CN1843343A - Methocarbamol dispersion tablet - Google Patents
Methocarbamol dispersion tablet Download PDFInfo
- Publication number
- CN1843343A CN1843343A CN 200610007558 CN200610007558A CN1843343A CN 1843343 A CN1843343 A CN 1843343A CN 200610007558 CN200610007558 CN 200610007558 CN 200610007558 A CN200610007558 A CN 200610007558A CN 1843343 A CN1843343 A CN 1843343A
- Authority
- CN
- China
- Prior art keywords
- methocarbamol
- solution
- dispersible tablet
- product
- amount
- 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.)
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Links
- GNXFOGHNGIVQEH-UHFFFAOYSA-N 2-hydroxy-3-(2-methoxyphenoxy)propyl carbamate Chemical compound COC1=CC=CC=C1OCC(O)COC(N)=O GNXFOGHNGIVQEH-UHFFFAOYSA-N 0.000 title claims abstract description 76
- 229960002330 methocarbamol Drugs 0.000 title claims abstract description 74
- 239000006185 dispersion Substances 0.000 title description 14
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims abstract description 22
- 238000002360 preparation method Methods 0.000 claims abstract description 22
- 239000007919 dispersible tablet Substances 0.000 claims abstract description 21
- 239000008101 lactose Substances 0.000 claims abstract description 21
- 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 abstract description 10
- 239000011734 sodium Substances 0.000 claims abstract description 10
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 10
- 239000000470 constituent Substances 0.000 claims abstract description 9
- 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 4
- 239000000243 solution Substances 0.000 claims description 51
- 239000003826 tablet Substances 0.000 claims description 36
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 32
- 239000008187 granular material Substances 0.000 claims description 30
- 238000012360 testing method Methods 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 24
- 239000000047 product Substances 0.000 claims description 23
- 239000003814 drug Substances 0.000 claims description 22
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 21
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 21
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 21
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 21
- 238000003556 assay Methods 0.000 claims description 20
- 230000001476 alcoholic effect Effects 0.000 claims description 18
- 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 16
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 16
- 238000004132 cross linking Methods 0.000 claims description 16
- 235000019359 magnesium stearate Nutrition 0.000 claims description 16
- 239000013558 reference substance Substances 0.000 claims description 16
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 16
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 15
- 238000004090 dissolution Methods 0.000 claims description 13
- 238000005070 sampling Methods 0.000 claims description 11
- 239000012535 impurity Substances 0.000 claims description 10
- 229920002472 Starch Polymers 0.000 claims description 9
- 239000000843 powder Substances 0.000 claims description 9
- 239000008107 starch Substances 0.000 claims description 9
- 235000019698 starch Nutrition 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 239000012071 phase Substances 0.000 claims description 8
- 238000005303 weighing Methods 0.000 claims description 8
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 7
- HSRJKNPTNIJEKV-UHFFFAOYSA-N Guaifenesin Chemical compound COC1=CC=CC=C1OCC(O)CO HSRJKNPTNIJEKV-UHFFFAOYSA-N 0.000 claims description 6
- 238000010521 absorption reaction Methods 0.000 claims description 6
- 229960002146 guaifenesin Drugs 0.000 claims description 6
- 230000014759 maintenance of location Effects 0.000 claims description 6
- 238000012545 processing Methods 0.000 claims description 6
- 239000007779 soft material Substances 0.000 claims description 6
- 239000000706 filtrate Substances 0.000 claims description 5
- 238000007689 inspection Methods 0.000 claims description 5
- 238000012856 packing Methods 0.000 claims description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- 238000010790 dilution Methods 0.000 claims description 4
- 239000012895 dilution Substances 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 239000004677 Nylon Substances 0.000 claims description 3
- 230000033228 biological regulation Effects 0.000 claims description 3
- 238000004364 calculation method Methods 0.000 claims description 3
- 238000011978 dissolution method Methods 0.000 claims description 3
- 239000000945 filler Substances 0.000 claims description 3
- 239000012530 fluid Substances 0.000 claims description 3
- 239000000314 lubricant Substances 0.000 claims description 3
- 229920001778 nylon Polymers 0.000 claims description 3
- 238000005453 pelletization Methods 0.000 claims description 3
- 238000003908 quality control method Methods 0.000 claims description 3
- 239000011265 semifinished product Substances 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 239000000080 wetting agent Substances 0.000 claims description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 2
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- 238000001514 detection method Methods 0.000 claims description 2
- 238000010812 external standard method Methods 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 2
- 239000007791 liquid phase Substances 0.000 claims description 2
- 229910000402 monopotassium phosphate Inorganic materials 0.000 claims description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 claims description 2
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 claims description 2
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 230000035945 sensitivity Effects 0.000 claims description 2
- 239000000377 silicon dioxide Substances 0.000 claims description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 2
- 238000011003 system suitability test Methods 0.000 claims description 2
- 239000012085 test solution Substances 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims 1
- 239000003158 myorelaxant agent Substances 0.000 abstract description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 abstract description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 abstract description 3
- 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 abstract description 2
- 210000000988 bone and bone Anatomy 0.000 abstract 1
- 239000001913 cellulose Substances 0.000 abstract 1
- 229920002678 cellulose Polymers 0.000 abstract 1
- 239000002932 luster Substances 0.000 description 7
- 238000012216 screening Methods 0.000 description 7
- 239000000825 pharmaceutical preparation Substances 0.000 description 6
- 210000002027 skeletal muscle Anatomy 0.000 description 6
- 208000002193 Pain Diseases 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 230000036407 pain Effects 0.000 description 5
- 238000013112 stability test Methods 0.000 description 5
- 230000001684 chronic effect Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000005286 illumination Methods 0.000 description 4
- 210000003205 muscle Anatomy 0.000 description 4
- 208000007101 Muscle Cramp Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 208000005392 Spasm Diseases 0.000 description 3
- TZFWDZFKRBELIQ-UHFFFAOYSA-N chlorzoxazone Chemical compound ClC1=CC=C2OC(O)=NC2=C1 TZFWDZFKRBELIQ-UHFFFAOYSA-N 0.000 description 3
- 229960003633 chlorzoxazone Drugs 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 206010025482 malaise Diseases 0.000 description 3
- 230000003387 muscular Effects 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 208000006820 Arthralgia Diseases 0.000 description 2
- 206010016228 Fasciitis Diseases 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000003195 fascia Anatomy 0.000 description 2
- 229960001375 lactose Drugs 0.000 description 2
- 210000003041 ligament Anatomy 0.000 description 2
- 208000004296 neuralgia Diseases 0.000 description 2
- 201000001119 neuropathy Diseases 0.000 description 2
- 230000007823 neuropathy Effects 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 229940063637 robaxin Drugs 0.000 description 2
- 210000004872 soft tissue Anatomy 0.000 description 2
- QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical compound O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 2
- 210000000225 synapse Anatomy 0.000 description 2
- 239000010924 used plastic bottle Substances 0.000 description 2
- GXFZCDMWGMFGFL-KKXMJGKMSA-N (+)-Tubocurarine chloride hydrochloride Chemical class [Cl-].[Cl-].C([C@H]1[N+](C)(C)CCC=2C=C(C(=C(OC3=CC=C(C=C3)C[C@H]3C=4C=C(C(=CC=4CC[NH+]3C)OC)O3)C=21)O)OC)C1=CC=C(O)C3=C1 GXFZCDMWGMFGFL-KKXMJGKMSA-N 0.000 description 1
- SQUNAWUMZGQQJD-UHFFFAOYSA-N 1-(4-ethylphenyl)-2-methyl-3-(piperidin-1-yl)propan-1-one Chemical compound C1=CC(CC)=CC=C1C(=O)C(C)CN1CCCCC1 SQUNAWUMZGQQJD-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- YXSLJKQTIDHPOT-UHFFFAOYSA-N Atracurium Dibesylate Chemical compound C1=C(OC)C(OC)=CC=C1CC1[N+](CCC(=O)OCCCCCOC(=O)CC[N+]2(C)C(C3=CC(OC)=C(OC)C=C3CC2)CC=2C=C(OC)C(OC)=CC=2)(C)CCC2=CC(OC)=C(OC)C=C21 YXSLJKQTIDHPOT-UHFFFAOYSA-N 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010057254 Connective tissue inflammation Diseases 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 101000607872 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 21 Proteins 0.000 description 1
- 208000008930 Low Back Pain Diseases 0.000 description 1
- 206010028391 Musculoskeletal Pain Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 1
- TXWBOBJCRVVBJF-YTGGZNJNSA-L Pipecuronium bromide Chemical compound [Br-].[Br-].N1([C@@H]2[C@@H](OC(C)=O)C[C@@H]3CC[C@H]4[C@@H]5C[C@@H]([C@@H]([C@]5(CC[C@@H]4[C@@]3(C)C2)C)OC(=O)C)N2CC[N+](C)(C)CC2)CC[N+](C)(C)CC1 TXWBOBJCRVVBJF-YTGGZNJNSA-L 0.000 description 1
- 208000007613 Shoulder Pain Diseases 0.000 description 1
- 201000002661 Spondylitis Diseases 0.000 description 1
- 208000010040 Sprains and Strains Diseases 0.000 description 1
- 241001279009 Strychnos toxifera Species 0.000 description 1
- 102100039918 Ubiquitin carboxyl-terminal hydrolase 21 Human genes 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 239000002643 anesthesia adjuvant Substances 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 229960001862 atracurium Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 229960001193 diclofenac sodium Drugs 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960002565 eperisone Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 239000000842 neuromuscular blocking agent Substances 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 229960004460 pipecuronium bromide Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 229960005453 strychnine Drugs 0.000 description 1
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- 230000008736 traumatic injury Effects 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention provides a dispersible tablet preparation containing Methocarbamol as a central bone muscle relaxant, wherein the constituents of the preparation include Methocarbamol, lactose, crystalline cellulose, sodium carboxymethylstarch, polyvidone and talcum powder.
Description
Technical field
The present invention relates to pharmaceutical preparation, particularly contain the new pharmaceutical preparation of the lax medicine methocarbamol of central skeletal muscle, the consisting of of said preparation: methocarbamol, lactose, microcrystalline Cellulose, carboxymethyl starch sodium, polyvidone, Pulvis Talci.
Background technology
Muscle relaxant is the medicine that can reduce skeletal muscle (striped muscle) tensity.Mainly be divided into neuromuscular blocking drug and central skeletal muscle relaxant, the former mainly acts on nerve synapse, usually as the anesthesia adjuvant, all belongs to this type of medicine as chlorine letter curare alkaloid, benzenesulfonic acid atracurium, pipecuronium bromide etc.; And the latter mainly acts on central nervous system's (beyond synapse), is generally used for the pain alleviating the skeletal muscle spasm and cause, example hydrochloric acid eperisone granule, and chlorzoxazone, methocarbamol etc. all belongs to this type of medicine.Wherein methocarbamol is just clinical at home and abroad the being extensive use of eighties.Be applicable to that clinically treating various acute and chronic soft tissues (muscle, ligament, fascia) sprains, dampens, motion back muscular soreness, the old pain that causes of decreasing of muscle, neuralgia, arthralgia, rheumatalgia, the fibrous connective tissue inflammation, spondylitis is by the muscle spasm that central neuropathy causes, chronic fascitis etc.
The acute and chronic soft tissue that a variety of causes causes (muscle, ligament, fascia) knob is hindered, is dampened, motion back muscular soreness, the caused pain of muscular strain, the muscle spasm that is caused by central neuropathy, chronic fascitis etc. and the light moderate pain that is caused by a variety of causes such as neuralgia, lumbago, shoulder pain, myalgia, arthralgia, traumatic injury pain etc. are frequently-occurring disease and commonly encountered diseases general, the most common in the daily life, bring many miseries and worry to people, have a strong impact on people's work, study and rest.It has seriously hindered people's work, the second largest commonly encountered diseases that becomes disability after 50 years old because of, be only second to the heart disease sickness rate.According to western countries statistics, osteoarthritis has accounted for 2.3% of clinic case at present, is just threatening people's health, and there are confidential relation at the generation and the age of osteoarthritis, and it is 2%-3% that the age is lower than 45 years old sickness rate; 45-64 year be 24.5%-30%, surpass 65 years old can be up to 58%-68%, and women's sickness rate is higher than the male.
For as above disease, domestic analgesic, the anti-inflammatory analgesic treatments of using are compared with above-mentioned medicine as the chlorzoxazone of aspirin, acetaminophen, diclofenac sodium and listing in recent years and compound chlorzoxazone etc. more,
Methocarbamol sheet (Robaxin
/ Robaxin
-750) be the lax medicine of central skeletal muscle of SCHWARZ PHARMA company exploitation, get permission listing at FDA January nineteen eighty-two.USP23 has recorded the tablet of methocarbamol raw material, injection and 500mg thereof and 750mg.Methocarbamol can make skeleton lax, but consciousness is disappeared, and has anticonvulsant action, can resist faint from fear due to strychnine and the electricity irritation, its mechanism is for suppressing the multisynaptic reflex of spinal cord.In addition still can calmness, analgesia, antiinflammatory.Clinical being extensive use of of methocarbamol reported the new purposes of methocarbamol when clinical heavy dose is used again in succession in recent years, and its curative effect is safe and reliable.
In recent years, the oral preparation of quick releasing development is very fast, and according to statistics, world's quick releasing formulation sales volume was nearly 200,000,000 dollars in 1996.Wherein disintegrate becomes the dispersible tablet of uniform viscosity suspension rapidly, because its taking convenience, absorbs soon, and characteristics such as bioavailability height are subjected to people's attention day by day.The kind of this kind dosage form also increases gradually.It is predicted that about 10% will occur with novel release dosage form in all sale medicines of the world following 10 years, its market sale share is estimated every year and increases by 1% that this quick dissolved, quick effect novel form of dispersible tablet is expected to obtain faster development.
The methocarbamol dosage form is mainly oral formulations (mainly being tablet and capsule), because the methocarbamol water solublity is bad, be difficult to absorb, the dosage form of methocarbamol being made dispersible tablet has run into difficulty, the present invention has found solution, and provides a kind of chance water rapid disintegrate through screening study, the medicine stripping is fast, the bioavailability height.Patient Geng Yi with respect to old man and dysphagia takes simultaneously, and mouthfeel is better, taking convenience, and the patient is easy to accept portable novel formulation.
Summary of the invention
The invention provides a kind of pharmaceutical preparation, particularly contain the lax new pharmaceutical preparation of medicine methocarbamol of central skeletal muscle, the consisting of of said preparation: methocarbamol, microcrystalline Cellulose, lactose, cross-linking sodium carboxymethyl cellulose, magnesium stearate, 50% alcoholic solution.
This pharmaceutical preparation is tablet form, dispersible tablet form particularly, and described dispersible tablet is that tablet is put in an amount of water, makes it to disperse disintegrate, the dosage form of together taking with water then.The present invention has found the particularly advantageous dispersible tablet prescription of methocarbamol through screening.
Therefore, the invention provides the Methocarbamol dispersion tablet preparation, wherein contain the medicine acceptable carrier of active constituents of medicine methocarbamol and suitable preparation dispersible tablet, the medicine acceptable carrier of wherein said suitable preparation dispersible tablet is selected from following composition: lactose, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, sodium lauryl sulphate, starch, magnesium stearate, carboxymethyl starch sodium, Pulvis Talci etc.Preferred composition is a lactose, microcrystalline Cellulose, and carboxymethyl starch sodium, magnesium stearate, 50% alcoholic solution is a wetting agent.
Therefore, Methocarbamol dispersion tablet preparation of the present invention is preferably write out a prescription composed as follows:
Methocarbamol 250-1000g
Microcrystalline Cellulose 100-400g
Lactose 50-200g
Cross-linking sodium carboxymethyl cellulose 40-160g
Magnesium stearate 10-40g
50% alcoholic solution 1-100ml
Make 1000
Most preferred prescription is composed as follows
Methocarbamol 500g
Microcrystalline Cellulose 200g
Lactose 100g
Cross-linking sodium carboxymethyl cellulose 80g
Magnesium stearate 20g
50% alcoholic solution is an amount of
Make 1000
The present invention also comprises the preparation method of Methocarbamol dispersion tablet, its basic step adopts the galenic pharmacy routine techniques, as active component and medicine acceptable carrier are mixed, tabletting etc., 50% alcoholic solution is a wetting agent, and consumption during use is so that make the granule that is fit to tabletting and be as the criterion, according to routine, use amount be between the 0.5-5% of inventory for suitable, be preferably 1%.
Specifically can adopt following method:
The preparation of 1 supplementary material and processing:
With methocarbamol pulverized that 200 mesh sieves are standby, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose, that lactose is crossed 100 mesh sieves is standby.
2 weighings with mix:
2.1 take by weighing above-mentioned supplementary material respectively through the double calculating inventory of checking according to recipe quantity.
2.2 with above-mentioned supplementary material by the equivalent method mix homogeneously that progressively increases.
3 granulate:
3.1 the system soft material is granulated with 20 order nylon wires with 50% alcoholic solution system soft material, the granule that makes should lack fine powder, does not neatly have rectangular.
3.2 it is dry: 55+2 ℃ temperature, in drying baker inner drying 5-7 hour.
3.3 the processing of dried granule before tabletting:
Granulate: in pelletization, excessive granule is arranged, the granulate that need sieve makes the single-size that becomes to be fit to tabletting; Sieve and select 16 mesh sieve granulate for use.
3.4 the adding lubricant, mix homogeneously is placed in the hermetic container, after the assay was approved tabletting.
4 measure granule content, and it is heavy to calculate sheet:
Sampling is pressed quality standard and is measured granule content, and theoretical sheet heavily should be 0.9g.
5 tablettings: heavy according to the actual sheet of result of calculation gained, regulate the tablet machine tabletting, put into hermetic container sampling check hardness after finishing.
6 inspections of semifinished product: pack after the assay was approved by the quality standard requirement.
7 pack according to the requirement of product, and packing back warehouse-in can dispatch from the factory after the assay was approved according to quality standard.
Methocarbamol dispersion tablet prescription of the present invention is to obtain through screening, and its screening process is as follows:
Prescription screening
In the 1 prescription screening process, the dispersing uniformity filler uses microcrystalline Cellulose in order to reach preferably, and disintegrating agent carboxymethyl starch sodium commonly used on probation, cross-linking sodium carboxymethyl cellulose, crospolyvinylpyrrolidone etc. are to reach comparatively satisfied stripping curve; Below be the screening of several supplementary product consumptions:
Prescription 1 prescription 2
Methocarbamol 500g methocarbamol 500g
Microcrystalline Cellulose 200g microcrystalline Cellulose 200g
Lactose 100g lactose 100g
Carboxymethyl starch sodium 80g crospolyvinylpyrrolidone 80g
Magnesium stearate 20g magnesium stearate 20g
An amount of 50% alcoholic solution of 50% alcoholic solution is an amount of
Make 1000 and make 1000
Prescription 3 prescriptions 4
Methocarbamol 500g methocarbamol 500g
Microcrystalline Cellulose 200g microcrystalline Cellulose 200g
Lactose 100g lactose 100g
Cross-linking sodium carboxymethyl cellulose 80g cross-linking sodium carboxymethyl cellulose 80g
Magnesium stearate 20g polyvidone 5g
An amount of magnesium stearate 20g of 50% alcoholic solution
It is an amount of to make 1,000 50% alcoholic solution
Make 1000
Dissolving-out method with reference to the WS-10001-of National Drug Administration (HD-0268)-2002 methocarbamol sheet; get this product according to dissolution method (two appendix XC second methods of Chinese Pharmacopoeia version in 2000); with water 900ml is solvent; rotating speed is that per minute 50 changes; got a little at 2,4,7,10,15 minutes respectively; precision measures that thin up to scale shakes up in subsequent filtrate 5ml → 50ml measuring bottle; mend dissolution fluid 5ml; according to spectrophotography (appendix IVA); the wavelength place at 274nm measures trap, the results are shown in Table 1
Table 1 stripping curve measurement result
| The prescription number | Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 |
| 2 minutes | 27.4％ | 25.9％ | 36.8％ | 31.0％ |
| 4 minutes | 44.3％ | 52.3％ | 62.4％ | 51.7％ |
| 10 minutes | 77.4％ | 79.6％ | 93.5％ | 78.4％ |
| 15 minutes | 90.0％ | 92.0％ | 99.2％ | 97.3％ |
| Hardness | 11.28kg | 10.59kg | 11.78kg | 10.76kg |
| Dispersing uniformity | 1 minute 47 seconds | 2 minutes 05 second | 1 minute 15 seconds | 2 minutes 35 seconds |
Shown by above result of the test: prescription 1-4 dispersing uniformity is best is that prescription 3 be 1 minute 15 seconds and it at 10 minutes dissolution is 93.5% the highest, and the dispersing uniformity of all the other 3 prescriptions and stripping curve are all not as 3 ideals of writing out a prescription; Still select to write out a prescription and 3 amplify, its lot number is 030903,030905,030907.
2 stability influence factorial experimentss:
(1) strong illumination test:
Get 030903 batch of Methocarbamol dispersion tablet and place glass dish, placed 10 days under the illumination of 4500LX ± 100LX, detect in sampling in 0,5,10 day, testing result sees Table 2:
Table 2 strong illumination result of the test
| Blanking time (my god) | Outward appearance, color and luster | Dissolution (10 minutes) (%) | Related substance | Dispersing uniformity | Content (%) | |
| Guaifenesin | Other impurity levels (%) | |||||
| 0 5 | The white tablets white tablets | 96.8 95.3 | 0.19 0.22 | 0.07 0.10 | Up to specification | 100.2 99.5 |
| 10 | White tablets | 95.6 | 0.23 | 0.08 | Up to specification | 99.3 |
(2) hot test:
Get 030903 batch of Methocarbamol dispersion tablet and place glass dish, placed 10 days in 60 ℃ calorstat, detect in sampling in 0,5,10 day, testing result sees Table 3:
60 ℃ of thimble test results of table 3
| In the time of at interval (my god) | Outward appearance, color and luster | Dissolution (10 minutes) (%) | Related substance | Dispersing uniformity | Content (%) | |
| Guaifenesin | Other impurity levels (%) | |||||
| 0 5 10 | White tablets white tablets white tablets | 96.8 94.0 94.8 | 0.19 0.22 0.22 | 0.07 0.08 0.08 | Up to specification up to specification | 100.2 100.6 99.7 |
(3) high humidity result of the test:
The Methocarbamol dispersion tablet of getting 030903 batch places glass dish, respectively at relative humidity 75% (NaCl saturated solution), 92.5% (KNO
3Saturated solution) placed in the calorstat 10 days, and detected in sampling in 0,5,10 day, testing result sees Table 4 and table 5:
Table 4 75% high humidity stability test
| Blanking time (my god) | Outward appearance, color and luster | Moisture absorption | Hygroscopicity (%) | Dissolution (10 minutes) (%) | Related substance | Dispersing uniformity | Content (%) | ||
| Preceding (g) | Back (g) | Guaifenesin | Other impurity levels (%) | ||||||
| 0 5 10 | White tablets white tablets white tablets | 0.9046 0.9028 | 0.9145 0.9156 | 1.09 1.42 | 96.8 95.4 94.9 | 0.19 0.23 0.22 | 0.07 0.06 0.08 | Up to specification up to specification | 100.2 98.8 99.6 |
Table 5 92.5% high humidity stability test result
| Blanking time (my god) preceding | Outward appearance, color and luster | Moisture absorption | Hygroscopicity (%) | Dissolution (10 minutes) (%) | Related substance | Dispersing uniformity | Content (%) | ||
| Preceding (g) | Back (g) | Guaifenesin | Other impurity levels (%) | ||||||
| 0 5 10 | White tablets white tablets white tablets | 0.9025 0.9047 | 0.9336 0.9446 | 3.44 4.41 | 96.8 96.1 95.2 | 0.19 0.24 0.23 | 0.07 0.09 0.12 | Up to specification up to specification | 100.2 99.2 98.5 |
Above result of the test shows, this product is all stable under the condition of illumination, 60 ℃ of high temperature and high humidity.
The present invention also provides the method for quality control of Methocarbamol dispersion tablet of the present invention, is the quality of control preparation of the present invention.At its characteristics and prescription of the present invention, we provide following method of quality control:
Character is observed, content is differentiated, official method is checked content, and the methocarbamol that contains is carried out assay.
Wherein character is observed, step is:
[character] this product is complete white tablets
Content is differentiated step is:
The fine powder an amount of (being equivalent to methocarbamol 0.5g approximately) of this product is got in [discriminating] (1), hydro-oxidation sodium test solution 5ml, and heating is promptly decomposed, and it is smelly that ammonia takes place, and meets moistening litmus red test paper, becomes blue.
(2) it is an amount of to get the fine powder of this product, adds ethanol and makes per 1 milliliter of solution that contains methocarbamol 50 μ g, measures according to spectrophotography (two appendix IVA of Chinese Pharmacopoeia version in 2000), and there is absorption maximum at the place at the 274nm wavelength, and there is minimal absorption at the place at the 245nm wavelength.
(3) in the high-efficient liquid phase chromatogram that writes down under the assay item, the retention time of need testing solution main peak is answered consistent with the main peak retention time of reference substance.
Official method checks that to content step is:
[inspection]
It is an amount of that related substance is got this product, makes dissolving with mobile phase is ultrasonic, and quantitatively dilution make contain methocarbamol 2mg among every 1ml solution as need testing solution.It is an amount of that other gets the guaifenesin reference substance, adds mobile phase dissolving and quantitatively be diluted to the solution product solution in contrast that contains 40 μ g among every 1ml.According to the method test under the assay item.Measure reference substance solution 20 μ l and inject chromatograph of liquid, regulate instrumental sensitivity, make the peak height of main constituent chromatographic peak be about the 10-20% of full scale.Precision is measured each 20 μ l of above-mentioned two kinds of solution again, injects chromatograph of liquid respectively, and the record chromatogram is to 2 times of main constituent peak retention time.In the chromatogram of need testing solution as occur and the corresponding chromatographic peak of reference substance solution main constituent, its peak area must not be greater than 1/2 (1.0%) of reference substance solution main peak area, the peak area of other impurity peaks and must not be greater than reference substance solution main peak area 1/4 (0.5%), total impurities must not cross 1.5%.
Dissolution is got this product, according to dissolution method (two appendix XC second methods of Chinese Pharmacopoeia version in 2000).With water 900ml is solvent, rotating speed is that per minute 50 changes, operation in accordance with the law, in the time of 10 minutes, to get solution 10ml and filter, precision is measured subsequent filtrate 5ml, put in the 50ml measuring bottle, be diluted with water to scale, shake up, as need testing solution, it is an amount of that other gets the methocarbamol reference substance, accurate claim surely, make the solution product solution in contrast that contains methocarbamol 55 μ g among every 1ml with dissolution fluid dissolving and dilution, according to spectrophotography (two appendix IV of Chinese Pharmacopoeia version in 2000 A), wavelength place at 272nm measures trap respectively, calculate every stripping quantity, limit is 80% of a labelled amount, should be up to specification.
Other should meet every regulation relevant under the tablet item (two appendix I of Chinese Pharmacopoeia version in 2000 A)
The methocarbamol that contains is carried out the assay step is
[assay] is according to high performance liquid chromatography (two appendix V of Chinese Pharmacopoeia version in 2000 D).
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica, with methanol-0.05mol/l potassium dihydrogen phosphate (regulating pH value to 4.5 ± 0.05 with phosphoric acid or 10mol/l potassium hydroxide solution)=35: 65 was mobile phase, and the detection wavelength is 272nm.Theoretical cam curve is calculated by the methocarbamol peak should be not less than 3000, and the separating degree of methocarbamol peak and adjacent impurity peaks should be up to specification, repeats sample introduction 5 times, and its relative standard deviation should be less than 2.0%.
Get 10 of this product, the accurate title, decide, porphyrize, and precision takes by weighing fine powder an amount of (being equivalent to methocarbamol 100mg approximately), put in the 100ml measuring bottle, it is an amount of to add mobile phase, ultrasonic make the dissolving and be diluted to scale, shake up, filter, get in the subsequent filtrate 20 μ l injecting chromatographs, the record chromatogram; It is an amount of that other gets the methocarbamol reference substance, measures with method, presses external standard method with calculated by peak area, promptly.
The testing data of stability study
The way of declaring by five kind new medicines, we have carried out the test that keeps sample of constant temperature accelerated test, room temperature to the Methocarbamol dispersion tablet of trial-production, thereby its stability has been carried out preliminary investigation, press the assay method of clinical quality standard (draft) regulation, sample appearance color and luster, dispersing uniformity, related substance, dissolution, content project are detected.
The source of sample is the Tianjin Hankang Medicine Bioisystech Co., Ltd, and lot number and quantity are respectively 030903,4713,030905,4742,030907,4808.Remove outer package as requested.
One, constant temperature accelerated stability test:
Get Methocarbamol dispersion tablet, lot number 030903,030905,030907 is used plastic bottle packing, and constant temperature is placed under 40 ℃ ± 2 ℃ relative humiditys 75% (NaCL saturated solution) condition, and respectively at 0,1,2,3, the sampling in June detects, testing result sees Table 6
Two, the room temperature study on the stability that keeps sample:
Get Methocarbamol dispersion tablet, lot number 030903,030905,030907 is used plastic bottle packing, places under the natural conditions in the breadboard sample cabinet, and respectively at 0,3, the sampling in June detects, testing result sees Table 7
The result shows: this product is under the condition of 40 ℃ ± 2 ℃ of relative humiditys 75%, and in 6 months of having investigated, each investigates every index of project does not have significant change, has stability preferably.
Pharmaceutical preparation of the present invention has overcome defective of the prior art, prepares stablely, and safety absorbs soon, and dissolving is fast, and taking convenience prepares simple novel drugs.
The specific embodiment
The present invention is described further by the following examples, but not as limitation of the present invention.
Embodiment 1
Methocarbamol 500g
Microcrystalline Cellulose 200g
Lactose 100g
Cross-linking sodium carboxymethyl cellulose 80g
Magnesium stearate 20g
50% alcoholic solution is an amount of
Make 1000
The present invention also comprises the preparation method of Methocarbamol dispersion tablet, and its basic step adopts the galenic pharmacy routine techniques, as active component and medicine acceptable carrier are mixed tabletting etc.
Specifically can adopt following method:
The preparation of 1 supplementary material and processing:
With methocarbamol pulverized that 200 mesh sieves are standby, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose, that lactose is crossed 100 mesh sieves is standby.
2 weighings with mix:
2.1 take by weighing above-mentioned supplementary material respectively through the double calculating inventory of checking according to recipe quantity.
2.2 with above-mentioned supplementary material by the equivalent method mix homogeneously that progressively increases.
3 granulate:
3.1 the system soft material is granulated with 20 order nylon wires with 50% alcoholic solution system soft material, the granule that makes should lack fine powder, does not neatly have rectangular.
3.2 it is dry: 55 ± 2 ℃ temperature, in drying baker inner drying 5-7 hour.
3.3 the processing of dried granule before tabletting:
Granulate: in pelletization, excessive granule is arranged, the granulate that need sieve makes the single-size that becomes to be fit to tabletting; Sieve and select 16 mesh sieve granulate for use.
3.4 the adding lubricant, mix homogeneously is placed in the hermetic container, after the assay was approved tabletting.
4 measure granule content, and it is heavy to calculate sheet:
Sampling is pressed quality standard and is measured granule content, and theoretical sheet heavily should be 0.9g.
5 tablettings: heavy according to the actual sheet of result of calculation gained, regulate the tablet machine tabletting, put into hermetic container sampling check hardness after finishing.
6 inspections of semifinished product: pack after the assay was approved by the quality standard requirement.
7 pack according to the requirement of product, and packing back warehouse-in can dispatch from the factory after the assay was approved according to quality standard.
Embodiment 2
Methocarbamol 250g
Microcrystalline Cellulose 100g
Lactose 50g
Cross-linking sodium carboxymethyl cellulose 40g
Magnesium stearate 10g
50% alcoholic solution is an amount of
Make 1000
Preparation method is with embodiment 1
Embodiment 3
Methocarbamol 1000g
Microcrystalline Cellulose 400g
Lactose 200g
Cross-linking sodium carboxymethyl cellulose 160g
Magnesium stearate 40g
50% alcoholic solution is an amount of
Make 1000
Preparation method is with embodiment 1
Table 6 constant temperature accelerated stability test result
| The project lot number | Blanking time (moon) | Appearance luster | Related substance (%) | Dissolution (%) | Content (%) |
| 030208 | 0 1 2 3 6 | The complete yellowish color chips of the complete yellowish color chips of the complete yellowish color chips of the complete yellowish color chips of complete yellowish color chips | 0.72 0.71 0.71 0.84 0.79 | 95.5 94.2 95.7 93.4 94.7 | 99.4 99.6 99.3 98.9 99.0 |
| 030210 | 0 1 2 3 6 | The complete yellowish color chips of the complete yellowish color chips of the complete yellowish color chips of the complete yellowish color chips of complete yellowish color chips | 0.67 0.70 0.73 0.71 0.79 | 94.0 96.1 93.5 93.5 94.0 | 98.9 99.5 98.7 99.0 98.6 |
| 030212 | 0 1 2 3 6 | The complete yellowish color chips of the complete yellowish color chips of the complete yellowish color chips of the complete yellowish color chips of complete yellowish color chips | 0.68 0.71 0.74 0.83 0.83 | 95.5 95.0 96.6 95.1 95.1 | 99.6 98.4 98.6 98.9 99.0 |
The table 7 room temperature stability test result that keeps sample
| The project lot number | Blanking time (moon) | Appearance luster | Related substance (%) | Dissolution (%) | Content (%) |
| 030208 | 0 3 6 | The complete yellowish color chips of the complete yellowish color chips of complete yellowish color chips | 0.72 0.71 0.70 | 95.5 94.9 94.4 | 99.4 99.2 99.0 |
| 030210 | 0 3 6 | The complete yellowish color chips of the complete yellowish color chips of complete yellowish color chips | 0.67 0.73 0.74 | 94.0 93.8 93.3 | 98.9 99.1 99.4 |
| 030212 | 0 3 6 | The complete yellowish color chips of the complete yellowish color chips of complete yellowish color chips | 0.68 0.74 0.72 | 95.5 94.2 94.5 | 99.6 98.9 99.2 |
Claims (10)
1, a kind of dispersible tablet of methocarbamol.
2, the dispersible tablet of claim 1, wherein said methocarbamol comprise methocarbamol and its pharmaceutical salts.
3, the dispersible tablet of claim 1 is characterized in that, wherein contains the medicine acceptable carrier of active constituents of medicine methocarbamol and suitable preparation dispersible tablet.
4, the dispersible tablet of claim 3 is characterized in that, the medicine acceptable carrier of wherein said suitable preparation dispersible tablet is selected from following composition: lactose, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, sodium lauryl sulphate, starch, magnesium stearate, carboxymethyl starch sodium, Pulvis Talci.
5, the dispersible tablet of claim 4 is characterized in that, the medicine acceptable carrier of wherein said suitable preparation dispersible tablet is a lactose, microcrystalline Cellulose, and carboxymethyl starch sodium, magnesium stearate, 50% alcoholic solution is a wetting agent.
6, the dispersible tablet of claim 5 is characterized in that,
It is composed as follows to write out a prescription:
Methocarbamol 250-1000g
Microcrystalline Cellulose 100-400g
Lactose 50-200g
Cross-linking sodium carboxymethyl cellulose 40-160g
Magnesium stearate 10-40g
50% alcoholic solution 1-100ml
Make 1000.
7, the dispersible tablet of claim 5 is characterized in that,
It is composed as follows to write out a prescription
Methocarbamol 500g
Microcrystalline Cellulose 200g
Lactose 100g
Cross-linking sodium carboxymethyl cellulose 80g
Magnesium stearate 20g
50% alcoholic solution is an amount of
Make 1000.
8, the preparation method of the dispersible tablet of claim 1 comprises active component methocarbamol and medicine acceptable carrier is mixed the step of tabletting.
9, the preparation method of claim 8, step is as follows:
1) preparation of supplementary material and processing:
With methocarbamol pulverized that 200 mesh sieves are standby, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose, that lactose is crossed 100 mesh sieves is standby;
2) weighing with mix:
2.1) take by weighing above-mentioned supplementary material according to recipe quantity respectively through the double calculating inventory of checking;
2.2) with above-mentioned supplementary material by the equivalent method mix homogeneously that progressively increases;
3) granulate:
3.1) make soft material with 50% alcoholic solution system soft material, to granulate with 20 order nylon wires, the granule that makes should lack fine powder, does not neatly have rectangular;
3.2) drying: 55 ± 2 ℃ temperature, in drying baker inner drying 5-7 hour;
3.3) processing of dried granule before tabletting:
Granulate: in pelletization, excessive granule is arranged, the granulate that need sieve makes the single-size that becomes to be fit to tabletting; Sieve and select 16 mesh sieve granulate for use;
3.4) adding lubricant, mix homogeneously is placed in the hermetic container, after the assay was approved tabletting;
4) measure granule content, it is heavy to calculate sheet:
Sampling is pressed quality standard and is measured granule content, and theoretical sheet heavily should be 0.9g;
5) tabletting: heavy according to the actual sheet of result of calculation gained, regulate the tablet machine tabletting, put into hermetic container sampling check hardness after finishing;
6) inspection of semifinished product: pack after the assay was approved by the quality standard requirement;
7) pack according to the requirement of product, packing back warehouse-in can dispatch from the factory after the assay was approved according to quality standard.
10, the method for quality control of the dispersible tablet of claim 1 may further comprise the steps:
Character is observed, content is differentiated, official method is checked content, and the methocarbamol that contains is carried out assay;
Wherein character is observed, step is:
[character] this product is complete white tablets;
Content is differentiated step is:
The fine powder an amount of (being equivalent to methocarbamol 0.5g approximately) of this product is got in [discriminating] (1), hydro-oxidation sodium test solution 5ml, and heating is promptly decomposed, and it is smelly that ammonia takes place, and meets moistening litmus red test paper, becomes blue;
(2) it is an amount of to get the fine powder of this product, adds ethanol and makes per 1 milliliter of solution that contains methocarbamol 50 μ g, measures according to spectrophotography (two appendix IV of Chinese Pharmacopoeia version in 2000 A), and there is absorption maximum at the place at the 274nm wavelength, and there is minimal absorption at the place at the 245nm wavelength;
(3) in the high-efficient liquid phase chromatogram that writes down under the assay item, the retention time of need testing solution main peak is answered consistent with the main peak retention time of reference substance;
Official method checks that to content step is:
[inspection]
It is an amount of that related substance is got this product, makes dissolving with mobile phase is ultrasonic, and quantitatively dilution make contain methocarbamol 2mg among every 1ml solution as need testing solution; It is an amount of that other gets the guaifenesin reference substance, adds mobile phase dissolving and quantitatively be diluted to the solution product solution in contrast that contains 40 μ g among every 1ml; According to the method test under the assay item; Measure reference substance solution 20 μ l and inject chromatograph of liquid, regulate instrumental sensitivity, make the peak height of main constituent chromatographic peak be about the 10-20% of full scale; Precision is measured each 20 μ l of above-mentioned two kinds of solution again, injects chromatograph of liquid respectively, and the record chromatogram is to 2 times of main constituent peak retention time; In the chromatogram of need testing solution as occur and the corresponding chromatographic peak of reference substance solution main constituent, its peak area must not be greater than 1/2 (1.0%) of reference substance solution main peak area, the peak area of other impurity peaks and must not be greater than reference substance solution main peak area 1/4 (0.5%), total impurities must not cross 1.5%;
Dissolution is got this product, according to dissolution method (two appendix X of Chinese Pharmacopoeia version in 2000 C, second method); With water 900ml is solvent, rotating speed is that per minute 50 changes, operation in accordance with the law, in the time of 10 minutes, to get solution 10ml and filter, precision is measured subsequent filtrate 5ml, put in the 50ml measuring bottle, be diluted with water to scale, shake up, as need testing solution, it is an amount of that other gets the methocarbamol reference substance, accurate claim surely, make the solution product solution in contrast that contains methocarbamol 55 μ g among every 1ml with dissolution fluid dissolving and dilution, according to spectrophotography (two appendix IV of Chinese Pharmacopoeia version in 2000 A), wavelength place at 272nm measures trap respectively, calculate every stripping quantity, limit is 80% of a labelled amount, should be up to specification;
Other should meet every regulation relevant under the tablet item (two appendix I of Chinese Pharmacopoeia version in 2000 A)
The methocarbamol that contains is carried out the assay step is;
[assay] is according to high performance liquid chromatography (two appendix V of Chinese Pharmacopoeia version in 2000 D);
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica, with methanol-0.05mol/l potassium dihydrogen phosphate (regulating pH value to 4.5 ± 0.05 with phosphoric acid or 10mol/l potassium hydroxide solution)=35: 65 was mobile phase, and the detection wavelength is 272nm; Theoretical cam curve is calculated by the methocarbamol peak should be not less than 3000, and the separating degree of methocarbamol peak and adjacent impurity peaks should be up to specification, repeats sample introduction 5 times, and its relative standard deviation should be less than 2.0%; Get 10 of this product, the accurate title, decide, porphyrize, and precision takes by weighing fine powder an amount of (being equivalent to methocarbamol 100mg approximately), put in the 100ml measuring bottle, it is an amount of to add mobile phase, ultrasonic make the dissolving and be diluted to scale, shake up, filter, get in the subsequent filtrate 20 μ l injecting chromatographs, the record chromatogram; It is an amount of that other gets the methocarbamol reference substance, measures with method, presses external standard method with calculated by peak area, promptly.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100075588A CN100411616C (en) | 2006-02-16 | 2006-02-16 | Methocarbamol dispersion tablet |
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|---|---|---|---|
| CNB2006100075588A CN100411616C (en) | 2006-02-16 | 2006-02-16 | Methocarbamol dispersion tablet |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101863917A (en) * | 2010-06-17 | 2010-10-20 | 天津市若围药物研究所 | Methocarbamol salt |
| CN103130684A (en) * | 2013-03-22 | 2013-06-05 | 南开大学 | Polymorphism of methocarbamol dipotassium phosphate and preparation method thereof |
| CN103193677A (en) * | 2013-03-22 | 2013-07-10 | 南开大学 | Polymorphic form of methocarbamol disodium phosphate and preparation method thereof |
-
2006
- 2006-02-16 CN CNB2006100075588A patent/CN100411616C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101863917A (en) * | 2010-06-17 | 2010-10-20 | 天津市若围药物研究所 | Methocarbamol salt |
| CN101863917B (en) * | 2010-06-17 | 2013-06-12 | 天津市若围药物研究所 | Methocarbamol salt |
| CN103130684A (en) * | 2013-03-22 | 2013-06-05 | 南开大学 | Polymorphism of methocarbamol dipotassium phosphate and preparation method thereof |
| CN103193677A (en) * | 2013-03-22 | 2013-07-10 | 南开大学 | Polymorphic form of methocarbamol disodium phosphate and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100411616C (en) | 2008-08-20 |
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Owner name: TIANJIN HANKANG PHARMACEUTICAL BIOTECHNOLOGY CO., Free format text: FORMER OWNER: YAN JIE Effective date: 20120213 |
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Effective date of registration: 20120213 Address after: 300203, Tianjin Dagu South Road, respect 4, 3, Hexi District Patentee after: Tianjin Hankang Pharmaceutical Biotechnology Co., Ltd. Address before: 300203, Tianjin Dagu South Road, respect 4, 3, Hexi District Patentee before: Yan Jie |
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Application publication date: 20061011 Assignee: Tianjin Junan Pharmaceutical Co. Ltd. Assignor: Tianjin Hankang Pharmaceutical Biotechnology Co., Ltd. Contract record no.: 2014120000035 Denomination of invention: Methocarbamol dispersion tablet Granted publication date: 20080820 License type: Common License Record date: 20140619 |
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