ES2852899T3 - Formulaciones estabilizadas de molindona - Google Patents
Formulaciones estabilizadas de molindona Download PDFInfo
- Publication number
- ES2852899T3 ES2852899T3 ES19184602T ES19184602T ES2852899T3 ES 2852899 T3 ES2852899 T3 ES 2852899T3 ES 19184602 T ES19184602 T ES 19184602T ES 19184602 T ES19184602 T ES 19184602T ES 2852899 T3 ES2852899 T3 ES 2852899T3
- Authority
- ES
- Spain
- Prior art keywords
- acid
- formulation
- molindone
- cellulose
- release
- 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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- 239000000203 mixture Substances 0.000 title claims abstract description 125
- 238000009472 formulation Methods 0.000 title claims abstract description 105
- KLPWJLBORRMFGK-UHFFFAOYSA-N Molindone Chemical compound O=C1C=2C(CC)=C(C)NC=2CCC1CN1CCOCC1 KLPWJLBORRMFGK-UHFFFAOYSA-N 0.000 title claims abstract description 79
- 229960004938 molindone Drugs 0.000 title claims abstract description 75
- 239000012729 immediate-release (IR) formulation Substances 0.000 claims abstract description 37
- 229920000642 polymer Polymers 0.000 claims abstract description 35
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000008186 active pharmaceutical agent Substances 0.000 claims abstract description 20
- 239000003381 stabilizer Substances 0.000 claims abstract description 20
- 230000001419 dependent effect Effects 0.000 claims abstract description 18
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 claims abstract description 16
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000013265 extended release Methods 0.000 claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229920002301 cellulose acetate Polymers 0.000 claims abstract description 10
- 229920002125 Sokalan® Polymers 0.000 claims abstract description 9
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 8
- 235000002639 sodium chloride Nutrition 0.000 claims abstract description 8
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims abstract description 7
- 235000019325 ethyl cellulose Nutrition 0.000 claims abstract description 7
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000002535 acidifier Substances 0.000 claims abstract description 6
- 229960001631 carbomer Drugs 0.000 claims abstract description 6
- 230000003111 delayed effect Effects 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- 239000001856 Ethyl cellulose Substances 0.000 claims abstract description 5
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims abstract description 5
- TYVWBCMQECJNSK-UHFFFAOYSA-N [2-methyl-3-(2-methylprop-2-enoyloxy)butan-2-yl]azanium;chloride Chemical compound [Cl-].CC([NH3+])(C)C(C)OC(=O)C(C)=C TYVWBCMQECJNSK-UHFFFAOYSA-N 0.000 claims abstract description 5
- 235000010443 alginic acid Nutrition 0.000 claims abstract description 5
- 239000000783 alginic acid Substances 0.000 claims abstract description 5
- 229920000615 alginic acid Polymers 0.000 claims abstract description 5
- 229960001126 alginic acid Drugs 0.000 claims abstract description 5
- 150000004781 alginic acids Chemical class 0.000 claims abstract description 5
- 229920006217 cellulose acetate butyrate Polymers 0.000 claims abstract description 5
- 229920001577 copolymer Polymers 0.000 claims abstract description 5
- 229920001249 ethyl cellulose Polymers 0.000 claims abstract description 5
- 229920001519 homopolymer Polymers 0.000 claims abstract description 5
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 5
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract description 5
- 229960003943 hypromellose Drugs 0.000 claims abstract description 4
- 239000011118 polyvinyl acetate Substances 0.000 claims abstract description 4
- 229920002689 polyvinyl acetate Polymers 0.000 claims abstract description 4
- 241000416162 Astragalus gummifer Species 0.000 claims abstract description 3
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims abstract description 3
- 229920008347 Cellulose acetate propionate Polymers 0.000 claims abstract description 3
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims abstract description 3
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims abstract description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims abstract description 3
- 235000010643 Leucaena leucocephala Nutrition 0.000 claims abstract description 3
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 claims abstract description 3
- 229920001615 Tragacanth Polymers 0.000 claims abstract description 3
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims abstract description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 claims abstract description 3
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims abstract description 3
- 235000010418 carrageenan Nutrition 0.000 claims abstract description 3
- 229920001525 carrageenan Polymers 0.000 claims abstract description 3
- 239000000679 carrageenan Substances 0.000 claims abstract description 3
- 229940113118 carrageenan Drugs 0.000 claims abstract description 3
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims abstract description 3
- 229940071826 hydroxyethyl cellulose Drugs 0.000 claims abstract description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims abstract description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims abstract description 3
- 229920000609 methyl cellulose Polymers 0.000 claims abstract description 3
- 235000010981 methylcellulose Nutrition 0.000 claims abstract description 3
- 239000001923 methylcellulose Substances 0.000 claims abstract description 3
- 229920002451 polyvinyl alcohol Polymers 0.000 claims abstract description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 3
- 229940069328 povidone Drugs 0.000 claims abstract description 3
- 235000010487 tragacanth Nutrition 0.000 claims abstract description 3
- 239000000196 tragacanth Substances 0.000 claims abstract description 3
- 229940116362 tragacanth Drugs 0.000 claims abstract description 3
- 229920001285 xanthan gum Polymers 0.000 claims abstract description 3
- 235000010493 xanthan gum Nutrition 0.000 claims abstract description 3
- 239000000230 xanthan gum Substances 0.000 claims abstract description 3
- 229940082509 xanthan gum Drugs 0.000 claims abstract description 3
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims abstract description 3
- 239000004569 hydrophobicizing agent Substances 0.000 claims abstract 4
- JUZXDNPBRPUIOR-UHFFFAOYSA-N chlormequat Chemical compound C[N+](C)(C)CCCl JUZXDNPBRPUIOR-UHFFFAOYSA-N 0.000 claims abstract 2
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 24
- 239000002775 capsule Substances 0.000 claims description 18
- 230000003204 osmotic effect Effects 0.000 claims description 17
- 239000011159 matrix material Substances 0.000 claims description 16
- 239000002552 dosage form Substances 0.000 claims description 13
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 claims description 12
- 239000008187 granular material Substances 0.000 claims description 11
- 239000000843 powder Substances 0.000 claims description 10
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 8
- 208000027691 Conduct disease Diseases 0.000 claims description 7
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 7
- 206010001488 Aggression Diseases 0.000 claims description 6
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 6
- 230000016571 aggressive behavior Effects 0.000 claims description 6
- FETSQPAGYOVAQU-UHFFFAOYSA-N glyceryl palmitostearate Chemical compound OCC(O)CO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O FETSQPAGYOVAQU-UHFFFAOYSA-N 0.000 claims description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 6
- 229920003145 methacrylic acid copolymer Polymers 0.000 claims description 6
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 6
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 5
- 229940046813 glyceryl palmitostearate Drugs 0.000 claims description 5
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 4
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 claims description 4
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-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
- DLRVVLDZNNYCBX-UHFFFAOYSA-N Polydextrose Polymers OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(O)O1 DLRVVLDZNNYCBX-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 claims description 4
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 4
- 229940049654 glyceryl behenate Drugs 0.000 claims description 4
- 239000008172 hydrogenated vegetable oil Substances 0.000 claims description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000001630 malic acid Substances 0.000 claims description 4
- 235000011090 malic acid Nutrition 0.000 claims description 4
- 229940099690 malic acid Drugs 0.000 claims description 4
- 239000001993 wax Substances 0.000 claims description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 3
- 235000021355 Stearic acid Nutrition 0.000 claims description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 3
- 235000010323 ascorbic acid Nutrition 0.000 claims description 3
- 229960005070 ascorbic acid Drugs 0.000 claims description 3
- 239000011668 ascorbic acid Substances 0.000 claims description 3
- 239000011324 bead Substances 0.000 claims description 3
- 235000015165 citric acid Nutrition 0.000 claims description 3
- 235000019359 magnesium stearate Nutrition 0.000 claims description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 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
- 239000008117 stearic acid Substances 0.000 claims description 3
- 229960004274 stearic acid Drugs 0.000 claims description 3
- 238000013268 sustained release Methods 0.000 claims description 3
- 239000012730 sustained-release form Substances 0.000 claims description 3
- 239000011975 tartaric acid Substances 0.000 claims description 3
- 235000002906 tartaric acid Nutrition 0.000 claims description 3
- 229960001367 tartaric acid Drugs 0.000 claims description 3
- 244000215068 Acacia senegal Species 0.000 claims description 2
- WZUKKIPWIPZMAS-UHFFFAOYSA-K Ammonium alum Chemical compound [NH4+].O.O.O.O.O.O.O.O.O.O.O.O.[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O WZUKKIPWIPZMAS-UHFFFAOYSA-K 0.000 claims description 2
- CIWBSHSKHKDKBQ-DUZGATOHSA-N D-araboascorbic acid Natural products OC[C@@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-DUZGATOHSA-N 0.000 claims description 2
- SHWNNYZBHZIQQV-UHFFFAOYSA-J EDTA monocalcium diisodium salt Chemical compound [Na+].[Na+].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O SHWNNYZBHZIQQV-UHFFFAOYSA-J 0.000 claims description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 2
- 229920000084 Gum arabic Polymers 0.000 claims description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 2
- 240000007472 Leucaena leucocephala Species 0.000 claims description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- 229920000148 Polycarbophil calcium Polymers 0.000 claims description 2
- 229920001100 Polydextrose Polymers 0.000 claims description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 2
- 235000010489 acacia gum Nutrition 0.000 claims description 2
- 239000000205 acacia gum Substances 0.000 claims description 2
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 2
- 235000011037 adipic acid Nutrition 0.000 claims description 2
- 239000001361 adipic acid Substances 0.000 claims description 2
- 229960000250 adipic acid Drugs 0.000 claims description 2
- 235000011124 aluminium ammonium sulphate Nutrition 0.000 claims description 2
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- DIZPMCHEQGEION-UHFFFAOYSA-H aluminium sulfate (anhydrous) Chemical compound [Al+3].[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O DIZPMCHEQGEION-UHFFFAOYSA-H 0.000 claims description 2
- 235000019270 ammonium chloride Nutrition 0.000 claims description 2
- 235000003704 aspartic acid Nutrition 0.000 claims description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 2
- 239000008298 dragée Substances 0.000 claims description 2
- 229960001484 edetic acid Drugs 0.000 claims description 2
- 235000010350 erythorbic acid Nutrition 0.000 claims description 2
- 239000004318 erythorbic acid Substances 0.000 claims description 2
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims description 2
- 239000001530 fumaric acid Substances 0.000 claims description 2
- 235000011087 fumaric acid Nutrition 0.000 claims description 2
- 239000004220 glutamic acid Substances 0.000 claims description 2
- 235000013922 glutamic acid Nutrition 0.000 claims description 2
- 229940075529 glyceryl stearate Drugs 0.000 claims description 2
- 235000011167 hydrochloric acid Nutrition 0.000 claims description 2
- 239000003456 ion exchange resin Substances 0.000 claims description 2
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 2
- 229940026239 isoascorbic acid Drugs 0.000 claims description 2
- 239000004310 lactic acid Substances 0.000 claims description 2
- 235000014655 lactic acid Nutrition 0.000 claims description 2
- 229940057948 magnesium stearate Drugs 0.000 claims description 2
- 239000011976 maleic acid Substances 0.000 claims description 2
- 229940111688 monobasic potassium phosphate Drugs 0.000 claims description 2
- 229940045641 monobasic sodium phosphate Drugs 0.000 claims description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 claims description 2
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 2
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 235000013856 polydextrose Nutrition 0.000 claims description 2
- 239000001259 polydextrose Substances 0.000 claims description 2
- 229940035035 polydextrose Drugs 0.000 claims description 2
- GRLPQNLYRHEGIJ-UHFFFAOYSA-J potassium aluminium sulfate Chemical compound [Al+3].[K+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O GRLPQNLYRHEGIJ-UHFFFAOYSA-J 0.000 claims description 2
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 claims description 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 2
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 2
- 229940001584 sodium metabisulfite Drugs 0.000 claims description 2
- 235000010262 sodium metabisulphite Nutrition 0.000 claims description 2
- 239000008109 sodium starch glycolate Substances 0.000 claims description 2
- 229940079832 sodium starch glycolate Drugs 0.000 claims description 2
- 229920003109 sodium starch glycolate Polymers 0.000 claims description 2
- 235000010199 sorbic acid Nutrition 0.000 claims description 2
- 239000004334 sorbic acid Substances 0.000 claims description 2
- 229940075582 sorbic acid Drugs 0.000 claims description 2
- 235000011044 succinic acid Nutrition 0.000 claims description 2
- 239000004246 zinc acetate Substances 0.000 claims description 2
- 229960000314 zinc acetate Drugs 0.000 claims description 2
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 claims description 2
- 229960001763 zinc sulfate Drugs 0.000 claims description 2
- 229910000368 zinc sulfate Inorganic materials 0.000 claims description 2
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims 1
- 229960005261 aspartic acid Drugs 0.000 claims 1
- 229960004106 citric acid Drugs 0.000 claims 1
- 229960002598 fumaric acid Drugs 0.000 claims 1
- 229960002989 glutamic acid Drugs 0.000 claims 1
- 229960000443 hydrochloric acid Drugs 0.000 claims 1
- 229960000448 lactic acid Drugs 0.000 claims 1
- 229940098895 maleic acid Drugs 0.000 claims 1
- 235000012431 wafers Nutrition 0.000 claims 1
- 241000220479 Acacia Species 0.000 abstract 1
- 239000003826 tablet Substances 0.000 description 81
- 239000003814 drug Substances 0.000 description 43
- 229940079593 drug Drugs 0.000 description 36
- 239000000546 pharmaceutical excipient Substances 0.000 description 31
- 229960004684 molindone hydrochloride Drugs 0.000 description 22
- 239000011248 coating agent Substances 0.000 description 20
- 238000000576 coating method Methods 0.000 description 20
- 239000002245 particle Substances 0.000 description 20
- GQWNECFJGBQMBO-UHFFFAOYSA-N Molindone hydrochloride Chemical compound Cl.O=C1C=2C(CC)=C(C)NC=2CCC1CN1CCOCC1 GQWNECFJGBQMBO-UHFFFAOYSA-N 0.000 description 18
- 230000002378 acidificating effect Effects 0.000 description 15
- 238000007906 compression Methods 0.000 description 15
- 230000006835 compression Effects 0.000 description 15
- 229940088679 drug related substance Drugs 0.000 description 14
- 229920002678 cellulose Polymers 0.000 description 12
- 238000011282 treatment Methods 0.000 description 12
- 239000012528 membrane Substances 0.000 description 10
- -1 sphere Substances 0.000 description 10
- 239000007916 tablet composition Substances 0.000 description 9
- 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 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 230000000087 stabilizing effect Effects 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 229920003139 Eudragit® L 100 Polymers 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 235000010980 cellulose Nutrition 0.000 description 6
- 239000001913 cellulose Substances 0.000 description 6
- 239000012943 hotmelt Substances 0.000 description 6
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Landscapes
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| US28278710P | 2010-03-31 | 2010-03-31 |
Publications (1)
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| ES2852899T3 true ES2852899T3 (es) | 2021-09-14 |
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| EP3572074B1 (en) * | 2010-03-31 | 2021-01-06 | Supernus Pharmaceuticals, Inc. | Stabilized formulations of molindone |
| EP3524251A1 (en) * | 2012-11-13 | 2019-08-14 | Supernus Pharmaceuticals, Inc. | Method of treatment of aggression |
| CA3022339A1 (en) * | 2016-04-29 | 2017-11-02 | Supernus Pharmaceuticals, Inc. | Methods, system, and kit for monitoring, diagnosing, and treating impulsive aggression |
| US20180078516A1 (en) * | 2016-09-19 | 2018-03-22 | Innovazone Labs LLC | Pharmaceutical Composition of Ibuprofen Sodium for Oral Administration |
| WO2019014201A1 (en) * | 2017-07-10 | 2019-01-17 | Apicore Us Llc | MOLINDONE COMPOSITIONS WITH EXTENDED RELEASE |
| EP4212149A1 (en) | 2022-01-18 | 2023-07-19 | Rijksuniversiteit Groningen | Oral dosage forms of acid-labile salt and methods and uses related thereto |
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| US20090208579A1 (en) * | 2004-12-27 | 2009-08-20 | Eisai R & D Management Co., Ltd. | Matrix Type Sustained-Release Preparation Containing Basic Drug or Salt Thereof, and Method for Manufacturing the Same |
| FR2891459B1 (fr) * | 2005-09-30 | 2007-12-28 | Flamel Technologies Sa | Microparticules a liberation modifiee d'au moins un principe actif et forme galenique orale en comprenant |
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| SE536078C2 (sv) | 2010-10-09 | 2013-04-30 | Core Link Ab | Anordning för bearbetning av hylsor |
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