CN108414466A - A kind of minocycline hydrochloride sustained release tablet In Vitro Dissolution assay method - Google Patents
A kind of minocycline hydrochloride sustained release tablet In Vitro Dissolution assay method Download PDFInfo
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- CN108414466A CN108414466A CN201810192485.7A CN201810192485A CN108414466A CN 108414466 A CN108414466 A CN 108414466A CN 201810192485 A CN201810192485 A CN 201810192485A CN 108414466 A CN108414466 A CN 108414466A
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- solution
- dissolution
- sustained release
- minocycline hydrochloride
- release tablet
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- 238000004090 dissolution Methods 0.000 title claims abstract description 36
- WTJXVDPDEQKTCV-UHFFFAOYSA-N 4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide;hydron;chloride Chemical compound Cl.C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2C1CC1C(N(C)C)C(=O)C(C(N)=O)=C(O)C1(O)C2=O WTJXVDPDEQKTCV-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 229960002421 minocycline hydrochloride Drugs 0.000 title claims abstract description 24
- 239000007939 sustained release tablet Substances 0.000 title claims abstract description 20
- 238000003556 assay Methods 0.000 title claims abstract description 12
- 238000000338 in vitro Methods 0.000 title claims abstract description 11
- 239000000243 solution Substances 0.000 claims abstract description 66
- 239000012738 dissolution medium Substances 0.000 claims abstract description 17
- 238000002360 preparation method Methods 0.000 claims abstract description 13
- 239000012085 test solution Substances 0.000 claims abstract description 13
- 239000013558 reference substance Substances 0.000 claims abstract description 12
- 238000010812 external standard method Methods 0.000 claims abstract description 7
- 238000002798 spectrophotometry method Methods 0.000 claims abstract description 5
- KVCWSJZUKMSPLM-UHFFFAOYSA-N O.O[PH2]=O Chemical compound O.O[PH2]=O KVCWSJZUKMSPLM-UHFFFAOYSA-N 0.000 claims abstract description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims abstract description 4
- 238000002835 absorbance Methods 0.000 claims abstract description 4
- 229940040526 anhydrous sodium acetate Drugs 0.000 claims abstract description 4
- 238000002156 mixing Methods 0.000 claims abstract description 4
- 239000012530 fluid Substances 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 13
- 238000012360 testing method Methods 0.000 claims description 9
- 239000000523 sample Substances 0.000 claims description 8
- 239000000706 filtrate Substances 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 6
- 239000012982 microporous membrane Substances 0.000 claims description 6
- 238000011978 dissolution method Methods 0.000 claims description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 4
- 229960004023 minocycline Drugs 0.000 claims description 4
- -1 hydroxypropyl Chemical group 0.000 claims description 3
- 239000002609 medium Substances 0.000 claims description 3
- 230000002572 peristaltic effect Effects 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- 238000005070 sampling Methods 0.000 claims description 3
- 239000013589 supplement Substances 0.000 claims description 3
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.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 WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 claims description 2
- 239000004203 carnauba wax Substances 0.000 claims description 2
- 239000011248 coating agent Substances 0.000 claims description 2
- 238000000576 coating method Methods 0.000 claims description 2
- 229960001021 lactose monohydrate Drugs 0.000 claims description 2
- 235000019359 magnesium stearate Nutrition 0.000 claims description 2
- 239000000377 silicon dioxide Substances 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims 1
- 229920002678 cellulose Polymers 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- DYKFCLLONBREIL-KVUCHLLUSA-N minocycline Chemical compound C([C@H]1C2)C3=C(N(C)C)C=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O DYKFCLLONBREIL-KVUCHLLUSA-N 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 238000013268 sustained release Methods 0.000 claims 1
- 239000012730 sustained-release form Substances 0.000 claims 1
- 239000004098 Tetracycline Substances 0.000 description 15
- 235000019364 tetracycline Nutrition 0.000 description 15
- 150000003522 tetracyclines Chemical class 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 229960002180 tetracycline Drugs 0.000 description 9
- 229930101283 tetracycline Natural products 0.000 description 9
- 239000000047 product Substances 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- 230000000844 anti-bacterial effect Effects 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 229940040944 tetracyclines Drugs 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- XIYOPDCBBDCGOE-IWVLMIASSA-N (4s,4ar,5s,5ar,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methylidene-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C=C1C2=CC=CC(O)=C2C(O)=C2[C@@H]1[C@H](O)[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O XIYOPDCBBDCGOE-IWVLMIASSA-N 0.000 description 3
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 description 3
- FFTVPQUHLQBXQZ-KVUCHLLUSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O FFTVPQUHLQBXQZ-KVUCHLLUSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 229960003722 doxycycline Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000002386 leaching Methods 0.000 description 3
- 229940042016 methacycline Drugs 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- GUXHBMASAHGULD-SEYHBJAFSA-N (4s,4as,5as,6s,12ar)-7-chloro-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1([C@H]2O)=C(Cl)C=CC(O)=C1C(O)=C1[C@@H]2C[C@H]2[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]2(O)C1=O GUXHBMASAHGULD-SEYHBJAFSA-N 0.000 description 2
- DHPRQBPJLMKORJ-XRNKAMNCSA-N (4s,4as,5as,6s,12ar)-7-chloro-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC(Cl)=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O DHPRQBPJLMKORJ-XRNKAMNCSA-N 0.000 description 2
- FMTDIUIBLCQGJB-UHFFFAOYSA-N Demethylchlortetracyclin Natural products C1C2C(O)C3=C(Cl)C=CC(O)=C3C(=O)C2=C(O)C2(O)C1C(N(C)C)C(O)=C(C(N)=O)C2=O FMTDIUIBLCQGJB-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241000191967 Staphylococcus aureus Species 0.000 description 2
- KIPLYOUQVMMOHB-MXWBXKMOSA-L [Ca++].CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O.CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O Chemical compound [Ca++].CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O.CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O KIPLYOUQVMMOHB-MXWBXKMOSA-L 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 235000019365 chlortetracycline Nutrition 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229960002398 demeclocycline Drugs 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229940063650 terramycin Drugs 0.000 description 2
- 229940072172 tetracycline antibiotic Drugs 0.000 description 2
- WTJXVDPDEQKTCV-VQAITOIOSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide;hydrochloride Chemical compound Cl.C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O WTJXVDPDEQKTCV-VQAITOIOSA-N 0.000 description 1
- GNMCGMFNBARSIY-UHFFFAOYSA-N 1,2,3,4,4a,4b,5,6,7,8,8a,9,10,10a-tetradecahydrophenanthrene Chemical compound C1CCCC2C3CCCCC3CCC21 GNMCGMFNBARSIY-UHFFFAOYSA-N 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 241000186046 Actinomyces Species 0.000 description 1
- 241000304886 Bacilli Species 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000606153 Chlamydia trachomatis Species 0.000 description 1
- 241001478240 Coccus Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 229930195503 Fortimicin Natural products 0.000 description 1
- 206010018612 Gonorrhoea Diseases 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
- 239000004100 Oxytetracycline Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 241000202921 Ureaplasma urealyticum Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- BIDUPMYXGFNAEJ-APGVDKLISA-N astromicin Chemical compound O[C@@H]1[C@H](N(C)C(=O)CN)[C@@H](OC)[C@@H](O)[C@H](N)[C@H]1O[C@@H]1[C@H](N)CC[C@@H]([C@H](C)N)O1 BIDUPMYXGFNAEJ-APGVDKLISA-N 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229940038705 chlamydia trachomatis Drugs 0.000 description 1
- CYDMQBQPVICBEU-UHFFFAOYSA-N chlorotetracycline Natural products C1=CC(Cl)=C2C(O)(C)C3CC4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-UHFFFAOYSA-N 0.000 description 1
- 229960004475 chlortetracycline Drugs 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 238000005008 domestic process Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006749 inflammatory damage Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- VYQNWZOUAUKGHI-UHFFFAOYSA-N monobenzone Chemical compound C1=CC(O)=CC=C1OCC1=CC=CC=C1 VYQNWZOUAUKGHI-UHFFFAOYSA-N 0.000 description 1
- AIDQCFHFXWPAFG-UHFFFAOYSA-N n-formylformamide Chemical compound O=CNC=O AIDQCFHFXWPAFG-UHFFFAOYSA-N 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229960000625 oxytetracycline Drugs 0.000 description 1
- IWVCMVBTMGNXQD-PXOLEDIWSA-N oxytetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-PXOLEDIWSA-N 0.000 description 1
- 235000019366 oxytetracycline Nutrition 0.000 description 1
- 230000003239 periodontal effect Effects 0.000 description 1
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000005375 photometry Methods 0.000 description 1
- 238000011020 pilot scale process Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 229940102079 solodyn Drugs 0.000 description 1
- IWVCMVBTMGNXQD-UHFFFAOYSA-N terramycin dehydrate Natural products C1=CC=C2C(O)(C)C3C(O)C4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/33—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using ultraviolet light
Abstract
The present invention provides a kind of minocycline hydrochloride sustained release tablet In Vitro Dissolution assay method, includes the following steps:The preparation of step 1 dissolution medium：Solution 1 is 500mL0.05N HCl；Adjust the adjusting solution that solution is 12 hypophosphite monohydrate trisodiums and anhydrous sodium acetate mixes；Solution 2 is the final solution for the 900ml that 500mL0.05N HCl and 400ml adjust solution mixing；The preparation of step 2 test solution：It is prepared by step 3 reference substance solution：His reference substance of minocycline hydrochloride sustained release tablet body is taken, the reference substance solution of 12~17 μ g of 1mL minocycline hydrochloride sustained release tablets body is diluted to final solution；Step 4 measures：Above-mentioned control and test solution are taken, according to ultraviolet spectrophotometry (Chinese Pharmacopoeia 2015 editions, two annex IVA), absorbance is surveyed respectively at 348nm wavelength, by external standard method, calculates the stripping quantity of piece.
Description
Technical field
The present invention relates to tablet dissolution assay method technical field more particularly to a kind of minocycline hydrochloride sustained release tablet are external
Dissolve out assay method.
Background technology
This product is semi-synthetic Tetracyclines broad-spectrum antibiotic, has efficient and long-term effect, in tetracycline antibiotics, this product
Antibacterial action it is most strong, antimicrobial spectrum is close with tetracycline.Include the staphylococcus aureus of resistance to tetracycline, chain to gram positive bacteria
The resistance to plucked instrument bacterium of gonorrhoea in coccus etc. and gram-negative bacteria has very strong effect；It is generally weaker to the effect of gram negative bacilli；
This product also has good inhibiting effect to chlamydia trachomatis and ureaplasma urealyticum.
The mechanism of action of this product is combined with the location A of ribosomes 30S subunits, and the extension of peptide chain is prevented, to inhibit thin
The protein of bacterium or other pathogenic microorganisms synthesizes.This strain bacteriostatic, but at high concentrations, it may have bactericidal effect.This class
The basic framework of perhydrophenanthrene is all had in the chemical constitution of drug, for acid, alkali amphiprotic substance, is relatively stablized in an acidic solution, in alkali
Property solution in destructible, clinic generally with its hydrochloride.
Tetracycline, terramycin (oxytetracycline), aureomycin (duomycin) and demeclocycline (demethylchlortetra cylinum) belong to natural
Tetracyclines.Metacycline (methacycline), Doxycycline (fortimicin, doxycycline) and minocycline (dimethylamine
Tetracycline) belong to semi-synthetic Tetracyclines.The antimicrobial spectrum of this class drug, antibacterial action mechanism and clinical application are more similar.Drug
Antibacterial activity be：Minocycline>Doxycycline>Metacycline>Demeclocycline>Tetracycline>Terramycin.
Minocycline hydrochloride (Minocycline Hydrochloride) is semi-synthetic tetracycline medication also known as diformazan
Amine tetracycline, the medicine are modified on the basis of tetracycline chemical structure on 6,7 side chains, are constituted the bis- formyl ammonia -6- of 7- and are gone
- 6 deoxytetra cycline of methyl.
Minocycline category wide spectrum class antibiotic, it is effective to sensitive tetracycline or drug resistant staphylococcus aureus；To green
The effect of color staphylococcus, star actinomyces, Diplococcus pneumopniae and bacteria-like organism, Neisseria gonorrheae is than other tetracyclines
Class is slightly strong, to Escherichia coli, proteus, salmonella, Shiga bacillus, klebsiella, Pseudomonas alba antibacterial
Intensity is close with Tetracyclines.
Commonly use its hydrochloride, be yellow crystalline powder, odorless, bitter, have draw it is moist, meet light can cause to go bad.Dissolving
Yu Shui is slightly soluble in ethyl alcohol, is soluble in the hydroxide or carbonate solution of alkali metal.For semi-synthetic Tetracyclines antibiosis
Element.Under dry pulverulence, room temperature (25 DEG C) can store 3-4 without changing.
Minocycline hydrochloride is the tetracycline antibiotics of new generation researched and developed by Lederle companies of the U.S. earliest, and in 20
Century 70 puts into world antibacterials market.In May, 2006, Medicis companies obtained hydrochloric acid minot ring in FDA for the first time
The approval of plain sustained release preparation, trade name Solodyn, specification 45mg, 90mg and 135mg suffer from for treating 12 years old or more
To the inflammatory damage caused by severe acne vulgaris in the non-nodular of person.
FDA has approved its 65mg and 115mg list marketings again within 2009.Specification：45mg、55mg、65mg、80mg、90mg、
105mg、115mg、135mg.After most of oral solid formulations need to reach through absorbed into serum upon administration certain blood concentration
Could work, so the dissolution or release of preparation are to influence the key factor that absorbs in vivo of drug, solid pharmaceutical preparation it is external molten
Trip is that can be used as one of quality of the pharmaceutical preparations evaluation index.Therefore, a kind of rational dissolution determination method, science visitor need to be established
The quality of the reaction oral solid formulation of sight, while should have and distinguish different compositions, the quality of Different Preparation sample
Difference.
This product country has tablet, capsule, granule, ointment and periodontal dosage form list marketing, and FDA successively ratifies
This product sustained release tablets and spansule list marketing, and the domestic method for having no corresponding this product dynamic regulation dissolving-out method.
Invention content
(1) technical problems to be solved
The problem to be solved in the present invention is to provide a kind of minocycline hydrochloride sustained release tablet In Vitro Dissolution assay method, to overcome
It needs to establish a kind of rational dissolution determination method in the prior art, science objectively reacts the quality of oral solid formulation, together
When should have and distinguish different compositions, the defect of the quality difference of Different Preparation sample.
(2) technical solution
To solve the technical problem, the present invention provides a kind of minocycline hydrochloride sustained release tablet In Vitro Dissolution assay method,
Include the following steps:
The preparation of step 1 dissolution medium：Solution 1 is 500mL0.05N HCl；
Adjust the adjusting solution that solution is 12 hypophosphite monohydrate trisodiums and anhydrous sodium acetate mixes；
Solution 2 is the final solution for the 900ml that 500mL0.05N HCl and 400ml adjust solution mixing；
The preparation of step 2 test solution：According to dissolution method (two annex XC second of Chinese Pharmacopoeia version in 2015
Method), it is first dissolution medium with solution 1, rotating speed is 50~75 turns, operates in accordance with the law, takes 8mL dissolution fluids respectively through 25,41min, together
When into stripping rotor supplement equality of temperature same volume solution 1, dissolution fluid taken after 0.45 μm of filtering with microporous membrane subsequent filtrate as supply
Test sample solution；Add the 400mL of equality of temperature to adjust solution into stripping rotor using peristaltic pump after 41min, all adds in 29min
Enter, be able to solution 2 be dissolution medium, adjust the position of sampling probe, operate in accordance with the law, through 70min, 120min, 150min,
180min, 240min, 300min, 420min, 480min take 8mL dissolution fluids respectively, while equality of temperature consubstantiality is supplemented into stripping rotor
Long-pending solution 2, dissolution fluid take subsequent filtrate as test solution after 0.45 μm of filtering with microporous membrane；
It is prepared by step 3 reference substance solution：His reference substance of minocycline hydrochloride sustained release tablet body is taken, is diluted to final solution
The reference substance solution of 12~17 μ g of 1mL minocycline hydrochloride sustained release tablets body；
Step 4 measures：Above-mentioned control and test solution are taken, according to ultraviolet spectrophotometry (Chinese Pharmacopoeia 2015 editions, two
Annex IVA), absorbance is surveyed respectively at 348nm wavelength, by external standard method, calculates the stripping quantity of piece.
Preferably, the dissolution medium is dynamic regulation solution.
Preferably, rotating speed is preferably 50 turns per minute in dissolution determination method.
Preferably, wherein, minocycline hydrochloride sustained release tablet body group becomes minocycline hydrochloride 13-34 parts by weight, Brazil
Palm wax 5-15 parts by weight, hydroxypropyl methylcellulose 5-15 parts by weight, lactose monohydrate 50-80 parts by weight, silica 0.5-1 weight
Part, magnesium stearate 0.5-1 parts by weight, coating powder 1-6 parts by weight.
Specific implementation mode
The following examples are described in further detail the specific implementation mode of the present invention.Following embodiment is for saying
The bright present invention, but it is not limited to the scope of the present invention.
A kind of minocycline hydrochloride sustained release tablet In Vitro Dissolution assay method of the present invention：With dynamic regulation solution (1 He of solution
Solution 2) it is dissolution medium, paddle method, rotating speed is 50~75rpm, and using ultraviolet spectrophotometry, trap is measured in 348nm,
In, solution 1:500mL initial solns (0.05N HCl solutions)；Adjust solution：12 hypophosphite monohydrate trisodiums and anhydrous sodium acetate are mixed
Close solution；Solution 2:(initial soln and 400ml of 500mL0.05N HCl solutions adjust the mixing of solution to 900mL final solutions
Solution)；It is that dissolution is situated between with the solution 1 of 500mL according to dissolution method (two the second methods of annex XC of Chinese Pharmacopoeia version in 2015)
Matter, rotating speed are 50~75 turns, are operated in accordance with the law, take 8mL dissolution fluids respectively through 25,41min, while supplement equality of temperature is same into stripping rotor
The solution 1 of volume, dissolution fluid take subsequent filtrate as test solution after 0.45 μm of filtering with microporous membrane.It is used after 41min
Peristaltic pump is into stripping rotor plus the 400mL of equality of temperature adjusts solution, is all added in 29min, and it is dissolution medium to be able to solution 2,
Adjust sampling probe position, operate in accordance with the law, through 70min, 120min, 150min, 180min, 240min, 300min, 420min,
480min takes 15mL dissolution fluids respectively, while the solution 2 of equality of temperature same volume is supplemented into stripping rotor, and dissolution fluid is through 0.45 μm of micropore
Take subsequent filtrate as test solution after membrane filtration.I compound control product of another modus ponens are diluted to 1mL with final solution and contain formula I
The reference substance solution of 12~17 μ g.Take above-mentioned control and test solution, according to ultraviolet spectrophotometry (Chinese Pharmacopoeia 2015 editions,
Two annex IVA), absorbance is surveyed respectively at 348nm wavelength, by external standard method, calculates the stripping quantity of piece.
The selection of dissolution medium
Experimental method：It is slow with the water of 900ml, 0.1mol/L hydrochloric acid, pH4.5 acetate buffers, pH6.8 phosphate respectively
Fliud flushing is dissolution medium, and according to dissolution method (two the second methods of annex XC of state's pharmacopeia version in 2015), rotating speed is per minute 50
Turn, operates in accordance with the law, take dissolution fluid 15mL, 0.45 μm of filtering with microporous membrane, fluid infusion that subsequent filtrate is taken to dilute respectively at 1,2,4,6,8h
Test solution is used as after 5 times；Separately match about 12~17 μ g/mL of working reference substance concentration, dissolution medium constant volume.According to UV, visible light point
Light photometry, measures the trap of test solution and reference substance solution at 348nm, and external standard method calculates the molten of different time points
Output.
Table 1 is four kinds of medium stripping curve results
Test result：Same batch of sample measures accumulation dissolution rate using four kinds of different dissolution mediums, the results showed that, chemical combination
Tablet prepared by object I dissolves out in four kinds of media, need to look for a dissolution medium curve with distinction again.We select one
The In Vitro Dissolution method of enteron aisle is moved to measure its stripping curve from gastric juice after item simulation minocycline hydrochloride sustained release tablet is oral.
The selection of rotating speed
It selects paddle method to carry out dissolution determination, and investigates the influence that different rotating speeds dissolve out chemical compounds I
Test method：Selection of speed 75rpm and 50rpm are first dissolution medium with 500mL solution 1, then with 900mL solution 2
For dissolution medium, remaining under [0017] item with reference to operating.
Influence of the 2 different rotating speeds condition of table to stripping curve
Test result：Compare under two kinds of speed conditions sample dissolution as a result, rotating speed is 50rpm, dissolution substantially completely, and with
There was no significant difference for result under the conditions of 75rpm, and preferably rotating speed is 50rpm.
Embodiment 1
Tablet format 55mg (100 lab scales)：
Each 6 of the reference preparation of the small test piece of two batches same specification (55mg) and same specification is taken, is first dissolution with 500mL solution 1
Medium, then with 900mL solution 2 be dissolution medium, remaining under [0017] item with reference to operating.
Influence 1 of the table 3 with leaching condition to different lab scale batch stripping curves
Test result：Under identical conditions, different batches are dissolved out without much variations, and 1 degree of fitting of preparation is some higher.
Embodiment 2
Tablet format 55mg (1000 pilot scales)：
Each 6 of test piece in two batches of same specifications (55mg) is taken, is dissolved out with reference to [0017] dissolving-out method, is obtained by external standard method
To accumulative releasing degree.
Influence 2 of the table 4 with leaching condition to different lab scale batch stripping curves
Test result：Under identical conditions, different batches are dissolved out without much variations, 3 degree of fitting higher of preparation.
Embodiment 3
Tablet format 55mg (10000 amplifications batch)：
Two batches of same specification (55mg) each 6 of pieces of amplification batch are taken, are dissolved out with reference to [0017] dissolving-out method, by external standard method
Obtain accumulative releasing degree.
Influence 3 of the table 5 with leaching condition to different lab scale batch stripping curves
Test result：Under identical conditions, different batches are dissolved out without much variations, and 6 degree of fitting higher of preparation.
In conclusion the above embodiment is not the restricted embodiment for being the present invention, all those skilled in the art
The modification carried out on the basis of the substantive content of the present invention or equivalent deformation, the technology scope in the present invention.
Claims (4)
1. a kind of minocycline hydrochloride sustained release tablet In Vitro Dissolution assay method, it is characterised in that：Include the following steps:
The preparation of step 1 dissolution medium：Solution 1 is 500mL0.05N HCl；
Adjust the adjusting solution that solution is 12 hypophosphite monohydrate trisodiums and anhydrous sodium acetate mixes；
Solution 2 is the final solution for the 900ml that 500mL0.05N HCl and 400ml adjust solution mixing；
The preparation of step 2 test solution：According to dissolution method (two the second methods of annex XC of Chinese Pharmacopoeia version in 2015), first
It is dissolution medium with solution 1, rotating speed is 50~75 turns, is operated in accordance with the law, and 8mL dissolution fluids are taken respectively through 25,41min, while to molten
Go out the solution 1 of supplement equality of temperature same volume in cup, dissolution fluid takes subsequent filtrate molten as test sample after 0.45 μm of filtering with microporous membrane
Liquid；Add the 400mL of equality of temperature to adjust solution into stripping rotor using peristaltic pump after 41min, is all added, is able in 29min
Solution 2 be dissolution medium, adjust the position of sampling probe, operate in accordance with the law, through 70min, 120min, 150min, 180min,
240min, 300min, 420min, 480min take 8mL dissolution fluids respectively, while the solution of equality of temperature same volume is supplemented into stripping rotor
2, dissolution fluid takes subsequent filtrate as test solution after 0.45 μm of filtering with microporous membrane；
It is prepared by step 3 reference substance solution：His reference substance of minocycline hydrochloride sustained release tablet body is taken, 1mL salt is diluted to final solution
The reference substance solution of 12~17 μ g of sour minocycline sustained release sheet body；
Step 4 measures：Above-mentioned control and test solution are taken, according to ultraviolet spectrophotometry (Chinese Pharmacopoeia 2015 editions, two annex
IVA), absorbance is surveyed respectively at 348nm wavelength, by external standard method, calculate the stripping quantity of piece.
2. minocycline hydrochloride sustained release tablet In Vitro Dissolution assay method according to claim 1, it is characterised in that：It is described molten
It is dynamic regulation solution to go out medium.
3. minocycline hydrochloride sustained release tablet In Vitro Dissolution assay method according to claim 1, it is characterised in that：Described step
Rotating speed is preferably 50 turns per minute in rapid 2 dissolution determination method.
4. minocycline hydrochloride sustained release tablet In Vitro Dissolution assay method according to claim 1, it is characterised in that：Wherein,
Minocycline hydrochloride sustained release tablet body group becomes minocycline hydrochloride 13-34 parts by weight, Brazil wax 5-15 parts by weight, hydroxypropyl first
Cellulose 5-15 parts by weight, lactose monohydrate 50-80 parts by weight, silica 0.5-1 parts by weight, magnesium stearate 0.5-1 parts by weight,
Coating powder 1-6 parts by weight.
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| CN113340833A (en) * | 2021-05-31 | 2021-09-03 | 珠海天凯生物科技有限公司 | Dissolution rate detection method of tannic acid particles |
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