CN102091048A - Preparation method and quality control method of arbidol hydrochloride tablet - Google Patents
Preparation method and quality control method of arbidol hydrochloride tablet Download PDFInfo
- Publication number
- CN102091048A CN102091048A CN2009102731195A CN200910273119A CN102091048A CN 102091048 A CN102091048 A CN 102091048A CN 2009102731195 A CN2009102731195 A CN 2009102731195A CN 200910273119 A CN200910273119 A CN 200910273119A CN 102091048 A CN102091048 A CN 102091048A
- Authority
- CN
- China
- Prior art keywords
- precision
- scale
- preparation
- solution
- shakes
- 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
- OMZHXQXQJGCSKN-UHFFFAOYSA-N ethyl 6-bromo-4-[(dimethylamino)methyl]-5-hydroxy-1-methyl-2-(phenylsulfanylmethyl)-1h-indol-1-ium-3-carboxylate;chloride Chemical compound Cl.CN1C2=CC(Br)=C(O)C(CN(C)C)=C2C(C(=O)OCC)=C1CSC1=CC=CC=C1 OMZHXQXQJGCSKN-UHFFFAOYSA-N 0.000 title claims abstract description 46
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 238000003908 quality control method Methods 0.000 title claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 19
- 229920002472 Starch Polymers 0.000 claims abstract description 15
- 239000008107 starch Substances 0.000 claims abstract description 15
- 235000019698 starch Nutrition 0.000 claims abstract description 15
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 12
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 9
- 238000004090 dissolution Methods 0.000 claims abstract description 9
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 8
- 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 abstract description 8
- 239000008187 granular material Substances 0.000 claims abstract description 8
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 8
- 239000002002 slurry Substances 0.000 claims abstract description 7
- 239000000126 substance Substances 0.000 claims abstract description 7
- 239000000853 adhesive Substances 0.000 claims abstract description 6
- 230000001070 adhesive effect Effects 0.000 claims abstract description 6
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 6
- 239000004615 ingredient Substances 0.000 claims abstract description 3
- 238000012360 testing method Methods 0.000 claims description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
- 239000007788 liquid Substances 0.000 claims description 25
- 239000000047 product Substances 0.000 claims description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- 238000005303 weighing Methods 0.000 claims description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 10
- 239000000706 filtrate Substances 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 239000013558 reference substance Substances 0.000 claims description 9
- 239000000470 constituent Substances 0.000 claims description 8
- 239000012535 impurity Substances 0.000 claims description 7
- 239000008101 lactose Substances 0.000 claims description 7
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 7
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 7
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-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 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- 238000002835 absorbance Methods 0.000 claims description 6
- 238000003556 assay Methods 0.000 claims description 6
- 239000011734 sodium Substances 0.000 claims description 6
- 229910052708 sodium Inorganic materials 0.000 claims description 6
- 238000000870 ultraviolet spectroscopy Methods 0.000 claims description 6
- 239000000377 silicon dioxide Substances 0.000 claims description 5
- 229920003081 Povidone K 30 Polymers 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 239000000314 lubricant Substances 0.000 claims description 4
- 230000014759 maintenance of location Effects 0.000 claims description 4
- 239000008363 phosphate buffer Substances 0.000 claims description 4
- 239000002994 raw material Substances 0.000 claims description 4
- 230000035945 sensitivity Effects 0.000 claims description 4
- 239000004094 surface-active agent Substances 0.000 claims description 4
- 206010013786 Dry skin Diseases 0.000 claims description 3
- 230000001476 alcoholic effect Effects 0.000 claims description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 3
- 238000004364 calculation method Methods 0.000 claims description 3
- 238000001514 detection method Methods 0.000 claims description 3
- 238000011978 dissolution method Methods 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 239000000945 filler Substances 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 claims description 3
- 239000007779 soft material Substances 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- AOFUBOWZWQFQJU-SNOJBQEQSA-N (2r,3s,4s,5r)-2,5-bis(hydroxymethyl)oxolane-2,3,4-triol;(2s,3r,4s,5s,6r)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O.OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O AOFUBOWZWQFQJU-SNOJBQEQSA-N 0.000 claims description 2
- 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 2
- 239000004375 Dextrin Substances 0.000 claims description 2
- 229920001353 Dextrin Polymers 0.000 claims description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 2
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 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
- 239000002671 adjuvant Substances 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims description 2
- 229940084030 carboxymethylcellulose calcium Drugs 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
- 235000019425 dextrin Nutrition 0.000 claims description 2
- 239000008103 glucose Substances 0.000 claims description 2
- 235000001727 glucose Nutrition 0.000 claims description 2
- 239000001341 hydroxy propyl starch Substances 0.000 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- 235000013828 hydroxypropyl starch Nutrition 0.000 claims description 2
- 229960003943 hypromellose Drugs 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 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
- 239000007935 oral tablet Substances 0.000 claims description 2
- 229940096978 oral tablet Drugs 0.000 claims description 2
- 229960000502 poloxamer Drugs 0.000 claims description 2
- 229920001983 poloxamer Polymers 0.000 claims description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 2
- 229920000053 polysorbate 80 Polymers 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 235000012239 silicon dioxide Nutrition 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- 238000004811 liquid chromatography Methods 0.000 claims 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 abstract description 2
- 230000007547 defect Effects 0.000 abstract 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 abstract 1
- 238000007781 pre-processing Methods 0.000 abstract 1
- 238000011002 quantification Methods 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 7
- 238000005286 illumination Methods 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 238000005070 sampling Methods 0.000 description 4
- 241001500351 Influenzavirus A Species 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000007689 inspection Methods 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010062106 Respiratory tract infection viral Diseases 0.000 description 2
- 208000019802 Sexually transmitted disease Diseases 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 239000003443 antiviral agent Substances 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 206010022000 influenza Diseases 0.000 description 2
- 230000004410 intraocular pressure Effects 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 238000004088 simulation Methods 0.000 description 2
- 235000002639 sodium chloride Nutrition 0.000 description 2
- 241000712461 unidentified influenza virus Species 0.000 description 2
- 241000713196 Influenza B virus Species 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 241000315672 SARS coronavirus Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical class C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 1
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 1
- 229960003805 amantadine Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- 229950005770 hyprolose Drugs 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000002932 luster Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 238000011020 pilot scale process Methods 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Images
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to a preparation method and a quality control method of an arbidol hydrochloride tablet. The arbidol hydrochloride tablet comprises the following major ingredients: arbidol hydrochloride, microcrystalline celluloses, milk sugar, starch, low-substituted hydroxypropyl celluloses, talcum powder, magnesium stearate and a right amount of adhesive starch slurry. The preparation method of the arbidol hydrochloride tablet comprises the following steps of: preprocessing; preparing granules; and tabletting. The quality control method of the arbidol hydrochloride tablet comprises the following steps of: measuring dissolution rate, related substances and content. For overcoming the defects of the traditional variety, the invention provides the preparation method of the arbidol hydrochloride tablet, which has the advantages of broad spectrum, high efficiency, stable quality, simple process, low cost, easy patient acceptance, and the quality control method of the arbidol hydrochloride tablet, which has the advantages of convenience, fastness, accurate quantification, good specificity and high applicability.
Description
Technical field
The present invention relates to a kind of antiviral Western medicine and make field, the particularly preparation method of arbidol HCl sheet and method of quality control thereof.
Background technology
The antigen transmutability of influenza virus and many tolerations of acute respiratory viral infection hamper people and obtain the vaccine of a safe enough to treat and to prevent this class disease.For these reasons, some uncertainty of the application of gamma interferon.In this field, chemotherapy influenza and the sense of acute respiration sexually transmitted disease (STD) poison played a part very important at that time.In modern practice, adamantane derivative such as amantadine have widely as antiviral substance to be used, yet, their narrow activity profiles (only acting on influenza virus A), sizable side effect and easily produce defectives such as toleration and reduced their clinical value.extensively seek treatment and the process of the antiviral drugs of flu-prevention and other acute respiratory viral infection in, arbidol HCl becomes final selection, it has immunomodulating simultaneously, disturbs and induce and antioxidative character.
The antiviral activity of arbidol HCl is primarily aimed at influenza virus A, Type B, and its pharmacologically active may be owing to activation 2, the 5-oligodenylate synthetase, and it does not stop the proteinic synthetic or transcription of virus-specific of A, Type B influenza virus.At the commitment of virus replication, Abiduoer shows the virus-specific effect, hinders viral lipoid envelope and cell membrane and merges.The Abiduoer selectivity suppresses duplicating of influenza virus A, B in cell cultivation process.Simultaneously macrophage phagocytic there is significant activation.Recent in addition studies show that, this medicine also has good inhibitory effect to SARS virus under lower safe concentration.
Domestic existing arbidol HCl capsule and granule listing at present, there is the condition of storage strictness in its product, and easily the moisture absorption is rotten, and production cost is higher, and the patient bears rate defective on the low side.Simultaneously, though the control method of bibliographical information to its quality arranged both at home and abroad, there is complex operation, to drawbacks such as having relatively high expectations of instrument and equipment.
Summary of the invention
The objective of the invention is to overcome the deficiency of the existing kind of arbidol HCl, the preparation method of a kind of broad-spectrum high efficacy, steady quality, technology is simple, with low cost, the patient is easy to accept arbidol HCl sheet is provided and provide a kind of simple and efficient, quantitatively accurately, the method for quality control of specificity is good, the suitability is strong arbidol HCl sheet.
The object of the present invention is achieved like this:
One, major ingredient weight ratio (1000 preparation units):
Arbidol HCl 100g
Microcrystalline Cellulose 10-30g
Lactose 10-50g
Starch 20-50g
Low-substituted hydroxypropyl cellulose 5-15g
Pulvis Talci 1-5g
Magnesium stearate 1-5g
5%-30% is an amount of for adhesive starch slurry concentration
Adjuvant mainly is selected from but is not limited to diluent starch, lactose, microcrystalline Cellulose, sucrose, glucose, dextrin, mannitol, Nulomoline, the disintegrating agent low-substituted hydroxypropyl cellulose, carboxymethylstach sodium, hydroxypropyl starch sodium, cross-linked cellulose sodium, crospolyvinylpyrrolidone, carboxymethylcellulose calcium, binding agent 30 POVIDONE K 30 BP/USP 30, starch slurry, 30 POVIDONE K 30 BP/USP 30 ethanol liquid, hypromellose ethanol liquid, fluidizer lubricant stearic acid and salt thereof, Pulvis Talci, silicon dioxide and the surfactant such as the poloxamer that add according to circumstances, tween 80, the oral tablet that Arlacel-60 is made.
2, main preparation process:
(1), pretreatment: supplementary material is pulverized, crossed 100 mesh sieves respectively.
(2), particulate preparation: press recipe quantity weighting raw materials, diluent, part disintegrating agent mix homogeneously, cross 60 mesh sieves, select suitable adhesive (surfactant can be added wherein) system soft material for use, cross 18 mesh sieve system wet granulars, wet granular was in 70 ℃ of dryings 3 hours, 20 order granulate add recipe quantity fluidizer lubricant and remaining disintegrating agent, mixing again.Measure granule content, basis of calculation sheet is heavy.
(3), tabletting: select the suitable tool tabletting that dashes, tablet hardness is controlled at 4-8kg.
According to practical situation, those skilled in the art can be made with the corresponding to adjustment of essence of the present invention and improve and belong to category of the present invention the present invention.
Two, the method for quality control of arbidol HCl sheet:
1, dissolution: get 6 of this product, according to dissolution method (two appendix XC second methods of Chinese Pharmacopoeia version in 2000), be solvent with 20% alcoholic solution 900mL, rotating speed is that per minute 50 changes, operation in accordance with the law, in the time of 45 minutes, get solution 10mL, filter, get subsequent filtrate 5mL in the 25mL measuring bottle, be diluted with water to scale, shake up, as need testing solution; Precision takes by weighing arbidol HCl reference substance 20mg in addition, in the 100mL measuring bottle, adds ethanol 20mL, and jolting makes dissolving, and thin up shakes up to scale, and precision is measured 5mL in the 50mL measuring bottle, and thin up shakes up to scale, in contrast product solution.Get above-mentioned two kinds of solution, according to ultraviolet visible spectrophotometry (two appendix IV of Chinese Pharmacopoeia version in 2005 A), measure absorbance at the wavelength place of 314nm, calculate every stripping quantity, limit is 75% of a labelled amount, should be up to specification.
2, related substance: after getting this product porphyrize, precision takes by weighing in right amount, adds the solution that mobile phase is made hydrochloric Abiduoer 0.1mg among every 1mL, filters, and gets subsequent filtrate as need testing solution; Precision is measured 1.0mL in the 100mL measuring bottle, adds mobile phase and is diluted to scale, shakes up, in contrast liquid; Measuring according to high performance liquid chromatography (two appendix V of Chinese Pharmacopoeia version in 2005 D), is filler with octadecylsilane chemically bonded silica; Acetonitrile-0.3% phosphate buffer (add phosphoric acid 1.7mL in the 1000mL water, add triethylamine and regulate pH value to 3.10) (49: 51) is mobile phase; The detection wavelength is 254nm; Number of theoretical plate should be not less than 2500.Precision is measured contrast liquid 20 μ L, injects chromatograph of liquid, regulates detector sensitivity, makes the peak height of main constituent chromatographic peak be about 10～25% of full scale; Precision is measured need testing solution 20 μ L in addition, injects chromatograph of liquid, and the record chromatogram is to 2 times of main constituent peak retention time.In the need testing solution chromatogram if any impurity peaks, desolventize each impurity peak area outside the peak and, must not be greater than the main peak area (1.0%) of contrast liquid.
3, assay: get 10 of test samples, the accurate title, decide, and it is heavy to calculate average sheet.Porphyrize, precision take by weighing in right amount (being equivalent to arbidol HCl 20mg approximately), put in the 100mL measuring bottle, add 20mL ethanol ultrasonic 10 minutes, thin up shakes up to scale, filters, and precision is measured subsequent filtrate 5mL in the 50mL measuring bottle, thin up shakes up to scale, as need testing solution; Precision takes by weighing arbidol HCl reference substance 20mg in addition, in the 100mL measuring bottle, adds 20mL ethanol, and jolting makes dissolving, and thin up shakes up to scale, and precision is measured 5mL in the 50mL measuring bottle, and thin up shakes up to scale, in contrast product solution.Get above-mentioned two kinds of solution,, measure absorbance, calculate, promptly at the wavelength place of 314nm according to ultraviolet visible spectrophotometry (two appendix IVA of Chinese Pharmacopoeia version in 2005).
Hydrochloric Abiduoer (the C of this product
22H
25BrN
2O
3SHClH
2O) should be 90.0～110.0% of labelled amount.
Description of drawings
Fig. 1 is the preparation method of arbidol HCl sheet of the present invention and the preparation method process chart of method of quality control thereof.
The specific embodiment
Describe in further detail below in conjunction with the preparation method and the method for quality control thereof of accompanying drawing, but the present invention is not limited to following examples arbidol HCl sheet of the present invention.
Embodiment one: its weight ratio of preparation method process chart of the present invention shown in Figure 1 (1000 preparation units).
Arbidol HCl 100g
Microcrystalline Cellulose 20g
Lactose 38g
Starch 25g
Low-substituted hydroxypropyl cellulose 10g
Pulvis Talci 3g
Magnesium stearate 1g
6% adhesive starch slurry is an amount of
Its preparation method:
1, pretreatment: with arbidol HCl, microcrystalline Cellulose, lactose, starch, the L-hyprolose, Pulvis Talci, magnesium stearate is crossed 100 mesh sieves respectively through necessary pulverizing.
2, particulate preparation: press recipe quantity weighting raw materials, microcrystalline Cellulose, lactose, starch, low-substituted hydroxypropyl cellulose 5g, mix homogeneously, cross 60 mesh sieves 10 times, add an amount of 6% starch slurry system soft material, cross 18 mesh sieve system wet granulars, wet granular is in 70 ℃ of dryings 3 hours, 20 order granulate, the low-substituted hydroxypropyl cellulose 5g that adds recipe quantity Pulvis Talci, magnesium stearate and add, mixing.Measure granule content, basis of calculation sheet is heavy.
3, tabletting: select the suitable tool tabletting that dashes, tablet hardness is controlled at 5-6kg.
The method of quality control of arbidol HCl.
Get the pilot scale product batch number and be 030702 arbidol HCl sheet, respectively it is carried out the investigation of dissolution, related substance, assay project.
1, dissolution: get 6 of this product, according to dissolution method (two appendix XC second methods of Chinese Pharmacopoeia version in 2000), be solvent with 20% alcoholic solution 900mL, rotating speed is that per minute 50 changes, operation in accordance with the law, in the time of 45 minutes, get solution 10mL, filter, get subsequent filtrate 5mL in the 25mL measuring bottle, be diluted with water to scale, shake up, as need testing solution; Precision takes by weighing arbidol HCl reference substance 20mg in addition, in the 100mL measuring bottle, adds ethanol 20mL, and jolting makes dissolving, and thin up shakes up to scale, and precision is measured 5mL in the 50mL measuring bottle, and thin up shakes up to scale, in contrast product solution.Get above-mentioned two kinds of solution, according to ultraviolet visible spectrophotometry (two appendix IV of Chinese Pharmacopoeia version in 2005 A), measure absorbance at the wavelength place of 314nm, calculate every stripping quantity, limit is 75% of a labelled amount, should be up to specification.
2, related substance: after getting this product porphyrize, precision takes by weighing in right amount, adds the solution that mobile phase is made hydrochloric Abiduoer 0.1mg among every 1mL, filters, and gets subsequent filtrate as need testing solution; Precision is measured 1.0mL in the 100mL measuring bottle, adds mobile phase and is diluted to scale, shakes up, in contrast liquid; Measuring according to high performance liquid chromatography (two appendix VD of Chinese Pharmacopoeia version in 2005), is filler with octadecylsilane chemically bonded silica; Acetonitrile-0.3% phosphate buffer (add phosphoric acid 1.7mL in the 1000mL water, add triethylamine and regulate pH value to 3.10) (49: 51) is mobile phase; The detection wavelength is 254nm; Number of theoretical plate should be not less than 2500.Precision is measured contrast liquid 20 μ L, injects chromatograph of liquid, regulates detector sensitivity, makes the peak height of main constituent chromatographic peak be about 10～25% of full scale; Precision is measured need testing solution 20 μ L in addition, injects chromatograph of liquid, and the record chromatogram is to 2 times of main constituent peak retention time.In the need testing solution chromatogram if any impurity peaks, desolventize each impurity peak area outside the peak and, must not be greater than the main peak area (1.0%) of contrast liquid.
3, assay: get 10 of test samples, the accurate title, decide, and it is heavy to calculate average sheet.Porphyrize, precision take by weighing in right amount (being equivalent to arbidol HCl 20mg approximately), put in the 100mL measuring bottle, add 20mL ethanol ultrasonic 10 minutes, thin up shakes up to scale, filters, and precision is measured subsequent filtrate 5mL in the 50mL measuring bottle, thin up shakes up to scale, as need testing solution; Precision takes by weighing arbidol HCl reference substance 20mg in addition, in the 100mL measuring bottle, adds 20mL ethanol, and jolting makes dissolving, and thin up shakes up to scale, and precision is measured 5mL in the 50mL measuring bottle, and thin up shakes up to scale, in contrast product solution.Get above-mentioned two kinds of solution,, measure absorbance, calculate, promptly at the wavelength place of 314nm according to ultraviolet visible spectrophotometry (two appendix IVA of Chinese Pharmacopoeia version in 2005).
Hydrochloric Abiduoer (the C of this product
22H
25BrN
2O
3SHClH
2O) should be 90.0～110.0% of labelled amount.
Stability experiment:
1, main experimental apparatus
High performance liquid chromatograph LC-10AT Japan Shimadzu Corporation
Ultrathermostat 501 type Shanghai experimental apparatus factories
Illumination experimental box illuminance 4500lx self-control
Photoelectric analytical balance TG 328A type Shanghai balance equipment factory
2, medicine
Supply test agent: arbidol HCl sheet self-control lot number: 030,701 030,702 030703
Reference substance: arbidol HCl (the arbidol HCl raw material is through three recrystallization)
3, content of the test and condition
3.1 accelerated test
Arbidol HCl sheet (030,701 030,702 030703) closed with plastic-aluminum bubble intraocular pressure pack back (intend going on the market and pack), in temperature is that 40 ℃, relative humidity are to place 6 months under the condition of 75% (saturated aqueous common salt), respectively at 0 month, 1 the end of month, 2 the end of month, 3 the end of month and 6 the end of month, detect by stable high spot reviews project (appearance character, dissolution, content, related substance).
The experiment 3.2 keep sample for a long time
Arbidol HCl sheet (030,701 030,702 030703) closed with plastic-aluminum bubble intraocular pressure pack back (intend going on the market and pack), in temperature is that 25 ℃, relative humidity are to place under 60% the condition, respectively at 0 month, 3 the end of month, 6 the end of month, 12 the end of month, at 18 the end of month, 24 the end of month and 36 the end of month, detect by stable high spot reviews project (appearance character, dissolution, content, related substance).
4 investigation project and assay methods
4.1 the sample character is checked
Variations such as the outward appearance of this product, color and luster, character before and after the checkout facility.
4.2 drug content is measured and the catabolite inspection
4.2.1 drug content is measured
Measure according to high performance liquid chromatography (two appendix VD of Chinese Pharmacopoeia version in 2000).
Chromatographic condition is checked chromatographic condition mensuration with reference to the crude drug related substance.Immobile phase: Sperisorb C18 (5 μ m, 4.6 * 250mm); Mobile phase: acetonitrile-0.3% phosphate buffer (get phosphatase 11 .7mL, add water 1000mL, transfer pH 3.1) (49: 51) with triethylamine; Detect wavelength: 254nm.
Linear relationship is got this product reference substance, adds the solution that mobile phase is made series concentration, and precision is measured 20 μ L, injecting chromatograph, and chromatographic peak area (A) is returned the drawing standard curve with sample size (M, μ g).The results are shown in following table.
Standard curve determination result
With sample size (M, μ g) to chromatographic peak area (A) return straight line:
M＝9.1513×10
-7A-0.0083(R＝0.9999)
The result shows that sample size is good linear relationship with chromatographic peak area in 0.432～4.320 μ g scope.
Algoscopy
Get this product of test front and back respectively, porphyrize, it is an amount of to get fine powder, adds mobile phase and makes the solution that contains principal agent 0.1mg among every 1mL approximately, filters, and gets subsequent filtrate as need testing solution; It is an amount of that other gets this product reference substance, and accurate the title decides, and adds mobile phase and makes the solution that contains 0.1mg among every 1mL, in contrast product solution.According to high performance liquid chromatography (two appendix V of Chinese Pharmacopoeia version in 2000 D), precision is measured above-mentioned solution 20uL, injects chromatograph of liquid, and the record chromatogram calculates this product content.
4.2.2 catabolite inspection method
Precision is measured the need testing solution 1mL of drug content under measuring in the 100mL measuring bottle, adds mobile phase and is diluted to scale, shakes up, in contrast liquid; Precision is measured contrast liquid 20 μ L, injects chromatograph of liquid, regulates detector sensitivity, and making the main constituent peak height is 10～25% of full scale; Other gets need testing solution 20 μ L, injects chromatograph of liquid, and the record chromatogram is to the twice of main constituent peak retention time, get each impurity peak area in the assay chromatogram and, calculate the content of catabolite by Self-control method.
4.3 stability experiment result
Accelerated test result's (RH75%, 40 ℃)
Long-term test results (25 ℃ of temperature, relative humidity 60%)
The arbidol HCl sheet is under simulation listing terms of packing, placed 6 months through 40 ℃ of temperature, relative humidity 75%, the result shows that its outward appearance, character, dissolution, content and catabolite inspection etc. all do not take place obviously to change, and illustrate that the arbidol HCl sheet is stable.
The arbidol HCl sheet is under simulation listing terms of packing, through temperature is that 25 ℃, relative humidity are to place 36 months under 60% the condition, the result shows that its outward appearance, character, dissolution, sample size, catabolite etc. all do not take place obviously to change, and illustrate that the arbidol HCl sheet is stable.
4.4 influence factor's experiment
Stipulate according to Chinese Pharmacopoeia version appendix in 2000 XIXC " medicine stability test guideline ", a batch sample (030701) of test agent is tested in the employing, experimental condition is respectively 60 ℃ of high temperature, high humidity 90% (25 ℃), high light (4500Lx ± 500Lx), measure respectively at sampling in 5,10 days, compare with 0 day measurement result.
4.4.1 hot test
Get this product and place culture dish in right amount, put in 60 ℃ of calorstats and placed 10 days,, compare with 0 day measurement result respectively at the 5th, 10 day sampling and measuring.
4.4.2 high wet test
Sample thief is put in the culture dish in right amount, and accurate the title decided weight, is placed in the container of constant humidity again, 25 ℃ of temperature, places under the condition of relative humidity 90%, in 5,10 days sampling and measuring, compares with 0 day measurement result.
4.2.3 strong illumination
Get an amount of sample and spread out in culture dish, be placed on 4500 ± 500Lx illumination and place, and, compare with 0 day measurement result in 5,10 days sampling and measuring.
4.4.4 experimental result
Stipulate according to pharmacopeia, with arbidol HCl sheet exposed placement 10 days under high temperature, high humidity, strong illumination, and, content heavy to character, sheet at the 5th day, the 10th day is investigated, compare with 0 day result, except that sheet focuses on moisture absorption weightening finish under the high humidity environment, content does not have significant change, meets the regulation of quality standard.Hydrochloric acid Ah Bi flower sheet steady quality under high temperature, high humidity, strong illumination.
Claims (2)
1. the preparation method of an arbidol HCl sheet and method of quality control thereof, its special major ingredient anharmonic ratio (1000 preparation units):
Arbidol HCl 100g
Microcrystalline Cellulose 10-30g
Lactose 10-50g
Starch 20-50g
Low-substituted hydroxypropyl cellulose 5-15g
Pulvis Talci 1-5g
Magnesium stearate 1-5g
5%-30% is an amount of for adhesive starch slurry concentration
Its special adjuvant mainly is selected from but is not limited to diluent starch, lactose, microcrystalline Cellulose, sucrose, glucose, dextrin, mannitol, Nulomoline, the disintegrating agent low-substituted hydroxypropyl cellulose, carboxymethylstach sodium, hydroxypropyl starch sodium, cross-linked cellulose sodium, crospolyvinylpyrrolidone, carboxymethylcellulose calcium, binding agent 30 POVIDONE K 30 BP/USP 30, starch slurry, 30 POVIDONE K 30 BP/USP 30 ethanol liquid, hypromellose ethanol liquid, fluidizer lubricant stearic acid and salt thereof, Pulvis Talci, silicon dioxide and the surfactant such as the poloxamer that add according to circumstances, tween 80, the oral tablet that Arlacel-60 is made.
Its special preparation method:
(1), pretreatment: supplementary material is pulverized, crossed 100 mesh sieves respectively.
(2), particulate preparation: press recipe quantity weighting raw materials, diluent, part disintegrating agent mix homogeneously, cross 60 mesh sieves, select suitable adhesive (surfactant can be added wherein) system soft material for use, cross 18 mesh sieve system wet granulars, wet granular was in 70 ℃ of dryings 3 hours, 20 order granulate add recipe quantity fluidizer lubricant and remaining disintegrating agent, mixing again.Measure granule content, basis of calculation sheet is heavy.
(3), tabletting: select the suitable tool tabletting that dashes, tablet hardness is controlled at 4-8kg.
According to practical situation, those skilled in the art can be made with the corresponding to adjustment of essence of the present invention and improve and belong to category of the present invention the present invention.
2. the preparation method of arbidol HCl sheet according to claim 1 and method of quality control thereof, its special method of quality control:
(1), dissolution: getting 6 of this product, according to dissolution method, is solvent with 20% alcoholic solution 900mL, and rotating speed is that per minute 50 changes, operation in the time of 45 minutes, is got solution 10mL in accordance with the law, filters, get subsequent filtrate 5mL in the 25mL measuring bottle, be diluted with water to scale, shake up, as need testing solution; Precision takes by weighing arbidol HCl reference substance 20mg in addition, in the 100mL measuring bottle, adds ethanol 20mL, and jolting makes dissolving, and thin up shakes up to scale, and precision is measured 5mL in the 50mL measuring bottle, and thin up shakes up to scale, in contrast product solution.Get above-mentioned two kinds of solution, according to ultraviolet visible spectrophotometry, measure absorbance at the wavelength place of 314nm, calculate every stripping quantity, limit is 75% of a labelled amount, should be up to specification.
(2), related substance: after getting this product porphyrize, precision takes by weighing in right amount, adds the solution that mobile phase is made hydrochloric Abiduoer 0.1mg among every 1mL, filters, and gets subsequent filtrate as need testing solution; Precision is measured 1.0mL in the 100mL measuring bottle, adds mobile phase and is diluted to scale, shakes up, in contrast liquid; According to high effective liquid chromatography for measuring, be filler with octadecylsilane chemically bonded silica; Acetonitrile-0.3% phosphate buffer (add phosphoric acid 1.7mL in the 1000mL water, add triethylamine and regulate pH value to 3.10) (49: 51) is mobile phase; The detection wavelength is 254nm; Number of theoretical plate should be not less than 2500.Precision is measured contrast liquid 20 μ L, injects chromatograph of liquid, regulates detector sensitivity, makes the peak height of main constituent chromatographic peak be about 10～25% of full scale; Precision is measured need testing solution 20 μ L in addition, injects chromatograph of liquid, and the record chromatogram is to 2 times of main constituent peak retention time.In the need testing solution chromatogram if any impurity peaks, desolventize each impurity peak area outside the peak and, must not be greater than the main peak area (1.0%) of contrast liquid.
(3), assay: get 10 of test samples, the accurate title, decide, and it is heavy to calculate average sheet.Porphyrize, precision take by weighing in right amount (being equivalent to arbidol HCl 20mg approximately), put in the 100mL measuring bottle, add 20mL ethanol ultrasonic 10 minutes, thin up shakes up to scale, filters, and precision is measured subsequent filtrate 5mL in the 50mL measuring bottle, thin up shakes up to scale, as need testing solution; Precision takes by weighing arbidol HCl reference substance 20mg in addition, in the 100mL measuring bottle, adds 20mL ethanol, and jolting makes dissolving, and thin up shakes up to scale, and precision is measured 5mL in the 50mL measuring bottle, and thin up shakes up to scale, in contrast product solution.Get above-mentioned two kinds of solution,, measure absorbance, calculate, promptly at the wavelength place of 314nm according to ultraviolet visible spectrophotometry.
Hydrochloric Abiduoer (the C of this product
22H
25BrN
2O
3SHClH
2O) should be 90.0～110.0% of labelled amount.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009102731195A CN102091048A (en) | 2009-12-09 | 2009-12-09 | Preparation method and quality control method of arbidol hydrochloride tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009102731195A CN102091048A (en) | 2009-12-09 | 2009-12-09 | Preparation method and quality control method of arbidol hydrochloride tablet |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102091048A true CN102091048A (en) | 2011-06-15 |
Family
ID=44124429
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009102731195A Pending CN102091048A (en) | 2009-12-09 | 2009-12-09 | Preparation method and quality control method of arbidol hydrochloride tablet |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102091048A (en) |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102836134A (en) * | 2012-08-31 | 2012-12-26 | 石家庄中硕药业集团有限公司 | Method for preparing mesylate arbidol freeze-dried powder injection preparation |
| CN104849388A (en) * | 2015-05-27 | 2015-08-19 | 湖北生物医药产业技术研究院有限公司 | Method for determining residual organic solvent content in arbidol hydrochloride crude drug |
| CN105343008A (en) * | 2015-12-15 | 2016-02-24 | 青岛华之草医药科技有限公司 | Pitavastatin calcium composition |
| CN108051530A (en) * | 2017-12-13 | 2018-05-18 | 南京双科医药开发有限公司 | A kind of detection method of Sulpiride tablet |
| CN108469398A (en) * | 2018-04-27 | 2018-08-31 | 丽珠医药集团股份有限公司 | A kind of dissolution determination method of Iprazole pharmaceutical composition |
| CN111678999A (en) * | 2020-05-28 | 2020-09-18 | 石家庄四药有限公司 | Method for detecting arbidol hydrochloride related substances |
| CN111689868A (en) * | 2020-07-03 | 2020-09-22 | 山东省食品药品检验研究院 | Preparation method and application of 1- [ 4-hydroxyethyl ] phenoxy ] -3- (isopropylamino) propan-2-ol |
| CN112098549A (en) * | 2020-09-03 | 2020-12-18 | 湖南华腾制药有限公司 | A kind of method for measuring impurity content in Arbidol hydrochloride solution |
| CN113712925A (en) * | 2021-08-24 | 2021-11-30 | 江苏吴中医药集团有限公司 | Arbidol hydrochloride tablet composition and preparation method thereof |
| CN113842370A (en) * | 2021-11-01 | 2021-12-28 | 石家庄四药有限公司 | Arbidol hydrochloride tablet and preparation method thereof |
| CN114397375A (en) * | 2021-12-09 | 2022-04-26 | 石家庄四药有限公司 | Method for detecting related substances of arbidol hydrochloride intermediate |
-
2009
- 2009-12-09 CN CN2009102731195A patent/CN102091048A/en active Pending
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102836134A (en) * | 2012-08-31 | 2012-12-26 | 石家庄中硕药业集团有限公司 | Method for preparing mesylate arbidol freeze-dried powder injection preparation |
| CN104849388A (en) * | 2015-05-27 | 2015-08-19 | 湖北生物医药产业技术研究院有限公司 | Method for determining residual organic solvent content in arbidol hydrochloride crude drug |
| CN104849388B (en) * | 2015-05-27 | 2017-02-22 | 湖北生物医药产业技术研究院有限公司 | Method for determining residual organic solvent content in arbidol hydrochloride crude drug |
| CN105343008A (en) * | 2015-12-15 | 2016-02-24 | 青岛华之草医药科技有限公司 | Pitavastatin calcium composition |
| CN108051530A (en) * | 2017-12-13 | 2018-05-18 | 南京双科医药开发有限公司 | A kind of detection method of Sulpiride tablet |
| CN108469398A (en) * | 2018-04-27 | 2018-08-31 | 丽珠医药集团股份有限公司 | A kind of dissolution determination method of Iprazole pharmaceutical composition |
| CN111678999A (en) * | 2020-05-28 | 2020-09-18 | 石家庄四药有限公司 | Method for detecting arbidol hydrochloride related substances |
| CN111689868A (en) * | 2020-07-03 | 2020-09-22 | 山东省食品药品检验研究院 | Preparation method and application of 1- [ 4-hydroxyethyl ] phenoxy ] -3- (isopropylamino) propan-2-ol |
| CN112098549A (en) * | 2020-09-03 | 2020-12-18 | 湖南华腾制药有限公司 | A kind of method for measuring impurity content in Arbidol hydrochloride solution |
| CN113712925A (en) * | 2021-08-24 | 2021-11-30 | 江苏吴中医药集团有限公司 | Arbidol hydrochloride tablet composition and preparation method thereof |
| CN113842370A (en) * | 2021-11-01 | 2021-12-28 | 石家庄四药有限公司 | Arbidol hydrochloride tablet and preparation method thereof |
| CN114397375A (en) * | 2021-12-09 | 2022-04-26 | 石家庄四药有限公司 | Method for detecting related substances of arbidol hydrochloride intermediate |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102091048A (en) | Preparation method and quality control method of arbidol hydrochloride tablet | |
| CN102920674B (en) | Technology for preparing hydroxychloroquine sulfate tablets | |
| CN101695480B (en) | Olopatadine hydrochloride dispersible tablets, preparation method thereof and quality control method thereof | |
| CN102125533B (en) | Pazufloxacin mesylate tablet and preparation method and detection method thereof | |
| CN103156819A (en) | Benzoic acid alogliptin composition troche and preparation method thereof | |
| CN102114011B (en) | Ibuprofen sustained-release preparation and preparation method thereof | |
| CN101322694A (en) | Piclofenac potassium sustained release tablets and preparing technique thereof | |
| Dharani et al. | Development and validation of a discriminatory dissolution method for rifaximin products | |
| CN100493511C (en) | Tablets of vacyclovir hydrochloride, and its preparing method | |
| CN106176653A (en) | A kind of pharmaceutical composition of sitagliptin | |
| CN102846575A (en) | Nifedipine sustained release tablet and preparation method thereof | |
| CN105055351B (en) | A kind of ticagrelor tablet composition | |
| CN104721158A (en) | Stable everolimus tablet | |
| CN104515816A (en) | Detection method of substances relative to raw material and preparation of ambrisentan | |
| CN112129842A (en) | A key method for evaluating the sustained and controlled release effect of pharmaceutical excipients hypromellose (HPMC) | |
| CN103301081B (en) | A kind of Cefdinir dispersible tablet and preparation method thereof | |
| CN101829068A (en) | Water soluble medicament sustained-release tablets and preparation method thereof | |
| CN112691084B (en) | Pharmaceutical composition and preparation method thereof | |
| Naqvi et al. | Pharmaceutical Surveillance Study of Moxifloxacin Formulations: Therapeutic Perspective in Terms of Quality and Efficacy | |
| CN104072400B (en) | Oxiracetam compound and pharmaceutical composition thereof | |
| CN102106839A (en) | Alprazolam sustained-release preparation and preparation method thereof | |
| CN101406462A (en) | Domperidone orally disintegrating tablets as well as preparation method and quality control method thereof | |
| CN105055353B (en) | A kind of Entecavir tablet and preparation method thereof | |
| CN109953965A (en) | A kind of pharmaceutical composition containing tartaric acid Mo Fanselin | |
| CN107569465A (en) | A kind of Nifedipine sustained release tablets and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| ASS | Succession or assignment of patent right |
Owner name: HUBEI QIANJIANG PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: WANG CHANGRUI Effective date: 20111202 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| C53 | Correction of patent for invention or patent application | ||
| CB03 | Change of inventor or designer information |
Inventor after: Guan Yihong Inventor before: Wang Changrui |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: WANG CHANGRUI TO: GUAN YIHONG Free format text: CORRECT: ADDRESS; FROM: 433100 QIANJIANG, HUBEI PROVINCE TO: 433199 QIANJIANG, HUBEI PROVINCE |
|
| TA01 | Transfer of patent application right |
Effective date of registration: 20111202 Address after: 433199 Qianjiang city of Hubei Province Zhang Hua Road No. 1. Applicant after: Hubei Qianjiang Pharmaceutical Co., Ltd. Address before: 433100 Qianjiang Central Hospital of Hubei Province Applicant before: Wang Changrui |
|
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20110615 |