CN102657625A - Acidic blank pellet core and preparation method thereof - Google Patents
Acidic blank pellet core and preparation method thereof Download PDFInfo
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- CN102657625A CN102657625A CN2012101343391A CN201210134339A CN102657625A CN 102657625 A CN102657625 A CN 102657625A CN 2012101343391 A CN2012101343391 A CN 2012101343391A CN 201210134339 A CN201210134339 A CN 201210134339A CN 102657625 A CN102657625 A CN 102657625A
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Abstract
The invention discloses an acidic blank pellet core, which comprises a blank pellet core and an organic acid and is used for substituting a common blank pellet core in a sustained-release pellet preparation. Medicaments can be prepared into the sustained-release pellet preparation which can be stably released under the condition that the pH is 1.5 to 7.4, the release pH dependency of most conventional weakly alkaline medicaments is eliminated, the medicinal preparation can be released in stomach and intestinal tracts stably and slowly, and the medicament effect is lasting. Moreover, the invention also discloses a preparation method for the acidic blank pellet core. The method is simple and convenient, and facilitates industrialized production; and the acidic blank pellet core substitutes the conventional blank pellet core, is used for the sustained-release pellet preparation, can eliminate the release pH dependency of the alkaline medicaments, and has a wide application prospect.
Description
Technical field
The invention belongs to the pharmaceutical preparations technology field, relate to a kind of preparation and use celphere, relate in particular to a kind of acid celphere and preparation method thereof.
Background technology
Micropill is meant all kinds of pills of diameter less than 2.5mm, can be made into rapid release or slow-release micro-pill according to different needs.Micropill can be suppressed in flakes, also can be loaded on and process capsule in the capsule shells.In recent years, micropill receives people's attention day by day, becomes a main trend slow, the controlled release preparation development.Domestic and international many companies all produce this preparation now; Contac (Contac) slow releasing capsule like the production of Sino-U.S. SmithKline company; The aspirin sustained release capsule that pharmaceutical factory of China Medicine University produces, the import drugs diclofenac sodium extended release capsule (Olfen-100) of China's Ministry of Public Health approval in 1997 etc.
Why micropill receives people's favor, is because the advantage that it has many other oral formulations to compare: 1. can process sustained-release preparation through slow controlled release micro pill coating; 2. big at the gastrointestinal tract distribution area, bioavailability is high, and zest is little; 3. because particle diameter is little, receive digestive tract to carry the food rhythm and pace of moving things to influence little (close like pylorus etc.); 4. slow-release micro-pill can make blood drug level reach curative effect concentration rapidly, and keeps steady, long valid density, and the fluctuation of blood medicine is little; 5. the good fluidity of micropill is evenly big or small, is easy to handle (like coating, divided dose); 6. improve medicine stability, cover disagreeable taste; 7. the compatibility that is fit to compound preparation.
At present the emphasis of research is a slow-release micro-pill, and slow-release micro-pill is to be mixed and made into or to process earlier a year pill core by medicine and blocker then to wrap release membranes again and form.Preparation technology commonly used adopts mode such as lamination medicine-feeding on general celphere, pharmaceutical pack is wrapped on the celphere, processes to contain pill core, and the bundled slow-releasing coating material is processed sustained-release pellet preparation again.
The sustained-release pellet preparation of processing has the advantages such as stable, lasting that discharge; Can stablize after taking and discharge more than 8 hours; Improve absorbing the time of medicine greatly; Reduce the peak valley situation of drug release, reduce medicine toxic and side effects and patient take number of times, have significant advantage than conventional formulation.
But the gastrointestinal environment is complicated than other administration route, and the relatively short holdup time has also been limited the application and the development of gastrointestinal tract durative action preparation.The changeable chemical environment of whole gastrointestinal tract also makes the design of dosage form become more complicated simultaneously.In fact medicine will meet with a series of pH value variations when gastrointestinal absorption, and the pH in normal human oral cavity is 7, and gastrointestinal pH is 1-7; The pH of gastric juice is 0.9-1.5, and duodenal pH is 7.6-8.2, and the pH of small intestinal is 7.6; The pH of large intestine is 8.3-8.4, and the pH of gastrointestinal tract environment can change because of several factors, and (pH of gastric juice is 0.9-1.5 on an empty stomach like food; After drinking-water or the feed, pH can rise to about 3.0-5.0), age, disease, combination with medication etc.And the dissociated state of different pH environment decision faintly acids of gastrointestinal and weakly basic drugs, the change of its pH can influence the dissolubility of oral drugs, and then the absorption of medicine is exerted an influence.In addition, the pH in the gastrointestinal tract possibly exert an influence to the stability of some drugs.
The oral sustained release pellet preparations since in vivo in the gastrointestinal tract time of staying longer, thereby the different pH environment of the different sections of gastrointestinal tract possibly exert an influence to its rate of releasing drug.Especially some weak acid and weak base property medicines, its dissolubility is tangible pH dependency.Thereby possibly cause the drug release individual variation to increase on the one hand, also cause the extracorporeal releasing test result who under controlled pH conditions, carries out to reflect exactly that preparation release conditions in vivo reduces on the other hand.Therefore, being prepared into pH independent form sustained-release pellet preparation can overcome the above problems.
The sustained-release pellet preparation Oxybrain processed of weakly basic drugs vincamine for example; It discharges and just has tangible pH dependency; It can discharge under acid condition preferably; But release is lower under neutrality or alkalescence property condition, and it is not good that this causes it in being weakly alkaline intestinal environment, to discharge, thereby influence effect of drugs.
Summary of the invention
One of technical problem that the present invention will solve provides a kind of acid celphere, is processed by celphere and organic acid, and alternative traditional celphere is widely used in the sustained-release pellet preparation of weakly basic drugs, solves the pH dependency of its drug release.
Two of the technical problem that the present invention will solve provides a kind of method for preparing of acid celphere; Adopt present general preparation equipment can realize the preparation of acid celphere; But the simple industrialization of technology; And can form a kind of preparation raw material of unified standard, extensive use in the preparation industry.
For addressing the above problem, the present invention adopts following technical proposals:
Acid celphere provided by the invention comprises celphere and organic acid, and its prescription is formed calculation by weight, and ratio is 10: (1～50), preferred weight ratio are 1: 2.
Described celphere is commercially available general kind.
Described organic acid can be selected from any one or a few in citric acid, tartaric acid, malic acid, caffeic acid, salicylic acid, adipic acid, the succinic acid etc., preferred tartaric acid.
In addition, the present invention also provides the method for preparing of described acid celphere: get water and/or ethanol that organic acid adds 2～10 times of weight, process organic acid soln, adopt preparation equipment that this organic acid soln is covered in the celphere surface, promptly get after the drying.
Described preparation equipment comprises fluid bed, extrudes round as a ball, centrifugal coating pelletizing machine and coating pan.
The present invention has following beneficial effect:
1, a kind of acid celphere provided by the invention; Process by celphere and organic acid; Alternative traditional celphere is widely used in the sustained-release pellet preparation of weakly basic drugs; Solve the pH dependency of its drug release, can realize that weakly basic drugs is stable in pH1.5～7.4, discharge uniformly, improve the release degree of medicine greatly and absorb efficient.
2, the method for preparing of a kind of acid celphere provided by the invention; Adopt present general preparation equipment can realize the preparation of acid celphere; But the simple industrialization of technology; And can form a kind of preparation raw material of unified standard, in the preparation industry, be widely used in having application promise in clinical practice in the sustained-release pellet preparation of weakly basic drugs.
Description of drawings
Fig. 1 is the vincamine release degree result of the test sketch map under the pH7.4 condition that adopts acid celphere of the present invention and common celphere to process;
Fig. 2 is the famotidine release degree result of the test sketch map under the pH7.4 condition that adopts acid celphere of the present invention and common celphere to process;
Fig. 3 is the clarithromycin release degree result of the test sketch map under the pH7.4 condition that adopts acid celphere of the present invention and common celphere to process;
Fig. 4 is the atenolol release degree result of the test sketch map under the pH7.4 condition that adopts acid celphere of the present invention and common celphere to process.
The specific embodiment
Below through embodiment the present invention is done further elaboration.Described preparation equipment can adopt fluid bed, extrudes spheronizator, centrifugal coating pelletizing machine or coating pan are this area common equipment, is the commercially available prod.
Celphere 50g
Tartaric acid 100g
Get tartaric acid adding 300ml water and make dissolving, process organic acid soln.Celphere is placed in the fluid bed, spray into organic acid soln, make it to be covered in the ball wicking surface, take out dry back, promptly gets acid celphere.
Celphere 100g
Citric acid 50g
Get citric acid adding 500ml water and make dissolving, process organic acid soln.Celphere is placed in the fluid bed, spray into organic acid soln, make it to be covered in the ball wicking surface, take out dry back, promptly gets acid celphere.
Celphere 100g
Tartaric acid 5g
Malic acid 5g
Get tartaric acid and malic acid adding 30ml water and make dissolving, process organic acid soln.Celphere placed extrude in the rolling circle equipment, spray into organic acid soln, make it to be covered in the ball wicking surface, take out dry back, promptly gets acid celphere.
Get caffeic acid, salicylic acid and adipic acid adding 500ml ethanol and make dissolving, process organic acid soln.Celphere is placed in the fluid unit, spray into organic acid soln, make it to be covered in the ball wicking surface, take out dry back, promptly gets acid celphere.
Celphere 50g
Tartaric acid 100g
Succinic acid 50g
Get that tartaric acid and succinic acid add 300ml ethanol, 300ml water makes dissolving, process organic acid soln.Celphere is placed in the centrifugal coating pelletizing equipment, spray into organic acid soln, make it to be covered in the ball wicking surface, take out dry back, promptly gets acid celphere.
Below beneficial effect of the present invention is done further to set forth through comparative experimental example.
For further specifying effect of the present invention, choose acid celphere and common celphere that weakly basic drugs commonly used adopts the embodiment of the invention respectively and process sustained-release pellet preparation and compare research.Investigate each preparation respectively and using the release degree under acid (pH1.5) and alkalescence (pH7.4) condition under two kinds of ball core situation.
The release profiles of each medicine under the pH7.4 condition seen Fig. 1-4, and Fig. 1 is the vincamine release degree result of the test sketch map under the pH7.4 condition that adopts acid celphere of the present invention and common celphere to process; Fig. 2 is the famotidine release degree result of the test sketch map under the pH7.4 condition that adopts acid celphere of the present invention and common celphere to process; Fig. 3 is the clarithromycin release degree result of the test sketch map under the pH7.4 condition that adopts acid celphere of the present invention and common celphere to process; Fig. 4 is the atenolol release degree result of the test sketch map under the pH7.4 condition that adopts acid celphere of the present invention and common celphere to process.Result like Fig. 1-Fig. 4 shows that the medicine releasing effect under acid condition that adopts two kinds of ball cores is similar; Under weak basic condition, discharge then obviously differently, adopt the medicament slow release pellet preparations releasing effect of acid celphere obviously to be superior to adopting the same medicament slow release pellet preparations of common celphere.It is thus clear that acid celphere of the present invention all can substitute traditional celphere, be applied in the weakly basic drugs sustained-release pellet preparation, solve the pH dependency of drug release, make medicine can in pH1.5～7.4 scopes, stablize release.
Claims (7)
1. an acid celphere is characterized in that, said acid celphere comprises celphere and organic acid.
2. acid celphere as claimed in claim 1 is characterized in that, said celphere and organic acid weight ratio are 10: (1～50).
3. acid celphere as claimed in claim 2 is characterized in that, said celphere and organic acid weight ratio are 1: 2.
4. acid celphere as claimed in claim 1 is characterized in that said organic acid is selected from any one or a few in citric acid, tartaric acid, malic acid, caffeic acid, salicylic acid, adipic acid, the succinic acid.
5. acid celphere as claimed in claim 4 is characterized in that, said organic acid is a tartaric acid.
6. method for preparing like each described acid celphere of claim 1-5; It is characterized in that; Get the water and/or the ethanol of 2～10 times of weight of organic acid adding and process organic acid soln, adopt preparation equipment that this organic acid soln is covered in the celphere surface, promptly get after the drying.
7. the method for preparing of acid celphere as claimed in claim 6 is characterized in that, said preparation equipment comprises fluid bed, extrudes round as a ball, centrifugal coating pelletizing machine and coating pan.
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| CN2012101343391A CN102657625A (en) | 2012-05-02 | 2012-05-02 | Acidic blank pellet core and preparation method thereof |
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| CN2012101343391A CN102657625A (en) | 2012-05-02 | 2012-05-02 | Acidic blank pellet core and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104274319A (en) * | 2013-07-11 | 2015-01-14 | 天士力制药集团股份有限公司 | Method for dropping drop pills by vibration |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101574328A (en) * | 2009-06-18 | 2009-11-11 | 中国药科大学 | Timing pulsed release micro-pill of zolpidem salt |
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- 2012-05-02 CN CN2012101343391A patent/CN102657625A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101574328A (en) * | 2009-06-18 | 2009-11-11 | 中国药科大学 | Timing pulsed release micro-pill of zolpidem salt |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104274319A (en) * | 2013-07-11 | 2015-01-14 | 天士力制药集团股份有限公司 | Method for dropping drop pills by vibration |
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Application publication date: 20120912 |