LV13114B - Wet granulation formulation for bisphosphonic acids - Google Patents
Wet granulation formulation for bisphosphonic acids Download PDFInfo
- Publication number
- LV13114B LV13114B LVP-03-109A LV030109A LV13114B LV 13114 B LV13114 B LV 13114B LV 030109 A LV030109 A LV 030109A LV 13114 B LV13114 B LV 13114B
- Authority
- LV
- Latvia
- Prior art keywords
- bisphosphonic acid
- amino
- hydroxybutylidene
- minutes
- mixture
- Prior art date
Links
- 239000002253 acid Substances 0.000 title claims abstract description 109
- 239000000203 mixture Substances 0.000 title claims abstract description 72
- 238000005550 wet granulation Methods 0.000 title claims abstract description 16
- 150000007513 acids Chemical class 0.000 title abstract description 11
- 238000009472 formulation Methods 0.000 title description 12
- 238000000034 method Methods 0.000 claims abstract description 61
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
- 239000011230 binding agent Substances 0.000 claims abstract description 18
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 60
- 239000008187 granular material Substances 0.000 claims description 54
- 239000004480 active ingredient Substances 0.000 claims description 38
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 38
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 37
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 37
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 37
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical group O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 36
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 36
- 238000002156 mixing Methods 0.000 claims description 36
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 33
- 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 33
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 33
- 235000019359 magnesium stearate Nutrition 0.000 claims description 30
- 238000001035 drying Methods 0.000 claims description 25
- 239000000314 lubricant Substances 0.000 claims description 23
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 21
- 229960001375 lactose Drugs 0.000 claims description 20
- 239000008101 lactose Substances 0.000 claims description 20
- 229960004977 anhydrous lactose Drugs 0.000 claims description 18
- -1 N, N-dimethylamino Chemical group 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 239000003085 diluting agent Substances 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 15
- 239000000843 powder Substances 0.000 claims description 13
- CAKRAHQRJGUPIG-UHFFFAOYSA-M sodium;[4-azaniumyl-1-hydroxy-1-[hydroxy(oxido)phosphoryl]butyl]-hydroxyphosphinate Chemical group [Na+].NCCCC(O)(P(O)(O)=O)P(O)([O-])=O CAKRAHQRJGUPIG-UHFFFAOYSA-M 0.000 claims description 11
- 239000008202 granule composition Substances 0.000 claims description 9
- 239000001913 cellulose Substances 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 6
- 229920000881 Modified starch Polymers 0.000 claims description 5
- 235000010980 cellulose Nutrition 0.000 claims description 5
- 229920002678 cellulose Polymers 0.000 claims description 5
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 229920002472 Starch Polymers 0.000 claims description 4
- 239000001506 calcium phosphate Substances 0.000 claims description 4
- 229960001714 calcium phosphate Drugs 0.000 claims description 4
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 4
- 235000011010 calcium phosphates Nutrition 0.000 claims description 4
- 238000005469 granulation Methods 0.000 claims description 4
- 230000003179 granulation Effects 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000000454 talc Substances 0.000 claims description 4
- 229910052623 talc Inorganic materials 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 3
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 claims description 3
- 235000021355 Stearic acid Nutrition 0.000 claims description 3
- 239000008116 calcium stearate Substances 0.000 claims description 3
- 235000013539 calcium stearate Nutrition 0.000 claims description 3
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- 235000019426 modified starch Nutrition 0.000 claims description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 3
- 229920000642 polymer Polymers 0.000 claims description 3
- 235000019814 powdered cellulose Nutrition 0.000 claims description 3
- BTURAGWYSMTVOW-UHFFFAOYSA-M sodium dodecanoate Chemical compound [Na+].CCCCCCCCCCCC([O-])=O BTURAGWYSMTVOW-UHFFFAOYSA-M 0.000 claims description 3
- 229940082004 sodium laurate Drugs 0.000 claims description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 3
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 3
- DAJSVUQLFFJUSX-UHFFFAOYSA-M sodium;dodecane-1-sulfonate Chemical compound [Na+].CCCCCCCCCCCCS([O-])(=O)=O DAJSVUQLFFJUSX-UHFFFAOYSA-M 0.000 claims description 3
- 239000008107 starch Substances 0.000 claims description 3
- 235000019698 starch Nutrition 0.000 claims description 3
- 239000008117 stearic acid Substances 0.000 claims description 3
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 3
- 239000004368 Modified starch Substances 0.000 claims description 2
- 229960001855 mannitol Drugs 0.000 claims description 2
- 229920003124 powdered cellulose Polymers 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims 6
- 239000008188 pellet Substances 0.000 claims 4
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 claims 3
- 229960005168 croscarmellose Drugs 0.000 claims 3
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 claims 3
- 150000003053 piperidines Chemical class 0.000 claims 3
- 230000001050 lubricating effect Effects 0.000 claims 2
- 239000002245 particle Substances 0.000 claims 2
- 239000002516 radical scavenger Substances 0.000 claims 2
- 150000004684 trihydrates Chemical group 0.000 claims 2
- 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 1
- 238000010790 dilution Methods 0.000 claims 1
- 239000012895 dilution Substances 0.000 claims 1
- 238000010410 dusting Methods 0.000 claims 1
- NEMFQSKAPLGFIP-UHFFFAOYSA-N magnesiosodium Chemical compound [Na].[Mg] NEMFQSKAPLGFIP-UHFFFAOYSA-N 0.000 claims 1
- 238000003825 pressing Methods 0.000 claims 1
- 235000013772 propylene glycol Nutrition 0.000 claims 1
- 230000002685 pulmonary effect Effects 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 238000003860 storage Methods 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 10
- 238000002360 preparation method Methods 0.000 abstract description 7
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 abstract description 4
- 229910019142 PO4 Inorganic materials 0.000 abstract description 4
- 239000011575 calcium Substances 0.000 abstract description 4
- 229910052791 calcium Inorganic materials 0.000 abstract description 4
- 239000010452 phosphate Substances 0.000 abstract description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 abstract description 4
- 230000004060 metabolic process Effects 0.000 abstract description 3
- 230000006806 disease prevention Effects 0.000 abstract description 2
- 238000011282 treatment Methods 0.000 abstract description 2
- 239000007884 disintegrant Substances 0.000 description 22
- 239000012530 fluid Substances 0.000 description 10
- 201000010099 disease Diseases 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 7
- 238000003801 milling Methods 0.000 description 7
- 230000036515 potency Effects 0.000 description 7
- PAYGMRRPBHYIMA-UHFFFAOYSA-N sodium;trihydrate Chemical compound O.O.O.[Na] PAYGMRRPBHYIMA-UHFFFAOYSA-N 0.000 description 7
- 239000007916 tablet composition Substances 0.000 description 7
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- 208000006386 Bone Resorption Diseases 0.000 description 5
- 230000024279 bone resorption Effects 0.000 description 5
- 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 description 3
- 229960005069 calcium Drugs 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 206010007027 Calculus urinary Diseases 0.000 description 2
- 239000006057 Non-nutritive feed additive Substances 0.000 description 2
- CZYWHNTUXNGDGR-UHFFFAOYSA-L Pamidronate disodium Chemical compound O.O.O.O.O.[Na+].[Na+].NCCC(O)(P(O)([O-])=O)P(O)([O-])=O CZYWHNTUXNGDGR-UHFFFAOYSA-L 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 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 2
- 238000011321 prophylaxis Methods 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-UHFFFAOYSA-N 2-(hydroxymethyl)-6-[4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxane-3,4,5-triol Chemical group OCC1OC(OC2C(O)C(O)C(O)OC2CO)C(O)C(O)C1O GUBGYTABKSRVRQ-UHFFFAOYSA-N 0.000 description 1
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010065687 Bone loss Diseases 0.000 description 1
- 206010006811 Bursitis Diseases 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 239000004097 EU approved flavor enhancer Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000037848 Metastatic bone disease Diseases 0.000 description 1
- 208000010358 Myositis Ossificans Diseases 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 206010029148 Nephrolithiasis Diseases 0.000 description 1
- 206010029240 Neuritis Diseases 0.000 description 1
- 206010030247 Oestrogen deficiency Diseases 0.000 description 1
- 206010031240 Osteodystrophy Diseases 0.000 description 1
- 208000003076 Osteolysis Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical class [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 208000003217 Tetany Diseases 0.000 description 1
- 208000009911 Urinary Calculi Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229940064582 akten Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 230000003416 augmentation Effects 0.000 description 1
- 159000000007 calcium salts Chemical group 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 201000001883 cholelithiasis Diseases 0.000 description 1
- 239000007931 coated granule Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000019264 food flavour enhancer Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 1
- 208000029791 lytic metastatic bone lesion Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 230000036244 malformation Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- MBKDYNNUVRNNRF-UHFFFAOYSA-N medronic acid Chemical class OP(O)(=O)CP(O)(O)=O MBKDYNNUVRNNRF-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- SOBHUZYZLFQYFK-UHFFFAOYSA-K trisodium;hydroxy-[[phosphonatomethyl(phosphonomethyl)amino]methyl]phosphinate Chemical class [Na+].[Na+].[Na+].OP(O)(=O)CN(CP(O)([O-])=O)CP([O-])([O-])=O SOBHUZYZLFQYFK-UHFFFAOYSA-K 0.000 description 1
- 208000008281 urolithiasis Diseases 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Claims (21)
1 LV 13114 Izgudrojuma formula 1. Paņēmiens tabletes izgatavošanai, kurā aktīvais ingredients ir arī tabletes saistviela no rindas: 4-amino-1-hidroksibutilidēn-1,1-bisfosfonskābe; N-metil-4-amino-1-hidroksibutilidēn-1,1-bisfosfonskābe; 4-(N,N-dimetilamino)-1-hidroksibutilidēn-1,1-bisfosfonskābe; 3-amino-1-hidroksipropilidēn-1,1-bisfosfonskābe; 3- (N,N-dimetilamino)-1-hidroksipropilidēn-1,1-bisfosfonskābe; 1-hidroksi-3-(N-metil-N-pentilamino)propilidēn-1,1-bisfosfonskābe; 1 -hidroksi-2-(3-piridil)etilidēn-1,1 -bisfosfonskābe; 4- hidroksimetilēn-1,1-bisfosfonskābes piperidīna sāls vai tā farmaceitiski pieņemamā sāls; kas ietver šādus soļus: (1) aktīvā ingredienta un atšķaidītāja pulverveida maisījuma iegūšanu, (2) granulu iegūšanu, veicot ar ūdeni samitrināta pulverveida maisījuma mitro granulāciju, (3) granulu žāvēšanu ūdens aizvākšanai, (4) izžāvētā granulētā maisījuma presēšanu vēlamajā tablešu formā pie nosacījuma, ka tad, kad aktīvais ingredients ir ekvivalents 4-amino-1-hidroksibutilidēn-1,1-bisfosfonskābes 5 mg, atšķaidītājs ir bezūdens laktoze un mikrokristāliskā celuloze, un žāvēšana notiek žāvēšanas skapī ar piespiedu gaisa cirkulāciju, iegūtās granulas netiek sajauktas ar nātrija kroskarmelozi un magnija stearātu.
2. Paņēmiens pēc 1. punkta, kurā aktīvais ingredients ir 4-amino-1-hidroksibutilidēn-1,1-bisfosfonskābe.
3. Paņēmiens pēc 1. punkta, kurā aktīvais ingredients ir 4-amino-1-hidroksibutilidēn-1,1-bisfosfonskābes mononātrija sāls.
4. Paņēmiens pēc 1. punkta, kurā aktīvais ingredients ir 4-amino-1-hidroksibutilidēn-1,1-bisfosfonskābes mononātrija sāls trihidrāts.
5. Paņēmiens pēc jebkura no iepriekšējiem punktiem, kas ietver šādus solus: i (1) aktīvā ingredienta un atšķaidītāja pulverveida maisījuma veidošanu, maisot tos 3 līdz 25 minūtes planetārajā vai spēcīgas cirpes granulātorā, (2) granulu iegūšanu, veicot pulverveida maisījuma mitro granulāciju, pievienojot ūdeni un maisot 2 līdz 30 minūtes, 2 (3) 10 minūšu līdz 24 stundu ilgu granulu žāvēšanu ūdens aizvākšanai, izmantojot siltu gaisu, (4) sauso granulu drupināšanu līdz vienādam izmēram, (5) uzirdinātāja pievienošanu un 10 minūšu līdz 24 stundu ilgu, rūpīgu maisīšanu ar sadrupinātajām granulām, (6) uzirdinātāju saturošas smērvielas pievienošanu maisījumam un tā 30 sekunžu līdz 20 minūšu ilgu maisīšanu, un (7) sauso granulu maisījuma presēšanu vēlamajā tablešu formā.
6. Paņēmiens pēc 5. punkta, kurā atšķaidītājs ir ņemts no rindas: laktoze, mikrokristāliskā celuloze, kalcija fosfāts, mannīts, pulverveida celuloze un želatinizēta ciete.
7. Paņēmiens pēc 6. punkta, kurā šķīdinātājs ir laktoze un mikrokristāliskā celuloze.
8. Paņēmiens pēc 7. punkta, kurā laktoze ir nacionālās farmakopejas kvalitātes prasībām atbilstoša bezūdens laktoze, un mikrokristāliskā celuloze ir Avicel PH101.
9. Paņēmiens pēc 5. punkta, kurā uzirdinātājs ir ņemts no rindās: modificētā ciete, modificētais celulozes polimērs un nātrija kroskarmeloze vai to kombinācija.
10. Paņēmiens pēc 9. punkta, kurā uzirdinātājs ir nātrija kroskarmeloze.
11. Paņēmiens pēc 10. punkta, kurā uzirdinātājs ir nacionālās farmakopejas kvalitātes prasībām atbilstoša A tipa nātrija kroskarmeloze.
12. Paņēmiens pēc 5. punkta, kurā smērviela ir ņemta no rindas: magnija stearāts, kalcija stearāts, stearīnskābe, nātrija laurilsulfāts, propilēnglikols, nātrija dodekānsulfonāts, nātrija oleātsulfonāts, nātrija laurāts maisījumā ar stearātiem un talku un nātrija stearilfumarāts.
13. Paņēmiens pēc 12. punkta, kurā smērviela ir magnija stearāts.
14. Paņēmiens pēc 5. punkta, kas ietver šādus soļus: (1) 4-amino-1-hidroksibutilidēn-1,1-bisfosfonskābes, mikrokristāliskās celulozes un laktozes pulverveida maisījuma iegūšanu, maisot komponentus 3 līdz 5 minūtes spēcīgas cirpes granulātorā, (2) granulu iegūšanu, veicot pulverveida maisījuma mitro granulāciju, pievienojot ūdeni, un maisot 2 līdz 5 minūtes spēcīgas cirpes granulātorā, (3) granulu žāvēšanu ūdens aizvākšanai, no 10 minūtēm līdz 1 stundai, izmantojot siltu gaisu pseidovirstošā slānī vai no 12 līdz 24 stundām, žāvējot uz paplātes, (4) sauso granulu drupināšanu līdz vienādam izmēram, izmantojot āmurtipa dzirnavas, (5) nacionālās farmakopejas kvalitātes prasībām atbilstošas A tipa nātrija kroskarmelozes uzirdinātāja pievienošanu un sastāva maisīšanu 3 līdz 8 minūtes, rūpīgu sajaucot ar sadrupinātajām granulām, 3 LV 13114 (6) nacionālās farmakopejas kvalitātes prasībām atbilstošas, A tipa nātrija kroskarmelozes uzirdinātāju saturošas magnija stearāta smērvielas pievienošanu maisījumam un 3 līdz 8 minūšu ilgu, rūpīgu maisīšanu lentes blenderī vai ar planetāro maisītāju, (7) smērvielu saturošā granulu maisījuma presēšanu vēlamajā tablešu formā, un (8) tablešu atputekļošanu un uzglabāšanu.
15. Paņēmiens pēc 5. punkta, kas ietver šādus soļus: (1) 4-amino-1-hidroksibutilidēn-1,1-bisfosfonskābes, mikrokristāliskās celulozes un laktozes pulverveida maisījuma iegūšanu, maisot komponentus 10 līdz 25 minūtes planetārajā granulātorā, (2) granulu iegūšanu, veicot pulverveida maisījuma mitro granulāciju, pievienojot ūdeni un 3 līdz 10 minūtes maisot planetārajā granulātorā. (3) granulu žāvēšanu ūdens aizvākšanai no 10 minūtēm līdz 1 stundai, izmantojot siltu gaisu pseidovirstošā slānī vai 12 līdz 24 stundas, žāvējot uz paplātes, (4) sauso granulu drupināšanu līdz vienādam izmēram, izmantojot āmurtipa dzirnavas, (5) nacionālās farmakopejas kvalitātes prasībām atbilstoša A tipa nātrija kroskarmelozes uzirdinātāja pievienošanu un 3 līdz 8 munūšu ilgu, rūpīgu maisīšanu ar sadrupinātajām daļiņām, (6) nacionālās farmakopejas kvalitātes prasībām atbilstošas, A tipa nātrija kroskarmelozes uzirdinātāju saturošas magnija stearāta smērvielas pievienošanu maisījumam un iegūtā maisījuma 3 līdz 8 minūšu ilgu, rūpīgu maisīšanu lentes blenderī vai ar planetāro maisītāju un (7) smērvielu saturošā granulu maisījuma presēšanu vēlamajā tablešu formā, un (8) tablešu atputekļošanu un glabāšanu.
16. Paņēmiens pēc 5. punkta, kas ietver šādus soļus: (1) 4-amino-1-hidroksibutilidēn-1,1-bisfosfonskābes, Avicel PH101 mikrokristāliskās celulozes un laktozes pulverveida maisījuma iegūšanu, maisot komponentus 3 līdz 5 minūtes spēcīgas cirpes granulātorā, (2) granulu iegūšanu, veicot pulverveida maisījuma mitro granulāciju, pievienojot ūdeni un 3 līdz 5 minūtes maisot to spēcīgas cirpes granulātorā, (3) 10 minūtes līdz 1 stundu ilgu granulu žāvēšanu ūdens aizvākšanai, izmantojot siltu gaisu pseidovirstošā slānī, (4) sauso granulu drupināšanu līdz vienādam izmēram, izmantojot āmurtipa dzirnavas, (5) nacionālās farmakopejas kvalitātes prasībām atbilstošas A tipa nātrija kroskarmelozes uzirdinātāja pievienošanu un 3 līdz 8 minūšu ilgu, rūpīgu maisīšanu ar sausām, sadrupinātām daļiņām, (6) nacionālās farmakopejas kvalitātes prasībām atbilstošu A tipa nātrija magnija kroskarmelozes uzirdinātāju saturošas stearāta smērvielas pievienošanu maisījumam un 3 līdz 8 minūšu ilgu, rūpīgu maisīšanu lentes blenderī un (7) smērvielu saturošā granulu maisījuma presēšanu vēlamajā tablešu formā, un 4 (8) tablešu atputekļošanu un glabāšana.
17. Cietā ārstnieciskā forma, kas ietver aktīvo ingredientu, kas ir ņemts no rindas: 4-amino-1 -hidroksibutilidēn-1,1 -bisfosfonskābe; N-metil-4-amino-1-hidroksibutilidēn-1,1-bisfosfonskābe; 4-(N,N-dimetilamino)-1 -hidroksibutilidēn-1,1-bisfosfonskābe; 3-amino-1-hidroksipropilidēn-1,1-bisfosfonskābe; 3- (N,N-dimetilamino)-1-hidroksipropilidēn-1,1-bisfosfonskābe; 1 -hidroksi-3-(N-metil-N-pentilamino)propilidēn-1,1 -bisfosfonskābe; 1-hidroksi-2-(3-piridil)etilidēn-1,1 -bisfosfonskābe; 4- hidroksimetilēn-1,1-bisfosfonskābes piperidīna sāls vai tā farmaceitiski pieņemama sāls; pie kam ārstnieciskā forma ir iegūta ar paņēmienu pēc jebkura no 1. līdz 16. punktam.
18. Farmaceitiskā kompozīcija, kas ir ar mitro granulāciju iegūta tablete, kas satur aktīvo gradientu, 0,5 līdz 25% no masas, kas reizē ir saistviela un ir ņemta no rindas: » 4-amino-1 -hidroksibutilidēn-1,1 -bisfosfonskābe; N-metil-4-amino-1 -hidroksibutilidēn-1,1 -bisfosfonskābe; 4-(N,N-dimetilamino)-1-hidroksibutilidēn-1,1-bisfosfonskābe; 3-amino-1-hidroksipropilidēn-1,1-bisfosfonskābe; 3- (N,N-dimetilamino)-1-hidroksipropilidēn-1,1-bisfosfonskābe; 1 -hidroksi-3-(N-metil-N-pentilamino)propilidēn-1,1 -bisfosfonskābe; 1-hidroksi-2-(3-piridil)etilidēn-1,1 -bisfosfonskābe; 4- hidroksimetilēn-1,1-bisfosfonskābes piperidīna sāls vai tā farmaceitiski pieņemama sāls; bezūdens laktozi vai viegli birstošu laktozes hidrātu, 30 līdz 70% no masas; mikrokristālisku celulozi, 30 līdz 50% no masas, un magnija stearātu, 0,1 līdz 2% no masas pie nosacījuma, ka kompozīcija papildus nesatur nātrija kroskarmelozi.
19. Farmaceitiskā kompozīcija pēc 17. vai 18. punkta, kurā aktīvais ingredients ir 4-amino-1 -hidroksibutilidēn-1,1 -bisfosfonskābe.
20. Farmaceitiskā kompozīcija pēc 17. vai 18. punkta, kurā aktīvais ingredients ir 4-amino-1-hidroksibutilidēn-1,1-bisfosfonskābes mononātrija sāls.
21. Farmaceitiskā kompozīcija pēc 17. vai 18. punkta, kurā aktīvais ingredients ir 4-amino-1-hidroksibutilidēn-1,1-bisfosfonskābes mononātrija sāls trihidrats.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23690494A | 1994-04-29 | 1994-04-29 |
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| Publication Number | Publication Date |
|---|---|
| LV13114B true LV13114B (en) | 2004-06-20 |
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ID=22891482
Family Applications (1)
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|---|---|---|---|
| LVP-03-109A LV13114B (en) | 1994-04-29 | 2003-10-08 | Wet granulation formulation for bisphosphonic acids |
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| EP (1) | EP0756484B1 (lv) |
| JP (1) | JP3838658B2 (lv) |
| KR (1) | KR100390719B1 (lv) |
| CN (2) | CN1147202A (lv) |
| AT (1) | ATE225661T1 (lv) |
| AU (1) | AU694217C (lv) |
| BG (1) | BG62878B1 (lv) |
| CA (1) | CA2188567C (lv) |
| CO (1) | CO4560546A1 (lv) |
| CZ (1) | CZ291574B6 (lv) |
| DE (1) | DE69528525T2 (lv) |
| DK (1) | DK0756484T3 (lv) |
| ES (1) | ES2183873T3 (lv) |
| FI (1) | FI118206B (lv) |
| HR (1) | HRP950261B1 (lv) |
| HU (1) | HUT76297A (lv) |
| IL (1) | IL113465A (lv) |
| LV (1) | LV13114B (lv) |
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| MY (1) | MY120491A (lv) |
| NO (1) | NO964567L (lv) |
| NZ (1) | NZ284719A (lv) |
| PL (1) | PL316987A1 (lv) |
| PT (1) | PT756484E (lv) |
| RU (1) | RU2149003C1 (lv) |
| SA (1) | SA95160013B1 (lv) |
| SK (1) | SK283785B6 (lv) |
| TW (1) | TW390813B (lv) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| DE19615812A1 (de) * | 1996-04-20 | 1997-10-23 | Boehringer Mannheim Gmbh | Pharmazeutische Zubereitung enthaltend Diphosphonsäuren zur oralen Applikation |
| DE19719680A1 (de) | 1997-05-09 | 1998-11-19 | Boehringer Mannheim Gmbh | Verwendung von Diphosphonsäuren zur präventiven Behandlung von Spätfolgen bei Harnblasenerweiterung oder Harnblasenersatz |
| CA2293815C (en) * | 1997-06-11 | 2004-06-29 | The Procter & Gamble Company | Film-coated tablet for improved upper gastrointestinal tract safety |
| IL121623A (en) | 1997-08-26 | 2000-06-29 | Unipharm Ltd | Process for the preparation of solid oral dosage forms comprising alendronic acid |
| GB9720061D0 (en) | 1997-09-19 | 1997-11-19 | Crosfield Joseph & Sons | Metal compounds as phosphate binders |
| EP0998933A1 (de) * | 1998-10-09 | 2000-05-10 | Boehringer Mannheim Gmbh | Verfahren zur Herstellung von bisphosphonathaltigen pharmazeutischen Zusammensetzungen zur oralen Applikation |
| EP0998932A1 (de) | 1998-10-09 | 2000-05-10 | Boehringer Mannheim Gmbh | Feste pharmazeutische Darreichungsform enthaltend Diphosphonsäure oder deren Salze und Verfahren zu ihrer Herstellung |
| GB9911926D0 (en) * | 1999-05-21 | 1999-07-21 | Okuno Tetsuji | Organic compounds |
| WO2000071104A2 (en) * | 1999-05-21 | 2000-11-30 | Novartis Ag | Use of bisphosphonic acids for treating angiogenesis |
| PL196485B1 (pl) * | 2000-05-11 | 2008-01-31 | Inst Farmaceutyczny | Stała doustna kompozycja farmaceutyczna zawierająca aminową pochodną kwasu bisfosfonowego i sposób jej wytwarzania |
| GB0029111D0 (en) * | 2000-11-29 | 2001-01-10 | Novartis Ag | Organic compounds |
| NZ535705A (en) | 2002-05-10 | 2007-08-31 | Hoffmann La Roche | Ibandronic acid for the treatment and prevention of osteoporosis |
| SG174628A1 (en) † | 2002-12-20 | 2011-10-28 | Hoffmann La Roche | High dose ibandronate formulation |
| RS20060009A (sr) * | 2003-07-11 | 2008-06-05 | F.Hoffmann-La Roche Ag., | Oralni oblik za doziranje sakvinavir mezilata |
| WO2007070843A2 (en) * | 2005-12-15 | 2007-06-21 | Acusphere, Inc. | Processes for making particle-based pharmaceutical formulations for oral administration |
| MY157620A (en) | 2006-01-31 | 2016-06-30 | Cytochroma Dev Inc | A granular material of a solid water-soluble mixed metal compound capable of binding phosphate |
| CN101489563A (zh) * | 2006-07-06 | 2009-07-22 | 拜耳先灵医药股份有限公司 | 用于避孕和预防先天性畸形风险的药物制剂 |
| GB0616794D0 (en) | 2006-08-24 | 2006-10-04 | Arrow Int Ltd | Solid dosage form |
| GB0714670D0 (en) | 2007-07-27 | 2007-09-05 | Ineos Healthcare Ltd | Use |
| GB0720220D0 (en) | 2007-10-16 | 2007-11-28 | Ineos Healthcare Ltd | Compound |
| GB0913525D0 (en) | 2009-08-03 | 2009-09-16 | Ineos Healthcare Ltd | Method |
| GB201001779D0 (en) | 2010-02-04 | 2010-03-24 | Ineos Healthcare Ltd | Composition |
| KR102622198B1 (ko) * | 2018-03-30 | 2024-01-09 | 한미약품 주식회사 | 빌다글립틴을 함유하는 경구용 고형제제 및 그의 제조 방법 |
| CN112972400A (zh) * | 2021-03-09 | 2021-06-18 | 华侨大学 | 可快速崩解的米诺膦酸颗粒及制备方法 |
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| DE2405254C2 (de) * | 1974-02-04 | 1982-05-27 | Henkel KGaA, 4000 Düsseldorf | Verwendung von 3-Amino-1-Hydroxypropan-1, 1-diphosphonsäure oder ihrer wasserlöslichen Salze bei der Beeinflußung von Calciumstoffwechselstörungen im menschlichen oder tierischen Körper |
| US4711886A (en) * | 1984-07-02 | 1987-12-08 | Merck & Co., Inc. | β-lactam derivatives as anti-inflammatory and antidegenerative agents |
| US4639338A (en) * | 1984-08-06 | 1987-01-27 | Ciba-Geigy Corporation | Preparation of crystalline disodium 3-amino-1-hydroxypropane-1,1-diphosphonate pentahydrate |
| DK126888A (da) * | 1987-03-10 | 1988-09-11 | Yamanouchi Pharma Co Ltd | Bisphosphonsyrederivater og terapeutiske praeparater indeholdende disse forbindelser |
| FR2629716B1 (fr) * | 1988-04-07 | 1991-07-19 | Sanofi Sa | Composition pharmaceutique pour administration orale a base d'un derive d'acide diphosphonique |
| PH27186A (en) * | 1989-09-07 | 1993-04-16 | Ciba Geigy Ag | Double-coated granules of disodium pamidronate |
| FI89366C (fi) * | 1990-12-20 | 1993-09-27 | Leiras Oy | Foerfarande foer framstaellning av nya farmakologiskt anvaendbara metylenbisfosfonsyraderivat |
| TW237386B (lv) * | 1992-04-15 | 1995-01-01 | Ciba Geigy | |
| SE501389C2 (sv) * | 1992-04-24 | 1995-01-30 | Leiras Oy | Farmaceutiskt preparat och förfarande för dess framställning |
| US5358941A (en) * | 1992-12-02 | 1994-10-25 | Merck & Co., Inc. | Dry mix formulation for bisphosphonic acids with lactose |
| FR2703590B1 (fr) * | 1993-04-05 | 1995-06-30 | Sanofi Elf | Utilisation de derives d'acide bisphosphonique pour la preparation de medicaments destines a favoriser la reparation osseuse . |
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|---|---|---|
| EP0756484B1 (en) | Wet granulation formulation for bisphosphonic acids | |
| RU2148405C1 (ru) | Способ получения таблеток, содержащих бисфосфоновые кислоты, твердая лекарственная форма и фармацевтическая композиция | |
| US6692764B2 (en) | Wet granulation formulation for bisphosphonic acids | |
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| HK1009246B (en) | Wet granulation formulation for bisphosphonic acids | |
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