicine A suspensions 500ml
Lactose 25g
Medicine A powder is made in suitable spray drying parameter
Preparation technology：After 10g hydroxypropyl celluloses are dissolved in into 500ml distilled water, 50g medicines are added under stirring
A is allowed to fully be suspended.It must be mixed using ESW-750 types laboratory sand mill (easily strangling electromechanical Co., Ltd in Shanghai) grinding suitable time
Suspension, drug particle average grain diameter is measured less than 1 μm using LS-230 types particle size analyzer (Beckman companies).Will be above-mentioned
500ml medicine A suspensions, by medicine：Lactose (2:1) ratio, 25g lactose is added as spray drying supporting agent, is slowly stirred, treats
After it is completely dissolved, it is spray-dried.Spray drying parameters are as follows：The blow rate required：60L/h, EAT：120 DEG C, go out wind-warm syndrome
Degree：65 DEG C, cleansing pin frequency：1 time/3s, material flow：9ml/min.Obtained medicine A powder average particle size≤5 μm, drug containing
Measure as 53.33%.
Medicine A powder is prepared by embodiment 8 in embodiment 9-11 prescriptions.
Embodiment 9 prepares tablet using wet granulation
Core formulation：
Coating fluid prescription：
Opadry (stomach dissolution type) 20g
Distilled water 200ml
The coating solution containing 10% solid content is made
Preparation technology：The lactose of medicine A powder and recipe quantity, starch, microcrystalline cellulose and Macrogol 6000 are pressed etc.
Method mixing of progressively increasing is measured, after mixing, with appropriate distilled water softwood, 30 mesh sieves is crossed and pelletizes, after 40 DEG C of dry 1h, it is whole to cross 20 mesh sieves
Grain, add recipe quantity low-substituted hydroxypropyl cellulose and magnesium stearate, tabletting after mixing, No. 7 punchings, piece weight 130mg, hardness 5-
7kg.(coating weight gain 2%) is coated using the Opadry coating solution of above-mentioned preparation, produced.
Embodiment 10 prepares tablet using dry granulation
Core formulation：
Coating fluid prescription：
Opadry (stomach dissolution type) 20g
Distilled water 200ml
The coating solution containing 10% solid content is made
Preparation technology：By the lactose of medicine A powder and recipe quantity, starch, microcrystalline cellulose, Macrogol 6000, it is interior plus
Amount low-substituted hydroxypropyl cellulose and magnesium stearate are mixed by equivalent method of progressively increasing, and after mixing, dry granulation, are weighed a certain amount of dry
Particle (30-80 mesh) and fine powder (being less than 80 mesh), particle：Fine powder (2:1) low-substituted hydroxypropyl of outer dosage, is added in prescription ratio
Base cellulose and magnesium stearate, tabletting after mixing, No. 7 punchings, piece weight 130mg, hardness 6-8kg.Using the Opadry of above-mentioned preparation
Coating solution is coated (coating weight gain 2%), produces.
Embodiment 11 prepares tablet using technique of direct powder compression
Core formulation：
Coating fluid prescription：
Opadry (stomach dissolution type) 20g
Distilled water 200ml
The coating solution containing 10% solid content is made
Preparation technology：By the lactose of medicine A powder and recipe quantity, starch, microcrystalline cellulose, Macrogol 6000, crosslinking
PVP, magnesium stearate by equivalent progressively increase method mixing, direct tablet compressing after mixing, No. 7 punching, piece weight 130mg, hardness 8-10kg.Adopt
(coating weight gain 2%) is coated with the Opadry coating solution of above-mentioned preparation, is produced.
The In Vitro Dissolution of embodiment 12 is tested
Thing A get it filled from film-making 1 (tablet obtained by embodiment 9), (removes and medicine A powder is replaced with into air-flow powder from film-making 2
Outside, other auxiliary materials are with embodiment 9 by medicine A (particle diameter is identical) after broken), (remove and medicine A powder is replaced with into medicine A from film-making 3
Outside, other auxiliary materials are with embodiment 9 for bulk drug (unprocessed)) according to dissolution determination method (Chinese Pharmacopoeia 2010 edition two
The methods of annex XC second), respectively using pH6.0, pH5.4 phosphate buffer 900ml as dissolution medium, rotating speed 50r/min, grasp in accordance with the law
Make, take out solution 10ml from stripping rotor in 5,10,15,20,30,45,60min respectively, while supplement same volume dissolution medium,
0.45 μm of filtering with microporous membrane, subsequent filtrate dilution suitable multiple is taken out, according to Ultraviolet spectrophotometry (Chinese Pharmacopoeia 2010 editions
Second annex IVA), absorbance is determined at 249nm wavelength, calculates accumulation dissolution rate, its stripping curve figure is shown in Fig. 1 and Fig. 2.
Conclusion：
From Fig. 1 and Fig. 2, with undressed bulk drug prepared by from film-making 3 and as described in CN102580097A
Prepared by method compares from film-making 2, is absorbed by medicine A powder prepared by the present invention with prepared by proper auxiliary materials from film-making 1 at it
Dissolution rate has significantly improved in the phosphate buffer (pH5.4 and pH6.0) of pH value at window.This to promote 2- ethyoxyls-
1- [[2'- (4,5- dihydro -5- oxo -1,2,4- oxadiazoles -3- bases) biphenyl -4- bases] methyl] -1H- benzimidazole -7- carboxylic acids
Inside absorb with raising its bioavilability it is significant.
Claims (6)
- A kind of 1. preparation method of medicine A powder, it is characterised in that：Using hydrophily suspending agent and medicine A co-grounds, utilize The average grain diameter of medicine is reduced to less than 5 μm by sand mill, and spray drying supporting agent is added in suspension after grinding, using spray 1-20 μm of medicine A powder of average grain diameter is made in mist seasoning, and described medicine A is 2- ethyoxyls -1- [[2'- (4,5- dihydro -5- Oxo -1,2,4- oxadiazoles -3- bases) biphenyl -4- bases] methyl] -1H- benzimidazole -7- carboxylic acids, described suspending agent is hydroxypropyl Base cellulose, the mass ratio 1 of the suspending agent and medicine A:2-1:20, the mass ratio of spray drying supporting agent and medicine is 1:2-2:1, The concentration of the suspending agent is 1-3%, and described spray drying supporting agent is lactose.
- 2. preparation method as claimed in claim 1, it is characterised in that：Medicine A average grain diameter is less than 5 μm after grinding.
- 3. preparation method as claimed in claim 1, it is characterised in that：Medicine A average grain diameter is less than 3 μm after grinding.
- 4. the preparation method described in claim 1, it is characterised in that：The technological parameter of spray drying process is as follows：The blow rate required：60L/ H, EAT：80-120 DEG C, leaving air temp：40-75 DEG C, cleansing pin frequency：1 time/3s, material flow：4-15ml/min.
- 5. the preparation method described in claim 4, it is characterised in that：What the drug powder after spray drying was dispersed in water again is averaged Particle diameter is less than 20 μm, obtained drug powder and pharmaceutically acceptable auxiliary material, can prepare piece by conventional technical means Agent, granule or hard shell capsules.
- 6. preparation method as claimed in claim 4, it is characterised in that：Drug powder after spray drying is dispersed in water flat again Equal particle diameter is less than 10 μm.
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| 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 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| 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 |
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| REVIEW ON SOLUBILITY ENHANCEMENT TECHNIQUES FOR HYDROPHOBIC DRUGS;Anuj Kumar etal;《PHARMACIE GLOBALE INTERNATIONAL JOURNAL OF COMPREHENSIVE PHARMACY》;20110305;第2卷(第3期);1-7 * |
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