CN102028659A - Valsartan bio-adhesive coated micro-pellet preparation and preparation method thereof - Google Patents
Valsartan bio-adhesive coated micro-pellet preparation and preparation method thereof Download PDFInfo
- Publication number
- CN102028659A CN102028659A CN2010105907905A CN201010590790A CN102028659A CN 102028659 A CN102028659 A CN 102028659A CN 2010105907905 A CN2010105907905 A CN 2010105907905A CN 201010590790 A CN201010590790 A CN 201010590790A CN 102028659 A CN102028659 A CN 102028659A
- Authority
- CN
- China
- Prior art keywords
- preparation
- valsartan
- coated micropill
- bioadhesive
- adhesiveness
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Abstract
The invention provides a valsartan bio-adhesive coated micro-pellet preparation and a preparation method thereof. The micro-pellet preparation consists of a medicine-loading pellet core for valsartan and pharmaceutic adjuvants, and an adhesive coat layer coating on the outside of the medicine-loading pellet core, and is characterized in that: the valsartan accounts for 20 to 80 weight percent of the pellet core; the adhesive coat layer consists of hydroxypropyl methyl cellulose and carbomer, wherein the carbomer accounts for 30 to 100 weight percent; and a weight part ratio of the coat layer to the medicine-loading pellet core is 5-25:100. The medicine-loading pellet core is prepared by an extrusion-spheronization method and is coated by a powder coating method. The bio-adhesive coated micro-pellet preparation has high bioadhesion and high retentivity in gastrointestinal tract, has the characteristics of simple preparation method, convenience, easy operation and the like, and can promote medicine absorption and improve bioavailability.
Description
Technical field
The present invention relates to pharmaceuticals novel form field, be specifically related to a kind of valsartan bioadhesive coated micropill preparation and preparation method thereof.
Background technology
Hypertension is a modal class cardiovascular and cerebrovascular disease.Nearly 9.72 hundred million people in the whole world suffer from hypertension or the higher disease of blood pressure.Be equivalent to adult population's 26.4%.China adult hypertension prevalence has risen to 18.8%.Whole nation number of patients has reached 1.6 hundred million people, has become the social problem that can not be ignored.Angiotensin II (ANG II) receptor antagonist is the another kind of antihypertensive drug after Angiotensin-Converting (ACE) inhibitor, compare with ACE inhibitor, the direct action receptor of this type of medicine, avoided ACE to suppress shortcoming, hypotensive effect is safe and reliable, side effect is little, and is bad or with light, the middle severe hypertension patient who occurs intractable dry cough behind the ACE preparation effect is preferably arranged to antihypertensive drugs curative effect commonly used.
Valsartan (Valsartan, trade name: DAIWEN) be another non-peptide class ANG II receptor antagonist behind losartan,, keep electrolyte body fluid balance aspect and play a crucial role regulating systemic blood pressure.Advantages such as that this medical instrument has is safe, long-acting, taking convenience, untoward reaction are slight, low price for clinical hypertensive treatment provides a kind of new drug, also have sure therapeutical effect to congestive heart failure, left ventricular hypertrophy, acute myocardial infarction etc.Valsartan (Valsartan) obtained drugs approved by FDA by Sweden CIBA and the exploitation of company of Switzerland Novartis (Novartis) in 1996, patent protection in 2012 expiration.Home products mainly is the DAIWEN of being produced by Switzerland Novartis, gets permission to produce at home in 2000.According to Datamonitor company report, 4,000,000,000 dollars have been reached to the world's 7 big medical market valsartan sales volumes in 2006.The domestic valsartan market sales revenue was 2.3 hundred million yuan in 2004.
The oral administration administration, the valsartan gastrointestinal absorption is rapid, and 2-4h can reach the blood drug level peak value.Because of drug absorption in the gastrointestinal tract mainly appears at digestive tract top, its bioavailability only is 23%.According to physical and chemical properties of drugs and pharmacokinetic characteristic, draw up and be equipped with gastrointestinal tract detention type bioadhesive preparation, by the medicine that slows down in the gastrointestinal transport speed, but or make medicine be positioned at the time of contact at approach prolong drug such as absorption window top and small intestinal position by gastric retention, absorb thereby the body that improves medicine is interior, if can improve bioavailability, can realize further that curative effect of medication increases, side effect reduces.Bioadhesive microparticle formulation (bioadhesive microparticles) is subject to people's attention as a kind of novel drug-supplying system.For the medicine in stomach or epimere intestinal absorption, gastric retention system is the most satisfied.The main preparation type that prolongs the gastric retention time comprises: in-stomach floating type, bioadhesion type, volumetric expansion type, high density type etc., recently, the application of microparticle formulation in the gastric retention medicine-releasing system, not only be confined to prolong the preparation holdup time under one's belt, microgranule unit in the preparation is dispersed in gastric with the independent individual form, can freely pass through pylorus, therefore can extensively be distributed in the gastrointestinal tract, longer gastrointestinal tract holdup time, littler individual variation, higher local drug concentration and better stability be arranged than single unit preparation.
Summary of the invention
For these reasons, by valsartan and the high molecular physicochemical property of bioadhesive are carried out deep analysis, inside and outside adhesiveness and drug release rate with coated micropill are index, experiment by science, determine ball core and coating membrane material, and excipient and adhesion material are carried out determining of weight percentage.By complete technical scheme, according to the preparation method of the micropill of prior art, just can prepare satisfactory bioadhesive pellet preparations, help improving bioavailability of medicament.Medicine and excipient are pushed round as a ball preparation ball core, main constituent can discharge rapidly along with the dissolving of excipient, coated micropill has stronger bioadhesive, but coatings does not influence the release of medicine, and this product by tens, micropill unit that the hundreds of grain is little forms, and disperses in vivo or to stick area big, the organ contacted specific surface area is also big with absorbing, so onset is rapid after making this product take, the bioavailability height.
Therefore, the object of the present invention is to provide a kind of epigranular, the surface is regular and have the coated micropill preparation of excellent inside and outside bioadhesive; Another object of the present invention is to provide the preparation method of above-mentioned coated micropill preparation, this method is simple, convenient, easy operating.
The objective of the invention is to be achieved through the following technical solutions.Coated micropill preparation of the present invention is formed by carrying pill core and adhesiveness coatings, the weight percentage that it is characterized in that valsartan in the ball core is 20～80%, the adhesiveness coatings is made up of hydroxypropyl emthylcellulose and carbomer, wherein the weight percentage of carbomer is 30～100%, and coatings is 5～25: 100 with carrying the pill core ratio of weight and number.
Said year pill core of the present invention is made up of medicine and pharmaceutic adjuvant.Wherein, pharmaceutic adjuvant comprises a kind of in sucrose, dextrin, microcrystalline Cellulose, starch, lactose, methylcellulose, hydroxy methocel, hydroxypropyl emthylcellulose, gelatin, the polyvinylpyrrolidone or several.Pharmaceutic adjuvant of the present invention is microcrystalline Cellulose and polyvinylpyrrolidone more preferably.
The said adhesiveness coatings of the present invention is by a kind of in cellulose derivative (for example methylcellulose, ethoxy propyl cellulose, hydroxypropyl emthylcellulose, hydroxypropyl cellulose), starch and starch derivatives, carbomer, polyacrylate, tragakanta, sodium alginate, gelatin, pectin, arabic gum, the polyvinylpyrrolidone or several.Adhesion material of the present invention is hydroxypropyl emthylcellulose and carbomer more preferably.
The invention provides the preparation method of above-mentioned adhesiveness coated micropill preparation, this method comprises the steps:
1. carry the preparation of pill core
After valsartan and microcrystalline Cellulose crossed 80 mesh sieves respectively, press 20-80%: the weight ratio mixing of 80-20%, it is an amount of dropwise to add 2% polyvinylpyrrolidone (PVP K30) aqueous solution, and the system soft material prepares the ball core with pushing round as a ball comminutor.Under 60 ℃ of conditions, dry 5h.
2. the preparation of coated micropill
By the hydroxypropyl emthylcellulose (HPMC K4M) of different proportion (be respectively 1: 2,1: 1,2: 1) and carbomer (CP934P) and mixture is coating material, and the alcoholic solution with 80% carries out powder coating and drying as binding agent to the ball core.
3. process conditions
The rotational frequency of extruder and spheronizator is between 30～40Hz; The centrifuge speed frequency is 20～30Hz during coating; The flow velocity of binding agent is 1～1.5ml/min; Nozzle atomization pressure is 0.1～0.5Mpa.
The invention effect
The bioadhesive coated micropill of the present invention's preparation has excellent water absorption, adhesion and gastrointestinal tract direct current ability, can promote drug absorption, and improves bioavailability, and advantage of the present invention is as follows:
1, year pill core and the coated micropill of the present invention's preparation, regular, the epigranular (85% above ball core, granularity is between the 24-30 order) in surface.
2, the micropill of the present invention's preparation, its coatings does not influence the drug release rate of micropill.
3, to select hydroxypropyl emthylcellulose (HPMC K4M) and carbomer (CP934P) be the bioadhesive coating material in the present invention, has stronger absorbability, can produce excellent inside and outside adhesiveness and gastrointestinal tract retentivity.
4, the bioadhesive coated micropill of the present invention preparation because micropill is not subjected to the influence of gastric emptying factor, can reduce between medication crowd's individuality or self difference.Compare with coated tablet, repeatability, the concordance of release rule are better; Can extensively be distributed in the gastrointestinal tract, long gastrointestinal tract holdup time, littler individual variation, higher local drug concentration are arranged.
The specific embodiment
Valsartan bioadhesive coated micropill preparation is further specified technical scheme of the present invention by following examples, but protection scope of the present invention is not limited to this.
Embodiment 1: the preparation of carrying pill core
Precision takes by weighing valsartan 60g and microcrystalline Cellulose 180g, cross 80 mesh sieves respectively after, mixing, it is an amount of dropwise to add 2% PVPK30 aqueous solution, the system soft material prepares the ball core with pushing round as a ball comminutor.Under 60 ℃ of conditions, dry 5h.The rotational frequency of extruder and spheronizator is between 30～40Hz.
Embodiment 2: the preparation of coated micropill
Precision takes by weighing carries pill core (embodiment a 1) 30g, is coating material by the mixture of HPMC K4M 4g, CP934P 2g and silicon dioxide 0.06g, and the alcoholic solution with 80% carries out powder coating as binding agent to the ball core, and dry 3h.The weightening finish ratio of coated micropill is 16.6%.The centrifuge speed frequency is 20～30Hz during coating; The flow velocity of binding agent is 1～1.5ml/min; Nozzle atomization pressure is 0.1～0.5Mpa.
Embodiment 3: the preparation of coated micropill
Precision takes by weighing carries pill core (embodiment a 1) 30g, is coating material by the mixture of HPMC K4M 3g, CP934P 3g and silicon dioxide 0.06g, and the alcoholic solution with 80% carries out powder coating as binding agent to the ball core, and dry 3h.The weightening finish ratio of coated micropill is 15.4%.The centrifuge speed frequency is 20～30Hz during coating; The flow velocity of binding agent is 1～1.5ml/min; Nozzle atomization pressure is 0.1～0.5Mpa.
Embodiment 4: the preparation of coated micropill
Precision takes by weighing carries pill core (embodiment a 1) 30g, is coating material by the mixture of HPMC K4M 2g, CP934P 4g and silicon dioxide 0.06g, and the alcoholic solution with 80% carries out powder coating as binding agent to the ball core, and dry 3h.The weightening finish ratio of coated micropill is 5.4%.The centrifuge speed frequency is 20～30Hz during coating; The flow velocity of binding agent is 1～1.5ml/min; Nozzle atomization pressure is 0.1～0.5Mpa.
Embodiment 5: the preparation of coated micropill
Precision takes by weighing carries pill core (embodiment a 1) 30g, is coating material by the mixture of HPMC K4M 2g and CP934P 4g and silicon dioxide 0.06g, and the alcoholic solution with 80% carries out powder coating as binding agent to the ball core, and dry 3h.The weightening finish ratio of coated micropill is 11.8%.The centrifuge speed frequency is 20～30Hz during coating; The flow velocity of binding agent is 1～1.5ml/min; Nozzle atomization pressure is 0.1～0.5Mpa.
Embodiment 6: the preparation of coated micropill
Precision takes by weighing carries pill core (embodiment a 1) 30g, is coating material by the mixture of HPMC K4M 2g, CP934P 4g and silicon dioxide 0.06g, and the alcoholic solution with 80% carries out powder coating as binding agent to the ball core, and dry 3h.The weightening finish ratio of coated micropill is 17.7%.The centrifuge speed frequency is 20～30Hz during coating; The flow velocity of binding agent is 1～1.5ml/min; Nozzle atomization pressure is 0.1～0.5Mpa.
Embodiment 7: the particle size distribution measuring that carries pill core
Precision takes by weighing carries pill core (embodiment 1) 20g, successively by 18 orders, 24 orders, 30 orders, 34 mesh sieves, and calculated weight percentage ratio.The result of particle size distribution measuring as shown in Figure 1.
Embodiment 8: the microscopic pattern of micropill is investigated
Utilize scanning electron microscopic observation to carry the surface and the cross section of pill core (embodiment 1) and coated micropill (embodiment 6).The result as shown in Figure 2.
Embodiment 9: the dissolution rate of micropill is measured
Take by weighing each 3 parts of the coated micropills ( embodiment 2,3,4,5,6) of the ball core (embodiment 1) that contains the 80mg valsartan and different prescriptions, according to second appendix XC of Chinese Pharmacopoeia version in 2005, adopt second method (oar method), PBS (PH=6.8) with 0.05M is a dissolution medium, bath temperature is adjusted to 37 ℃, rotating speed is 50rpm, respectively 5,15,30,60,120,240, the 360min 1ml that takes a sample.After dissolution fluid filters, analyze, calculate the stripping percentage rate through HPLC.What dissolution rate was measured the results are shown in Figure 3, shown in Figure 4.
Embodiment 10: the absorbability of micropill is measured
Take by weighing and carry pill core (embodiment 1) and different each 320mg of prescription coated micropill (embodiment 2,3,6), add water 1ml, behind the moistening 5min, excessive moisture around the micropill surface is removed, calculate the water absorption of ball core and coated particle with filter paper.The experiment triplicate is averaged.The result as shown in Figure 5.
Embodiment 11: the adhesion of micropill is measured
Adopt self-control adhesion determinator, estimate the adhesiveness of different prescription micropills.With pressure sensitive adhesive double coated fresh eggshell membrane is attached to the lower surface of plastic sheet and the upper surface of following plastic sheet, the microgranule 160mg of difference prescription to be measured again is tiled on the plastic sheet, and it is moistening to add about 0.5ml water, applies external force 3N, continues 5min.Remove external force behind the 5min, open fluid-delivery valve, drop to the bottom plastic bag and come off, record drips the water yield, comes comparison water absorbing capacity size with this.Repeat above operation three times, average.The result as shown in Figure 6.
Embodiment 12: the gastrointestinal tract retentivity of micropill relatively
4 of the SD rats of selection 250～300g body weight, experiment is preceding with fasting 24 hours.Rat is divided into 2 groups at random, 2 every group.To carry pill core (embodiment 1) and coated micropill (embodiment 6) [principal agent: 1.67mg/200g] is respectively charged into microencapsulation, as reference preparation with for test preparation.Rat is fixed on the operating-table with etherization, respectively with reference preparation with for the test preparation gastric infusion.After 6 hours, its stomach, small intestinal and large intestine are got in its execution, the place cuts off along the stomach cardia, observes the position of microgranule on rat gastrointestinal tract mucosa wall, measures the distance of microgranule apart from stomach cardia place.The result as shown in Figure 7.
Description of drawings
Fig. 1 carries the particle size distribution figure of pill core (embodiment 1)
Fig. 2 carries the surface and the cross-sectional view (A: ball wicking surface of pill core (embodiment 1) and coated micropill (embodiment 6); B: coated micropill surface; C: ball core cross section; D: the coated micropill cross section)
The dissolution rate curve of Fig. 3,4 years pill cores (embodiment 1) and coated micropill ( embodiment 2,3,4,5,6)
The water absorbing properties that Fig. 5 carries pill core (embodiment 1) and coated micropill (embodiment 2,3,6) compares
The adhesion that Fig. 6 carries pill core (embodiment 1) and coated micropill (embodiment 2,3,6) compares
The gastrointestinal tract retentivity that Fig. 7 carries pill core (embodiment 1) and coated micropill (embodiment 2,3,6) compares.
Claims (8)
1. a valsartan bioadhesive coated micropill preparation is formed by carrying pill core and being wrapped in its outer adhesiveness coatings, and coatings is 5～30: 100 with carrying the pill core ratio of weight and number.
2. bioadhesive coated micropill preparation as claimed in claim 1 is characterized in that carrying pharmaceutic adjuvant in the pill core and comprises a kind of in microcrystalline Cellulose, starch, lactose, the polyvinylpyrrolidone or several.
3. bioadhesive coated micropill preparation as claimed in claim 2 is characterized in that the pharmaceutic adjuvant of medicine carrying in intact is more preferably in microcrystalline Cellulose and polyvinylpyrrolidone.
4. bioadhesive coated micropill preparation as claimed in claim 1 or 2, the weight percentage that it is characterized in that carrying valsartan in the pill core is 20～80%.
5. bioadhesive coated micropill preparation as claimed in claim 1, what it is characterized in that the adhesiveness coatings consists of a kind of in hydroxypropyl emthylcellulose, carbomer, polyacrylate, tragakanta, the sodium alginate or several.
6. bioadhesive coated micropill preparation as claimed in claim 5, the composition that it is characterized in that the adhesiveness coatings is more preferably in hydroxypropyl emthylcellulose and carbomer.
7. bioadhesive coated micropill preparation as claimed in claim 6, the weight percentage that it is characterized in that carbomer in the adhesiveness coatings is 30～100%.
8. the preparation method of valsartan bioadhesive coated micropill preparation according to claim 1, carry out as follows:
(1) valsartan is mixed with pharmaceutic adjuvant, and the mixing that sieves.
(2) add binder solution system soft material, carry pill core with the round as a ball comminutor preparation of extruding, and dry.
(3) adhesiveness material by different proportion is a coating material, is binding agent with the alcoholic solution, and the ball core is carried out powder coating, and dry.
(4) rotational frequency of extruder and spheronizator is between 30～40Hz; The centrifuge speed frequency is 20～30Hz during coating; The flow velocity of binding agent is 1～1.5ml/min; Nozzle atomization pressure is 0.1～0.5Mpa.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105907905A CN102028659A (en) | 2010-12-16 | 2010-12-16 | Valsartan bio-adhesive coated micro-pellet preparation and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105907905A CN102028659A (en) | 2010-12-16 | 2010-12-16 | Valsartan bio-adhesive coated micro-pellet preparation and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102028659A true CN102028659A (en) | 2011-04-27 |
Family
ID=43882470
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010105907905A Pending CN102028659A (en) | 2010-12-16 | 2010-12-16 | Valsartan bio-adhesive coated micro-pellet preparation and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102028659A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107837374A (en) * | 2017-09-20 | 2018-03-27 | 江西中医药大学 | A kind of Tibetan medicine five tastes pomegranate stomach adhesive pellet and its preparation technology |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007086078A2 (en) * | 2006-01-30 | 2007-08-02 | Panacea Biotec Ltd. | Novel pharmaceutical compositions and process of preparation thereof |
| WO2009148990A1 (en) * | 2008-06-03 | 2009-12-10 | Novartis Ag | Pulsatile release of valsartan |
-
2010
- 2010-12-16 CN CN2010105907905A patent/CN102028659A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007086078A2 (en) * | 2006-01-30 | 2007-08-02 | Panacea Biotec Ltd. | Novel pharmaceutical compositions and process of preparation thereof |
| WO2009148990A1 (en) * | 2008-06-03 | 2009-12-10 | Novartis Ag | Pulsatile release of valsartan |
Non-Patent Citations (1)
| Title |
|---|
| JINGSHU PIAO等: "Development of Novel Mucoadhesive Pellets of Metformin Hydrochloride chloride", 《ARCHIVES OF PHARMACAL RESEARCH》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107837374A (en) * | 2017-09-20 | 2018-03-27 | 江西中医药大学 | A kind of Tibetan medicine five tastes pomegranate stomach adhesive pellet and its preparation technology |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8920835B2 (en) | Paliperidone double-layered osmotic pump controlled release tablet and preparation method thereof | |
| EP1878444B1 (en) | Composition containing anti-dementia drug | |
| Cao et al. | Enhanced oral bioavailability of novel mucoadhesive pellets containing valsartan prepared by a dry powder-coating technique | |
| CN101574323B (en) | Migltol microcapsule tablet and preparation method thereof | |
| US7192608B2 (en) | Method of manufacturing drug granules, the drug granules and pharmaceutical preparation containing the drug granules | |
| CN101495103A (en) | Pharmaceutical preparation for oral administration with controlled drug release in the small intestine colon and process of prepartion thereof | |
| CN101808665A (en) | The drug regimen of aliskiren and valsartan | |
| WO2014040548A1 (en) | Metoprolol sustained-release drug and preparation method therefor | |
| CN106619520B (en) | A kind of dry suspensoid agent and preparation method thereof of R-lansoprazole sodium | |
| CN103379901B (en) | Formula containing Desmoidpillen | |
| CN100571703C (en) | Sustained-release micro-pellet of trimetazidine and preparation method thereof | |
| CN102762198A (en) | Multi-unit compositions | |
| CN102028659A (en) | Valsartan bio-adhesive coated micro-pellet preparation and preparation method thereof | |
| CN101099762B (en) | Blood pressue lowering sustained-release preparation with chrysanthemum flower and pearl | |
| CN101991720A (en) | Jiechangning target-oriented drug delivery preparation and application thereof | |
| CN110251473A (en) | Hydroxyl piperazine pyrrone oral slow-releasing preparation | |
| CN106074442B (en) | A kind of doxycycline hyclate enteric-coated piller and preparation method thereof | |
| CN107019680B (en) | A kind of preparation process of sodium rabeprazole enteric-coated capsule | |
| CN102058564A (en) | Zaltoprofen slow-release/controlled-release preparation and preparation method thereof | |
| CN105764509B (en) | Dabigatran etcxilate or the dispensing preparation of its salt and preparation method thereof | |
| CN102247326B (en) | Oral chronopharmacologic drug delivery mini-pill preparation of propranolol and its salts | |
| CN108283628A (en) | A kind of anticancer drug microcapsule formulation and preparation method thereof | |
| Muskó et al. | Study of in vitro and in vivo dissolution of theophylline from film-coated pellets | |
| CN115671054A (en) | Mannitol pellet core and preparation method and application thereof | |
| CN103948558B (en) | A kind of posaconazole double-layer osmotic pump controlled-release tablet and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20110427 |