CN101829111B - Valsartan-containing solid preparation and preparation method thereof - Google Patents
Valsartan-containing solid preparation and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a valsartan-containing medicine preparation which at least comprises valsartan or pharmaceutically acceptable salt thereof that is taken as active ingredient, and at least two disintegrating agents, wherein the proportion of the two disintegrating agents is within the range of 1:2-2:1. The invention also relates to a preparation method of the valsartan-containing medicine preparation, which comprises the steps of: first, pelletizing the valsartan or the pharmaceutically acceptable salt thereof by a roller press way, and then mixing with the at least two disintegrating agents and other pharmaceutic adjuvant; and finally, tabletting or filling into capsules. Compared with the prior art, the valsartan-containing medicine preparation has better stability. The method has simple technique and high production efficiency, and is suitable for industrialized production.
Description
Technical field
The present invention relates to a kind of pharmaceutical preparation and preparation method thereof, be specifically related to preparation of valsartan or its pharmaceutically acceptable salt and preparation method thereof.
Background technology
Valsartan is a kind of angiotensin (AT) II receptor antagonist of high specificity, it optionally acts on AT1 receptor subtype, AT1 receptor subtype produces reaction to the known action of angiotensinⅡ, AT2 receptor subtype and Cardiovascular have nothing to do, and valsartan is to the activity of AT1 receptor without any partial agonist.Valsartan is stronger than AT2 receptor 20000 times with the affinity of AT1 receptor.The oral rear peak time of valsartan is 2 ~ 4 hours, and absolute bioavailability is about 25%.
Structural formula:
Valsartan Yuan Yan company is Novartis, and commodity are called
respectively at nineteen ninety-five December and in July, 1996 Europe and the U.S. approval go on the market, specification has 40mg, 80mg, 160mg, 320mg.In October, 1997,
valsartan and Hydrochlorothiade sheet is first in Germany's listing, and specification has 80/12.5mg, 160/12.5mg, 160/25mg, 320/12.5mg and 320/25mg.2007,
amlodipine and valsartan sheet is successively in Britain, and the ground listings such as the U.S., the specification of wherein U.S.'s listing has 5/160mg, 10/160mg, 5/320mg, 10/320mg.
Valsartan is the minimum and medicine that is indissoluble in water of a kind of bulk density, and the stripping of the slice, thin piece adopting conventional method to prepare is all undesirable.Pharmaceutically, in order to accelerate stripping, usually need reduce raw material particle size and add a large amount of disintegrating agents, to reach the effect of rapid disintegrate and Fast Stripping.
Disintegrating agent is often referred to and can makes tablet in gastro-intestinal Fluid, split rapidly the material being broken into fine particle, thus makes the rapid solution absorption of active component, plays a role.This kind of material mostly has good water absorption and dilatancy, thus realizes the disintegrate of tablet.
Due to disintegrating agent very easily moisture absorption itself, add a large amount of disintegrating agent in tablets and can cause the easy moisture absorption of tablet, in storage process, moisture raises, and valsartan raw material is clamminess after meeting water, and cause hardness to become large, cause slice, thin piece disintegrate difficulty, dissolution rate is slack-off.Thus finished product is not easy storage.Sheet is ground by former
(Novartis), at 60 DEG C, places 10 days under 90% relative humidities, or at 40 DEG C, places and find for 3 months under 75% relative humidity, and slice, thin piece becomes very hard, cannot disintegrate.
Chinese patent application CN1636561A, applicant Novartis, disclose the composition of the valsartan formulation containing the microcrystalline Cellulose of more than 30% and the polyvinylpolypyrrolidone of 2 ~ 13%.But for ensureing the dissolution rate of product, the polyvinylpolypyrrolidone of low dosage can not be used, such as in embodiment, the minimum scale of disintegrating agent polyvinylpolypyrrolidone is 9.6% (disregarding coating weight gain or capsule shells weight), because polyvinylpolypyrrolidone itself draws by force moist, if the ratio accounted in preparation is very large, product moisture in long storage periods can be made to increase very fast, cause disintegrate to slow down, stripping is defective.
European patent EP 1994926A1 discloses the pharmaceutical preparation of valsartan containing 20 ~ 34%, and wherein the ratio of microcrystalline Cellulose and partially pregelatinized starch is 1: 1 ~ 5: 1.Because valsartan is often by large gauge administration, as 160mg and 320mg, in prescription, valsartan ratio is less, and the gross weight of preparation will inevitably be caused to increase, and sheet shape is comparatively large, and inconvenient patient takes.
International patent application WO05089720 discloses the valsartan and (or) hydrochlorothiazide tablet that contain at least two kinds of disintegrating agents.But mostly containing 3 kinds of disintegrating agents in embodiment disclosed in it, and disintegrating agent total amount accounts for more than 45% of tablet total weight amount.A high proportion of disintegrant content like this must cause the hygroscopicity of product comparatively large, the easy moisture absorption of tablet in storage process, and as mentioned before, after tablet moisture absorption, valsartan raw material is met water and is clamminess, and cause hardness to become large, cause slice, thin piece disintegrate difficulty, dissolution rate is slack-off.So the technology of present patent application is also unfavorable for the stripping stability ensureing valsartan formulation product, and a high proportion of disintegrating agent consumption must cause the weight of formulation products to increase, and sheet deformation is large, and inconvenient patient takes.In such as embodiment, the weight of 320mg tablet is up to 1100mg.
Summary of the invention
Technical problem to be solved by this invention is that research design is applicable to solid orally ingestible containing valsartan and pharmaceutically acceptable salt thereof and preparation method thereof, makes the stability of product better.
Therefore, the invention provides the preparation of a kind of valsartan or its pharmaceutically acceptable salt on the one hand, its at least include be equivalent to total formulation weight amount 40 ~ 80% valsartan or its pharmaceutically acceptable salt, and at least two kinds of disintegrating agents, wherein the ratio of two kinds of disintegrating agents is between 1: 3 to 3: 1, and disintegrating agent total amount is no more than 30% of total formulation weight amount (as deducted coatings weight for coated tablet, as should a Computed-torque control thing weight for capsule, hereafter herewith illustrating).
According to valsartan pharmaceutical preparation of the present invention, include and be equivalent to total formulation weight amount:
The valsartan of 40 ~ 80% or its pharmaceutically acceptable salt,
The filler of 5 ~ 50%,
The disintegrating agent of 2 ~ 30%,
The fluidizer of 0 ~ 5%,
The lubricant of 0.5 ~ 2%.
According to the present invention, valsartan or its pharmaceutically acceptable salt are selected from valsartan, the valsartan sodium or valsartan calcium etc. of amorphous or crystal form.
According to the present invention, described valsartan or its pharmaceutically acceptable salt are preferably valsartan, are more preferably unbodied valsartan.
Because valsartan dissolubility is poor, usually need to reduce raw material particle size to reach the object promoting stripping.The particle diameter D (v, 0.9) of the valsartan that preparation according to the present invention uses is below 500 μm, and preferred D (v, 0.9) is below 300 μm, and preferred D (v, 0.9) is below 250 μm.In multiple embodiment of the present invention, the valsartan particle diameter D (v, 0.9) of employing is respectively 51 μm, 110 μm, 154 μm, 190 μm, 223 μm.Wherein said particle diameter adopts laser particle analyzer to measure.
According to the present invention, the ratio that valsartan or its pharmaceutically acceptable salt account for total formulation weight is preferably 45 ~ 75%, and preferred 45 ~ 60%, especially, according to several embodiments of the present invention, the ratio of valsartan is 46.8%, 50% or 53.3%.
According to valsartan pharmaceutical preparation of the present invention, the active component that one or more are pharmaceutically compatible with valsartan can also be included, as hydrochlorothiazide, amlodipine, and pharmaceutically acceptable salt.
According to the present invention, hydrochlorothiazide, amlodipine, and pharmaceutically acceptable salt accounts for 0 ~ 20% of total formulation weight amount, preferably 0 ~ 10%, be more preferably 0-5%.
The indissoluble of valsartan own, because solubilising needs, requires the disintegration rate improving slice, thin piece usually.But due to the self-characteristic of disintegrating agent, mostly there is good water absorption, and to be easily clamminess after valsartan water suction, accelerate or in long storage periods along with the increase of slice, thin piece water absorption, viscosity increases, and causes slice, thin piece hardness to become large, disintegrate difficulty.Inventor finds in test, Novartis produce valsartan sheet (trade name:
) after accelerating March, slice, thin piece disintegrate is slack-off, and stripping is defective.Therefore, the consumption of the disintegrating agent in prescription and the selection of kind particularly important.
As what mention in background technology, use single disintegrating agent, or several disintegrating agent coupling but ratio is too high, be all unfavorable for the stripping stability ensureing product.Two prescriptions once attempting of such as the present inventor again, containing valsartan 50%, optimize microcrystalline Cellulose 28.5%, Powderd cellulose 10%, polyvinylpolypyrrolidone 10%, silicon dioxide 0.5%, magnesium stearate 1%, or containing valsartan 50%, optimize microcrystalline Cellulose 20%, Powderd cellulose 18.5%, polyvinylpolypyrrolidone 10%, silicon dioxide 0.5%, magnesium stearate 1%, although can ensure product new production out time dissolution rate, acceleration or prolonged storage in, dissolution rate can be slack-off gradually, until stripping is defective.
The present inventor finds, adopt two or more disintegrating agent, product can be made to have better stability, guarantee that product is after accelerated test, its disintegrating property can not obviously be deteriorated, and the stripping of product is still qualified.And, when the ratio of two kinds of disintegrating agents is in specific scope, just desirable effect can be reached.
Therefore, according to the present invention, in preparation, the ratio of two kinds of disintegrating agents is 1: 3 ~ 3: 1, preferably 1: 2 ~ 2: 1, and the total amount of disintegrating agent is no more than 30% of total formulation weight amount, is preferably no more than 25%, be preferredly no more than 20%.
According to the present invention, disintegrating agent is selected from least two kinds in polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose, cross-linked carboxymethyl cellulose sodium, partially pregelatinized starch, carboxymethylstach sodium.Preferably, can be polyvinylpolypyrrolidone and low-substituted hydroxypropyl cellulose coupling, or cross-linked carboxymethyl cellulose sodium and low substituted cellulose coupling, or polyvinylpolypyrrolidone and partially pregelatinized starch coupling, or polyvinylpolypyrrolidone and carboxymethylstach sodium coupling, wherein the ratio of two kinds of disintegrating agents is 1: 3 ~ 3: 1, preferred between 1: 2 to 2: 1.
According to the present invention, filler is selected from optimizes microcrystalline Cellulose, microcrystalline Cellulose, Powderd cellulose, lactose, lactose starch complex, mannitol and calcium hydrogen phosphate.
According to the present invention, filler preferably from lactose, optimize microcrystalline Cellulose, microcrystalline Cellulose, Powderd cellulose.More preferably optimize microcrystalline Cellulose, as JRS company
According to the present invention, the ratio that described filler accounts for total formulation weight amount is preferably 15 ~ 40%; Be more preferably 20 ~ 30%.
According to the present invention, fluidizer is selected from: silicon dioxide, micropowder silica gel etc.Preferred micropowder silica gel.Its ratio accounts for 0 ~ 5% of total formulation weight amount, is preferably 0 ~ 2%.
According to the present invention, lubricant is selected from: magnesium stearate, Polyethylene Glycol etc., preferred magnesium stearate, and its ratio accounts for 0.5 ~ 2% of total formulation weight amount, and preferably 0.5 ~ 1.5%.
According to valsartan pharmaceutical preparation of the present invention, preferably include the coating material being equivalent to total formulation weight amount 1 ~ 6%, preferred comprise 2 ~ 4% coating material.Described coating material is selected from
series, is preferably selected from
85G 62572,85G 64894,85G 62545,85G 64757,85G 62511.According to a preferred embodiment of the invention a, the tablet total weight amount of being equivalent to is included:
The valsartan of 45 ~ 60%,
The microcrystalline Cellulose of 20 ~ 30%,
The polyvinylpolypyrrolidone of 1 ~ 15%,
The partially pregelatinized starch of 1 ~ 30%,
The micropowder silica gel of 0 ~ 2%,
The magnesium stearate of 0.5 ~ 2%.
Wherein, the ratio of polyvinylpolypyrrolidone and partially pregelatinized starch is 1: 2 ~ 2: 1, and both total amounts are no more than 30% of total formulation weight amount.
According to another preferred embodiment of the invention, the tablet total weight amount of being equivalent to is included:
The valsartan of 45 ~ 60%,
The hydrochlorothiazide of 2 ~ 10%,
The microcrystalline Cellulose of 20 ~ 30%,
The polyvinylpolypyrrolidone of 1 ~ 15%,
The partially pregelatinized starch of 1 ~ 30%,
The micropowder silica gel of 0 ~ 2%,
The magnesium stearate of 0.5 ~ 2%.
Wherein, the ratio of polyvinylpolypyrrolidone and partially pregelatinized starch is 1: 2 ~ 2: 1, and both total amounts are no more than 30% of total formulation weight amount.
According to another preferred embodiment of the present invention, include the tablet total weight amount that is equivalent to:
The valsartan of 45 ~ 60%,
The amlodipine of 2 ~ 10%,
The microcrystalline Cellulose of 20 ~ 30%,
The polyvinylpolypyrrolidone of 1 ~ 15%,
The partially pregelatinized starch of 1 ~ 30%,
The micropowder silica gel of 0 ~ 2%,
The magnesium stearate of 0.5 ~ 2%.
Wherein, the ratio of polyvinylpolypyrrolidone and partially pregelatinized starch is 1: 2 ~ 2: 1, and both total amounts are no more than 30% of total formulation weight amount.
According to another preferred embodiment of the present invention, include the tablet total weight amount that is equivalent to:
The valsartan of 45 ~ 60%,
The microcrystalline Cellulose of 20 ~ 30%,
The polyvinylpolypyrrolidone of 1 ~ 15%,
The low-substituted hydroxypropyl cellulose of 1 ~ 30%,
The micropowder silica gel of 0 ~ 2%,
The magnesium stearate of 0.5 ~ 2%.
Wherein, the ratio of polyvinylpolypyrrolidone and low-substituted hydroxypropyl cellulose is 1: 2 ~ 2: 1, and both total amounts are no more than 30% of total formulation weight amount.
On the other hand, the invention provides the preparation technology of described valsartan pharmaceutical preparation, the technical characteristic of these techniques comprises and adopts roll-in mode to granulate valsartan or its pharmaceutically acceptable salt, then mixes with other adjuvant, tabletting or record into capsule.Specifically describe as follows:
Preparation in accordance with the present invention comprises the following steps:
A, by valsartan or its pharmaceutically acceptable salt roll-in method compacting obtain compact a;
B, compact a sieves or ground obtains granulate b;
C, again granulate b and pharmaceutic adjuvant mixing, optionally add other active component, obtain mixture c;
D, mixture c tabletted or fill are become capsule.
E, optional, described tablet or capsule are carried out coating.
Rolling device described in said method is a kind of conventional equipment, and rolling device pressure roller is extruded the material passed between pressure roller by screw rod transmission system.Roller speed is 2 ~ 10rpm, and compact screening or grinding, within the scope of 20 ~ 80bar, are formed granulate by pressure.Obtained grain diameter is most of below 850 μm, preferably below 700 μm.
Above-mentioned granulate and pharmaceutic adjuvant are mixed about 10 ~ 20min in mixed container.
Said mixture adopts suitable circle or oval scrobicula to be punched on high speed tablet press and suppresses slice, thin piece, or becomes capsule with the capsule shells fill of suitable size.
Further, obtained tablet or capsule are carried out coating, and coating material is selected from
series, is preferably selected from
85G 62572,85G 64894,85G 62545,85G 64757,85G 62511.By slice, thin piece prepared in accordance with the present invention and prior art products, as
(Novartis), synchronously carries out drawing moist and study on the stability.Result shows, and slice, thin piece prepared in accordance with the present invention obtains very large improvement drawing in moist and stripping stability.It is simple that preparation method of the present invention has technique, and the features such as cost is low, and product stability is good, improve production efficiency to a certain extent, is applicable to suitability for industrialized production.Detect the sample adopting the present invention to produce according to quality standard, indices all conforms with the regulations.
Detailed description of the invention
By following object lesson, understanding the present invention that can be more concrete, but the present invention is not limited to following example.
Embodiment 1: the preparation of valsartan sheet
Material composition is in table 1;
Table 1 material proportion of composing
* prescription 1 and 2 is not herein only as a comparison, belong to content of the present invention, and wherein prescription 1 is from the embodiment 7 of background technology Patent application CN1636561A, and prescription 2 is from the prescription 1 of the embodiment form 1 of background technology Patent application WO05089720.
Prepare label: undertaken granulate (Alexandria WP120V) by roll-in method by the valsartan of recipe quantity, pressure: 40bar, roller speed: 3rpm.By obtained granule and the mixing of all the other adjuvants, then according to the drift of sheet reselection procedure suitable dimension, adopt high speed tablet press tabletting.
Prepare coated tablet: take
85G series coating powder is mixed with solid content at the coating solution of 20 ~ 25%, carries out coating to plain sheet.Until slice, thin piece weightening finish about 3%.
By the 80mg coated tablet prepared according to prescription in the present embodiment 1 ~ 5 and prior art products
80mg sheet (manufacturer: Novartis) all adopts PVC/PE/PVDC/AL to pack, and places 3 months under acceleration environment (T40 DEG C/75%RH), measures stripping curve situation of change.Result shows, and after slice, thin piece prepared in accordance with the present invention places 3 months, stripping change is less than prior art products, specifically in table 2:
Table 2 acceleration environment (T40 DEG C/75%RH) places 3 months stripping measurement results
Embodiment 2: the preparation of valsartan sheet
Material composition is in table 3.
Table 3 material proportion of composing
Prepare label: undertaken granulate (Alexandria WP120V) by roll-in method by the valsartan of recipe quantity, pressure: 60bar, roller speed: 3rpm.Obtained granule and optimization microcrystalline Cellulose, polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose, micropowder silica gel are mixed, then add magnesium stearate mixing in total mixed bucket, for subsequent use.Adopt the oval scrobicula punching press system element sheet of 14*5.5mm.
Prepare coated tablet: take
85G series coating powder preparation solid content is the coating solution of 20%, carries out coating to plain sheet.Until slice, thin piece weightening finish about 3%.Coated tablet indices meets relevant regulations.Concrete outcome is in table 4.
Table 4 valsartan sheet testing result
Embodiment 3: the preparation of valsartan sheet
Material composition is in table 5.
Table 5 material proportion of composing
Prepare label: undertaken granulate (Alexandria WP120V) by roll-in method by the valsartan of recipe quantity, pressure: 70bar, roller speed: 3rpm.Obtained granule and Powderd cellulose, low-substituted hydroxypropyl cellulose, cross-linked carboxymethyl cellulose sodium, silicon dioxide are mixed, then add magnesium stearate mixing in total mixed bucket, for subsequent use.Adopt the circular scrobicula stamping of φ 8.0mm.
Prepare coated tablet: take
preparation coating solution, carries out coating to plain sheet.Until slice, thin piece weightening finish about 3%.The results are shown in Table 6.
Table 6 valsartan sheet testing result
Embodiment 4: the preparation of valsartan and Hydrochlorothiade sheet
Material composition is in table 7.
Table 7 material proportion of composing
Prepare label: undertaken granulate (Alexandria WP120V) by roll-in method by the valsartan of recipe quantity, pressure: 70bar, roller speed: 3rpm.Obtained granule and microcrystalline Cellulose, polyvinylpolypyrrolidone, partially pregelatinized starch, hydrochlorothiazide, silicon dioxide are mixed, then add magnesium stearate mixing in total mixed bucket, for subsequent use.Adopt the circular scrobicula stamping of φ 8.0mm.
Prepare coated tablet: take
preparation coating solution, carries out coating to plain sheet.Until slice, thin piece weightening finish about 3%.The results are shown in Table 8.
Table 8 valsartan and Hydrochlorothiade sheet testing result
Embodiment 5: the preparation of amlodipine and valsartan sheet
Material composition is in table 9;
Table 9 material proportion of composing
Prepare label: undertaken granulate (Alexandria WP120V) by roll-in method by the valsartan of recipe quantity, pressure: 80bar, roller speed: 3rpm.Obtained granule and microcrystalline Cellulose, polyvinylpolypyrrolidone, partially pregelatinized starch, Amlodipine Besylate Tablet, silicon dioxide are mixed, then add magnesium stearate mixing in total mixed bucket, for subsequent use.Adopt the oval scrobicula stamping of 12.5*6.5mm.
Prepare coated tablet: take
preparation coating solution, carries out coating to plain sheet.Until slice, thin piece weightening finish about 3%.Coated tablet indices meets relevant regulations.The results are shown in Table 10.
Table 10 amlodipine and valsartan sheet testing result
Embodiment 6: the preparation of valsartan and Hydrochlorothiade sheet
Material composition is in table 11;
Table 11 material proportion of composing
Prepare label: undertaken granulate (Alexandria WP120V) by roll-in method by the valsartan of recipe quantity, pressure: 70bar, roller speed: 3rpm.Obtained granule and microcrystalline Cellulose, polyvinylpolypyrrolidone, partially pregelatinized starch, hydrochlorothiazide, silicon dioxide are mixed, then add magnesium stearate mixing in total mixed bucket, for subsequent use.Adopt the oval scrobicula stamping of 12.5*6.5mm.
Prepare coated tablet: take
coating solution processed, carries out coating to plain sheet.Until slice, thin piece weightening finish about 3%.Coated tablet indices meets relevant regulations.The results are shown in Table 12.
Table 12 valsartan and Hydrochlorothiade sheet testing result
Embodiment 7: the preparation of valsartan capsule
Material composition is in table 13.
Table 13 material forms
Prepare label: undertaken granulate (Alexandria WP120V) by roll-in method by the valsartan of recipe quantity, pressure: 40bar, roller speed: 3rpm.Mix in total mixed bucket with microcrystalline Cellulose, polyvinylpolypyrrolidone, partially pregelatinized starch, micropowder silica gel, then adopt No. 00 capsule-filling after adding magnesium stearate mixing again.And the weight differential to capsule, disintegration and stripping detect.The results are shown in Table 14.
Table 14 valsartan amlodipine capsule testing result
Embodiment 8: the preparation of valsartan sheet
Material composition is in table 15.
Table 15 material proportion of composing
Prepare label: undertaken granulate (Alexandria WP120V) by roll-in method by the valsartan of recipe quantity, pressure: 60bar, roller speed: 3rpm.Obtained granule and microcrystalline Cellulose, polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose, micropowder silica gel are mixed, then add magnesium stearate mixing in total mixed bucket, for subsequent use.Adopt the oval scrobicula punching press system element sheet of 14*5.5mm.
Prepare coated tablet: take
85G series coating powder preparation solid content is the coating solution of 20%, carries out coating to plain sheet.Until slice, thin piece weightening finish about 3%.Coated tablet indices meets relevant regulations.Concrete outcome is in table 16.
Table 16 valsartan sheet testing result
Claims (8)
1. the pharmaceutical preparation containing valsartan, its at least include be equivalent to total formulation weight amount 40 ~ 80% valsartan, and the two kinds of disintegrating agents be selected from polyvinylpolypyrrolidone, partially pregelatinized starch, low-substituted hydroxypropyl cellulose, sodium carboxymethyl cellulose, wherein the ratio of two kinds of disintegrating agents is between 1: 2 to 2: 1, and disintegrating agent total amount is no more than 30% of total formulation weight amount, the preparation method of described valsartan formulation comprises:
A, valsartan roll-in method is obtained compact a;
B, compact a sieves or ground obtains granulate b;
C, again granulate b and other pharmaceutic adjuvants, optionally add other active component, obtain mixture c;
E, mixture c tabletted or fill are become capsule;
F, optional, described tablet or capsule are carried out coating.
2. valsartan pharmaceutical preparation according to claim 1, can also include the active component that one or more are pharmaceutically compatible with valsartan, it is characterized in that described active component is selected from hydrochlorothiazide, amlodipine, or its pharmaceutically acceptable salt.
3. valsartan pharmaceutical preparation according to claim 1, is characterized in that valsartan accounts for 45 ~ 60% of total formulation weight amount.
4. valsartan pharmaceutical preparation according to claim 1, can also include acceptable filler, fluidizer and lubricant on pharmaceutics.
5. valsartan pharmaceutical preparation according to claim 4, is characterized in that filler is selected from and optimizes microcrystalline Cellulose, microcrystalline Cellulose, lactose, lactose starch complex, mannitol, one or more in calcium hydrogen phosphate.
6. valsartan pharmaceutical preparation according to claim 4, is characterized in that fluidizer is selected from: silicon dioxide, micropowder silica gel.
7. valsartan pharmaceutical preparation according to claim 4, is characterized in that lubricant is selected from: magnesium stearate.
8. a preparation method for valsartan formulation as claimed in claim 1, its feature comprises:
A, valsartan roll-in method is obtained compact a;
B, compact a sieves or ground obtains granulate b;
C, again granulate b and other pharmaceutic adjuvants, optionally add other active component, obtain mixture c;
E, mixture c tabletted or fill are become capsule;
F, optional, described tablet or capsule are carried out coating.
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| CN102247376B (en) * | 2011-08-15 | 2012-11-28 | 华润赛科药业有限责任公司 | Compound solid preparation of valsartan and hydrochlorothiazide, and preparation method thereof |
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| CN107684549A (en) * | 2016-08-05 | 2018-02-13 | 华仁药业股份有限公司 | A kind of Valsartan tablet and preparation method thereof |
| CN108567759B (en) * | 2018-07-26 | 2019-06-04 | 北京百奥药业有限责任公司 | A kind of valsartan and Hydrochlorothiade piece and preparation method thereof |
| CN113171352A (en) * | 2021-04-15 | 2021-07-27 | 海南锦瑞制药有限公司 | Preparation method of sartan antihypertensive compound preparation |
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| WO2005089720A1 (en) * | 2004-03-10 | 2005-09-29 | Ranbaxy Laboratories Limited | Valsartan tablets and the process for the preparation thereof |
| CN101167723A (en) * | 2006-10-27 | 2008-04-30 | 陈益智 | Valsartan dispersible tablet and preparation method thereof |
| CN101478956A (en) * | 2006-06-27 | 2009-07-08 | 诺瓦提斯公司 | Solid dosage forms of valsartan, amlodipine and hydrochlorothiazide and method of making the same |
| CN101485657A (en) * | 2009-03-04 | 2009-07-22 | 浙江华海药业股份有限公司 | Diovan compound preparation and preparation method thereof |
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|---|---|---|---|---|
| WO2005089720A1 (en) * | 2004-03-10 | 2005-09-29 | Ranbaxy Laboratories Limited | Valsartan tablets and the process for the preparation thereof |
| CN101478956A (en) * | 2006-06-27 | 2009-07-08 | 诺瓦提斯公司 | Solid dosage forms of valsartan, amlodipine and hydrochlorothiazide and method of making the same |
| CN101167723A (en) * | 2006-10-27 | 2008-04-30 | 陈益智 | Valsartan dispersible tablet and preparation method thereof |
| CN101485657A (en) * | 2009-03-04 | 2009-07-22 | 浙江华海药业股份有限公司 | Diovan compound preparation and preparation method thereof |
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