CN105168165B - A kind of Lercanidipine hydrochloride piece and preparation method thereof - Google Patents
A kind of Lercanidipine hydrochloride piece and preparation method thereof Download PDFInfo
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- CN105168165B CN105168165B CN201510541492.XA CN201510541492A CN105168165B CN 105168165 B CN105168165 B CN 105168165B CN 201510541492 A CN201510541492 A CN 201510541492A CN 105168165 B CN105168165 B CN 105168165B
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Abstract
The invention discloses a kind of Lercanidipine hydrochloride pieces, are made of the following components, and the weight ratio of each component is：Lercanidipine hydrochloride, lactose, microcrystalline cellulose, sodium carboxymethyl starch, 5% PVP K30 solution, magnesium stearate weight ratio be 10:70~75:29~33:8~12:0.8~1.2:0.7~3.The present invention also provides the preparation processes of Lercanidipine hydrochloride piece, are uniformly mixed again with other auxiliary materials after first Lercanidipine hydrochloride is mixed with lactose equal increments, with.The Lercanidipine hydrochloride piece supplementary material of the present invention is uniformly mixed, and Lercanidipine hydrochloride content is uniform, and dissolution rate is high, conducive to body absorption, improves its bioavilability.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, and in particular to a kind of Lercanidipine hydrochloride piece and preparation method thereof.
Background technology
Hypertension is a kind of disease as caused by many factors.Various complication can be caused with high blood pressure for a long time, such as
Apoplexy, congestive heart failure, ischemic heart disease, kidney failure etc..Experiment proves that lasting hypertension can cause coronary artery hard
Change and cardiomegaly, can generate myocardial ischemia, angina pectoris, myocardial infarction and block again later.The high morbidity of Chinese hypertension, height
Disable and high death state, hypertension control is made greatly to be challenged.There are higher simple receipts with reference to Chinese hypertensive patient
Contracting phase hypertension ratio has the characteristics of high salt diet custom, and calcium ion antagonist is not in the treatment to this kind of hypertensive patient
Weary is a kind of good medicine.
Lercanidipine is a kind of novel dihydropyridine type calcium antagonists, has direct diastole to act on to vascular smooth muscle,
With stronger antihypertensive effect, and the influence to heart rate and cardiac output is smaller.Lercanidipine hydrochloride mechanism of action is similar to its,
The Ca of the i.e. reversible stagnant vascular smooth muscle cells film L-type calcium channel of ground resistance2+Interior stream, expand peripheral blood vessel and reduce blood pressure, have compared with
The features such as strong cardioselective, antihypertensive effect is strong, and negative inotropic action is few.Lercanidipine hydrochloride has larger hydrophobic group
Group, it is fat-soluble strong, into rear rapid distribution to histoorgan in vivo, it can be tightly combined, release with vascular smooth muscle cells film
Slow down slowly, therefore, although the medicine serum eliminates half-life short, persistent.Its structural formula is：
The preparation being administered in oral or other non-vascular, the absorption of active ingredient are influenced by many factors.Including system
Binder, lubricant, disintegrant, coating material, suspending agent, solvent in agent technique, diameter of aspirin particle, prescription etc..Existing salt
Sour contents of lercanidipine tablets preparation process cost of material is higher, and the yield rate of Lercanidipine hydrochloride and dissolution rate all need to be carried in tablet
It is high.
Invention content
The object of the present invention is to provide a kind of high finished product rates and the Lercanidipine hydrochloride piece of high-dissolution, pass through accurate work
Skill controls and the selection of supplementary material, and the Lercanidipine hydrochloride piece supplementary material mixture homogeneity is good, stable quality, and dissolution rate is high, profit
In the absorption of active constituent in vivo.
In order to reach goal of the invention, the technical solution adopted by the present invention is as follows：
Lercanidipine hydrochloride, lactose, microcrystalline cellulose, sodium carboxymethyl starch, 5% poly- dimension in the Lercanidipine hydrochloride piece
Ketone K30 solution, magnesium stearate weight ratio be 10:70~75:29~33:8~12:0.8~1.2:0.7~3.
The preparation method of the Lercanidipine hydrochloride piece is as follows：
(1) Lercanidipine hydrochloride raw material is crushed, sieved with 100 mesh sieve, by lactose, microcrystalline cellulose, sodium carboxymethyl starch point
80 mesh sieve is not crossed, PVP K30 is dissolved in purified water, and the PVP K30 solution that mass concentration is 5% is made；
(2) first the Lercanidipine hydrochloride of recipe quantity with the lactose of recipe quantity by equal increments method is uniformly mixed, added
Microcrystalline cellulose, the sodium carboxymethyl starch of recipe quantity are uniformly mixed；
(3) by 5% PVP K30 softwood of the mixed-powder that step 2 obtains recipe quantity, 30~50 mesh sieve series are crossed
Grain, in 50 DEG C of dryings；
(4) dry particl is crossed into 30 mesh sieve whole grain, the magnesium stearate of additional recipe quantity is uniformly mixed, obtains intermediate；
(5) content of intermediate, tabletting are detected；
(6) coating solution is prepared using stomach dissolved film coating pre-mix dose, be coated；
(7) it dispenses, labelling, warehousing finished products.
The present invention using first Lercanidipine hydrochloride is mixed with lactose equal increments in a manner that, make lactose as filler and
Disintegrant is uniformly mixed with Lercanidipine hydrochloride, while conducive to tabletting, on the one hand improves containing for Lercanidipine hydrochloride piece
The uniformity is measured, on the other hand improves the dissolution rate of Lercanidipine hydrochloride again.The present invention is by accurately controlling process conditions and sieve
Supplementary material formula is selected, high yield rate and the high Lercanidipine hydrochloride piece of dissolution rate has been prepared.The prescription and preparation process can
Row is suitble to large-scale production.
Specific embodiment
The present invention will be described in detail with reference to embodiments, the embodiment described be in order to further describe the present invention, without
It is the limitation present invention.
Embodiment 1
Prescription 1
Preparation process is as follows：
(1) Lercanidipine hydrochloride raw material is crushed, sieved with 100 mesh sieve, by lactose, microcrystalline cellulose, sodium carboxymethyl starch point
80 mesh sieve is not crossed, PVP K30 is dissolved in purified water, and the PVP K30 solution that mass fraction is 5% is made；
(2) first 10g Lercanidipine hydrochlorides with 70g lactose by equal increments method are uniformly mixed, add 29g microcrystalline celluloses
Element, 8g sodium carboxymethyl starches are placed in mixing machine and are uniformly mixed；
(3) mixed-powder is transferred in oscillating granulator, with 0.8g, 5% PVP K30 softwood, crosses 30 mesh sieve series
Grain, in 50 DEG C of dryings；
(4) dry particl is crossed into 30 mesh sieve whole grain, additional 0.7g magnesium stearates are uniformly mixed, obtain intermediate；
(5) content of intermediate, tabletting are detected；
(6) coating solution is prepared using stomach dissolved film coating pre-mix dose, be coated；
(7) it dispenses, labelling, warehousing finished products.
Embodiment 2
Prescription 2
Preparation process is as follows：
(1) Lercanidipine hydrochloride raw material is crushed, sieved with 100 mesh sieve, by lactose, microcrystalline cellulose, sodium carboxymethyl starch point
80 mesh sieve is not crossed, PVP K30 is dissolved in purified water, and the PVP K30 solution that mass fraction is 5% is made；
(2) first 10g Lercanidipine hydrochlorides with 72g lactose by equal increments method are uniformly mixed, add 31g microcrystalline celluloses
Element, 9g sodium carboxymethyl starches are placed in mixing machine and are uniformly mixed；
(3) mixed-powder is transferred in oscillating granulator, with 1g, 5% PVP K30 softwood, crosses 30 mesh sieve series grains,
In 50 DEG C of dryings；
(4) dry particl is crossed into 40 mesh sieve whole grain, additional 0.8g magnesium stearates are uniformly mixed, obtain intermediate；
(5) content of intermediate, tabletting are detected；
(6) coating solution is prepared using stomach dissolved film coating pre-mix dose, be coated；
(7) it dispenses, labelling, warehousing finished products.
Embodiment 3
Prescription 3
Preparation process is as follows：
(1) Lercanidipine hydrochloride raw material is crushed, sieved with 100 mesh sieve, by lactose, microcrystalline cellulose, sodium carboxymethyl starch point
80 mesh sieve is not crossed, PVP K30 is dissolved in purified water, and the PVP K30 solution that mass fraction is 5% is made；
(2) first 10g Lercanidipine hydrochlorides with 73.5g lactose by equal increments method are uniformly mixed, add 31.5g crystallites
Cellulose, 10g sodium carboxymethyl starches are placed in mixing machine and are uniformly mixed；
(3) mixed-powder is transferred in oscillating granulator, with 1.1g, 5% PVP K30 softwood, crosses 30 mesh sieve series
Grain, in 50 DEG C of dryings；
(4) dry particl is crossed into 50 mesh sieve whole grain, additional 1g magnesium stearates are uniformly mixed, obtain intermediate；
(5) content of intermediate, tabletting are detected；
(6) coating solution is prepared using stomach dissolved film coating pre-mix dose, be coated；
(7) it dispenses, labelling, warehousing finished products.
Embodiment 4
Prescription 4
Preparation process is as follows：
(1) Lercanidipine hydrochloride raw material is crushed, sieved with 100 mesh sieve, by lactose, microcrystalline cellulose, sodium carboxymethyl starch point
80 mesh sieve is not crossed, PVP K30 is dissolved in purified water, and the PVP K30 solution that mass fraction is 5% is made；
(2) first 10g Lercanidipine hydrochlorides with 75g lactose by equal increments method are uniformly mixed, add 33g microcrystalline celluloses
Element, 12g sodium carboxymethyl starches are placed in mixing machine and are uniformly mixed；
(3) mixed-powder is transferred in oscillating granulator, with 1.2g, 5% PVP K30 softwood, crosses 30 mesh sieve series
Grain, in 50 DEG C of dryings；
(4) dry particl is crossed into 50 mesh sieve whole grain, additional 3g magnesium stearates are uniformly mixed, obtain intermediate；
(5) content of intermediate, tabletting are detected；
(6) coating solution is prepared using stomach dissolved film coating pre-mix dose, be coated；
(7) it dispenses, labelling, warehousing finished products.
Test example 1
Drug feed postition
Lercanidipine hydrochloride piece is small dose drug tablet, and the uniformity of dosage units of drug is one of important indicator, to ensure
The mixing uniformity of drug and auxiliary material need to determine Lercanidipine hydrochloride feed postition.Since Lercanidipine hydrochloride is yellowish toner
End, auxiliary material used are white powder, therefore can judge the mixed of drug and auxiliary material according to color (faint yellow to the yellow) depth
Close uniformity.
This test example compares three kinds of different feed postitions, and drug feed postition is determined according to the degree of being evenly distributed of color,
The results are shown in Table 1.
Influence of the 1 drug feed postition of table to the tablet content uniformity
Note：5%PVP-K30 (50% ethyl alcohol) refers to that PVP-K30 is dissolved in 50% ethyl alcohol, forms 5% PVP-K30.
The result shows that the mode mixed with auxiliary material equal increments can obtain the Lercanidipine hydrochloride piece of good evenness.
Test example 2
This experiment has carried out the quality research of following aspect to the Lercanidipine hydrochloride piece that each prescription obtains, including softwood
Fine powder ratio, angle of repose, the tabletting feelings of gained dry particl after the degree of bonding, the complexity of granulation, wet granular character, whole grain
Condition.
(1) the bonding degree of softwood：After adding in adhesive, whether softwood mixture is uniformly mixed in observation device, bonding
Can agent uniformly disperse.
(2) complexity of granulation：Observe the whether stifled sieve of softwood.
(3) wet granular character：Whether wet granular is uniform during observation sieving granulation, observes fine powder amount.
(4) after whole grain gained dry particl fine powder ratio：Dry particl is sieved with 100 mesh sieve, detects the fine powder amount in dry particl.
(5) angle of repose：Angle of repose is measured, uses and is measured with fixed funnel method, respectively level altitude 1-5cm, it is each to survey
Determine to be averaged for 6 times, detect the mobility of supplementary material.
Each testing result for investigating project is as shown in table 2.
The quality research result of 2 each prescription of table
From wet granular character it is found that the particle of prescription 2,3 and 4 is uniform, thickness is moderate, illustrates that process parameter control is reasonable,
Effectively enhance the uniformity of material.The fine powder ratio of gained dry particl is it is found that the fine powder ratio of prescription 2,3 and 4 after whole grain
Example illustrates the uniformity enhancing of particle less than 6%, and material is uniformly mixed, and bonding effect is good.From angle of repose testing result it is found that
The angle of repose of prescription 3 and prescription 4 is less than 35 °, illustrates that the material fluidity of prescription 3 and prescription 4 is good, conducive to tabletting.
Test example 3
Dissolution determination
(a) selection of dissolving-out method
Using dissolving-out method of Chinese Pharmacopoeia two annex X the second methods of C of version in 2010 as this product.
(b) dissolution medium is determining
Using hydrochloric acid solution (9 → 1000) 900ml of the Tween 80 containing 0.3% (w/v) as dissolution medium.
(c) selection of rotating speed
Hydrochloric acid solution (9 → 1000) 900ml of the Tween 80 containing 0.3% (w/v) is selected as dissolution medium, by middle traditional Chinese medicines
Allusion quotation two annex X the second methods of C of version in 2010, rotating speed are 50 revs/min, at 45 minutes, take solution 5ml, filter, take subsequent filtrate
As test solution；Lercanidipine hydrochloride reference substance about 10mg separately is taken, precision weighing is put in 100ml measuring bottles, adds about 80ml first
50ml measuring bottles are put with methanol dilution to scale, then the accurate 5ml that measures after alcohol dissolving, scale is diluted to dissolution medium, shakes up, make
For contrast solution.By Chinese Pharmacopoeia two annex V D high effective liquid chromatography for measuring of version in 2010, it is bonded with octadecylsilane
Silica gel is filler, acetonitrile：Water：Triethylamine (55：44.8：0.2,3.0) it is mobile phase to be with phosphorus acid for adjusting pH, Detection wavelength is
356nm detects dissolution rate.
3 each prescription dissolution results of table
| Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 | |
| Dissolution rate (%) | 91.84±4.50 | 93.73±3.61 | 95.31±3.07 | 94.15±3.62 |
As can be known from the above table, the dissolution rate of each prescription has all reached more than 90%, and the wherein dissolution rate of prescription 3 is more than 95%,
Illustrate that the Lercanidipine hydrochloride piece that the present invention is prepared has preferable dissolution rate.
Claims (2)
1. the preparation method of Lercanidipine hydrochloride piece, which is characterized in that be as follows：
(1) Lercanidipine hydrochloride raw material is crushed, sieved with 100 mesh sieve, by lactose, microcrystalline cellulose, sodium carboxymethyl starch mistake respectively
80 mesh sieve, and PVP K30 is dissolved in purified water, and the PVP K30 solution that mass concentration is 5% is made；
(2) first the Lercanidipine hydrochloride of recipe quantity with the lactose of recipe quantity by equal increments method is uniformly mixed, adds prescription
Microcrystalline cellulose, the sodium carboxymethyl starch of amount are uniformly mixed；
(3) by 5% PVP K30 softwood of the mixed-powder that step 2 obtains recipe quantity, 30~50 mesh sieve series grains are crossed, in
50 DEG C of dryings；
(4) dry particl is crossed into 30 mesh sieve whole grain, the magnesium stearate of additional recipe quantity is uniformly mixed, obtains intermediate；
(5) content of intermediate, tabletting are detected；
(6) coating solution is prepared using stomach dissolved film coating pre-mix dose, be coated；
(7) it dispenses, labelling, warehousing finished products；
The Lercanidipine hydrochloride piece is made of the following components, and the weight ratio of each component is：It is Lercanidipine hydrochloride, lactose, micro-
Crystalline cellulose, sodium carboxymethyl starch, 5% PVP K30 solution, magnesium stearate weight ratio be 10:70~75:29~33:8~
12:0.8~1.2:0.7~3.
2. the preparation method of Lercanidipine hydrochloride piece as described in claim 1, which is characterized in that the hydrochloric acid pleasure card ground
Flat, lactose, microcrystalline cellulose, sodium carboxymethyl starch, 5% PVP K30 solution, magnesium stearate weight ratio be 10:73.5:
31.5:10:1.1:1。
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1901888A (en) * | 2003-12-01 | 2007-01-24 | 生命周斯药物公司 | Pharmaceutical compositions comprising lercanidipine |
| CN101784260A (en) * | 2007-07-23 | 2010-07-21 | 法尔玛赞公司 | Pharmaceutical composition containing dihydropyridine calcium channel antagonist and method for the preparation thereof |
| CN104069500A (en) * | 2014-06-20 | 2014-10-01 | 湖南天地恒一制药有限公司 | Pharmaceutical composition containing lercanidipine |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1901888A (en) * | 2003-12-01 | 2007-01-24 | 生命周斯药物公司 | Pharmaceutical compositions comprising lercanidipine |
| CN101784260A (en) * | 2007-07-23 | 2010-07-21 | 法尔玛赞公司 | Pharmaceutical composition containing dihydropyridine calcium channel antagonist and method for the preparation thereof |
| CN104069500A (en) * | 2014-06-20 | 2014-10-01 | 湖南天地恒一制药有限公司 | Pharmaceutical composition containing lercanidipine |
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