CN102379854A - Manidipine hydrochloride oral quick release preparation and preparation method thereof - Google Patents
Manidipine hydrochloride oral quick release preparation and preparation method thereof Download PDFInfo
- Publication number
- CN102379854A CN102379854A CN2010102673154A CN201010267315A CN102379854A CN 102379854 A CN102379854 A CN 102379854A CN 2010102673154 A CN2010102673154 A CN 2010102673154A CN 201010267315 A CN201010267315 A CN 201010267315A CN 102379854 A CN102379854 A CN 102379854A
- Authority
- CN
- China
- Prior art keywords
- oral
- preparation
- disintegrating agent
- oral preparation
- quick releasing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 45
- 229960003963 manidipine Drugs 0.000 title abstract 9
- ANEBWFXPVPTEET-UHFFFAOYSA-N manidipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ANEBWFXPVPTEET-UHFFFAOYSA-N 0.000 title abstract 9
- 239000000203 mixture Substances 0.000 claims abstract description 43
- 239000003826 tablet Substances 0.000 claims abstract description 39
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 20
- 210000000214 mouth Anatomy 0.000 claims abstract description 14
- 239000007919 dispersible tablet Substances 0.000 claims abstract description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 10
- XVIXARVAOCTOLU-BVNFUTIRSA-N chembl312176 Chemical compound CC=1N=C(C)C(=C(O)/OC)/C(C=2C=C(C=CC=2)[N+]([O-])=O)C=1C(=O)OCCN(CC1)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 XVIXARVAOCTOLU-BVNFUTIRSA-N 0.000 claims description 75
- 239000003795 chemical substances by application Substances 0.000 claims description 29
- 239000008187 granular material Substances 0.000 claims description 27
- 238000005303 weighing Methods 0.000 claims description 26
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 24
- 239000002671 adjuvant Substances 0.000 claims description 23
- 239000000945 filler Substances 0.000 claims description 16
- 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 12
- 229930195725 Mannitol Natural products 0.000 claims description 12
- 235000019359 magnesium stearate Nutrition 0.000 claims description 12
- 239000000594 mannitol Substances 0.000 claims description 12
- 235000010355 mannitol Nutrition 0.000 claims description 12
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 11
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 11
- 239000000853 adhesive Substances 0.000 claims description 9
- 230000001070 adhesive effect Effects 0.000 claims description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 8
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 8
- 239000000314 lubricant Substances 0.000 claims description 8
- 239000000741 silica gel Substances 0.000 claims description 8
- 229910002027 silica gel Inorganic materials 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 7
- 239000011734 sodium Substances 0.000 claims description 7
- 229910052708 sodium Inorganic materials 0.000 claims description 7
- 239000004094 surface-active agent Substances 0.000 claims description 7
- 108010011485 Aspartame Proteins 0.000 claims description 6
- 229920002472 Starch Polymers 0.000 claims description 6
- 239000000605 aspartame Substances 0.000 claims description 6
- 235000010357 aspartame Nutrition 0.000 claims description 6
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 6
- 229960003438 aspartame Drugs 0.000 claims description 6
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 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
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 6
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 6
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 6
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 6
- 239000008107 starch Substances 0.000 claims description 6
- 235000019698 starch Nutrition 0.000 claims description 6
- 108010010803 Gelatin Proteins 0.000 claims description 5
- 239000008273 gelatin Substances 0.000 claims description 5
- 229920000159 gelatin Polymers 0.000 claims description 5
- 235000019322 gelatine Nutrition 0.000 claims description 5
- 235000011852 gelatine desserts Nutrition 0.000 claims description 5
- 238000005550 wet granulation Methods 0.000 claims description 5
- 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 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 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 4
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 4
- 238000004132 cross linking Methods 0.000 claims description 4
- 239000008101 lactose Substances 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 4
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 4
- 229920001353 Dextrin Polymers 0.000 claims description 3
- 239000004375 Dextrin Substances 0.000 claims description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 3
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 3
- 235000019425 dextrin Nutrition 0.000 claims description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 3
- 229920000053 polysorbate 80 Polymers 0.000 claims description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
- 229920001817 Agar Polymers 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
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- 239000004378 Glycyrrhizin Substances 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- 229920000881 Modified starch Polymers 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 claims description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- 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 2
- 235000010489 acacia gum Nutrition 0.000 claims description 2
- 239000001785 acacia senegal l. willd gum Substances 0.000 claims description 2
- 239000008272 agar Substances 0.000 claims description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 2
- 229910021502 aluminium hydroxide Inorganic materials 0.000 claims description 2
- 235000010980 cellulose Nutrition 0.000 claims description 2
- 229920002678 cellulose Polymers 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims description 2
- 235000015165 citric acid Nutrition 0.000 claims description 2
- 238000000576 coating method Methods 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
- 235000019441 ethanol Nutrition 0.000 claims description 2
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 claims description 2
- 229960004949 glycyrrhizic acid Drugs 0.000 claims description 2
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 claims description 2
- 235000019410 glycyrrhizin Nutrition 0.000 claims description 2
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 claims description 2
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
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- 229940013618 stevioside Drugs 0.000 claims description 2
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 claims description 2
- 235000019202 steviosides Nutrition 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
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- 125000003118 aryl group Chemical group 0.000 claims 3
- 239000003906 humectant Substances 0.000 claims 3
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 claims 1
- LBZFKNUMOLETLH-UHFFFAOYSA-N CCCCCCCCCCCCCCCCO[S-](=O)=O.OC(CCC(O)=O)=O.[Na+] Chemical compound CCCCCCCCCCCCCCCCO[S-](=O)=O.OC(CCC(O)=O)=O.[Na+] LBZFKNUMOLETLH-UHFFFAOYSA-N 0.000 claims 1
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 claims 1
- YHAIUSTWZPMYGG-UHFFFAOYSA-L disodium;2,2-dioctyl-3-sulfobutanedioate Chemical compound [Na+].[Na+].CCCCCCCCC(C([O-])=O)(C(C([O-])=O)S(O)(=O)=O)CCCCCCCC YHAIUSTWZPMYGG-UHFFFAOYSA-L 0.000 claims 1
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- 238000000034 method Methods 0.000 abstract description 27
- 206010020772 Hypertension Diseases 0.000 abstract description 14
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- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
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Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to a manidipine hydrochloride oral quick release preparation and a preparation method thereof, wherein the manidipine hydrochloride oral quick release preparation cures hypertension, can be quickly disintegrated and released, and includes oral fast dissolving tablets, oral disintegrating tablets and dispersible tablets. The manidipine hydrochloride oral quick release preparation comprises medicinal active ingredient manidipine hydrochloride and excipients, according to the weight percentage, the manidipine hydrochloride occupies 0.1swung dash95%, and the pharmaceutical excipients occupy 5swung dash99.9%. The manidipine hydrochloride oral quick release preparation is prepared through the method, the preparation formulation range of the manidipine hydrochloride is expanded, the manidipine hydrochloride oral quick release preparation has reasonable formula, good disintegration performance, no oral grit taste and discomfort tastes, a simple preparation technology and quick absorption rate, so the pharmaceutical bioavailability and blood medicine solubility can be improved, accordingly, the curative effect for curing hypertension is improved, the preparation is convenient to take, has good tastes, can be quickly disintegrated with saliva in the oral cavity, so convenience is brought to the old or patients who have the difficulty in swallowing medicines and have inconvenience in taking water.
Description
Technical field
The present invention relates to the hypertensive CV-4093 oral preparation of quick releasing of treatment and the method for preparing of a kind of disintegrate rapidly, release, comprise oral instant-dissolving tablet, oral cavity disintegration tablet, dispersible tablet.
Background technology
Hypertension is one of modal cardiovascular disease in the world today.Epidemiological study shows that there are hyperpietic 600,000,000 people in the whole world at present, and the hypertension prevalence is about 10%, and more American-European developed countries are 20%.Recent statistics result according to health ministry announcement on October 12nd, 2004 shows that China 18 years old and above resident's hypertension prevalence are 18.8%, estimate national number of patients more than 1.6 hundred million.Compared with 1991, prevalence rises 31%, and number of patients increases about more than 7,000 ten thousand people.The rural area prevalence rises rapidly, and the town and country gap is not obvious.Big city, small and medium-sized cities, one to four type of rural area hypertension prevalence are followed successively by 20.4%, 18.8%, 21.0%, 19.0%, 20.2% and 12.6%.In the huge hyperpietic crowd of China's quantity, the hypertension awareness is 30.2% in addition, and treatment rate is 24.7%, and control rate is merely 6.1%; With 26.6%, 12.2% compare with 2.9% and to increase in 1991, but still be in relatively poor level.Hypertension is the important risk factor that causes apoplexy, coronary heart disease and renal failure, and in clinical trial, the apoplexy that antihypertensive therapy on average can reduce 35-40% takes place, the myocardial infarction of 20-25% and surpass 50% heart failure.This shows that the research antihypertensive agent is our vital task, and market potential is very huge.
CV-4093 is a dihydropyridine class calcium channel blocker; Can block L passage on the vascular smooth muscle; Suppress flow of calcium ions; Vasodilator smooth muscle and produce hypotensive effect has no negative inotropic action, does not accelerate heart rate, advantage such as extra natriuretic diuretic effect, renal function protecting, increase insulin sensitivity.Hypotensive effect is remarkable, and the good blood pressure lowering paddy/p-ratio of having taken medicine once a day is used to treat each phase hypertension; Especially with the patient of kidney disease; Patient's antihypertensive effect to low renin and low blood calcium level is more obvious, and can improve uric acid metabolism, to the hyperpietic with renal failure; Single with or unite use with α, beta-blocker, can obtain the effect of being satisfied with.Patient for hypertensive patients type ii diabetes patient or carbohydrate tolerance reduction also has good hypotensive effect.
Tablet is one of present most widely used oral dosage form, and it has takes and store and transport convenient and the stable advantage of medicine.But often, disintegrate and medicine stripping fully absorb because of slowly influencing medicine; Simultaneously, when dosage is big and need once take medicine more for a long time, often make troubles for the patient of old man, child and dysphagia.In this case, oral solution, suspensoid and Emulsion etc. are comparatively superior, but liquid preparation have again medicine stability relatively poor with shortcoming such as storing inconvenience etc.For the advantage that combines tablet and liquid preparation and avoid its shortcoming, over nearly 20 years, get final product the dissolved oral preparation of quick releasing of rapid disintegrate after having developed chance water abroad; Major part can be dissolved rapidly after oral preparation of quick releasing was met saliva, became solution state, and mouthfeel is good; No grittiness; Taking convenience, rapid-action, bioavailability is high, patient bad for old man, child and function of deglutition and water intaking inconvenience provides convenience, so oral preparation of quick releasing more and more receives patient's welcome with its unique advantages.
The successful exploitation of CV-4093 oral preparation of quick releasing; With the compliance that improves the hypertensive patient greatly, can be for hypertensive patient's housecoat usefulness below the state of emergency, onset is rapid; Absorb fully; Also lay the foundation in the exploitation and the listing of China,, will produce good economic benefits and social benefit in case put on market for new oral formulation-oral preparation of quick releasing.The CV-4093 oral preparation of quick releasing of our development can satisfy old man on the market and other swallows the patient's who takes inconvenience medication requirement.
Summary of the invention
The present invention seeks to develop a kind of oral preparation of quick releasing of CV-4093, comprise oral instant-dissolving tablet, oral cavity disintegration tablet, dispersible tablet and preparation method thereof, dosage form disintegrate rapidly, release.
In the present invention; The CV-4093 dispersible tablet is except the principal agent CV-4093; Also comprising pharmaceutic adjuvant, is 0.1%～95% in the weight percent content CV-4093 wherein, and pharmaceutic adjuvant is 5%～99.9%; Preferred CV-4093 content is 1%～30%; Pharmaceutic adjuvant is 70%～99%, and pharmaceutic adjuvant comprises that disintegrating agent 3%～70%, wet adhesive are 0%～5%, lubricant is 0.1%～5%, correctives 0%～5%, surfactant 0%～5%, surplus are filler, and each content and 100%, preparation specification are 40mg～600mg.
In the present invention; The CV-4093 oral instant-dissolving tablet is except the principal agent CV-4093; Also comprising pharmaceutic adjuvant, is 0.1%～95% in the weight percent content CV-4093 wherein, and pharmaceutic adjuvant is 5%～99.9%; Preferred CV-4093 content is 1%～30%; Pharmaceutic adjuvant is 70%～99%, and pharmaceutic adjuvant comprises that disintegrating agent 0%～70%, wet adhesive are 0%～5%, lubricant is 0.1%～5%, correctives 0%～5%, surfactant 0%～5%, surplus are filler, and each content and 100%, preparation specification are 20mg～600mg.
In the present invention; The CV-4093 oral cavity disintegration tablet is except the principal agent CV-4093; Also comprising pharmaceutic adjuvant, is 0.1%～95% in the weight percent content CV-4093 wherein, and pharmaceutic adjuvant is 5%～99.9%; Preferred CV-4093 content is 1%～30%; Pharmaceutic adjuvant is 70%～99%, and pharmaceutic adjuvant comprises that disintegrating agent 3%～70%, effervescent 0.5%～20%, wet adhesive are 0%～5%, lubricant is 0.1%～5%, correctives 0%～5%, surfactant 0%～5%, surplus are filler, and each content and 100%, preparation specification are 40mg～600mg.
The key of oral instant-dissolving tablet, dispersible tablet, oral cavity disintegration tablet is the disintegration rate in the water; So it is extremely important that the disintegrating agent system in the tablet is selected, the disintegrating agent that the present invention selects comprises one or more in crospolyvinylpyrrolidone, carboxymethyl starch sodium, crosslinked carboxymethyl fecula sodium, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, AmberliteIRP-88, the microcrystalline Cellulose etc.
Filler is in order to increase the weight and volume of tablet; Be beneficial to molding and formulate drug dose, filler comprises one or more in lactose, sucrose, mannitol, sorbitol, starch, pregelatinized Starch, cellulose, processing agar, gelatin, the dextrin etc. in dispersible tablet of the present invention, oral instant-dissolving tablet and the oral cavity disintegration tablet.
Wet adhesive is to be convenient to granulate pharmaceutic adjuvant with the tabletting binding agent, and the binding agent of oral instant-dissolving tablet, dispersible tablet, oral cavity disintegration tablet comprises the water of one or more adjuvants in water, ethanol, polyvinylpyrrolidone, hydroxypropyl methylcellulose, tween 80, hydroxypropyl cellulose, sodium alginate, arabic gum, the Polyethylene Glycol etc. or the solution of alcohol among the present invention.
The lubricant that dispersible tablet, oral instant-dissolving tablet and oral cavity disintegration tablet use among the present invention comprises one or more in magnesium stearate, micropowder silica gel, Pulvis Talci, sodium lauryl sulphate, stearic acid, Polyethylene Glycol, the aluminium hydroxide etc.
The correctives that uses in the invention comprises one or more in aspartame, glycyrrhizin, stevioside, dextrin sodium, the medicinal essence etc.
Effervescent be can also use in the oral cavity disintegration tablet, sodium carbonate, sodium bicarbonate, potassium bicarbonate, citric acid, tartaric acid etc. comprised.
Concrete technical scheme is following:
The method for preparing of CV-4093 dispersible tablet comprises raw material pulverizing, weighing, mixing, granulation, sheeting process, and concrete processing step is following:
Method one,
Step 1: with CV-4093 and various adjuvant pulverize separately, cross 50 orders～120 mesh sieves then, preserve subsequent use respectively:
Step 2: take by weighing CV-4093 by recipe quantity, take by weighing various adjuvants by accessory formula, and with its abundant mix homogeneously:
Step 3: above-mentioned mixed uniformly component is sent into tablet machine, carry out tabletting.
Method two,
Step 1: with CV-4093 and various adjuvant pulverize separately, cross 50 orders～120 mesh sieves then, preserve subsequent use respectively:
Step 2: take by weighing CV-4093 by recipe quantity, take by weighing the disintegrating agent of filler and part amount by accessory formula, and with its abundant mix homogeneously:
Step 3: with above-mentioned mixed uniformly component, adopt wet granulation, under 40～80 ℃ temperature, dry granulate then:
Step 4: in above-mentioned granule, add the disintegrating agent of surplus and other adjuvant in the accessory formula, fully mix homogeneously;
Step 5: the granule of above-mentioned mix homogeneously is sent into tablet machine, carry out tabletting;
In this method, add in the disintegrating agent and the ratio that adds is 10%～90%.
The method for preparing of CV-4093 oral cavity disintegration tablet comprises raw material pulverizing, weighing, mixing, granulation, sheeting process, and concrete steps are following:
Method one,
Step 1: with CV-4093 and various adjuvant pulverize separately, cross 50 orders～120 mesh sieves then, preserve subsequent use respectively:
Step 2: take by weighing CV-4093 by recipe quantity, take by weighing various adjuvants by accessory formula, and with its abundant mix homogeneously:
Step 3: above-mentioned mixed uniformly component is sent into tablet machine, carry out tabletting.
Method two,
Step 1: with CV-4093 and various adjuvant pulverize separately, cross 50 orders～120 mesh sieves then, preserve subsequent use respectively:
Step 2: take by weighing CV-4093 by recipe quantity, take by weighing the disintegrating agent of filler and part amount by accessory formula, and with its abundant mix homogeneously:
Step 3: with above-mentioned mixed uniformly component, adopt wet granulation, under 40～80 ℃ temperature, dry granulate then:
Step 4: in above-mentioned granule, add the disintegrating agent of surplus and other adjuvant in the accessory formula, fully mix homogeneously;
Step 5: the granule of above-mentioned mix homogeneously is sent into tablet machine, carry out tabletting;
In this method, add in the disintegrating agent and the ratio that adds is 10%～90%.
Method three,
Step 1: with CV-4093 and various adjuvant pulverize separately, cross 50 orders～120 mesh sieves then, preserve subsequent use respectively:
Step 2: take by weighing CV-4093 by 50% recipe quantity, take by weighing the disintegrating agent of filler and part amount by 50% accessory formula, and with its abundant mix homogeneously:
Step 3: take by weighing CV-4093 by 50% recipe quantity, take by weighing the disintegrating agent of filler and part amount by 50% accessory formula, and with its abundant mix homogeneously:
Step 4: with above-mentioned mixed uniformly component, adopt wet granulation, under 40～80 ℃ temperature, dry granulate then:
Step 5: in above-mentioned granule, add the disintegrating agent of surplus and other adjuvant in the accessory formula, fully mix homogeneously;
Step 6: the granule of above-mentioned mix homogeneously is sent into tablet machine, carry out tabletting;
The method for preparing of CV-4093 oral instant-dissolving tablet comprises and adopts freeze-drying, solid solution method, spray drying method, direct compression process and sudden strain of a muscle interpretation of the law, and concrete processing step is following:
Method one,
Step 1: with CV-4093 and various adjuvant pulverize separately, cross 50 orders～120 mesh sieves then, preserve subsequent use respectively:
Step 2: the suspension of CV-4093, water-soluble base and all the other adjuvants is sub-packed in the fixed mold, is frozen into solid-stately, heat up, remove moisture, obtain the solid preparation of high porosity through sublimation in decompression
Method two,
Step 1: will support framework ingredient, volatile material and buffer agent to adopt spray drying technology to process porous particles, and preserve subsequent use:
Step 2: take by weighing CV-4093 by recipe quantity, take by weighing various adjuvants by accessory formula, and with its abundant mix homogeneously:
Step 3: above-mentioned mixed uniformly component is sent into tablet machine, carry out tabletting;
Method three,
Step 1: CV-4093 is rolled into granule with gelatin, and all the other various adjuvant pulverize separately are crossed 50 orders～120 mesh sieves then, preserve subsequent use respectively:
Step 2: take by weighing CV-4093 gelatin coatings thing by recipe quantity, take by weighing various adjuvants by accessory formula, and with its abundant mix homogeneously:
Step 3: above-mentioned mixed uniformly component is sent into tablet machine, carry out tabletting.
Technical characterstic of the present invention and superiority
The CV-4093 oral preparation of quick releasing for preparing among the present invention has not only been expanded the dosage form scope of CV-4093, and fills a prescription rationally, and disintegrating property is good, the no grittiness of inlet.
The oral preparation of quick releasing infiltration rate of developing among the present invention is fast, thereby can improve bioavailability of medicament and the hypertensive curative effect of blood drug level raising treatment.
The CV-4093 oral preparation of quick releasing taking convenience that the present invention relates to, mouthfeel is good, in the oral cavity, runs into just disintegrate rapidly of saliva, provides convenience for some old peoples and the patient that the medicine obstacle of swallowing, water intaking inconvenience are arranged.
The specific embodiment:
Come the oral preparation of quick releasing of CV-4093 of the present invention done further specifying through following embodiment, but do not represent the embodiment limitation of the present invention.
Dispersible tablet and oral instant-dissolving tablet:
Embodiment 1:
Prescription:
The composition weight percent content
CV-4093 15%
Cross-linking sodium carboxymethyl cellulose 6%
Polyvidone (1% aqueous solution) 1%
Magnesium stearate 0.5%
All the other are that mannitol adds to 100%
Method for preparing:
Earlier above-mentioned material pulverize separately is crossed 100 mesh sieves,, use the 1%PVP aqueous solution to be binding agent, the system soft material CV-4093, mannitol, cross-linking sodium carboxymethyl cellulose mix homogeneously; Cross 20 mesh sieves and granulate 80 ℃ of oven dry, 20 order granulate; Add magnesium stearate, mix homogeneously, tabletting.
Embodiment 2
Prescription:
The composition weight percent content
CV-4093 15%
Carboxymethyl starch sodium 7%
Polyvidone (2% aqueous solution) 1%
Micropowder silica gel 0.5%
All the other are that mannitol adds 100%
Method for preparing:
Earlier above-mentioned material pulverize separately is crossed 100 mesh sieves,, use the 2%PVP aqueous solution to be binding agent, the system soft material CV-4093, mannitol, carboxymethyl starch sodium mix homogeneously; Cross 24 mesh sieves and granulate 80 ℃ of oven dry, 24 order granulate; Add micropowder silica gel, mix homogeneously, tabletting.
Embodiment 3
Prescription:
The composition weight percent content
CV-4093 15%
Polyvinylpolypyrrolidone 6%
Hydroxypropyl methylcellulose (5% aqueous solution) 1%
Magnesium stearate 0.5%
All the other are that lactose adds to 100%
Method for preparing:
Earlier above-mentioned material pulverize separately is crossed 100 mesh sieves,, use 5% hydroxypropyl methylcellulose solution to be binding agent, the system soft material CV-4093, lactose, polyvinylpolypyrrolidone mix homogeneously; Cross 28 mesh sieves and granulate 60 ℃ of oven dry, 28 order granulate; Add magnesium stearate, mix homogeneously, tabletting.
Embodiment 4
Prescription:
The composition weight percent content
CV-4093 15%
Low-substituted hydroxypropyl cellulose 6%
Hydroxypropyl methylcellulose (6% aqueous solution) 1%
Magnesium stearate 0.5%
Micropowder silica gel 0.5%
All the other are that mannitol adds to 100%
Method for preparing:
Earlier above-mentioned material pulverize separately is crossed 100 mesh sieves,, use 6% hydroxypropyl methylcellulose solution to be binding agent CV-4093, mannitol, low-substituted hydroxypropyl cellulose mix homogeneously; The system soft material is crossed 20 mesh sieves and is granulated 70 ℃ of oven dry; 20 order granulate; Add magnesium stearate and micropowder silica gel, mix homogeneously, tabletting.
Embodiment 5
Prescription:
The composition weight percent content
CV-4093 15%
Low-substituted hydroxypropyl cellulose 6%
Polyvinylpolypyrrolidone 6%
Polyvidone (1% aqueous solution) 1%
Magnesium stearate 0.5%
Micropowder silica gel 0.5%
Aspartame 0.4%
All the other are that mannitol adds to 100%
Method for preparing:
Earlier above-mentioned material pulverize separately is crossed 100 mesh sieves, with CV-4093, mannitol, low-substituted hydroxypropyl cellulose mix homogeneously, the abundant mix homogeneously of 50% polyvinylpolypyrrolidone; Use the 1%PVP aqueous solution to be binding agent, the system soft material is crossed 24 mesh sieves and is granulated; 60 ℃ of oven dry, 20 order granulate, the polyvinylpolypyrrolidone of adding residue 50%; Aspartame, magnesium stearate and micropowder silica gel, mix homogeneously, tabletting.
Embodiment 6
Prescription:
The composition weight percent content
CV-4093 15%
Low-substituted hydroxypropyl cellulose 8%
Polyvinylpolypyrrolidone 6%
Polyvidone (3% aqueous solution) 1%
Magnesium stearate 0.5%
Aspartame 0.4%
All the other are that mannitol adds to 100%
Method for preparing:
Earlier above-mentioned material pulverize separately is crossed 100 mesh sieves, with CV-4093, mannitol, low-substituted hydroxypropyl cellulose mix homogeneously, the abundant mix homogeneously of 50% polyvinylpolypyrrolidone; Use the 3%PVP aqueous solution to be binding agent, the system soft material is crossed 24 mesh sieves and is granulated; 80 ℃ of oven dry, 20 order granulate, the polyvinylpolypyrrolidone of adding residue 50%; Aspartame, magnesium stearate, mix homogeneously, tabletting.
Claims (13)
1. CV-4093 oral preparation of quick releasing; Be selected from oral cavity disintegration tablet, dispersible tablet and mouthful molten sheet; It is characterized in that: its oral cavity disintegration tablet, dispersible tablet, oral instant-dissolving tablet are 0.1～95% in the weight percent content CV-4093, and pharmaceutic adjuvant is 5～99.9%.
Dispersible tablet:
Pharmaceutic adjuvant comprises disintegrating agent 3%～70%; Wet adhesive 0%～10%, to draw humectant 0%～10%, lubricant 0.5%～5%, correctives 0%～2%, aromatic 0%～5%, surfactant 0%～2%, surplus be filler, and summation is 100%.
Oral instant-dissolving tablet:
Pharmaceutic adjuvant comprises disintegrating agent 0%～70%; Wet adhesive 0%～10%, to draw humectant 0%～10%, lubricant 0.5%～5%, correctives 0%～2%, aromatic 0%～5%, surfactant 0%～2%, surplus be filler, and summation is 100%.
Oral cavity disintegration tablet:
Pharmaceutic adjuvant comprises disintegrating agent 3%～70%; Effervescent 0.5%～10%, wet adhesive 0%～10%, to draw humectant 0%～10%, lubricant 0.5%～5%, correctives 0%～2%, aromatic 0%～5%, surfactant 0%～2%, surplus be filler, and summation is 100%.
2. the described CV-4093 oral preparation of quick releasing of claim 1 is characterized in that CV-4093 content is 2%～30%, pharmaceutic adjuvant 70%～98%.
3. the described CV-4093 oral preparation of quick releasing of claim 1 is characterized in that disintegrating agent is one or more in crospolyvinylpyrrolidone, carboxymethyl starch sodium, crosslinked carboxymethyl fecula sodium, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, AmberliteIRP-88, the microcrystalline Cellulose etc.
4. the described CV-4093 oral preparation of quick releasing of claim 1 is characterized in that filler is one or more in lactose, sucrose, mannitol, sorbitol, starch, pregelatinized Starch, cellulose, processing agar, gelatin, the dextrin etc.
5. the described CV-4093 oral preparation of quick releasing of claim 1 is characterized in that wet adhesive is the water of one or more adjuvants in water, ethanol, polyvinylpyrrolidone, hydroxypropyl methylcellulose, tween 80, hydroxypropyl cellulose, sodium alginate, arabic gum, the Polyethylene Glycol etc. or the solution of alcohol.
6. the described CV-4093 oral preparation of quick releasing of claim 1 is characterized in that wet adhesive is the water or the dilute alcohol solution of polyvinylpyrrolidone, and solution solubility is 0%～10%.
7. the described CV-4093 oral preparation of quick releasing of claim 1 is characterized in that lubricant comprises one or more in magnesium stearate, micropowder silica gel, Pulvis Talci, sodium lauryl sulphate, stearic acid, Polyethylene Glycol, the aluminium hydroxide etc.
8. the described CV-4093 oral preparation of quick releasing of claim 1 is characterized in that surfactant is one or more in sodium lauryl sulphate, cetyl sulfo-sodium succinate, sodium dioctyl sulfosuccinate, the tween 80 etc.
9. the described CV-4093 oral preparation of quick releasing of claim 1 is characterized in that correctives is medium one or more of aspartame, glycyrrhizin, stevioside, saccharin sodium or medicinal essence.
10. the described CV-4093 oral preparation of quick releasing of claim 1 is characterized in that effervescent is one or more in sodium carbonate, sodium bicarbonate, potassium bicarbonate, citric acid, the tartaric acid etc.
11. a CV-4093 oral preparation of quick releasing is characterized in that: it is prescription according to claim 1 and ratio:
Step 1: with CV-4093 and various adjuvant pulverize separately, cross 50 orders～120 mesh sieves then, preserve subsequent use respectively:
Step 2: take by weighing CV-4093 by recipe quantity, take by weighing the disintegrating agent and the effervescent of filler and part amount by accessory formula, and with its abundant mix homogeneously:
Step 3; With above-mentioned mixed uniformly component, adopt wet granulation, under 40～60 ℃ temperature, dry granulate then:
Step 4: in above-mentioned granule, add the disintegrating agent of surplus and other adjuvant in the accessory formula, fully mix homogeneously;
Step 5 is sent the granule of above-mentioned mix homogeneously into tablet machine, carries out tabletting;
The ratio that adds in the disintegrating agent and add is 20%～80%.
12. a CV-4093 oral preparation of quick releasing is characterized in that: it is prescription according to claim 1 and ratio:
Step 1: with CV-4093 and various adjuvant pulverize separately, cross 50 orders～120 mesh sieves then, preserve subsequent use respectively:
Step 2: take by weighing CV-4093 by 50% recipe quantity, take by weighing the disintegrating agent and the effervescent of filler and part amount by 50% accessory formula, and with its abundant mix homogeneously:
Step 3: take by weighing CV-4093 by 50% recipe quantity, take by weighing the disintegrating agent and the effervescent of filler and part amount by 50% accessory formula, and with its abundant mix homogeneously:
Step 3: with above-mentioned mixed uniformly component, adopt wet granulation, under 40～80 ℃ temperature, dry granulate then:
Step 4: in above-mentioned granule, add the disintegrating agent of surplus and other adjuvant in the accessory formula, fully mix homogeneously;
Step 5 is sent the granule of above-mentioned mix homogeneously into tablet machine, carries out tabletting;
The ratio that adds in the disintegrating agent and add is 20%～80%.
13. a CV-4093 oral preparation of quick releasing is characterized in that: it is prescription according to claim 1 and ratio:
Step 1: CV-4093 is rolled into granule with substrate, and all the other various adjuvant pulverize separately are crossed 50 orders～120 mesh sieves, preserve subsequent use respectively:
Step 2: take by weighing CV-4093 gelatin coatings thing by recipe quantity, take by weighing various adjuvants by accessory formula, and with its abundant mix homogeneously:
Step 3: above-mentioned mixed uniformly component is sent into tablet machine, carry out tabletting.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104434823A (en) * | 2013-09-17 | 2015-03-25 | 许昌恒生制药有限公司 | Manidipine hydrochloride tablets and preparation method thereof |
| CN118717697A (en) * | 2024-09-04 | 2024-10-01 | 杭州沐源生物医药科技有限公司 | A benidipine hydrochloride tablet composition and its preparation method and application |
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| CN1310613A (en) * | 1998-07-28 | 2001-08-29 | 武田药品工业株式会社 | Rapidly disintegrable solid preparation |
| CN1732935A (en) * | 2004-08-10 | 2006-02-15 | 胡才忠 | Compound orally administered formulation of Carvedilol and manidipine |
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- 2010-08-31 CN CN2010102673154A patent/CN102379854A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1310613A (en) * | 1998-07-28 | 2001-08-29 | 武田药品工业株式会社 | Rapidly disintegrable solid preparation |
| CN1732935A (en) * | 2004-08-10 | 2006-02-15 | 胡才忠 | Compound orally administered formulation of Carvedilol and manidipine |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104434823A (en) * | 2013-09-17 | 2015-03-25 | 许昌恒生制药有限公司 | Manidipine hydrochloride tablets and preparation method thereof |
| CN118717697A (en) * | 2024-09-04 | 2024-10-01 | 杭州沐源生物医药科技有限公司 | A benidipine hydrochloride tablet composition and its preparation method and application |
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Application publication date: 20120321 |