CN104906060A - Indapamide slow-release hypertension pill and preparation method thereof - Google Patents
Indapamide slow-release hypertension pill and preparation method thereof Download PDFInfo
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- CN104906060A CN104906060A CN201510353159.6A CN201510353159A CN104906060A CN 104906060 A CN104906060 A CN 104906060A CN 201510353159 A CN201510353159 A CN 201510353159A CN 104906060 A CN104906060 A CN 104906060A
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Abstract
The invention discloses an indapamide slow-release hypertension pill and a preparation method thereof. The indapamide slow-release hypertension pill comprises the following components in parts by weight: 0.75 part of indapamide, 40-55 parts of a framework material, 5-10 parts of a disintegration material, 40-50 parts of a diluent and 0.5 part of a lubricant. The indapamide slow-release hypertension pill is prepared by using a direct powder tabletting method which comprises the following steps: pretreating main materials and assistant materials, premixing the assistant materials, performing equivalent progressive increase mixing on the materials, tabletting, and coating. By adopting the indapamide slow-release hypertension pill disclosed by the invention, burst release can be relatively well inhibited, thorough later release can be ensured, the hypertension effect can be relatively stable and long-lasting, the production cost is reduced as a domestic framework material is adopted, and due to the adoption of a direct dry powder tabletting process, the phenomenon of too intense burst release caused by gelatinization of functional groups and water when a wet granulation method is adopted can be prevented, the pill can be prepared according to the formula ratio, the product quality can be relatively stable, and the in-batch product difference can be reduced.
Description
Technical field
The present invention relates to slow releasing pharmaceutical field, be specifically related to a kind of indapamide slow release hypertension pill and preparation method thereof.
Background technology
Indapamide slow release tablet is the antihypertensive for cardiovascular and cerebrovascular vessel, because it obviously can improve the effect of hypotensive effect, safe ratio, meet the low dose of depressor of use that international professional guideline recommends and the medication requirement that diuretic is treated as depressor, be widely used clinically, the framework material of the indapamide slow release tablet of current domestic production all adopts external imported raw material, just can reach the standard of sustained release hypotensive, therefore expensive, add the financial burden of consumer.
The preparation technology of current employing is all wet granule compression tablets, and wet granule compression tablet adds adhesive in drug powder, powder is coalesced together and prepares granule, then granule is carried out tabletting by the crane span structure of adhesive or cohesive action.Its technical process is: supplementary material weighs, mix, granulate, dry, granulate always mixes, tabletting.In wet-granulation process, consider adhesive addition, baking temperature is on the impact of drug quality, drying time, the factors such as granule order number and fine powder amount, and, functional group propoxyl and water produce gelling, cause consuming the slow-release function destroying part hypromellose, occurring dashing forward, it is excessive to release, release controls failed phenomenon, medicine does not meet quality criteria requirements of becoming a full member, in addition, the number of devices of need of production is many, take up room large, and due to some factor need rely on micro-judgment, therefore unstable product quality may be caused, the defect such as between batch difference is large.
Summary of the invention
For solving the problem, the invention provides a kind of indapamide slow release hypertension pill and preparation method thereof, the combination of each composition and the preparation method of employing direct powder compression in the formula of this tablet, the framework material achieving medicine adopts home made materials, greatly reduce production cost, drug effect conformance with standard, release is steadily lasting.
The every sheet of indapamide slow release hypertension pill in the present invention is prepared according to following percentage by weight:
Wherein, described framework material is hypromellose RT4000 and hypromellose RT5, and described disintegrate material is microcrystalline Cellulose, and described diluent is lactose, and described lubricant is magnesium stearate, and in its formula, the percentage by weight of each component is:
Prepare this indapamide slow release hypertension pill and adopt direct powder compression, comprise the steps:
1) major ingredient and adjuvant pretreatment: indapamide, framework material, disintegrate material and diluent are all crossed 80 mesh sieves, each Self-enclosing storage is for subsequent use;
2) premixing of adjuvant: take the pretreated described framework material of formula ratio, described disintegrate material, described diluent mix;
3) major ingredient equivalent is progressively increased mixing: the mode that the indapamide of formula ratio progressively increases with equivalent mixed with described adjuvant, then add the lubricant of formula ratio, forms uniform powder;
4) tabletting: described uniform powder is directly carried out tabletting, formin sheet;
5) coating: described plain sheet is carried out film coating.
Wherein, described major ingredient is indapamide, percentage by weight is 0.75 part, and described framework material is hypromellose RT4000 and hypromellose RT5, and percentage by weight is respectively 25 ~ 30 parts, 15 ~ 25 parts, described disintegrate material is microcrystalline Cellulose, its percentage by weight is 5 ~ 10 parts, and described diluent is lactose, and its percentage by weight is 40 ~ 50 parts, described lubricant is magnesium stearate, and percentage by weight is 0.5 part.
Wherein, the ratio that described major ingredient equivalent is progressively increased is 1:1.
Wherein, described coating weight gain is 2.5 ~ 3% of tablet fill weights.
Compared with prior art, beneficial effect of the present invention is: the indapamide slow release hypertension pill in (1) the present invention can be released effectively suppressing the prominent of medicine, ensure later stage release thoroughly, meet the quality criteria requirements after raising, make antihypertensive effect more mild lasting; (2) framework material is domestic, reduces production cost, reduces consumer's financial burden; (3) adopt dry powder direct tabletting technique, prevent functional group propoxyl and water from producing gelling, avoid drug effect to dash forward releasing the generation of excessive phenomenon; (4) preparation technology is simple, and equipment is few and take up room little, and production efficiency is high; (5) only need operate according to formula ratio, product quality is more stable, and between batch, product differentiation reduces.
Accompanying drawing explanation
Fig. 1 is the flow chart that in the present invention, direct powder compression prepares indapamide slow release hypertension pill.
Detailed description of the invention
Also by reference to the accompanying drawings the present invention is described in further detail below by specific embodiment.
Indapamide slow release hypertension pill in the present invention, each weight percentages of components in its formula is:
Indapamide, 0.75 part; Framework material, 40 ~ 55 parts; Disintegrate material, 5 ~ 10; Part diluent, 40 ~ 50 parts; Lubricant, 0.5 part.
Indapamide proportion in indapamide slow release hypertension pill in the present invention is determined by this product specification, and the weight of every sheet is 0.2g, containing indapamide 1.5mg in every sheet.The combination of this formula, achieves and adopts domestic framework material, while reaching the drug effect and release conformed with the regulations, greatly reduce the production cost of this medicine, therefore also reduce the financial burden of consumer.
Embodiment 1
On the basis of the above, select framework material to be hypromellose RT4000 and hypromellose RT5, disintegrate material is microcrystalline Cellulose, and diluent is lactose, and lubricant is magnesium stearate, and the percentage by weight of each component is: indapamide, 0.75 part; Hypromellose RT4000,25 parts; Hypromellose RT5,23.75 parts; Microcrystalline Cellulose, 10 parts; Lactose, 40 parts; Magnesium stearate, 0.5 part.
The hypromellose RT4000 that framework material adopts and hypromellose RT5, wherein RT4000/5 represents its viscosity model, it includes two key functional groups, be respectively methoxyl group and propoxyl, wherein methoxyl group is hydrophobic group, resistance to corrosion and rise slow releasing function, propoxyl is hydrophilic group, namely form gel layer fast after contact water, the prominent of medicine can be suppressed to release.Lactose plays dilution in this prescription, and compressibility is good, has good dissolubility simultaneously, have good facilitation to the release completely in medicine later stage because of it.Microcrystalline Cellulose plays the effect of disintegrate after medicine enters human body, contributes to the absorption of human body, and the compressibility of microcrystalline Cellulose is better, and the compressibility of medicine in preparation process is improved.Magnesium stearate mainly plays the effect of lubrication fluidizer.The combination of this formula, achieves framework material and adopts domestic hypromellose, while reaching the drug effect and release conformed with the regulations, greatly reduces the production cost of this medicine, therefore also reduces the financial burden of consumer.
Embodiment 2
On the basis of the above, be hypromellose RT4000 and hypromellose RT5 with framework material, disintegrate material is microcrystalline Cellulose, and diluent is lactose, and lubricant is magnesium stearate, and the percentage by weight of each component is: indapamide, 0.75 part; Hypromellose RT4000,28.75 parts; Hypromellose RT5,15 parts; Microcrystalline Cellulose, 5 parts; Lactose, 50 parts; Magnesium stearate, 0.5 part.
Embodiment 3
On the basis of the above, be hypromellose RT4000 and hypromellose RT5 with framework material, disintegrate material is microcrystalline Cellulose, and diluent is lactose, and lubricant is magnesium stearate, and the percentage by weight of each component is: indapamide, 0.75 part; Hypromellose RT4000,30 parts; Hypromellose RT5,25 parts; Microcrystalline Cellulose, 8 parts; Lactose, 35.75 parts; Magnesium stearate, 0.5 part.
Embodiment 4
The present embodiment provides a kind of method preparing above-mentioned indapamide slow release hypertension pill, and utilize the method for direct powder compression to be prepared, refer to Fig. 1, it is the flow chart of this preparation method, and concrete steps are as follows:
1) major ingredient and adjuvant pretreatment: indapamide, framework material, disintegrate material and diluent are all crossed 80 mesh sieves, each Self-enclosing storage is for subsequent use.This step main purpose is the raw material particle size homogenization more in order to make pharmacy.
2) premixing of adjuvant: take the pretreated described framework material of formula ratio, described disintegrate material and described diluent and mix.
3) major ingredient equivalent is progressively increased mixing: the mode that the indapamide of formula ratio progressively increases with equivalent mixed with described adjuvant, then add the lubricant of formula ratio, forms uniform powder.
The ratio that major ingredient equivalent in this step is progressively increased is 1:1, to produce 1000, the quality of tablet is 200g, and the consumption of indapamide is 1.5g, supplementary product consumption is 198.5g, then the indapamide powder of this 1.5g is mixed homogeneously with 1.5g adjuvant, form 3g uniform powder, this 3g uniform powder is mixed homogeneously with 3g adjuvant, form 6g uniform powder, again this 6g uniform powder is mixed homogeneously with 6g adjuvant, mix according to this mixed method always, until adjuvant uses until exhausted.The object of carrying out mixed in equal amounts is to make indapamide be dispersed in more uniformly in adjuvant, and the drug effect of final each tablet is consistent.Adjuvant wherein refers to above-mentioned framework material, disintegrate material, diluent.
4) tabletting: described uniform powder is directly carried out tabletting, formin sheet; Need select suitable punch die, tab weight, pressure and the speed of a motor vehicle, make the plain blade weight of extrusion, tablet weight variation, friability and outward appearance etc. meet the requirements.
5) coating: described plain sheet is carried out film coating.
Framework material in above-mentioned steps is hypromellose RT4000 and hypromellose RT5, and disintegrate material is microcrystalline Cellulose, and diluent is lactose, and lubricant is magnesium stearate, and coating weight gain accounts for 2.5 ~ 3% of tablet fill weights.
In above-mentioned preparation method; because the hypromellose in this formula, lactose and microcrystalline Cellulose compressibility are good; tablet hardness is guaranteed; and the density of three is substantially consistent; ensure that particle size distribution is consistent through sieving; guarantee mix homogeneously, make product quality more stable, between batch, product differentiation reduces.
Adopt direct powder compression, the propoxyl of framework material hypromellose does not contact with water, thus its gelation function is not destroyed, good resistancing action is served to prominent releasing in the early stage of tablet, and the later stage dissolve the hydrotropy effect brought because of the disintegration of microcrystalline Cellulose and lactose, the release of its later stage is also comparatively complete, and avoid simultaneously and adopt heating process in wet granulation to the destruction of slow-release material, slow releasing function is improved significantly.Therefore its 4 hours release general controls are at 21-23%, within 8 hours, release general control is at 40-45%, within 16 hours, release is not less than 75%, meet quality criteria requirements of becoming a full member completely, indapamide slow release hypertension pill is enable to reach standard compliant burst size in shorter interval, make antihypertensive effect more mild lasting, avoiding and prominently releasing excessive early stage, release controls failed phenomenon.Meanwhile, preparation technology is simple, and occupies little space.
The method of testing contrast of this product tentative standard release and standard release of becoming a full member.
1. the method for testing of this medicine release in tentative standard and regulation:
Get this product, according to drug release determination method (China's coastal port two annex Ⅹ D first methods), adopt dissolution method the 3rd subtraction unit, with water 250ml for dissolution fluid, water is put into rotation slot, arranging rotating speed is 50 turns per minute, indapamide slow release hypertension pill of the present invention is added in above-mentioned water, operate in accordance with the law, through 2 hours, 8 hours, 16 is constantly little, each sampling 10ml, filter, and timely supplementing water 10ml, get filtrate 20ul according to high efficiency chromatography method (Chinese Pharmacopoeia version in 2000 two annex VD), chromatographic condition is with under assay, determined wavelength is 242nm, measure respectively, separately get indapamide reference substance 25mg, accurately weighed, put in 100ml measuring bottle and add methanol in right amount, ultrasonic dissolution, add methanol dilution to scale, shake up, precision measures the solution that 2ml thin up makes 2ug/ml, shakes up, filter, be measured in the same method, calculate the burst size of every sheet at different time.The every sheet of this product should be equivalent to 15%-30%, 45-65% and more than 75% of labelled amount respectively in 2,8,16 little burst sizes constantly.
2. this medicine is in the method for testing of the release in standard of becoming a full member and regulation:
This product is measured in the release in standard of becoming a full member, measure according to drug release determination method (Chinese Pharmacopoeia version in 2010 two annex Ⅹ D first methods), adopt dissolution method second subtraction unit, with the hydrochloric acid 500ml of 0.01mol/l for dissolution fluid, hydrochloric acid is put into rotation slot, arranging rotating speed is 50 turns per minute, indapamide slow release hypertension pill of the present invention is added in above-mentioned hydrochloric acid solution, 4,8,16 constantly little, get solution respectively appropriate, and supplement the dissolution medium of the pre-temperature of same volume to 37 ± 0.5 DEG C in time.The solution taken out, with the centrifugation 10 minutes of 3000 revs/min, gets supernatant as test article solution (measuring immediately after configuration).Separately get indapamide reference substance appropriate, accurately weighed, add appropriate amount of ethanol, shake well makes dissolving, and makes the solution containing indapamide 1ug in every 1ml with mobile phase dilution, shakes up, in contrast product solution.Precision measures above-mentioned each time point test article solution and each 20ul of reference substance solution, respectively injection liquid chromatography, and record chromatogram, calculates the burst size of every sheet at different time by external standard method.The every sheet of this product should be equivalent to 17%-27%, 35-55% and more than 75% of labelled amount respectively in 4,8,16 little burst sizes constantly, all meets the release regulation of becoming a full member in standard.
Become a full member in the test of standard release above-mentioned, release dissolution medium becomes the hydrochloric acid of 500ml 0.01mol/l by the purified water in the test of tentative standard release, little for cuvette oar is altered to the large slurry of mug, and release is altered to 17%-27%, the 35-55% and more than 75% of 4,8,16 hours of becoming a full member in standard by hour corresponding 15%-30%, the 45-65% and more than 75% of 2,8,16 in tentative standard.Become a full member quality standard compared to tentative quality standard, the large oar of mug is larger to the impulsive force of tablet in medicine corrosion process, dissolution medium changes to the hydrochloric acid of 0.01mol/l by purified water, closer to gastric acid environment, therefore the leaching condition of tablet is harsher, to before drug release, mid-term prominent to release control overflow stricter.The execution of quality standard of becoming a full member can ensure that the antihypertensive effect of indapamide slow release tablet is more mild lasting, and therefore, indapamide slow release hypertension pill of the present invention can realize antihypertensive effect lasting gently.
This formula is in former wet granulation technology, main slow-release material hypromellose is adding water in pelletization, its functional group propoxyl and water produce gelling, cause consuming the slow-release function destroying part hypromellose, occur dashing forward and release excessive phenomenon, its 4 hours releases reach more than 35%, 8 hours releases of labelled amount more than 65%, do not meet quality criteria requirements of becoming a full member.For avoiding the slow-release function of hypromellose to be destroyed, wet granulation technology can not be adopted again in process of production.
These are only the preferred embodiments of the present invention, be not limited to the present invention, for a person skilled in the art, the present invention can have various modifications and variations.Within the spirit and principles in the present invention all, any amendment done, equivalent replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (6)
1. an indapamide slow release hypertension pill, is characterized in that, the every sheet of described sustained release hypotensive sheet is prepared according to following percentage by weight:
2. indapamide slow release hypertension pill according to claim 1, it is characterized in that, described framework material is hypromellose RT4000 and hypromellose RT5, described disintegrate material is microcrystalline Cellulose, described diluent is lactose, described lubricant is magnesium stearate, and in its formula, the percentage by weight of each component is:
3. prepare an arbitrary described indapamide slow release hypertension pill method in claim 1-2, it is characterized in that, adopt direct powder compression, comprise the steps:
1) major ingredient and adjuvant pretreatment: indapamide, framework material, disintegrate material and diluent are all crossed 80 mesh sieves, each Self-enclosing storage is for subsequent use;
2) premixing of adjuvant: take the pretreated described framework material of formula ratio, described disintegrate material, described diluent mix;
3) major ingredient equivalent is progressively increased mixing: the mode that the indapamide of formula ratio progressively increases with equivalent mixed with described adjuvant, then add the lubricant of formula ratio, forms uniform powder;
4) tabletting: described uniform powder is directly carried out tabletting, formin sheet;
5) coating: described plain sheet is carried out film coating.
4. the preparation method of indapamide slow release hypertension pill according to claim 3, it is characterized in that, described major ingredient is indapamide, percentage by weight is 0.75 part, described framework material is hypromellose RT4000 and hypromellose RT5, percentage by weight is respectively 25 ~ 30 parts, 15 ~ 25 parts, described disintegrate material is microcrystalline Cellulose, its percentage by weight is 5 ~ 10 parts, described diluent is lactose, its percentage by weight is 40 ~ 50 parts, and described lubricant is magnesium stearate, and percentage by weight is 0.5 part.
5. the preparation method of indapamide slow release hypertension pill according to claim 3, is characterized in that, the ratio that described major ingredient equivalent is progressively increased is 1:1.
6. the preparation method of indapamide slow release hypertension pill according to claim 3, is characterized in that, described coating weight gain is 2.5 ~ 3% of tablet fill weights.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107951854A (en) * | 2017-12-22 | 2018-04-24 | 南京易亨制药有限公司 | The indapamide slow release tablet and its preparation process of a kind of stable storing |
| CN108578379A (en) * | 2018-07-18 | 2018-09-28 | 天津力生制药股份有限公司 | A kind of preparation method of indapamide slow release tablet |
| CN112370433A (en) * | 2020-12-07 | 2021-02-19 | 石家庄市华新药业有限责任公司 | Indapamide sustained release tablet and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2006069705A1 (en) * | 2004-12-23 | 2006-07-06 | Merckle Gmbh | Directly pressed indapamide tablets with delayed release of the active substance |
| CN103142529A (en) * | 2013-03-07 | 2013-06-12 | 宁夏康亚药业有限公司 | Indapamide sustained-release drug composite and preparation method thereof |
-
2015
- 2015-06-24 CN CN201510353159.6A patent/CN104906060A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006069705A1 (en) * | 2004-12-23 | 2006-07-06 | Merckle Gmbh | Directly pressed indapamide tablets with delayed release of the active substance |
| CN103142529A (en) * | 2013-03-07 | 2013-06-12 | 宁夏康亚药业有限公司 | Indapamide sustained-release drug composite and preparation method thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107951854A (en) * | 2017-12-22 | 2018-04-24 | 南京易亨制药有限公司 | The indapamide slow release tablet and its preparation process of a kind of stable storing |
| CN108578379A (en) * | 2018-07-18 | 2018-09-28 | 天津力生制药股份有限公司 | A kind of preparation method of indapamide slow release tablet |
| CN112370433A (en) * | 2020-12-07 | 2021-02-19 | 石家庄市华新药业有限责任公司 | Indapamide sustained release tablet and preparation method thereof |
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Application publication date: 20150916 |