CN115671066A - Lercanidipine hydrochloride sustained release tablet and preparation method thereof - Google Patents
Lercanidipine hydrochloride sustained release tablet and preparation method thereof Download PDFInfo
- Publication number
- CN115671066A CN115671066A CN202211455019.6A CN202211455019A CN115671066A CN 115671066 A CN115671066 A CN 115671066A CN 202211455019 A CN202211455019 A CN 202211455019A CN 115671066 A CN115671066 A CN 115671066A
- Authority
- CN
- China
- Prior art keywords
- lercanidipine hydrochloride
- sustained release
- release tablet
- hydrochloride sustained
- lercanidipine
- 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.)
- Granted
Links
- 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 64
- 229960002162 lercanidipine hydrochloride Drugs 0.000 title claims abstract description 64
- 239000007939 sustained release tablet Substances 0.000 title claims abstract description 35
- 238000002360 preparation method Methods 0.000 title abstract description 14
- 239000000463 material Substances 0.000 claims abstract description 21
- 238000013268 sustained release Methods 0.000 claims abstract description 15
- 239000012730 sustained-release form Substances 0.000 claims abstract description 15
- 239000000945 filler Substances 0.000 claims abstract description 11
- 239000000314 lubricant Substances 0.000 claims abstract description 11
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 6
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 9
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 9
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 229920002472 Starch Polymers 0.000 claims description 8
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 8
- 239000002245 particle Substances 0.000 claims description 8
- 239000008107 starch Substances 0.000 claims description 8
- 235000019698 starch Nutrition 0.000 claims description 8
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 239000007884 disintegrant Substances 0.000 claims description 6
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 5
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 5
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 4
- 235000019359 magnesium stearate Nutrition 0.000 claims description 4
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 4
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 4
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 4
- 238000005550 wet granulation Methods 0.000 claims description 4
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 3
- 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 description 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 3
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 3
- 229960000913 crospovidone Drugs 0.000 claims description 3
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 3
- 239000001530 fumaric acid Substances 0.000 claims description 3
- 239000008101 lactose Substances 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 3
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 3
- 229940032147 starch Drugs 0.000 claims description 3
- 239000011975 tartaric acid Substances 0.000 claims description 3
- 235000002906 tartaric acid Nutrition 0.000 claims description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 3
- 238000005303 weighing Methods 0.000 claims description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- 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 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 235000015165 citric acid Nutrition 0.000 claims description 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 2
- 235000011087 fumaric acid Nutrition 0.000 claims description 2
- 239000001630 malic acid Substances 0.000 claims description 2
- 235000011090 malic acid Nutrition 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 239000001384 succinic acid Substances 0.000 claims description 2
- 235000011044 succinic acid Nutrition 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 27
- 229940079593 drug Drugs 0.000 abstract description 19
- 230000000694 effects Effects 0.000 abstract description 12
- 239000003826 tablet Substances 0.000 abstract description 10
- 210000004369 blood Anatomy 0.000 abstract description 5
- 239000008280 blood Substances 0.000 abstract description 5
- 239000003405 delayed action preparation Substances 0.000 abstract description 5
- 206010067484 Adverse reaction Diseases 0.000 abstract description 3
- 230000006838 adverse reaction Effects 0.000 abstract description 3
- LUEWUZLMQUOBSB-FSKGGBMCSA-N (2s,3s,4s,5s,6r)-2-[(2r,3s,4r,5r,6s)-6-[(2r,3s,4r,5s,6s)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2r,4r,5s,6r)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol 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]2[C@H](O[C@@H](OC3[C@H](O[C@@H](O)[C@@H](O)[C@H]3O)CO)[C@@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O LUEWUZLMQUOBSB-FSKGGBMCSA-N 0.000 description 20
- 241001312219 Amorphophallus konjac Species 0.000 description 20
- 235000001206 Amorphophallus rivieri Nutrition 0.000 description 20
- 229920002581 Glucomannan Polymers 0.000 description 20
- 229920002752 Konjac Polymers 0.000 description 20
- 229940046240 glucomannan Drugs 0.000 description 20
- 239000000252 konjac Substances 0.000 description 20
- 235000010485 konjac Nutrition 0.000 description 20
- VBUYCZFBVCCYFD-UHFFFAOYSA-N D-arabino-2-Hexulosonic acid Natural products OCC(O)C(O)C(O)C(=O)C(O)=O VBUYCZFBVCCYFD-UHFFFAOYSA-N 0.000 description 14
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
- 150000001263 acyl chlorides Chemical class 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 239000012738 dissolution medium Substances 0.000 description 3
- 239000013558 reference substance Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 229920003134 Eudragit® polymer Polymers 0.000 description 2
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 1
- -1 3-nitrophenyl Chemical group 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 229920003153 Eudragit® NE polymer Polymers 0.000 description 1
- 229920003155 Eudragit® RL 100 Polymers 0.000 description 1
- 229920003151 Eudragit® RL polymer Polymers 0.000 description 1
- 229920003159 Eudragit® RS 100 Polymers 0.000 description 1
- 229920003152 Eudragit® RS polymer Polymers 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 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
- 238000002835 absorbance Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- FSXVSUSRJXIJHB-UHFFFAOYSA-M ethyl prop-2-enoate;methyl 2-methylprop-2-enoate;trimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azanium;chloride Chemical compound [Cl-].CCOC(=O)C=C.COC(=O)C(C)=C.CC(=C)C(=O)OCC[N+](C)(C)C FSXVSUSRJXIJHB-UHFFFAOYSA-M 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229960004294 lercanidipine Drugs 0.000 description 1
- 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 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000010016 myocardial function Effects 0.000 description 1
- DNKKLDKIFMDAPT-UHFFFAOYSA-N n,n-dimethylmethanamine;2-methylprop-2-enoic acid Chemical compound CN(C)C.CC(=C)C(O)=O.CC(=C)C(O)=O DNKKLDKIFMDAPT-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000002522 swelling effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a lercanidipine hydrochloride sustained release tablet and a preparation method thereof, relating to the technical field of drug sustained release preparations, wherein the lercanidipine hydrochloride sustained release tablet comprises lercanidipine hydrochloride, a sustained release material, a filler, a disintegrating agent and a lubricant; compared with the existing common lercanidipine hydrochloride tablets, the lercanidipine hydrochloride sustained release tablets prepared by the invention can reduce the fluctuation of blood concentration, reduce the administration times, improve the curative effect of the medicine, reduce the occurrence of adverse reaction of the medicine and improve the medication compliance of patients; meanwhile, the preparation process is simple and easy to implement and has good repeatability.
Description
The technical field is as follows:
the invention relates to the technical field of drug sustained release preparations, in particular to a lercanidipine hydrochloride sustained release tablet and a preparation method thereof.
Background art:
lercanidipine hydrochloride belongs to the third-generation dihydropyridine calcium ion channel antagonist, and has the chemical name of 1,4-dihydro-2,6-dimethyl-4- (3-nitrophenyl) -3,5-dipicolinic acid 2- [ (3,3-diphenylpropyl) methyl amino]-1,1-dimethylethyl methyl ester hydrochloride of formula C 36 H 42 ClN 3 O 6 . The action mechanism of the lercanidipine hydrochloride is similar to that of other similar medicines, and the lercanidipine hydrochloride reversibly blocks calcium ion inflow of an L-type calcium channel of a vascular smooth muscle cell membrane, expands peripheral blood vessels and reduces blood pressure. The chemical structural formula of lercanidipine hydrochloride is as follows:
compared with other similar medicines, the lercanidipine hydrochloride has the following characteristics: (1) Has unique double benzene ring side chain and larger volume of stereo molecular structure, strong lipophilicity, can be permanently combined with vascular smooth muscle cell membranes, so that the half-life period of blood plasma is short and the effect is durable; (2) The effect on myocardial function indexes is small in the process of reducing blood pressure, and the blood vessel selectivity is more obvious; (3) Has effects in lowering blood pressure and blood lipid, resisting atherosclerosis, and protecting target organs such as kidney, heart, retina and brain; (4) The adverse reaction rate is low, and the tolerance and the safety are better.
The sustained release preparation prepared by taking lercanidipine hydrochloride as an active ingredient has the advantages of stable drug release rate, long drug sustained release time and high bioavailability, and can overcome the peak-valley phenomenon generated after the administration of a common preparation. The invention aims to provide a preparation method of lercanidipine hydrochloride sustained-release tablets, which can effectively prolong the release time of the drug, improve the bioavailability and reduce the administration times.
The invention content is as follows:
the invention aims to solve the technical problems of providing a lercanidipine hydrochloride sustained release tablet and a preparation method thereof, aiming at reducing the fluctuation of blood concentration, reducing the administration times, improving the curative effect of the medicament, reducing the occurrence of adverse reaction of the medicament and improving the medication compliance of patients; meanwhile, the preparation process is simple and easy to implement and has good repeatability.
The technical problem to be solved by the invention is realized by adopting the following technical scheme:
the invention aims to provide a lercanidipine hydrochloride sustained-release tablet, which comprises lercanidipine hydrochloride, a sustained-release material, a filler, a disintegrating agent and a lubricant.
Preferably, the D90 particle size of the lercanidipine hydrochloride is 10-40 μm. The size of the drug particle diameter directly influences the dissolution rate and the dissolution speed of the drug, thereby influencing the clinical curative effect. For solid preparations, the dissolution rate of a poorly soluble drug can be significantly improved by reducing the particle size of the drug particles.
Preferably, the mass ratio of the lercanidipine hydrochloride, the sustained-release material, the filler, the disintegrating agent and the lubricant is (5-20): 20-40): 30-60: (1-10): 1-10).
Preferably, the slow release material is at least one of hydroxyethyl cellulose, sodium carboxymethyl cellulose and Ewing. The slow release material has the functions of carrying the effective components of the medicine and slowly releasing the effective components of the medicine, and delays the release, absorption, distribution, metabolism and excretion processes of the medicine in vivo so as to prolong the action time of the medicine. Wherein, eudragit is selected from permeable acrylic resin, such as Eudragit RL, eudragit RS and Eudragit NE.
Preferably, the filler is at least one of microcrystalline cellulose, lactose, mannitol, and compressible starch. The filler acts to increase the weight or volume of the tablet, facilitating shaping and portioning.
Preferably, the disintegrant is at least one of sodium carboxymethyl starch, crospovidone, and croscarmellose sodium. The disintegrant serves to remove the binding force generated by tableting, and realizes disintegration of the tablet by virtue of its water absorption and swelling properties.
Preferably, the lubricant is at least one of talc, magnesium stearate and polyethylene glycol. The lubricant can reduce the friction force among tabletting particles, increase the flowability of the particles, reduce the difference of tablet weight, avoid the adhesion of the particles on the surfaces of a punch and a die and ensure the smoothness of the tablet surface.
The lercanidipine hydrochloride sustained release tablet also comprises a pH regulator.
Preferably, the pH regulator is at least one of citric acid, tartaric acid, fumaric acid, malic acid and succinic acid. A pH modifying agent is used to alter the pH of the microenvironment within the tablet, thereby altering the pH dependence of drug dissolution.
The invention also aims to provide a preparation method of the lercanidipine hydrochloride sustained-release tablet, which comprises the steps of weighing lercanidipine hydrochloride and auxiliary materials according to the formula amount, and preparing the lercanidipine hydrochloride sustained-release tablet by wet granulation tabletting or dry tabletting. Wherein, the auxiliary materials comprise a slow release material, a filling agent, a disintegrating agent, a lubricant and a pH regulator. Wet granulation tableting and dry tableting belong to tablet preparation processes commonly used in the art and are not described herein.
The invention also aims to provide a slow-release material, which is konjac glucomannan grafted fructonic acid, and the preparation method comprises the following steps: firstly, reacting the fructonic acid with thionyl chloride to prepare an acyl chloride intermediate, and then reacting the acyl chloride intermediate with the konjac glucomannan to prepare the konjac glucomannan grafted fructonic acid.
Preferably, the molar ratio of the fructonic acid to the thionyl chloride is 1 (2-5), and the mass ratio of the acyl chloride intermediate to the konjac glucomannan is 0.5-1: 1.
The selection of a proper sustained-release material is particularly critical for sustained-release preparations, and people skilled in the art generally select hydroxyethyl cellulose, sodium carboxymethyl cellulose, ewing and the like as the sustained-release material, but a good sustained-release effect can not be necessarily obtained when the sustained-release preparation is used for preparing specific drugs. Therefore, the inventor also develops a sustained-release material which can achieve the effect superior to hydroxyethyl cellulose, sodium carboxymethyl cellulose and Eudragit when being used for preparing the lercanidipine hydrochloride sustained-release tablets. Because konjac glucomannan has the characteristics of high viscosity, much water absorption and quick swelling, the expected slow release effect cannot be obtained by directly using konjac glucomannan as a slow release material, and chemical structure modification needs to be carried out on the konjac glucomannan.
The invention has the beneficial effects that: the lercanidipine hydrochloride sustained release tablet is prepared by taking lercanidipine hydrochloride as a raw drug and taking a sustained release material, a filler, a disintegrant and a lubricant as auxiliary materials through wet granulation and tabletting or dry tabletting; compared with the existing common lercanidipine hydrochloride tablets, the lercanidipine hydrochloride sustained release tablets prepared by the invention can reduce the fluctuation of blood concentration, ensure that the drug is kept in an effective blood concentration range within a certain time, reduce the administration times, improve the drug curative effect, reduce the occurrence of adverse drug reactions and improve the drug compliance of patients; the preparation process of the lercanidipine hydrochloride sustained release tablet is simple, convenient and easy to implement, has good repeatability and is suitable for batch production.
The specific implementation mode is as follows:
in order to make the technical means, the creation characteristics, the achievement purposes and the effects of the invention easy to understand, the invention is further described with the specific embodiments.
Lercanidipine hydrochloride, sustained-release materials, fillers, disintegrants, and lubricants in the following examples and comparative examples were previously ground and sieved through a 100-mesh sieve for use.
Sustained-release lercanidipine hydrochloride tablets having a tablet weight of 125mg were prepared in the following examples and comparative examples.
Example 1
The lercanidipine hydrochloride sustained-release tablets are prepared by uniformly mixing 10g of lercanidipine hydrochloride, 25g of sodium carboxymethylcellulose, 45g of microcrystalline cellulose, 5g of sodium carboxymethyl starch and 2g of magnesium stearate, and directly tabletting by a dry method.
Example 2
And uniformly mixing 12g of lercanidipine hydrochloride, 25g of hydroxyethyl cellulose, 50g of compressible starch, 10g of crospovidone and 3g of talcum powder, and directly tabletting by a dry method to obtain the lercanidipine hydrochloride sustained-release tablet.
Example 3
Mixing 15g lercanidipine hydrochloride, 30g Eudragit RL 100, 55g lactose, 5g sodium carboxymethyl starch and 3g polyethylene glycol 400 uniformly, and directly tabletting by dry method to obtain the lercanidipine hydrochloride sustained release tablet.
Example 4
The lercanidipine hydrochloride sustained release tablet is prepared by uniformly mixing 15g of lercanidipine hydrochloride, 20g of Eudragit RS 100, 50g of mannitol, 8g of croscarmellose sodium, 2g of magnesium stearate and 5g of tartaric acid, and directly tabletting by a dry method.
Example 5
The lercanidipine hydrochloride sustained-release tablet is prepared by uniformly mixing 10g of lercanidipine hydrochloride, 30g of hydroxyethyl cellulose, 60g of microcrystalline cellulose, 8g of sodium carboxymethyl starch, 4g of polyethylene glycol 400 and 5g of fumaric acid, and directly tabletting by a dry method.
Example 6
Example 6 differs from example 5 in that hydroxyethyl cellulose was replaced with the same mass of konjac glucomannan grafted fructonic acid described below, and the rest is the same as example 5.
Preparing konjac glucomannan grafted fructonic acid: adding 11.6g and 0.1mol of fructonic acid into dichloroethane, dropwise adding thionyl chloride (41.6 g and 0.35mol), stirring for reaction, heating to 60 ℃ after dropwise adding is finished, reacting for 3 hours, and carrying out reduced pressure distillation to recover the thionyl chloride and the dichloroethane to obtain an acyl chloride intermediate; and adding 20g of konjac glucomannan and 20g of pyridine into 10g of acyl chloride intermediate, heating to a reflux state, reacting for 5 hours, cooling to room temperature, carrying out suction filtration, washing a filter cake with a small amount of absolute ethyl alcohol, and carrying out vacuum drying to obtain the konjac glucomannan grafted fructonic acid.
Example 7
Example 7 differs from example 5 in that hydroxyethyl cellulose was replaced with the same mass of konjac glucomannan grafted fructonic acid described below, and the rest is the same as example 5.
Preparing konjac glucomannan grafted fructonic acid: adding 11.6g and 0.1mol of fructonic acid into dichloroethane, dropwise adding 41.6g and 0.35mol of thionyl chloride, stirring for reaction, heating to 60 ℃ after dropwise adding is finished, reacting for 3 hours, and recovering the thionyl chloride and the dichloroethane by reduced pressure distillation to obtain an acyl chloride intermediate; and adding 10g of konjac glucomannan and 20g of pyridine into 10g of acyl chloride intermediate, heating to a reflux state, reacting for 5 hours, cooling to room temperature, carrying out suction filtration, washing a filter cake with a small amount of absolute ethyl alcohol, and carrying out vacuum drying to obtain the konjac glucomannan grafted fructonic acid.
Comparative example 1
Comparative example 1 differs from example 6 in that konjac glucomannan grafted fructonic acid was replaced with the same mass of konjac glucomannan grafted acrylic acid described below, and the rest is the same as example 6.
Konjac glucomannan grafted acrylic acid was prepared as in example 6, except that the fructose acid was replaced by the same molar amount of acrylic acid.
Comparative example 2
Comparative example 2 differs from example 5 in that hydroxyethyl cellulose is replaced with konjac glucomannan of the same mass, as in example 5.
The prepared lercanidipine hydrochloride sustained release tablets are subjected to dissolution rate test according to a second method of 'Chinese pharmacopoeia' 2015 edition, 900mL of phosphate buffer solution with pH =6.8 is used as a dissolution medium, the rotating speed is 50r/min, 10mL of the solution is respectively taken at 1h, 2h, 4h, 8h, 12h and 16h, and the dissolution medium with the same temperature and volume is instantly supplemented. And precisely weighing a proper amount of lercanidipine hydrochloride reference substance, adding a dissolution medium to dissolve the lercanidipine hydrochloride reference substance, and quantitatively diluting the lercanidipine hydrochloride reference substance to prepare a solution containing 10 mu g of lercanidipine hydrochloride in each 1 mL. Absorbance was measured at 254nm by UV-visible spectrophotometry, and in vitro release was calculated as shown in Table 1.
TABLE 1
As can be seen from the table 1, the lercanidipine hydrochloride sustained release tablet prepared by the invention has a good sustained release effect, and the release rate of lercanidipine can be better controlled by adopting konjac glucomannan grafted fructonic acid as a sustained release material.
The foregoing shows and describes the general principles and broad features of the present invention and advantages thereof. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (10)
1. A lercanidipine hydrochloride sustained release tablet is characterized in that: comprises lercanidipine hydrochloride, a sustained-release material, a filler, a disintegrating agent and a lubricant.
2. The lercanidipine hydrochloride sustained release tablet of claim 1, wherein: the D90 particle size of the lercanidipine hydrochloride is 10-40 μm.
3. The lercanidipine hydrochloride sustained release tablet of claim 1, wherein: the mass ratio of the lercanidipine hydrochloride to the sustained-release material to the filler to the disintegrant to the lubricant is (5-20): 20-40): 30-60): 1-10.
4. The lercanidipine hydrochloride sustained release tablet of claim 1, wherein: the slow release material is at least one of hydroxyethyl cellulose, sodium carboxymethyl cellulose and Ewing.
5. The lercanidipine hydrochloride sustained release tablet of claim 1, wherein: the filler is at least one of microcrystalline cellulose, lactose, mannitol and compressible starch.
6. The lercanidipine hydrochloride sustained release tablet of claim 1, wherein: the disintegrant is at least one of sodium carboxymethyl starch, crospovidone and croscarmellose sodium.
7. The lercanidipine hydrochloride sustained release tablet of claim 1, wherein: the lubricant is at least one of talcum powder, magnesium stearate and polyethylene glycol.
8. The lercanidipine hydrochloride sustained release tablet of claim 1, wherein: the lercanidipine hydrochloride sustained release tablet also comprises a pH regulator.
9. The lercanidipine hydrochloride sustained release tablet of claim 8, wherein: the pH regulator is at least one of citric acid, tartaric acid, fumaric acid, malic acid and succinic acid.
10. A method for preparing lercanidipine hydrochloride sustained release tablets according to any one of claims 1 to 9, wherein: the lercanidipine hydrochloride sustained release tablets are prepared by weighing the lercanidipine hydrochloride and the auxiliary materials according to the formula ratio and carrying out wet granulation tabletting or dry tabletting.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211455019.6A CN115671066B (en) | 2022-11-21 | 2022-11-21 | Lercanidipine hydrochloride tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211455019.6A CN115671066B (en) | 2022-11-21 | 2022-11-21 | Lercanidipine hydrochloride tablet and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115671066A true CN115671066A (en) | 2023-02-03 |
| CN115671066B CN115671066B (en) | 2024-07-02 |
Family
ID=85053116
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211455019.6A Active CN115671066B (en) | 2022-11-21 | 2022-11-21 | Lercanidipine hydrochloride tablet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115671066B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003014084A1 (en) * | 2001-08-06 | 2003-02-20 | Recordati Ireland Limited | Novel crystalline polymorphic forms of lercanidipine hydrochloride and process for their preparation |
| CN101658481A (en) * | 2008-08-26 | 2010-03-03 | 北京科信必成医药科技发展有限公司 | Lercanidipine hydrochloride sustained release preparation and preparation method thereof |
| CN102399301A (en) * | 2010-09-08 | 2012-04-04 | 中国科学院成都生物研究所 | Preparation method for amphiphilic konjac glucomannan cholesterol grafted polymer and application |
| CN106719929A (en) * | 2017-01-03 | 2017-05-31 | 河南科技学院 | A kind of pharmaceutical composition for extending the plant florescence and preparation method thereof |
-
2022
- 2022-11-21 CN CN202211455019.6A patent/CN115671066B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003014084A1 (en) * | 2001-08-06 | 2003-02-20 | Recordati Ireland Limited | Novel crystalline polymorphic forms of lercanidipine hydrochloride and process for their preparation |
| CN101658481A (en) * | 2008-08-26 | 2010-03-03 | 北京科信必成医药科技发展有限公司 | Lercanidipine hydrochloride sustained release preparation and preparation method thereof |
| CN102399301A (en) * | 2010-09-08 | 2012-04-04 | 中国科学院成都生物研究所 | Preparation method for amphiphilic konjac glucomannan cholesterol grafted polymer and application |
| CN106719929A (en) * | 2017-01-03 | 2017-05-31 | 河南科技学院 | A kind of pharmaceutical composition for extending the plant florescence and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 刘俊成等: "柠檬酸交联魔芋葡甘聚糖多孔材料的制备及机械性能", 《华南师范大学学报（自然科学版）》, vol. 54, no. 01, 28 February 2022 (2022-02-28), pages 42 - 47 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115671066B (en) | 2024-07-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20070026065A1 (en) | Solid, modified-release pharmaceutical dosage forms which can be administered orally | |
| CA2388560A1 (en) | Sustained-release form of administration containing tramadol saccharinate | |
| EP2481411A1 (en) | Oral dosage forms for modified release comprising the JAK3 inhibitor tasocitinib | |
| JP6154878B2 (en) | Tablet composition containing atazanavir | |
| EP1814528A2 (en) | Process for making a highly compressible controlled delivery compositions of metformin | |
| JPWO2008072532A1 (en) | Pharmaceutical composition with improved storage stability | |
| JP2010530889A (en) | Tablet composition containing atazanavir | |
| JP2010530892A (en) | Tablet composition containing atazanavir | |
| WO2021238978A1 (en) | Pharmaceutical composition containing nitroxoline prodrug, and preparation method and application therefor | |
| CN109875972B (en) | Olmesartan medoxomil and amlodipine pharmaceutical composition | |
| EP2620140A1 (en) | Crizotinib containing compositions | |
| CN115518066A (en) | Pharmaceutical composition for treating anticoagulation and application | |
| JP2010530890A (en) | Tablet composition containing atazanavir | |
| CN115671066A (en) | Lercanidipine hydrochloride sustained release tablet and preparation method thereof | |
| WO2004069234A1 (en) | Pharmaceutical compositions and process of production thereof | |
| CN115006361A (en) | Tofacitinib slow-release core-spun tablet and preparation method thereof | |
| CN102614141A (en) | Verapamil hydrochloride delayed-release tablet and its preparation method | |
| CN107744509B (en) | Mosapride citrate tablet and preparation method thereof | |
| JP2018514530A (en) | Ribastigmine-containing sustained release pharmaceutical composition | |
| CN114099500B (en) | Edaravone sustained-release pharmaceutical composition, preparation method and application | |
| KR101944085B1 (en) | Solid oral dosage form containing valsartan, and preparation method therefor | |
| JPH0466846B2 (en) | ||
| CN108186696B (en) | Bilobalide double-layer controlled release tablet and preparation method thereof | |
| CN111759850A (en) | Pharmaceutical composition of tenofovir oxalate | |
| RU2214234C1 (en) | PHARMACEUTICAL COMPOSITION SHOWING PROPERTY OF CARDIOSELECTIVE β1-ADRENOCEPTIVE ANTAGONIST |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant |