CN1714789A - Candesartan hydrochlorothiazine dispersible tablet and its preparing method - Google Patents
Candesartan hydrochlorothiazine dispersible tablet and its preparing method Download PDFInfo
- Publication number
- CN1714789A CN1714789A CN 200410049755 CN200410049755A CN1714789A CN 1714789 A CN1714789 A CN 1714789A CN 200410049755 CN200410049755 CN 200410049755 CN 200410049755 A CN200410049755 A CN 200410049755A CN 1714789 A CN1714789 A CN 1714789A
- Authority
- CN
- China
- Prior art keywords
- candesartan
- hydrochlorothiazide
- sodium
- silica gel
- magnesium stearate
- 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
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention discloses a kind of dispersible Candesartan hydrochlorothiazide tablet and its preparation process. The preparation process of the dispersible Candesartan hydrochlorothiazide tablet includes mixing Candesartan, hydrochlorothiazide, lactose, microcrystal cellulose, starch pre-gel, sodium carboxymethyl starch, superfine silicone gel powder, magnesium stearate, etc. in certain proportion; pelletizing in 16-24 mesh sieve, drying at 40-60 deg.c, finishing pelletizing, adding superfine silicone gel powder or magnesium stearate, and tabletting. The dispersible Candesartan hydrochlorothiazide tablet can disintegrate fast in water, and has the features of homogeneous dispersion, high leaching degree, fast absorption, etc.
Description
Technical field
The present invention relates to dispersible tablet of a kind of compound medicinal formulation of Candesartan, particularly Candesartan and hydrochlorothiazide and preparation method thereof.
Background technology
Candesartan is a kind of orally active antihypertensive drug.It is by blocking the vasoconstrictive and the aldosterone secretory action of Angiotensin II mediation specifically, and makes blood pressure drops.Hydrochlorothiazide is a thiazide diuretic.It directly increases the secretion of sodium ion and chloride ion by influencing renal tubules to electrolytical heavy absorption, and the urine amount is increased, and blood volume reduces.Simultaneously, hydrochlorothiazide reduces plasma volume by its diuresis, and plasma renin activity is increased, and the aldosterone secretion increases, and urine potassium is discharged and increased, and blood potassium is reduced.The effect of feritin-aldosterone system is by Angiotensin II mediation, and therefore, hydrochlorothiazide share the angiotensin ii receptor antagonist Candesartan, can strengthen drug effect and reverse mistake potassium effect due to the hydrochlorothiazide.
The tablet of common candesartan cilexetil/hydrochlorothiazide (16mg/12.5mg) compound recipe of developing of military field of Japan and AstraZeneca company, commodity are called AtacandHCT, obtain the approval of FDA in JIUYUE in 2000 on the 5th, can be used as the hypertensive two wires of treatment medicine.AtacandHCT goes on the market with the specification of two kinds of fixed dosage compatibilities: 32mg candesartan Cilexetil and 12.5mg hydrochlorothiazide and 16mg candesartan Cilexetil and 12.5mg hydrochlorothiazide.This compound preparation has also obtained European Union's approval and has been used for hypertensive treatment.Multinomial clinical trial shows that candesartan Cilexetil-hydrochlorothiazide compound preparation side effect is little, and safety and better tolerance are the hypertensive desirable line medications of treatment.
The Candesartan that uses clinically and the compound preparation of hydrochlorothiazide are tablet and capsule at present, in view of tablet and capsule oral absorb shortcomings such as slow, that bioavailability is low, be made into dispersible tablet, in the hope of reaching the raising bioavailability, bring into play purposes such as curative effect of medication, convenient clinical use more fully.
Summary of the invention
The purpose of this invention is to provide a kind of Candesartan and hydrochlorothiazide dispersible tablets and preparation method thereof, it disperses insoluble drug rapidly by quickening the medicine disintegrate, and strengthens the dissolution of medicine.
For achieving the above object, the present invention has adopted following technical scheme:.
Candesartan of the present invention and hydrochlorothiazide dispersible tablets, every contains Candesartan 16～32mg, hydrochlorothiazide 12.5mg and pharmaceutic adjuvant, and related pharmaceutic adjuvant comprises filler 5～100mg, binding agent 0～50mg, disintegrating agent 0.5～100mg, lubricant 0.1～10mg, fluidizer 0.1～20mg.Wherein: filler comprises one or more in lactose, mannitol, microcrystalline Cellulose, pregelatinized starch, the carboxymethyl starch sodium; Binding agent comprises one or more in polyvinylpyrrolidone, starch, hydroxypropyl emthylcellulose, the methylcellulose; Disintegrating agent comprises one or more in microcrystalline Cellulose, low-substituted hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, crospolyvinylpyrrolidone, carboxymethyl starch sodium, tween 80, the sodium lauryl sulphate; Lubricant and fluidizer comprise one or more in micropowder silica gel, magnesium stearate, Pulvis Talci, Stepanol MG, the sodium lauryl sulphate.
The preferred composition of candesartan hydrochlorothiazide dispersible tablets of the present invention is that Candesartan 12～36mg, hydrochlorothiazide 12.5mg, lactose 0～100mg, microcrystalline Cellulose 0～100mg, pregelatinized starch 0～100mg, carboxymethyl starch sodium 0～100mg, micropowder silica gel 0～50mg, magnesium stearate 0～20mg, 5% polyvinylpyrrolidone 30 and alcoholic solution are an amount of.
Preparation method of the present invention comprises following order and step:
(1) takes by weighing Candesartan, hydrochlorothiazide, microcrystalline Cellulose, pregelatinized starch, carboxymethyl starch sodium, micropowder silica gel, mix homogeneously;
(2) add 2% hypromellose and make soft material, 16～24 mesh sieves are granulated;
(3) wet granular is in 40～60 ℃ of dryings, 16～24 mesh sieve granulate;
(4) add magnesium stearate or micropowder silica gel mix homogeneously, tabletting, promptly.
Candesartan hydrochlorothiazide dispersible tablets of the present invention is compared with existing ordinary tablet has following benefit:
1. have stronger disintegrate and dissolving out capability.Disintegrate and even stripping are the prerequisites that oral formulations absorbs, and rapid disintegrate of candesartan hydrochlorothiazide dispersible tablets energy of the present invention and homodisperse become fine particle, strengthen the dissolution of insoluble drug.Experiment showed, that two index-dispersing uniformities of candesartan hydrochlorothiazide dispersible tablets experiment in vitro of the present invention and dissolution all are better than conventional tablet.
(1) the disintegrate situation of candesartan hydrochlorothiazide dispersible tablets and ordinary tablet is relatively:
Dispersing uniformity is measured: get each 2 of candesartan hydrochlorothiazide dispersible tablets and ordinary tablets, place 20 ℃ ± 1 ℃ 100ml water jolting respectively, all disintegrate also can be by No. 2 sieves in 3 minutes.Result of the test is as follows:
Candesartan hydrochlorothiazide dispersible tablets is limited to 1.8 ± 0.2 minutes when disperseing, and ordinary tablet disperses the time limit: 6.8 ± 0.6 minutes.
(2) the stripping situation of candesartan hydrochlorothiazide dispersible tablets and ordinary tablet is relatively:
Dissolution determination: get candesartan hydrochlorothiazide dispersible tablets and ordinary tablet respectively, with 0.5% lauryl sodium sulfate aqueous solution 900ml is solvent, Revolution Per Minute 100 changes candesartan hydrochlorothiazide dispersible tablets stripping more than 85% in the time of 45 minutes, ordinary tablet stripping 75%.
2, Candesartan of the present invention and hydrochlorothiazide dispersible tablets are disintegratable in water and are uniformly dispersed, and in the dissolving of gastric juice Chinese medicine thoroughly, thereby absorption is more complete, and bioavailability is higher; Candesartan of the present invention and hydrochlorothiazide dispersible tablets stable quality after long time storage, disintegrate and dissolution are unaffected, stable content.
Specific implementation method
By following concrete embodiment, can further understand the present invention, but following example not a limitation of the invention.
Example 1
Take by weighing Candesartan 16mg, hydrochlorothiazide 12.5mg, microcrystalline Cellulose 50mg, pregelatinized starch 8.1mg, carboxymethyl starch sodium 0.12mg, micropowder silica gel 0.18mg, add 2% hypromellose behind the mix homogeneously and make soft material, 18～20 mesh sieves are granulated, 40～60 ℃ of oven dry, 18～20 mesh sieve granulate add magnesium stearate 2.5mg and micropowder silica gel 2.5mg, and tabletting promptly behind the mix homogeneously.
Example 2
Take by weighing Candesartan 16mg, hydrochlorothiazide 12.5mg, lactose 50mg, mannitol 10mg, crospolyvinylpyrrolidone 10mg, sodium lauryl sulphate 0.5mg, the 70% alcoholic solution system soft material that adds 5%PVPK30 behind the mix homogeneously, 18～20 mesh sieves are granulated, 40～60 ℃ of oven dry, 18～20 mesh sieve granulate, add magnesium stearate 1.5mg and micropowder silica gel 1.5mg, tabletting promptly behind the mix homogeneously.
Example 3
Take by weighing Candesartan 32mg, hydrochlorothiazide 12.5mg, lactose 30mg, microcrystalline Cellulose 5mg, carboxymethyl starch sodium 10mg, the 50% alcoholic solution system soft material that adds the 5%PVPK30-3% Tween 80 behind the mix homogeneously, 18～20 mesh sieves are granulated, 40～60 ℃ of oven dry, 18～20 mesh sieve granulate, add magnesium stearate 2.5mg and micropowder silica gel 2.5mg, tabletting promptly behind the mix homogeneously.
Example 4
Take by weighing Candesartan 32mg, hydrochlorothiazide 12.5mg, crospolyvinylpyrrolidone 50mg, sodium lauryl sulphate 0.5mg, the 70% alcoholic solution system soft material that adds 5% polyvinylpyrrolidone 30 behind the mix homogeneously, 18～20 mesh sieves are granulated, 40～60 ℃ of oven dry, 18～20 mesh sieve granulate, add micropowder silica gel 5mg, tabletting promptly behind the mix homogeneously.
Example 5
Take by weighing Candesartan 32mg, hydrochlorothiazide 12.5mg, pregelatinized starch 30mg, low-substituted hydroxypropyl methylcellulose 10mg, crospolyvinylpyrrolidone 10mg, sodium lauryl sulphate 0.5mg, the 60% alcoholic solution system soft material that adds 5%PVPK30 behind the mix homogeneously, 18～20 mesh sieves are granulated, 40～60 ℃ of oven dry, 18～20 mesh sieve granulate add magnesium stearate 1.5mg and micropowder silica gel 1.5mg, and tabletting promptly behind the mix homogeneously.
Claims (4)
1. the dispersible tablet of Candesartan and hydrochlorothiazide, every contains Candesartan 12～36mg, chlorothiazide 12.5mg and pharmaceutic adjuvant, and related pharmaceutic adjuvant comprises filler 5～100mg, binding agent 0～50mg, disintegrating agent 0.5～100mg, lubricant 0.1～10mg, fluidizer 0.1～20mg.
2. dispersible tablet according to claim 1 is characterized in that: filler comprises one or more in lactose, mannitol, microcrystalline Cellulose, pregelatinized starch, the carboxymethyl starch sodium; Binding agent comprises one or more in polyvinylpyrrolidone, starch, hydroxypropyl emthylcellulose, the methylcellulose; Disintegrating agent comprises one or more in microcrystalline Cellulose, low-substituted hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, crospolyvinylpyrrolidone, carboxymethyl starch sodium, tween 80, the sodium lauryl sulphate; Lubricant and fluidizer comprise one or more in micropowder silica gel, magnesium stearate, Pulvis Talci, Stepanol MG, the sodium lauryl sulphate.
3. dispersible tablet according to claim 1 is characterized in that: every to comprise Candesartan 12～36mg, hydrochlorothiazide 12.5mg, lactose 0～100mg, microcrystalline Cellulose 0～100mg, pregelatinized starch 0～100mg, carboxymethyl starch sodium 0～100mg, micropowder silica gel 0～50mg, magnesium stearate 0～20mg, 5% polyvinylpyrrolidone 30 and alcoholic solution an amount of.
4. dispersible tablet according to claim 1, its preparation method comprises following order and step:
(1) takes by weighing Candesartan, hydrochlorothiazide, lactose, microcrystalline Cellulose, pregelatinized starch, carboxymethyl starch sodium, micropowder silica gel, mix homogeneously;
(2) add 2% hypromellose and make soft material, 18～24 mesh sieves are granulated;
(3) wet granular is in 40～60 ℃ of dryings, 16～24 mesh sieve granulate;
(4) add magnesium stearate or micropowder silica gel mix homogeneously, tabletting, promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410049755 CN1714789A (en) | 2004-06-28 | 2004-06-28 | Candesartan hydrochlorothiazine dispersible tablet and its preparing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410049755 CN1714789A (en) | 2004-06-28 | 2004-06-28 | Candesartan hydrochlorothiazine dispersible tablet and its preparing method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1714789A true CN1714789A (en) | 2006-01-04 |
Family
ID=35821152
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410049755 Pending CN1714789A (en) | 2004-06-28 | 2004-06-28 | Candesartan hydrochlorothiazine dispersible tablet and its preparing method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1714789A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1952806A1 (en) * | 2007-02-01 | 2008-08-06 | Helm AG | Process for the preparation of adsorbates of candesartan |
-
2004
- 2004-06-28 CN CN 200410049755 patent/CN1714789A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1952806A1 (en) * | 2007-02-01 | 2008-08-06 | Helm AG | Process for the preparation of adsorbates of candesartan |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1275391B1 (en) | Pharmaceutical compositions containing irbesartan and a diuretic | |
| US10166234B2 (en) | Pharmaceutical preparation comprising phenylalanine derivative | |
| EP3120871B1 (en) | Solid dispersion | |
| CN109875972B (en) | Olmesartan medoxomil and amlodipine pharmaceutical composition | |
| EP3856162A1 (en) | Pharmaceutical composition comprising vildagliptin and metformin and method of preparation thereof | |
| WO2008074098A1 (en) | Pharmaceutical composition | |
| CN110237073B (en) | Olmesartan medoxomil amlodipine tablet and preparation method thereof | |
| US20080008751A1 (en) | Stable formulation comprising a combination of a moisture sensitive drug and a second drug and manufacturing procedure thereof | |
| CN1714794A (en) | Irbesartan hydrochlorothiazine dispersible tablet an dits preparing method | |
| CN101554381A (en) | Candesartan cilexetil hydrochlorothiazide double-layer tablets and preparation mehtod thereof | |
| JP4698000B2 (en) | Easily water-soluble drug-containing tablets | |
| CN1903208A (en) | Adefovir dipivoxil oral disintegration tablets medicine prepn., and prepn. method therefor | |
| CN1714789A (en) | Candesartan hydrochlorothiazine dispersible tablet and its preparing method | |
| CN102526061A (en) | Medicinal composition and preparation method thereof | |
| CZ301299B6 (en) | Solid pharmaceutical composition with atorvastatin and telmisartan active ingredients | |
| CN100577152C (en) | Losartan potassium and hydrochlorothiazide tablets and preparation method thereof | |
| CN101062038A (en) | Candesartan hydrochlorothiazide dispersible tablets and the preparing method thereof | |
| CN113456601A (en) | Preparation method of candesartan cilexetil hydrochlorothiazide compound tablet | |
| TW202139977A (en) | Double-layer tablet comprising atorvastatin and ezetimibe and manufacturing method thereof | |
| CN101912390A (en) | Medicinal composite containing irbesartan | |
| EP1889629B1 (en) | Stable formulation comprising a combination of a moisture sensitive drug and a second drug and manufacturing procedure thereof | |
| KR101944085B1 (en) | Solid oral dosage form containing valsartan, and preparation method therefor | |
| WO2022042646A1 (en) | Lurasidone hydrochloride composition and preparation method therefor | |
| EP3691614B1 (en) | Pharmaceutical composition comprising vildagliptin and method of preparation thereof | |
| KR100754239B1 (en) | Controlled releasable oral administrative composition comprising cetirizine HCl and pseudoephedrine HCl and manufacturing method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C57 | Notification of unclear or unknown address | ||
| DD01 | Delivery of document by public notice |
Addressee: Liu Fengming Document name: Notice of publication of application for patent for invention |
|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |