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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- lercanidipine hydrochloride
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- WMFYOYKPJLRMJI-UHFFFAOYSA-N Lercanidipine hydrochloride Chemical compound Cl.COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)(C)CN(C)CCC(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 WMFYOYKPJLRMJI-UHFFFAOYSA-N 0.000 title claims abstract description 41
- 229960002162 lercanidipine hydrochloride Drugs 0.000 title claims abstract description 41
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims abstract description 24
- 229920003081 Povidone K 30 Polymers 0.000 claims abstract description 24
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims abstract description 19
- 239000008101 lactose Substances 0.000 claims abstract description 19
- 229920002472 Starch Polymers 0.000 claims abstract description 16
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 16
- 239000011734 sodium Substances 0.000 claims abstract description 16
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 16
- 235000019698 starch Nutrition 0.000 claims abstract description 16
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 15
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 14
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 12
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 12
- 239000008107 starch Substances 0.000 claims abstract description 12
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 10
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims abstract description 3
- 229960001375 lactose Drugs 0.000 claims abstract description 3
- 229940083542 sodium Drugs 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 14
- 239000011122 softwood Substances 0.000 claims description 10
- 235000020985 whole grains Nutrition 0.000 claims description 9
- 239000011248 coating agent Substances 0.000 claims description 7
- 238000000576 coating method Methods 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 206010013786 Dry skin Diseases 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 235000013339 cereals Nutrition 0.000 claims description 6
- UHZZMRAGKVHANO-UHFFFAOYSA-M chlormequat chloride Chemical compound [Cl-].C[N+](C)(C)CCCl UHZZMRAGKVHANO-UHFFFAOYSA-M 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 239000007888 film coating Substances 0.000 claims description 6
- 238000009501 film coating Methods 0.000 claims description 6
- 238000002372 labelling Methods 0.000 claims description 6
- 239000011812 mixed powder Substances 0.000 claims description 6
- 239000008213 purified water Substances 0.000 claims description 6
- 239000002994 raw material Substances 0.000 claims description 6
- 210000002784 stomach Anatomy 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 238000004090 dissolution Methods 0.000 abstract description 13
- 239000000463 material Substances 0.000 abstract description 10
- 238000010521 absorption reaction Methods 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 16
- 239000003814 drug Substances 0.000 description 9
- 206010020772 Hypertension Diseases 0.000 description 8
- 229940079593 drug Drugs 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 229960004294 lercanidipine Drugs 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- -1 Lercanidipine hydrochlorides Chemical class 0.000 description 4
- 239000012738 dissolution medium Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 238000005469 granulation Methods 0.000 description 3
- 230000003179 granulation Effects 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000003276 anti-hypertensive effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 230000001631 hypertensive effect Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- ZDXUKAKRHYTAKV-UHFFFAOYSA-N lercanidipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)(C)CN(C)CCC(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZDXUKAKRHYTAKV-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 208000031225 myocardial ischemia Diseases 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 208000006029 Cardiomegaly Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 102000004016 L-Type Calcium Channels Human genes 0.000 description 1
- 108090000420 L-Type Calcium Channels Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 229940127292 dihydropyridine calcium channel blocker Drugs 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 230000000297 inotrophic effect Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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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| Application Number | Priority Date | Filing Date | Title |
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| CN201510541492.XA CN105168165B (en) | 2015-08-28 | 2015-08-28 | A kind of Lercanidipine hydrochloride piece and preparation method thereof |
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| 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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| 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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