NZ225058A - Drug dispenser containing discrete drug units - Google Patents
Drug dispenser containing discrete drug unitsInfo
- Publication number
- NZ225058A NZ225058A NZ225058A NZ22505888A NZ225058A NZ 225058 A NZ225058 A NZ 225058A NZ 225058 A NZ225058 A NZ 225058A NZ 22505888 A NZ22505888 A NZ 22505888A NZ 225058 A NZ225058 A NZ 225058A
- Authority
- NZ
- New Zealand
- Prior art keywords
- housing
- fluid
- dispenser according
- units
- drug
- Prior art date
Links
- 229940079593 drug Drugs 0.000 title claims description 89
- 239000003814 drug Substances 0.000 title claims description 89
- 239000012530 fluid Substances 0.000 claims description 70
- 239000000203 mixture Substances 0.000 claims description 43
- -1 antipreservatives Substances 0.000 claims description 33
- 239000000463 material Substances 0.000 claims description 26
- 230000003204 osmotic effect Effects 0.000 claims description 22
- 239000013543 active substance Substances 0.000 claims description 19
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 239000012528 membrane Substances 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 8
- 241001465754 Metazoa Species 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- 230000035558 fertility Effects 0.000 claims description 4
- 239000003619 algicide Substances 0.000 claims description 2
- 229940035676 analgesics Drugs 0.000 claims description 2
- 239000000730 antalgic agent Substances 0.000 claims description 2
- 230000000078 anti-malarial effect Effects 0.000 claims description 2
- 230000000845 anti-microbial effect Effects 0.000 claims description 2
- 229940125681 anticonvulsant agent Drugs 0.000 claims description 2
- 239000001961 anticonvulsive agent Substances 0.000 claims description 2
- 239000003472 antidiabetic agent Substances 0.000 claims description 2
- 239000003430 antimalarial agent Substances 0.000 claims description 2
- 229940033495 antimalarials Drugs 0.000 claims description 2
- 239000004599 antimicrobial Substances 0.000 claims description 2
- 239000003963 antioxidant agent Substances 0.000 claims description 2
- 235000006708 antioxidants Nutrition 0.000 claims description 2
- 239000000939 antiparkinson agent Substances 0.000 claims description 2
- 239000003139 biocide Substances 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 239000003433 contraceptive agent Substances 0.000 claims description 2
- 229940124558 contraceptive agent Drugs 0.000 claims description 2
- 239000002537 cosmetic Substances 0.000 claims description 2
- 239000000645 desinfectant Substances 0.000 claims description 2
- 229940039227 diagnostic agent Drugs 0.000 claims description 2
- 239000000032 diagnostic agent Substances 0.000 claims description 2
- 235000015872 dietary supplement Nutrition 0.000 claims description 2
- 238000006073 displacement reaction Methods 0.000 claims description 2
- 239000002934 diuretic Substances 0.000 claims description 2
- 229940030606 diuretics Drugs 0.000 claims description 2
- 239000003792 electrolyte Substances 0.000 claims description 2
- 238000000855 fermentation Methods 0.000 claims description 2
- 230000004151 fermentation Effects 0.000 claims description 2
- 235000013305 food Nutrition 0.000 claims description 2
- 239000000417 fungicide Substances 0.000 claims description 2
- 239000007952 growth promoter Substances 0.000 claims description 2
- 239000004009 herbicide Substances 0.000 claims description 2
- 229940125697 hormonal agent Drugs 0.000 claims description 2
- 229940126904 hypoglycaemic agent Drugs 0.000 claims description 2
- 230000002218 hypoglycaemic effect Effects 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 claims description 2
- 210000003205 muscle Anatomy 0.000 claims description 2
- 229940035363 muscle relaxants Drugs 0.000 claims description 2
- 239000003158 myorelaxant agent Substances 0.000 claims description 2
- 230000001613 neoplastic effect Effects 0.000 claims description 2
- 235000015097 nutrients Nutrition 0.000 claims description 2
- 239000000575 pesticide Substances 0.000 claims description 2
- 230000008635 plant growth Effects 0.000 claims description 2
- 239000002373 plant growth inhibitor Substances 0.000 claims description 2
- 239000003755 preservative agent Substances 0.000 claims description 2
- 230000003236 psychic effect Effects 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- 239000003128 rodenticide Substances 0.000 claims description 2
- 230000001954 sterilising effect Effects 0.000 claims description 2
- 238000004659 sterilization and disinfection Methods 0.000 claims description 2
- 239000003204 tranquilizing agent Substances 0.000 claims description 2
- 230000002936 tranquilizing effect Effects 0.000 claims description 2
- 239000011782 vitamin Substances 0.000 claims description 2
- 229940088594 vitamin Drugs 0.000 claims description 2
- 235000013343 vitamin Nutrition 0.000 claims description 2
- 229930003231 vitamin Natural products 0.000 claims description 2
- 229940035674 anesthetics Drugs 0.000 claims 1
- 239000002260 anti-inflammatory agent Substances 0.000 claims 1
- 229940121363 anti-inflammatory agent Drugs 0.000 claims 1
- 230000003110 anti-inflammatory effect Effects 0.000 claims 1
- 229940125688 antiparkinson agent Drugs 0.000 claims 1
- 239000003193 general anesthetic agent Substances 0.000 claims 1
- 239000003326 hypnotic agent Substances 0.000 claims 1
- 230000000147 hypnotic effect Effects 0.000 claims 1
- 230000000590 parasiticidal effect Effects 0.000 claims 1
- 239000002297 parasiticide Substances 0.000 claims 1
- 229940125723 sedative agent Drugs 0.000 claims 1
- 239000000932 sedative agent Substances 0.000 claims 1
- 229920000642 polymer Polymers 0.000 description 31
- 229920002678 cellulose Polymers 0.000 description 29
- 239000001913 cellulose Substances 0.000 description 27
- 239000007789 gas Substances 0.000 description 16
- 229920002301 cellulose acetate Polymers 0.000 description 15
- 239000013583 drug formulation Substances 0.000 description 12
- 239000000243 solution Substances 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 9
- 238000012377 drug delivery Methods 0.000 description 9
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 7
- 238000005192 partition Methods 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 239000004698 Polyethylene Substances 0.000 description 4
- 241000282849 Ruminantia Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 229920006217 cellulose acetate butyrate Polymers 0.000 description 4
- 229920001577 copolymer Polymers 0.000 description 4
- 229910052742 iron Inorganic materials 0.000 description 4
- 229920000573 polyethylene Polymers 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 229940022663 acetate Drugs 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- 235000010419 agar Nutrition 0.000 description 3
- 239000013060 biological fluid Substances 0.000 description 3
- 150000005690 diesters Chemical class 0.000 description 3
- 230000001747 exhibiting effect Effects 0.000 description 3
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 3
- 239000000017 hydrogel Substances 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical group O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000004014 plasticizer Substances 0.000 description 3
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 3
- 210000004767 rumen Anatomy 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 229920008347 Cellulose acetate propionate Polymers 0.000 description 2
- 229920001747 Cellulose diacetate Polymers 0.000 description 2
- DQEFEBPAPFSJLV-UHFFFAOYSA-N Cellulose propionate Chemical compound CCC(=O)OCC1OC(OC(=O)CC)C(OC(=O)CC)C(OC(=O)CC)C1OC1C(OC(=O)CC)C(OC(=O)CC)C(OC(=O)CC)C(COC(=O)CC)O1 DQEFEBPAPFSJLV-UHFFFAOYSA-N 0.000 description 2
- 229920002284 Cellulose triacetate Polymers 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- KCXZNSGUUQJJTR-UHFFFAOYSA-N Di-n-hexyl phthalate Chemical compound CCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCCCC KCXZNSGUUQJJTR-UHFFFAOYSA-N 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 229910000831 Steel Inorganic materials 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- NNLVGZFZQQXQNW-ADJNRHBOSA-N [(2r,3r,4s,5r,6s)-4,5-diacetyloxy-3-[(2s,3r,4s,5r,6r)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6s)-4,5,6-triacetyloxy-2-(acetyloxymethyl)oxan-3-yl]oxyoxan-2-yl]methyl acetate Chemical compound O([C@@H]1O[C@@H]([C@H]([C@H](OC(C)=O)[C@H]1OC(C)=O)O[C@H]1[C@@H]([C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](COC(C)=O)O1)OC(C)=O)COC(=O)C)[C@@H]1[C@@H](COC(C)=O)O[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O NNLVGZFZQQXQNW-ADJNRHBOSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000002009 allergenic effect Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229920006218 cellulose propionate Polymers 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 229920001971 elastomer Polymers 0.000 description 2
- 229960005309 estradiol Drugs 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 229920001477 hydrophilic polymer Polymers 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920002223 polystyrene Polymers 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 239000005060 rubber Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 1
- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 description 1
- BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- NVUUMOOKVFONOM-GPBSYSOESA-N 19-Norprogesterone Chemical compound C1CC2=CC(=O)CC[C@@H]2[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 NVUUMOOKVFONOM-GPBSYSOESA-N 0.000 description 1
- LYRSLMWAHYTKIG-UHFFFAOYSA-N 3-(1h-inden-1-yl)furan-2,5-dione Chemical compound O=C1OC(=O)C(C2C3=CC=CC=C3C=C2)=C1 LYRSLMWAHYTKIG-UHFFFAOYSA-N 0.000 description 1
- ZOLBALGTFCCTJF-UHFFFAOYSA-N 4-[1-hydroxy-2-(propan-2-ylamino)ethyl]benzene-1,2-diol;sulfuric acid Chemical compound OS(O)(=O)=O.CC(C)NCC(O)C1=CC=C(O)C(O)=C1.CC(C)NCC(O)C1=CC=C(O)C(O)=C1 ZOLBALGTFCCTJF-UHFFFAOYSA-N 0.000 description 1
- DMIMWGHYIPFAIF-UHFFFAOYSA-N 5-nitro-2-piperidin-1-ylaniline Chemical compound NC1=CC([N+]([O-])=O)=CC=C1N1CCCCC1 DMIMWGHYIPFAIF-UHFFFAOYSA-N 0.000 description 1
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
- QMNAQPMXDMLOLD-UHFFFAOYSA-N 6-methyl-4-oxo-5,6-dihydrothieno[2,3-b]thiopyran-2-sulfonamide Chemical compound S1C(C)CC(=O)C2=C1SC(S(N)(=O)=O)=C2 QMNAQPMXDMLOLD-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 229920002799 BoPET Polymers 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- QMBJSIBWORFWQT-DFXBJWIESA-N Chlormadinone acetate Chemical compound C1=C(Cl)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 QMBJSIBWORFWQT-DFXBJWIESA-N 0.000 description 1
- RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 1
- 239000005751 Copper oxide Substances 0.000 description 1
- ITRJWOMZKQRYTA-RFZYENFJSA-N Cortisone acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)CC2=O ITRJWOMZKQRYTA-RFZYENFJSA-N 0.000 description 1
- 241000938605 Crocodylia Species 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 244000303965 Cyamopsis psoralioides Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- 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 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 1
- ZVFDTKUVRCTHQE-UHFFFAOYSA-N Diisodecyl phthalate Chemical compound CC(C)CCCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCCCCCC(C)C ZVFDTKUVRCTHQE-UHFFFAOYSA-N 0.000 description 1
- JYGLAHSAISAEAL-UHFFFAOYSA-N Diphenadione Chemical compound O=C1C2=CC=CC=C2C(=O)C1C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 JYGLAHSAISAEAL-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- 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 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 208000006968 Helminthiasis Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
- BFSMWENDZZIWPW-UHFFFAOYSA-N Isopropamide iodide Chemical compound [I-].C=1C=CC=CC=1C(C(N)=O)(CC[N+](C)(C(C)C)C(C)C)C1=CC=CC=C1 BFSMWENDZZIWPW-UHFFFAOYSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- OCJYIGYOJCODJL-UHFFFAOYSA-N Meclizine Chemical compound CC1=CC=CC(CN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC(Cl)=CC=2)=C1 OCJYIGYOJCODJL-UHFFFAOYSA-N 0.000 description 1
- 229910000861 Mg alloy Inorganic materials 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 239000005041 Mylar™ Substances 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- ICTXHFFSOAJUMG-SLHNCBLASA-N Norethynodrel Chemical compound C1CC(=O)CC2=C1[C@H]1CC[C@](C)([C@](CC3)(O)C#C)[C@@H]3[C@@H]1CC2 ICTXHFFSOAJUMG-SLHNCBLASA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- VJNXVAVKCZJOFQ-UHFFFAOYSA-N Phenmetrazine hydrochloride Chemical compound Cl.CC1NCCOC1C1=CC=CC=C1 VJNXVAVKCZJOFQ-UHFFFAOYSA-N 0.000 description 1
- MURWRBWZIMXKGC-UHFFFAOYSA-N Phthalsaeure-butylester-octylester Natural products CCCCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC MURWRBWZIMXKGC-UHFFFAOYSA-N 0.000 description 1
- 229920012485 Plasticized Polyvinyl chloride Polymers 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 1
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000015125 Sterculia urens Nutrition 0.000 description 1
- 240000001058 Sterculia urens Species 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
- HOBWAPHTEJGALG-JKCMADFCSA-N [(1r,5s)-8-methyl-8-azoniabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate;sulfate Chemical compound [O-]S([O-])(=O)=O.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1 HOBWAPHTEJGALG-JKCMADFCSA-N 0.000 description 1
- BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical compound CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- IYKJEILNJZQJPU-UHFFFAOYSA-N acetic acid;butanedioic acid Chemical compound CC(O)=O.OC(=O)CCC(O)=O IYKJEILNJZQJPU-UHFFFAOYSA-N 0.000 description 1
- MFOPEVCFSVUADB-UHFFFAOYSA-N acetic acid;methyl carbamate Chemical compound CC(O)=O.COC(N)=O MFOPEVCFSVUADB-UHFFFAOYSA-N 0.000 description 1
- UDJCTHZWTUFHSJ-UHFFFAOYSA-N acetic acid;octanoic acid Chemical compound CC(O)=O.CCCCCCCC(O)=O UDJCTHZWTUFHSJ-UHFFFAOYSA-N 0.000 description 1
- ASRPLWIDQZYBQK-UHFFFAOYSA-N acetic acid;pentanoic acid Chemical compound CC(O)=O.CCCCC(O)=O ASRPLWIDQZYBQK-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000005910 alkyl carbonate group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 description 1
- 229960003459 allopurinol Drugs 0.000 description 1
- MANKSFVECICGLK-UHFFFAOYSA-K aloxiprin Chemical compound [OH-].[Al+3].CC(=O)OC1=CC=CC=C1C([O-])=O.CC(=O)OC1=CC=CC=C1C([O-])=O MANKSFVECICGLK-UHFFFAOYSA-K 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229940024544 aluminum aspirin Drugs 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 229940008238 amphetamine sulfate Drugs 0.000 description 1
- PYHRZPFZZDCOPH-UHFFFAOYSA-N amphetamine sulfate Chemical compound OS(O)(=O)=O.CC(N)CC1=CC=CC=C1.CC(N)CC1=CC=CC=C1 PYHRZPFZZDCOPH-UHFFFAOYSA-N 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- XRCFXMGQEVUZFC-UHFFFAOYSA-N anisindione Chemical compound C1=CC(OC)=CC=C1C1C(=O)C2=CC=CC=C2C1=O XRCFXMGQEVUZFC-UHFFFAOYSA-N 0.000 description 1
- 229960002138 anisindione Drugs 0.000 description 1
- 229940124339 anthelmintic agent Drugs 0.000 description 1
- 239000000921 anthelmintic agent Substances 0.000 description 1
- 230000000648 anti-parkinson Effects 0.000 description 1
- 125000003435 aroyl group Chemical group 0.000 description 1
- 229960002028 atropine sulfate Drugs 0.000 description 1
- 229960003515 bendroflumethiazide Drugs 0.000 description 1
- HDWIHXWEUNVBIY-UHFFFAOYSA-N bendroflumethiazidum Chemical compound C1=C(C(F)(F)F)C(S(=O)(=O)N)=CC(S(N2)(=O)=O)=C1NC2CC1=CC=CC=C1 HDWIHXWEUNVBIY-UHFFFAOYSA-N 0.000 description 1
- ANFSNXAXVLRZCG-RSAXXLAASA-N benzphetamine hydrochloride Chemical compound [Cl-].C([C@H](C)[NH+](C)CC=1C=CC=CC=1)C1=CC=CC=C1 ANFSNXAXVLRZCG-RSAXXLAASA-N 0.000 description 1
- 229960003228 benzphetamine hydrochloride Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- XXRMYXBSBOVVBH-UHFFFAOYSA-N bethanechol chloride Chemical compound [Cl-].C[N+](C)(C)CC(C)OC(N)=O XXRMYXBSBOVVBH-UHFFFAOYSA-N 0.000 description 1
- 229960002123 bethanechol chloride Drugs 0.000 description 1
- JEJBBWQXAMSBQT-UHFFFAOYSA-N butanedioic acid;propanoic acid Chemical compound CCC(O)=O.OC(=O)CCC(O)=O JEJBBWQXAMSBQT-UHFFFAOYSA-N 0.000 description 1
- NKWPZUCBCARRDP-UHFFFAOYSA-L calcium bicarbonate Chemical compound [Ca+2].OC([O-])=O.OC([O-])=O NKWPZUCBCARRDP-UHFFFAOYSA-L 0.000 description 1
- 229910000020 calcium bicarbonate Inorganic materials 0.000 description 1
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
- 239000001527 calcium lactate Substances 0.000 description 1
- 235000011086 calcium lactate Nutrition 0.000 description 1
- 229960002401 calcium lactate Drugs 0.000 description 1
- PBUBJNYXWIDFMU-UHFFFAOYSA-L calcium;butanedioate Chemical compound [Ca+2].[O-]C(=O)CCC([O-])=O PBUBJNYXWIDFMU-UHFFFAOYSA-L 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 229920003086 cellulose ether Polymers 0.000 description 1
- 229960001616 chlormadinone acetate Drugs 0.000 description 1
- 229960001761 chlorpropamide Drugs 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- 229940088560 citric acid / sodium bicarbonate Drugs 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229910000428 cobalt oxide Inorganic materials 0.000 description 1
- IVMYJDGYRUAWML-UHFFFAOYSA-N cobalt(ii) oxide Chemical compound [Co]=O IVMYJDGYRUAWML-UHFFFAOYSA-N 0.000 description 1
- 229920000891 common polymer Polymers 0.000 description 1
- 238000013267 controlled drug release Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229910000431 copper oxide Inorganic materials 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 229960003290 cortisone acetate Drugs 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- UCVPKAZCQPRWAY-UHFFFAOYSA-N dibenzyl benzene-1,2-dicarboxylate Chemical compound C=1C=CC=C(C(=O)OCC=2C=CC=CC=2)C=1C(=O)OCC1=CC=CC=C1 UCVPKAZCQPRWAY-UHFFFAOYSA-N 0.000 description 1
- 229960005156 digoxin Drugs 0.000 description 1
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 1
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 1
- HBGGXOJOCNVPFY-UHFFFAOYSA-N diisononyl phthalate Chemical compound CC(C)CCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCCCCC(C)C HBGGXOJOCNVPFY-UHFFFAOYSA-N 0.000 description 1
- MUCZHBLJLSDCSD-UHFFFAOYSA-N diisopropyl fluorophosphate Chemical compound CC(C)OP(F)(=O)OC(C)C MUCZHBLJLSDCSD-UHFFFAOYSA-N 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- PSHRANCNVXNITH-UHFFFAOYSA-N dimethylamino acetate Chemical compound CN(C)OC(C)=O PSHRANCNVXNITH-UHFFFAOYSA-N 0.000 description 1
- XWVQUJDBOICHGH-UHFFFAOYSA-N dioctyl nonanedioate Chemical compound CCCCCCCCOC(=O)CCCCCCCC(=O)OCCCCCCCC XWVQUJDBOICHGH-UHFFFAOYSA-N 0.000 description 1
- 229960000267 diphenadione Drugs 0.000 description 1
- OGAKLTJNUQRZJU-UHFFFAOYSA-N diphenidol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(O)CCCN1CCCCC1 OGAKLTJNUQRZJU-UHFFFAOYSA-N 0.000 description 1
- 229960003520 diphenidol Drugs 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000003822 epoxy resin Substances 0.000 description 1
- 229960005450 eritrityl tetranitrate Drugs 0.000 description 1
- SNFOERUNNSHUGP-ZXZARUISSA-N erythrityl tetranitrate Chemical compound [O-][N+](=O)OC[C@@H](O[N+]([O-])=O)[C@@H](O[N+]([O-])=O)CO[N+]([O-])=O SNFOERUNNSHUGP-ZXZARUISSA-N 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 229960002568 ethinylestradiol Drugs 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 229960001781 ferrous sulfate Drugs 0.000 description 1
- 239000011790 ferrous sulphate Substances 0.000 description 1
- 235000003891 ferrous sulphate Nutrition 0.000 description 1
- 229960005051 fluostigmine Drugs 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 230000002070 germicidal effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 229920000578 graft copolymer Polymers 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- BZIRFHQRUNJZTH-UHFFFAOYSA-N hexadecanoic acid;pentanoic acid Chemical compound CCCCC(O)=O.CCCCCCCCCCCCCCCC(O)=O BZIRFHQRUNJZTH-UHFFFAOYSA-N 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- JUMYIBMBTDDLNG-OJERSXHUSA-N hydron;methyl (2r)-2-phenyl-2-[(2r)-piperidin-2-yl]acetate;chloride Chemical compound Cl.C([C@@H]1[C@H](C(=O)OC)C=2C=CC=CC=2)CCCN1 JUMYIBMBTDDLNG-OJERSXHUSA-N 0.000 description 1
- 230000002706 hydrostatic effect Effects 0.000 description 1
- 229940065346 hydroxyprogesterone acetate Drugs 0.000 description 1
- 239000005554 hypnotics and sedatives Substances 0.000 description 1
- 229940005535 hypnotics and sedatives Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- 230000000622 irritating effect Effects 0.000 description 1
- 229960001543 isopropamide iodide Drugs 0.000 description 1
- 229940018435 isoproterenol sulfate Drugs 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000013563 matrix tablet Substances 0.000 description 1
- 229940018415 meclizine hydrochloride Drugs 0.000 description 1
- IMSSROKUHAOUJS-MJCUULBUSA-N mestranol Chemical compound C1C[C@]2(C)[C@@](C#C)(O)CC[C@H]2[C@@H]2CCC3=CC(OC)=CC=C3[C@H]21 IMSSROKUHAOUJS-MJCUULBUSA-N 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 1
- 229960002532 methamphetamine hydrochloride Drugs 0.000 description 1
- FLOSMHQXBMRNHR-DAXSKMNVSA-N methazolamide Chemical compound CC(=O)\N=C1/SC(S(N)(=O)=O)=NN1C FLOSMHQXBMRNHR-DAXSKMNVSA-N 0.000 description 1
- 229960004083 methazolamide Drugs 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- LZCOQTDXKCNBEE-IKIFYQGPSA-N methscopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)C)=CC=CC=C1 LZCOQTDXKCNBEE-IKIFYQGPSA-N 0.000 description 1
- 229960001033 methylphenidate hydrochloride Drugs 0.000 description 1
- 229960001383 methylscopolamine Drugs 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- ZAGYPHYWSKQMPX-UHFFFAOYSA-N morpholin-4-yl butanoate Chemical compound CCCC(=O)ON1CCOCC1 ZAGYPHYWSKQMPX-UHFFFAOYSA-N 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 229940053934 norethindrone Drugs 0.000 description 1
- VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 description 1
- 229960001858 norethynodrel Drugs 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-M oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC([O-])=O ZQPPMHVWECSIRJ-KTKRTIGZSA-M 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- 150000002892 organic cations Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000002357 osmotic agent Substances 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 208000014837 parasitic helminthiasis infectious disease Diseases 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- HTYIXCKSEQQCJO-UHFFFAOYSA-N phenaglycodol Chemical compound CC(C)(O)C(C)(O)C1=CC=C(Cl)C=C1 HTYIXCKSEQQCJO-UHFFFAOYSA-N 0.000 description 1
- 229950005116 phenaglycodol Drugs 0.000 description 1
- 229960001753 phenformin hydrochloride Drugs 0.000 description 1
- 229960002315 phenmetrazine hydrochloride Drugs 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
- 125000005498 phthalate group Chemical class 0.000 description 1
- RNAICSBVACLLGM-GNAZCLTHSA-N pilocarpine hydrochloride Chemical compound Cl.C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C RNAICSBVACLLGM-GNAZCLTHSA-N 0.000 description 1
- 229960002139 pilocarpine hydrochloride Drugs 0.000 description 1
- 229920001084 poly(chloroprene) Polymers 0.000 description 1
- 229920001390 poly(hydroxyalkylmethacrylate) Polymers 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000447 polyanionic polymer Polymers 0.000 description 1
- 229920000867 polyelectrolyte Polymers 0.000 description 1
- 229920000647 polyepoxide Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229910000057 polysulfane Inorganic materials 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 229960002816 potassium chloride Drugs 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- IWZKICVEHNUQTL-UHFFFAOYSA-M potassium hydrogen phthalate Chemical compound [K+].OC(=O)C1=CC=CC=C1C([O-])=O IWZKICVEHNUQTL-UHFFFAOYSA-M 0.000 description 1
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
- 229910052939 potassium sulfate Inorganic materials 0.000 description 1
- 235000011151 potassium sulphates Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- ABTXGJFUQRCPNH-UHFFFAOYSA-N procainamide hydrochloride Chemical compound [H+].[Cl-].CCN(CC)CCNC(=O)C1=CC=C(N)C=C1 ABTXGJFUQRCPNH-UHFFFAOYSA-N 0.000 description 1
- 229960003253 procainamide hydrochloride Drugs 0.000 description 1
- WIKYUJGCLQQFNW-UHFFFAOYSA-N prochlorperazine Chemical compound C1CN(C)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 WIKYUJGCLQQFNW-UHFFFAOYSA-N 0.000 description 1
- 229960003111 prochlorperazine Drugs 0.000 description 1
- DSKIOWHQLUWFLG-SPIKMXEPSA-N prochlorperazine maleate Chemical compound [H+].[H+].[H+].[H+].[O-]C(=O)\C=C/C([O-])=O.[O-]C(=O)\C=C/C([O-])=O.C1CN(C)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 DSKIOWHQLUWFLG-SPIKMXEPSA-N 0.000 description 1
- 229960002153 prochlorperazine maleate Drugs 0.000 description 1
- 230000001072 progestational effect Effects 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 1
- 229960003147 reserpine Drugs 0.000 description 1
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000001797 sucrose acetate isobutyrate Substances 0.000 description 1
- 235000010983 sucrose acetate isobutyrate Nutrition 0.000 description 1
- UVGUPMLLGBCFEJ-SWTLDUCYSA-N sucrose acetate isobutyrate Chemical compound CC(C)C(=O)O[C@H]1[C@H](OC(=O)C(C)C)[C@@H](COC(=O)C(C)C)O[C@@]1(COC(C)=O)O[C@@H]1[C@H](OC(=O)C(C)C)[C@@H](OC(=O)C(C)C)[C@H](OC(=O)C(C)C)[C@@H](COC(C)=O)O1 UVGUPMLLGBCFEJ-SWTLDUCYSA-N 0.000 description 1
- JFNWFXVFBDDWCX-UHFFFAOYSA-N sulfisoxazole acetyl Chemical compound C=1C=C(N)C=CC=1S(=O)(=O)N(C(=O)C)C=1ON=C(C)C=1C JFNWFXVFBDDWCX-UHFFFAOYSA-N 0.000 description 1
- 229950006904 sulfisoxazole acetyl Drugs 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- OKUCEQDKBKYEJY-UHFFFAOYSA-N tert-butyl 3-(methylamino)pyrrolidine-1-carboxylate Chemical compound CNC1CCN(C(=O)OC(C)(C)C)C1 OKUCEQDKBKYEJY-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229960004869 thiethylperazine Drugs 0.000 description 1
- RVBRTNPNFYFDMZ-SPIKMXEPSA-N thiethylperazine maleate Chemical compound [H+].[H+].[H+].[H+].[O-]C(=O)\C=C/C([O-])=O.[O-]C(=O)\C=C/C([O-])=O.C12=CC(SCC)=CC=C2SC2=CC=CC=C2N1CCCN1CCN(C)CC1 RVBRTNPNFYFDMZ-SPIKMXEPSA-N 0.000 description 1
- OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 1
- 229960002277 tolazamide Drugs 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 229960005294 triamcinolone Drugs 0.000 description 1
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- XJGONMZLEDGBRM-UHFFFAOYSA-M tridihexethyl chloride Chemical compound [Cl-].C=1C=CC=CC=1C(O)(CC[N+](CC)(CC)CC)C1CCCCC1 XJGONMZLEDGBRM-UHFFFAOYSA-M 0.000 description 1
- 229960001205 tridihexethyl chloride Drugs 0.000 description 1
- 150000005691 triesters Chemical class 0.000 description 1
- 125000005591 trimellitate group Chemical group 0.000 description 1
- PVNIQBQSYATKKL-UHFFFAOYSA-N tripalmitin Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCC PVNIQBQSYATKKL-UHFFFAOYSA-N 0.000 description 1
- YPDXSCXISVYHOB-UHFFFAOYSA-N tris(7-methyloctyl) benzene-1,2,4-tricarboxylate Chemical compound CC(C)CCCCCCOC(=O)C1=CC=C(C(=O)OCCCCCCC(C)C)C(C(=O)OCCCCCCC(C)C)=C1 YPDXSCXISVYHOB-UHFFFAOYSA-N 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
-
- 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0004—Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
- A61M31/002—Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Medicinal Preparation (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
m
22 5 0 58
/*%
SK
\ i
-)cr.—l.^a.
Priority Date(s): . .tTr?.
Complete Specification Filed: C?.*.^ .'$?.. Class: .O.l?.!.M.2).l/oo.:
2? NOV i990
Publication Date: Tr.
P.O. Journal. No:
N.Z. No,
NEW ZEALAND Patents Act 1953 COMPLETE SPECIFICATION
t7jUNl<%$y
MULTI-UNIT DELIVERY SYSTEM
We, ALZA CORPORATION, incorporated under the laws of the Stance of California, United States of America of 950 Page Mill Road, Palo Alto, California 94303-0802, United States of America,
do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:-
- 1 - (Followed by 1A)
MULTI-UNIT OELIVERY SYSTEM
Field of the Invention
This invention relates to patterned drug delivery. More particularly, this invention relates to patterned drug delivery by means of a plurality of individual drug delivery units or tablets. Still more particularly, but without limitation thereto, this invention relates to delivery of multi-agents orally or in other media in a pre-programmed delivery profile.
Definition of Terms
The expressions "active agent" and "drug" are used interchangeably and as used herein broadly include any compound, composition of matter or mixture thereof, that can be delivered from the system to produce a beneficial and useful result. This includes pesticides, herbicides, germicides, biocides, algicides, rodenticides, fungicides, insecticides, anti-oxidants, plant growth promoters, plant growth inhibitors, preservatives, antipreservatives, disinfectants, sterilization agents, catalysts, chemical reactants, fermentation agents, foods, food supplements, nutrients, cosmetics, drugs, vitamins, sex sterilants, fertility inhibitors, fertility promoters, air
ff- .
y;i^;
o if*
'"w'
0 5 8
1 purifiers, micro-organism attenuators and other agents that
2 benefit the environment of use.
3 The terms "active agent" and "drug" as used herein further
4 includes any physiologically or pharmacologically active
substance that produces a localized or systemic effect or effects
6 in animals, including warm blooded manmals, humans and primates,
7 avians, domestic household, sport or farm animals such as sheep,
8 goats, cattle, horses and pigs, or is administered to laboratory i
9 animals such as mice, rats and guinea pigs, to fish, reptiles,
zoo and wild animals. The active drug which can be delivered
11 includes inorganic and organic compounds including without
I 12 limitation, those materials that act upon the central nervous
I
| 13 system such as hypnotics and sedatives, psychic energizers,
3
I 14 tranquilizers, anticonvulsants, muscle relaxants, antiparkinson
| 15 agents, analgesics, anti-inflamnatory, local anesthetics, muscle
| 16 contractants, anti-microbials, anti-malarials, hormonal agents
| 17 including contraceptives, sympathomimetrics, diuretics, anti-
1
I 18 parasites, neoplastics, hypoglycemics, nutritional, fats,
i
19 ophthalmic, electrolytes and diagnostic agents.
* The term "drug unit" as used herein includes units that are
21 capable of maintaining their physical and chemical integrity
22 while housed within the di-spenser. This includes, without
23 limitation, tablets with or without a density element; matrix
24 tablets; capsules; elementary osmotic pumps, such as that
described in U.S.Pat.No. 3,845,770; mini osmotic pumps such as
26 those described in U.S.Pat.Nos. 3,995,631, 4,034,756 and
27 4,111,202; and multichamber osmotic systems referred to as push-
28 pull and push-melt osmotic pumps such as those described in
'■hsmms-i-.-
o
O
V ;
^ .--wr■■■*■«
1 U.S.Pat.Nos. 4,320,759 and 4,449,983, all of which are
2 incorporated herein by reference.
3 As used herein the expression "external fluid" includes
4 water and other biological fluids.
Background of the Invention
7 The concept of patterned drug delivery covers a broad range
8 of systems from time release capsules whose components have
9 coatings which erode at different rates, to controlled release
* *»
rate tablets which operate by osmosis.
11 Despite the development of the art however, there remains a 12' continuing need for improved methods and systems for providing
13 controlled drug release profiles.
14
Sunmary of the Invention
16 An object of this invention is to provide sequential timing
17 and dispensing of delivery units containing the same or different
18 active agents.
19 Another object of this invention is to provide both a novel
and useful agent formulation delivery system that is self-
21 contained, self-powered, and also represents an improvement in
22 the delivery arti
These and other objects are demonstrated by the present Invention wherein a drug dispenser for use in a fluid-containing vironment comprising in combination:
; a rigid housing;
a fluid activated driving member that is activated by the fluid in said fluid-containing environment, said driving member £
beirag within a portion of said housing proximate the end of said housing opposite to said outlet and in contact with said housing,
o
G
2:-'5053
at least a portion of said housing opposite to said outlet and containing said driving member being permeable to the fluid in said fluid-containing environment;
a fluid activated driving member filling a portion of the space within said housing and being in contact with the housing;
a plurality of discrete drug units longitudinally aligned and contained within said housing, said units maintaining their physical arid chemical integrity while contained within said housing; and a drug unit outlet means in said housing that communicates with the units.
Brief Description of the Drawings
The invention will be described in further detail with reference to the accompanying drawings wherein:
Figure 1 is a partial cross-sectional view of the dispenser of this invention, illustrating one embodiment of the dispensing confi gurat ion;
Figure 2 is a partial cross-sectional view of the dispenser of this invention, illustrating a second embodiment of the dispensing configuration;
Figure 3 is a partial cross-sectional view of the dispenser of this invention, illustrating still another embodiment of the dispensing configuration;
Figure 4 is a partial cross-sectional view of one embodiment of the driving member for the dispenser of fchis,., inventioa-utilizing a hydrophilic expandable member;
3a
|| • " J: - -n nrmr-iW.W.
0
-Sri,-; * - e
—V.?*|«
->V"
:-li ,,
Figure 5 Is a partial cross-sectional view of a second embodiment of the driving member for the dispenser of this invention, utilizing an osmotically effective solute;
Figure 6 is a partial cross-sectional view of another embodiment of the driving member for the dispenser of this invention, utilizing an elementary osmotic pump;
Figure 7 is a partial cross-sectional view of another embodiment of the driving member for the dispenser of this invention, utilizing a gas generating composition; and
Figure 8 is a partial cross-sectional view of the dispenser of this invention, illustrating another embodiment of the
. .. ;
22 5 0 5 8
1
O
4
6
7
8
9
11
12
13
14
i 16
17
19
21
.26
dispensing configuration.
1
2
2 Description of the Preferred Embodiment
This invention can provide a variety of drug delivery profiles including, but not limited to, pulsed delivery of a single drug or drug formulation, pulsed delivery of a sequence of different drugs or drug formulations, pulsed delivery of one drug or drug formulation superimposed on continuous delivery of a different drug or drug formulation, and simultaneous continuous delivery of several drugs or drug formulations.
The drug dispenser of this invention is designed to deliver a plurality of discrete longitudinally aligned individual drug units by the linear expansion of a fluid activated driving member. The drug units are such that they retain their physical and chemical integrity while contained within the system and do not substantially commence delivery of active agent until after they have been dispensed into the environment. It is comprised of CD ^ 3 dlsPensin9 component and a driving component, representative embodiments of which are disclosed herein. Figures 1, 2, 3 and 8 iilustrate various embodiments of the dispensing component suitable for use in the dispenser of this invention. These ^ configurations can be combined with various embodiments of the po driving component, representative embodiments of which are ^ illustrated in Figures 4-7.
The dispensing and driving component designs are for use in a fluid-containing environment and are merely exemplary of the numerous embodiments suitable for use in this invention. The
28
. ..wcoiv ..r>;--,. .......
n
22 5 0 5 8
1 portion of the housing adjacent to the dispenser component is
2 of a material which may be either semipermeable or impermeable to
3 the passage of external fluid. Typical suitable impermeable
4 materials include without limitation, polyethylene, polyethylene
terephthalate (Mylar), plasticized polyvinyl chloride, metal-foil
6 polyethylene laminates, neoprene rubber, natural gum rubber and
7 Pliofilm (rubber hydrochloride). These materials are
8 additionally flexible, insoluble and chemically compatible with
9 the active agent contained in the units positioned therein, and,
in the instance of providing a drug or like depot within the body
11 of a living organism, are biologically inert, non-irritating to
12 body tissues and non-allergenic. Additional suitable materials
13 include polystyrene, polypropylene, polyvinyl chloride,
14 reinforced epoxy resin, polymethylmethacrylate, etc., sheet metal
(e.g., aluminum, copper, steel, etc.), galvanized pipe, or
16 sty reae/acrylonit rile copolymer. Again, for drug depot
17 applications the same are advantageously biologically inert, non-
18 irritating to body tissue and non-allergenic. Suitable
19 semipermeable materials include without limitation, all
cellulosic polymers such as cellulose acetates, ethylcellulose,
21 methyl cellulose, cellulose acetate butyrate, cellulose acetate
22 propionate, etc., ' or impermeable material blended with a
23 hydrophilic polymer or a low molecular weight water soluble
24 enhancer to render the material semipermeable.
Many other materials including those which are biologically
26 acceptable are suitable for fabrication of the impermeable
27 component of the device of this invention. While the impermeable
28 portion of the housing has previously been described as being
225058
W> i
I
S 2
-M
$ 3
insoluble under the conditions and in the environment of intended use, it is also within the scope of the invention that such
| 4 materials be insoluble only during the period of said intended
| _ use; thereafter dissolving or otherwise degrading into the
I 5
environment of the device. Thus, a dispenser is here contemplated which is unaffected by its environment, solubility-wise, at the
6
7
,**"*) situs of use, or which is only slightly soluble during the period of intended use, such that once all the units have been dispensed, it will then dissolve or erode away, leaving no objectionable residue or empty container at the said situs of use.
The portion of the housing adjacent to the driving component must be semipermeable so as to allow for passage of external fluid, since the driving member is fluid activated. Suitable materials will be discussed at length with regards to specific embodiments of the driving member.
The dispensing component shown in Figure 1 is comprised of a rigid housing member 20. Housing 20 is also designed with an outlet means, exit port 22. A plurality of movable discrete units 24, 26, 28, 30 and 32 are aligned within the housing 20. This configuration is merely illustrative and the dispenser may have numerous drug units in excess of the number shown in Fig. 1.
The drug units are in the form of a solid core, matrix tablet or in any of a variety of forms which are capable of maintaining their physical and c'hemical integrity, i.e do not erode. The driving member 34 operates to displace the units towards the exit port 22. As unit 24 comes into contact with the
9
11
12
13
14
16
17
18
'■*—/
19
21
O 22
23
24
..26
27
28
1
fc *4,.-J- "• , .TV- /- - • • ' t> •
r~\
f
I
i )
«
'■3
» 22 5 0 5 8
1 exit, it is dispensed into the environment and begins to deliver
2 drug in a controlled or semi-controlled fashion. Once unit 24 is
3 dispensed, linear displacement pushes unit 30 through the housing
4 20 so that it then comes into contact with exit 22 and is
likewise dispensed. This continues until the dispenser is
6 depleted of drug units.
7 The units can provide a variety of drug delivery profiles | 8 depending upon their composition. They can all contain the same ! 9 drug(s) at the same concentrations) to deliver identical pulses i ✓
of drug over time as each unit is dispensed or they can contain
I
11 the same drug(s) at different concentrations to give different i .
1
j 12 pulses of drug. Alternately, the units may contain a different i
13 drug or drug formulation.
14 In the preferred embodiment, units 24, 26 and 28 contain a
drug or drug formulation and alternate units 30 and 32 contain no
16 drug, ..such that when they are dispensed, an "off" period is
17 provided, during which time no drug is being delivered. The
18 additional advantage of this "alternating" configuration is that
19 once unit 24 is dispensed, the surface of unit 30 is exposed and
may begin the erode. Having 30 as a non-drug containing unit
21 guarantees that the drug being delivered to the environment comes
22 from the dispensed unit rather-than from the units still retained
23 within the housing.
24 The dispensing configuration shown in Figure 2 is also
designed to deliver a plurality of discrete units to the ,26 environment, and operates similar to the embodiment of Fig. 1.
27 In Fig. 1, the geometry of the units permits close alignment so
28 as not to have any space between adjacent units. This aspect is
8
I
, . . " -• „ '•'. • ; *v- S»()'s1 -j .y.u r _ , > , • V ,/j.
225058
I
1 1
-iff not critical to the effectiveness of the invention as is shown by
3 2
M
3
^jS? 4
Fig. 2 where the units are curved and therefore do not fit
A
i aclosely together within the housing.
The dispensing configuration of Fig. 2 is comprised of a rigid housing 38 and a plurality of discrete drug units 40, 42 and 44, aligned therein. Three drug units are shown but in actual
7
f~\ application, any number of units may be used. The driving member
6
8
9
11
12
13
14
16
17
18
19
21
22
23
24
.26
27
28
46 displaces the units at the desired rate and dispenses them 'individually through the exit port 48.
The units, 40 for example, can be elementary osmotic pumps or mini-osmotic pumps, for example. They can also be coated with a degradable coating to delay delivery until the units are actually dispensed into the environment.
The dispensing configuration shown in Figure 3 is comprised of a housing member 50 and a plurality of discrete drug units 52, 54, 56 and 58 aligned therein. As with Figs. 1 and 2, the number of units shown is merely illustrative and is not intended to limit the invention in any manner.
The driving member 60 operates to linearly displace the units and dispense them through the exit port 62. The units, 52 for example, are comprised of a plastic or polyethylene cap 64 with a drug mixture 66 compressed within. The units may be bowl-shaped as shown or they may be box-shaped to hold a larger quantity of drug.The units are separated by partitions 68, 70, 72 and 74, which can be a rigid soliti or a gel. As the unit 52 is dispensed, the drug mixture 66 is exposed to the environment (external fluid) and is thus delivered. Subsequently the
-%
o
CD
22 5 0 5 8
1 partition 68 is dispensed through the exit port 62.
2 This dispensing configuration provides pulsed drug delivery.
3 As unit 52 is dispensed, a burst of drug is delivered which is
4 followed by another pulse when unit 54 is dispensed and so forth.
The units may contain the same drug in the same or different
6 concentrations, or different drugs. In this manner, any pattern
\ 7 of delivery may be fashioned.
8 Example I
9 The dispenser of Fig. 3 is especially suited for treatment
of helminth infections in ruminants, specifically cattle.
11 Depending upon the nature of delivery desired, several drug
12 formulations can be used in this dispenser.
13 A suitable drug formulation is comprised of about 80 weight
14 percent Hapadex® which is an anthelmintic agent for cattle sold
by Schering-Plough Corporation. About 0.5 grams of the
16 formulation 66 is compressed into cap 64. Units 54, 56 and 58 are
17 also filled with the drug formulation. However, if an off period
I 18 is desired, units 52 and 56 can contain drug and the alternate j W
j 19 units 54 and 58 can be empty.
|
; 20 • For fast pulse delivery of Hapadex®, the drug formulation is i
j 21 100% drug. However, this system can be designed to provide a
I 22 short duration pulse where the drug formulation has a gas
23 generator contained therein. Especially suitable is a formulation
24 comprised of about 80% Hapadex® and 20% citric acid/sodium
bicarbonate.
26 If a longer period of delivery is desired, a disintegrating
27 agent such as Ac-Di-Sol (FMC Corporation), otherwise known as
28 croscarmellose sodium, can be incorporated into the drug
22 5 0 5 8
formulation in an amount up to 20 weight percent.
For even longer duration of drug delivery, the drug formulation can be 80% Hapadex® and 20% polymer, such as Polyox® or hydroxypropyl rnethylcellulose.
For rumenal systems, an important criteria is that the system remain in the rumen of an animal over a prolonged period of time. This is accomplished by placement of a density element within the dispenser. The housing 50 itself, may be the density ' element. Alternately, one of the partitions, 74 for example, can act as the density element. In still another embodiment, unit 58 can be a density element, placed so as to remain within the housing 50 after all of the drug containing units have been dispensed.
The density element suitable for use in the dispenser of this invention must be dense enough to retain the dispenser in the rumen-reticular sac of a ruminant. The presence of a density element allows the dispenser to remain in the rumen over a prolonged period of time rather than letting it pass into the alimentary tract and be eliminated therefrom. As the dispenser remains in the rumen, a beneficial agent can be delivered to the ruminant at a controlled rate over an extended period of time. Generally, a density element will have a density of from about 0.8 to 8, or higher, with the density in a presently preferred embodiment exhibiting a specific gravity of from about 2.2 to 7.6. For the ruminants cattle-and sheep, it is presently preferred that the density element exhibit a density such that there is a resulting dispenser density of about 3. Materials that
11
22 5 0 5 8
have a density that can be used for forming a suitable density element include iron, iron shot, iron shot coated with iron oxide, iron shot magnesium alloy, steel, stainless steel, copper oxide, a mixture of cobalt oxide and iron powder, and the like.
Exemplary of drugs that are soluble or very soluble in water and can be delivered by the dispenser systems of this invention include prochlorperazine edisylate, ferrous sulfate, aminocaproic acid, potassium chloride, mecarnyl amine hydrochloride, procainamide hydrochloride, amphetamine sulfate, benzphetamine hydrochloride, isoproterenol sulfate, methamphetamine hydrochloride, phenmetrazine hydrochloride, bethanechol chloride, metacholine chloride, pilocarpine hydrochloride, atropine sulfate, methscopolamine bromide, isopropamide iodide, tridihexethyl chloride, phenformin hydrochloride, methylphenidate hydrochloride, and mixtures thereof.
Exemplary of agents that have limited solubility or are very slightly soluble, or insoluble in water and biological fluids that can be delivered by the dispenser systems of this invention include diphenidol, meclizine hydrochloride, prochlorperazine maleate, thiethylperazine maleate, anisindione, diphenadione, erythrityl tetranitrate, digoxin, isoflurophate, reserpine, azetazolamide, methazolamide, bendroflumethiazide,
chlorpropamide, tolazamide, chlormadinone acetate, phenaglycodol, allopurinol, aluminum aspirin, methotrexate, acetyl sulfisoxazole, erythromycin, and mixtures thereof, steroids including corticosteroids such as hydrocortisone, hydrocorticosterone acetate, cortisone acetate and triamcinolone,
12
jm 5 o 5 8
anhydrogens such as methyltesterone, esterogerric steroids such as 17 p -estradiol, ethinyl estradiol, ethinyl estradiol 3-methyl ether and estradiol, progestational steroids such as prednisolone, 17 oO -hydroxy-progesterone acetate, 19-nor-progesterone, norethindrone, progesterone, norethynodrel, and the like.
The drug can also be in the various chemical and physical forms such as uncharged molecules, molecular complexes, ,pharmacologically acceptable acid addition and base addition salts such as hydrochlorides, hydrobromides, sulfate, laurylate, palmitate, phosphate, nitrate, borate, acetate, maleate, tartrate, oleate and salicylate. For acidic drugs, salts of metals, amines or organic cations, for example quaternary ammonium can be used. Derivatives of drugs such as esters, ethers and amides can be used alone or mixed with other drugs. Also, a drug Which is water insoluble can be used in a form that on its release from the dispenser, is converted by enzymes, hydrolyzed by body pH or other metabolic processes to the original form, or to a biologically active form.
The dispensing configuration of Figures 1, 2 and 3, can be combined with any of the driving members illustrated in Figures 4, 5, 6, and 7, to provide a tailored drug delivery system.
Figure 4 illustrates a driving member system 76 utilizing an expandable driving member 78 comprised of an external fluid insoluble, external fluid swellable composition. Member 78 is encased in housing 80 which is a semipermeable membrane substantially permeable to the passage of an external fluid and
13
1 -
H
225058
1 substantially impermeable to the passage of any ingredients
' %
A-1 »
| 2 contained in member 78. The driving member 78 is positioned
'$
i 3 adjacent to one of the drug units at interface 82.
I
| 4 External fluid is imbibed through the housing 80 by the i
j
[ 5 expandable hydrophilic member 78 in a tendency toward osmotic i
1 g equilibrium, to continuously swell and expand member 78. Member
7 78 expands while maintaining an intact immiscible boundary at g interface 82, defined by the surface of drug unit 86 and g expandable member 78.
✓
Expandable member 78 has a shape that corresponds to
11 internal shape of housing 80 and is preferably made from a
12 hydrogel composition. The hydrogel composition is noncross-1inked
13 or optionally cross-linked and it possesses osmotic properties,
14 such as the ability to imbibe an external fluid through
semipermeable housing 80, and exhibit an osmotic pressure 15 gradient across semipermeable housing 80 against a fluid outside 17 the • dispenser system. The materials used for forming the
^ i8 swell able, expandable member 78 are polymeric materials neat, and
polymeric materials blended with osmotic agents that interact
with water or a biological fluid, absorb the fluid and swell or
21 expand to an equilibrium state. The polymer exhibits the ability
22 retain a significant fraction of imbibed fluid in the polymer
23 molecular structure. The polymers in a preferred embodiment are
24 gel polymers that can swell or expand to a very high degree,
usually exhibiting a 2 to 50 fold volume increase. The swell able, 25 hydrophilic polymers, also known as osmopolymers, can be 27 noncross-1inked or lightly cross-linked. The cross-links can be 2g covalent, ionic or hydrogen bonds with the polymer possessing the
14
. ^ '<• •', ,S^^'' «/ , '• •' - ,r^, . ,. ,f
' v ~..i^..
s.mA.
1
>k
I 2
3
6
8
9
11
12
1 13
j 14
j 15
| 16
I 17
j o 18
j 19
! 20
i
I 21
! o 22
23
24
26
27
28
22 5 0 5 8
ability to swell in the presence of fluid, and when cross-linked it will not dissolve in the fluid. The polymer can be of plant,
animal, or synthetic origin. Polymeric materials useful for the
O 4
present purpose include poly(hydroxyalkyl methacrylate) having a molecular weight of from 5,000 to 5,000,000; poly(vinylpyrrolidone) having a molecular weight of from 10,000
7
to 360,000; anionic and cationic hydrogels; poly (electrolyte)
complexes; polyvinyl alcohol) having a low acetate residual; a 'swellable mixture of agar and carboxymethyl cellulose; a swellable composition comprising methyl cellulose mixed with a sparingly cross-linked agar; a water swellable copolymer produced by a dispersion of finely divided copolymer of maleic anhydride with styrene, ethylene, propylene, or isobutylene; a water swellable polymer of N-vinyl lactams; swellable sodium salts of carboxyl methyl cellulose; and the like.
Other gelable, fluid imbibing and retaining polymers useful for forming the hydrophilic, expandable driving member 78 include pectin having a molecular weight ranging from 30,000 to 300,000; polysaccharides such as agar, acacia, karaya, tragacanth, algins and guar; Carbopol® acidic carboxy polymer and its salt derivatives; polyacrylamides; water swellable indene maleic anhydride polymers; Good-rite® polyacrylic acid having a molecular weight of 80,000 to 200,000; Polyox® polyethylene oxide polymers having a molecular weight of 100,000 to 5,000,000; starch graft copolymers; Aqua-Keep® acrylate polymers with water absorbability of about 400 times its original weight; diesters of polyglucan; a mixture of cross-linked polyvinyl alcohol and
i
- -yaw*
22 5 0 5 8
? 1 poly(N-vinyl-2-pyrrolidone); poly(ethylene glycol) having a
I 2 molecular weight of 4,000 to 100,000; and the like. In a
£
| 2 preferred embodiment, the expandable member 78 is formed from
^ 4 polymers and polymeric compositions that are thermoformable.
g Representative polymers possessing hydrophilic properties g are known in U.S.Pat.Nos. 3,865,108, 4,002,173, 4,207,893,
j 4,220,152, 4,327,725, 4,350,271, all of which are incorporated
C~) 0 herein by reference and in Scott et al, "Handbook of Common g Polymers", CRC Press, Cleveland, Ohio (1971).
i
1Q The osmotically effective compound that can be blended i
i homogeneously or heterogeneously with the swellable polymer, to
I 12 form a driving member, are the osmotically effective solutes that
1
j are soluble in fluid imbibed into the swellable polymer, and
^ exhibit an osmotic pressure gradient across the semipermeable jg housing 80 against an external fluid. Osmotically effective lg compounds are known also as osmagents. Osmotically effective jy osmagents useful for the present purpose include magnesium
____ jg sulfate, magnesium chloride, sodium chloride, lithium chloride,
w jg potassium sulfate, sodium sulfate, mannitol, urea, sorbitol,
2q irjositol, sucrose, glucose and the like. The osmotic pressure in
2^ atmospheres, atm, of the osmagents suitable for the invention
22 ^e greater than zero atm, generally from 8 atm up to 500
23 atm» or higher.
24 Representative materials for forming the semipermeable housing include without limitation, semipermeable homopolymers, semipermeable copolymers, and the like. In one embodiment typical
2^ materials include cellulose esters, cellulose monoesters, cellulose diesters, cellulose triesters, cellulose ethers, and
28
16
'M3SBBBk'..,*:,
,.v*
•Js&sCi ■ ^ , ■ ,, ,v . (
? 2 5 0 5 8
If 1
cellulose ester-ethers, mixtures thereof, and the like. These
I 2
|| cellulose polymers have a degree of substitution, D.S., on their o
3
4
6
anhydroglucose unit form greater than 0 up to 3 inclusive. By
"degree of substitution" is meant the average number of hydroxyl groups originally present on the anhydroglucose unit that are replaced by a substituting group, or converted into another 7
group. The anhydroglucose unit can be partially or completely
8
9
11
12
13
14
16
17
18
19
21
22
23
24
..26
27
28
substituted with groups such as acyl, alkanoyl, aroyl, alkyl, •alkenyl, alkoxy, halogen, carboalkyl, alkylcarbamate, alkylcarbonate, alkylsulfonate, alkylsulfamate, and like semipermeable polymer forming groups.
The semipermeable materials typically include a member selected from the group consisting of cellulose acylate, cellulose dlacylate, cellulose triacylate, cellulose acetate, cellulose diacetate, cellulose triacetate, mono-, di- and tri-cellulose alkanylates, mono-, di- and tri-alkenylates, mono-, di-and tri-aroylates, and the like. Exemplary polymers including cellulose acetate having a D.S. of 1.8 to 2.3 and an acetyl content of 32 to 39.9%; cellulose diacetate having a D.S. of 1 to 2 and an acetyl content of 21 to 35%; cellulose triacetate having a D.S. of 2 to 3 and an acetyl content of 34 to 44.8% and the like. More specific cellulosic polymers include cellulose propionate having a D.S. of 1.8 and a propionyl content of 38.5%; cellulose acetate propionate having an acetyl content of 1.5 to 7% and a propionyl content of 39 to 42%; cellulose acetate propionate having an acetyl content of 2.5 to 3%, an average propionyl content of 39.2 to 45% and a hydroxyl content of 2.8 to
17
• - *». ,. ... ,, - -V-V- 1 s 1 ... .
22 5 0 5 8
'v 1
h ■1
o m
1 5.4%; cellulose acetate butyrate having a D.S. of 1.8, and acetyl f 2 content of 13 to 15%, and a butyryl content of 34 to 39%;
3 cellulose acetate butyrate having an acetyl content of 2 to
4 29.5%, a butyryl content of 17 to 53%, and a hydroxyl content of
I 5 0.5 to 4.7%; cellulose triacylates having a D.S. of 2.9 to 3 such j 6 as cellulose trivalerate, cellulose trilaurate, cellulose
7 tripalmitate, cellulose trioctanoate, and cellulose
8 tripropionate; cellulose diesters having a D.S. of 2.2 to 2.6
9 such as cellulose disuccinate , cellulose dipalmitate, cellulose
dioctanoate, cellulose dlcarpylate; cellulose propionate
11 morpholinobutyrate; cellulose acetate butyrate; cellulose acetate
12 phthalate; and the like; mixed cellulose esters such as cellulose
13 acetate valerate, cellulose acetate succinate, cellulose
14 propionate succinate, cellulose acetate octanoate, cellulose
valerate palmitate, cellulose acetate heptonate, and the like.
16 Semipermeable polymers are known in U.S.Pat.No. 4,077,407, and
17 they can be made by procedures described in "Encyclopedia of
18 Polymer Science and Technology", Vol. 3, pages 325-354,
19 Interscience Publishers, Inc., New York, (1964).
* Additional semipermeable polymers include cellulose
21 acetaldehyde; dimethyl cellulose acetate; cellulose acetate
22 ethyl carbamate; cellulose acetate methyl carbamate; cellulose
23 dimethylaminoacetate; a cellulose composition comprising
24 cellulose acetate and hydroxypropyl methylcellulose; a
composition comprising cellulose acetate and cellulose acetate
26 butyrate; a cellulose composition comprising cellulose acetate
27 butyrate and hydroxypropyl methylcellulose; semipermeable
28 polyamides; semipermeable polyurethanes; semipermeable
18
Itms&m',-
— .v-~^ .. ,.„ , , ' - ■ v
1
2
3
4
6
7
9
11
12
13
14
16
17
18
21
22
23
24
..26
27
28
225058
polysulfanes; semipermeable sulfonated polystyrenes; crosslinked, selectively semipermeable polymers formed by the coprecipitation of a polyanion and a polycation as disclosed in U.S.Pat.Nos. 3,173,876, 3,276,586, 3,541,005, 3,541,006 and 3,546,142, all of which are incorporated herein by reference; selectively semipermeable silicon rubbers; semipermeable polymers as disclosed by Loeb and Sourirajan in U.S.Pat.No. 3,133,132,
8
incorporated herein by reference; semipermeable polystyrene derivatives; semipermeable (polysodiumstyrenesulfonate); semipermeable poly(vinylbenzyltrimethyl) ammonium chloride;
semipermeable polymers exhibiting a fluid permeability of 10~* to -7 2
(cc.mil/cm hr-atm) expressed as per atmosphere of hydrostatic or osmotic pressure difference across a semipermeable wall. The polymers are known to the art in U.S.Pat.Nos. 3,845,770, 3,916,899 and 4,160,020, all of which are incorporated herein by reference; and in J.R. Scott and W.J. Roff, "Handbook of Common Polymers", CRC Press, Cleveland, Ohio (1971).
^ Other materials that can be used to form the semipermeable
19
housing for imparting flexibility and elongation properties to the wall, for making the housing less to non-brittle and to render tear strength include phthalate plasticizers such as dibenzyl phthalate, dihexyl phthalate, butyl octyl phthalate, straight chain phthalates of six to eleven carbons, diisononyl phthalate, diisodecyl phthalate, and the like. The plasticizers include nonphthalates such as citric acid esters, triacetin, dioctyl azelate, epoxidized tallate, triisoctyl trimellitate, triisononyl trimellitate, sucrose acetate isobutyrate, epoxidized
19
4* ■
Srfe
-A.V _
- ■1 ■ fv-
f*
22 5 0 5 8
;it i o
J i 3
1 soybean oil, and the like. The amount of plasticizer in the
2 housing when incorporated therein, is about 0.01 to 20% by
3 weight, or higher.
4 Figure 5 illustrates a driving member 88 utilizing an
osmotically effective solute. The osmotically effective solute is
6 in solution 90 which is retained within a rigid housing 92
7 comprised of a semipermeable membrane substantially permeable to
8 the passage of an external fluid and substantially impermeable to
9 the passage of the osmotically effective solute contained in
✓
solution 90. The solution 90 is separated from the drug units 94
11 for example, by means of a flexible membrane 96.
12 The ability of driving member 88 to displace the drug units,
13 94 for example, housed within a dispenser depends upon the
14 osmotic pressure generated by the solution 90 of the osmotically
effective solute confined within housing 92. This solution
16 exhibi.ts an osmotic pressure gradient against fluid in the
17 environment into which the dispenser is placed, and is preferably
18 a saturated aqueous salt solution. To maintain the solution
19 saturated and therefore to achieve a constant osmotic pressure
throughout operation of the dispenser, the housing containing the
21 solution also contains excess solute in solid form. Various
22 osmotically effective solutes-' can be used. These include
23 magnesium sulfate, magnesium chloride, sodium chloride, potassium
24 sulfate, sodium carbonate, sodium sulfite, sodium sulfate, sodium
bicarbonate, potassium acid phthalate, calcium bicarbonate,
26 potassium acid phosphate, raffinose, tartaric acid, succinic
27 acid, calcium succinate, calcium lactate and magnesium succinate.
28 The excess solid solute can be in the form of dispersed particles
225058
or preferably in the form of a pellet. The solution can initially be a solution of the same or of an osmotically effective solute different than the solid excess solute.
Figure 6 illustrates a driving member 98 which is similar in operation to that of Fig. 5. An elementary osmotic pump 100, such as that disclosed in U.S.Pat.No. 3,845,770 is held rigidly in place in the impermeable housing 102, being exposed to the environment at surface 104. External fluid is imbibed through the *" semipermeable wall 106 by the osmotically effective solute 108 contained within the pump 100. As the osmotic pressure within the pump 100 increases, solution (external fluid and osmotic solute) is forced through the orifice 110 into chamber 112, thereby exerting pressure on piston 114 which subsequently moves through the housing 102 to dispense the drug units 116 contained therein. In order for this driving member to be operable, the wall of the housing 102 immediately surrounding the pump 100, must be impermeable to the passage of fluid so that external fluid does not enter chamber 112. Therefore, use of driving member 98 mandates that the housing be at least in part of an impermeable composition. In this manner, the housing in contact with the drug units can be semipermeable or impermeable.
Figure 7 illustrates a driving member 118 which operates by means of a gas generating composition 120. Housing 122 is made of a semipermeable material which is substantially impermeable to the passage of gas generating • composition 120, has a low permeability to the passage of an internally generated gas and is substantially permeable to the passage of an external fluid.
21
'■%'
% ;t>
I
I ^ J;
i
22 5 0 5 8
1 Membrane 124 is made of a semipermeable material which is
2 substantially impermeable to the passage of gas generating
3 composition 120 and substantially permeable to the passage of a
4 generated gas. Its main function is to keep the gas generating
composition 120 apart from the drug units contained in the
6 dispenser.
7 In operation, external fluid is imbibed through housing 122 j -•" 8 to continuously wet and dissolve the gas generating composition j
j 9 120, causing it to react and produce a large volume of gas. This
\ ' y
gas expands and passes through membrane 124, filling the area
: 11 126. This action correspondingly causes pressure to be exerted on
(
j 12 the drug unit 128 which thereby pushes this and the other units
| 13 contained therein, through the housing 122.
I 14 Gas generating composition 120 consists essentially of a dry
|
! 15 compound or an anhydrous mixture of compounds that when
I
I 16 intimately contacted by an external fluid that enters the housing
I
H 17 122, generates a gas that exerts a pressure to drive the
18 dispensing system. The composition 120 comprises a preferably
19 solid acidic material, and a preferably solid basic material that
dissolve and react in the presence of fluid that enters the
21 housing 122. This composition may be in powder, crystalline,
22 granular or layered form. -Alternately, the gas generating
23 composition may be present homogeneously or heterogeneously
24 dispersed in a matrix. The matrix is a polymer permeable to the
passage of external fluid and permeable to the passage of the
26 generated gas. The rate of gas generated in this embodiment is
27 governed by the rate of fluid passage through the polymer coupled
28 with the rate of fluid passage through the housing 122. Suitable
22
22 5 0 5 8
materials are disclosed in Theeuwes, U.S.Pat.No. 4,203,441, incorporated herein by reference.
Another embodiment of the dispensing configuration of this invention is illustrated in Figure 8. This embodiment is especially suited for delivery of units which all contain drug, where it is desired to prevent delivery from units which are still contained within the housing. The dispenser of Fig. 8 is comprised of a rigid housing member 130 which is designed with an ^outlet means, exit port 132. A plurality of movable discrete units 134, 136, 138, 140 and 142 are aligned within the housing 130, and are displaced towards the exit port 132 by means of driving member 144. The drug units are similar in form to those described in reference to Fig. 1 but are all drug containing units rater then drug- alternating with non-drug containing units.
I ft Fig. 8, while the units are contained within the housing they are protected from exposure to the environmental fluid by means of a plurality of plastic or polyethylene partitions 146, 148, 150, 152 and 154. When the dispenser is placed in the environment of use, the driving member 144 becomes fluid activated and linearly displaces the units, first dispelling the partition 146 and then unit 134. As unit 134 is delivering drug, unit 136 is gradually being displaced towards the exit 132 and in the meantime is protected from the environment by partition 148.
The amount of drug incorporated in the units of the dispenser of this invention varies widely depending on the particular drug, the desired therapeutic effect, and the time
23
1
2
3
4
6
7
8
9
11
12
13
14
16
17
18
19
21
22
23
24
26
27
28
225058
span for which it takes the drug to be released. Since a variety of units in a variety of sizes, shapes and compositions are intended to provide complete dosage regimes for therapy for a variety of maladies, there is no critical upper limit on the amount of drug incorporated in the units of the dispenser. The lower limit too will depend on the activity of the drug and the time span of its release from the units. Thus, it is not practical to define a range for the therapeutically effective amount of drug to be released by the individual units, or the dispenser as a whole.
This invention has been described in detail with particular reference to certain preferred embodiments thereof, but it will be understood that variations and modifications can be effected within the spirit and scope of the invention.
24 1.
-i.
■-<'<: ^.nv'V»;:vi
225058
Claims (35)
1. A drug dispenser suitable for use in a fluid-containing environment comprising in combination: a rigid housing; a fluid activated driving member that is activated by the fluid in said fluid-containing environment, said driving member being within a portion of said housing proximate the end of said housing opposite to said outlet and in contact with said housing, at least a portion of said housing opposite to said outlet and containing said driving member being permeable to the fluid in said fluid-containing environment; a plurality of discrete drug units longitudinally aligned and contained within said housing, said units maintaining their physical and chemical integrity while contained within said housing; and a drug unit outlet means in said housing that communicates with the units.
2. A dispenser according to claim 1 wherein said plurality of drug units contain the same drug.
3. A dispenser according to claim 1 wherein said plurality of drug units contain different drugs.
4. A dispenser according to any one of claims 1 to 3, wherein said drug units are separated by non-drug containing units.
5. A dispenser according to any one of claims 1 to 4, wherein the portion of said housing in contact with said driving member is permeable to the passage of fluid.
6. A dispenser according to any one of claims 1 to 5, wherein said driving member comprises a fluid swellable composition.
L, 235058 wherein said driving member comprises an osmotically effective solute.
8. A dispenser according to claim 7, wherein said solute and said drug units are separated by a flexible membrane.
9. A dispenser according to any one of claims 1 to 5, wherein said driving member is a gas generating composition.
10. A dispenser according to claim 9. wherein said gas generating composition and said drug units are separated by a semipermeable membrane.
11. A dispenser according to any one of claims 1 to 4, wherein the portion of said housing in contact with said driving member is impermeable to the passage of fluid.
12. A dispenser according to claim 11, wherein said driving member comprises an elementary osmotic pump.
13. A dispenser according to claim 12, wherein said elementary osmotic pump and said drug units are separated by a movable piston.
14. A dispenser according to any one of claims 1 to 13, which further comprises a density element.
15. An active agent dispenser suitable for use in a fluid-containing environment comprising, in combination: a. a rigid housing open at one end to provide outlet means therefor, at least a portion of said housing proximate the end of said housing opposite the outlet means permitting passage of the fluid in said environment to the interior of said housing J _ . o o rn ", P, m i-j \.i \J J u b. a fluid actuated driving member within said housing in fluid transmitting relationship with the fluid passing portion of said housing proximate the end of said housing opposite said outlet means, said driving member, upon exposure of said dispenser to said fluid environment, being the source of motive power for moving the contents of said housing through said outlet; and c. a plurality of solid, discrete dosage units containing the active agent longitudinally disposed within said housing between said driving member and said outlet means, whereby said dosage units will be sequentially displaced from said housing into said fluid environment by said driving member upon exposure of said dispenser to said fluid environment, at least a portion of said dosage units being adapted to maintain their chemical and physical integrity while within the housing and to dispense a substantial portion of their active agent content into the fluid environment after their displacement from said housing into said environment.
16. A dispenser according to claim 15. wherein said plurality of active agent units contain the same active agent.
17. A dispenser according to claim 15, wherein said plurality of active agent units contain different active agents.
18. A dispenser according to any one of claims 15 to 17, wherein said active agent units are separated by non-active agent containing units.
19. A dispenser according to any one of claims 15 to 18, wherein the portion of said housing in contact with said driving member is permeable to the passage of fluid. 27 /'V or ml, 2 5 OCT 1939 /; o o r A r p r,, UUUmU
20. A dispenser according to any one of claims 15 to 19. wherein said driving member comprises a fluid swellable composition.
21. A dispenser according to any one of claims 15 to 19, wherein said driving member comprises an osmotically effective solute.
22. A dispenser according to claim 21, wherein said solute and said active agent units are separated by a flexible membrane
23. A dispenser according to any one of claims 15 to 19, wherein said driving member is a gas generating composition.
24. A dispenser according to claim 23, wherein said gas generating composition and said active agent units are separated by a semipermeable membrane.
25. A dispenser according to any one of claims 15 to 18, wherein the portion of said housing in contact with said driving member is impermeable to the passage of fluid.
26. A dispenser according to claim 25 wherein said driving member comprises an elementary osmotic pump.
27. A dispenser according to claim 26 wherein said elementary osmotic pump and said drug units are separated by a movable piston.
28. A dispenser according to any one of claims 15 to 27, which further comprises a density element.
29. A dispenser according to any one of claims 1 to 28, 225058 O Q wherein the portion of said housing adjacent to said dosage units is impermeable to the fluid in said fluid environment.
30. A dispenser according to any one of claims 1 to 28. wherein the portion of said housing adjacent said dosage units is permeable to the fluid in said fluid environment.
31. A dispenser according to any one of claims 1 to 28. wherein said housing is formed from a material permeable to the fluid in said fluid environment.
32. A dispenser according to any one of claims 15 to 31, wherein said active agent is selected from the group consisting of pesticides, herbicides, biocides, algicides, rodenticides, fungicides, anti-oxidants, plant growth promoters, plant growth inhibitors, preservatives, antipreservatives, disinfectants, sterilization agents, catalysts, chemical reactants, fermentation agents, foods, food supplements, nutrients, cosmetics, drugs vitamins, sex steri1izants, fertility inhibitors, fertility promoters, air purifiers and niicroorganism attenuators.
33. A dispenser according to any one of claims 15 to 31, wherein said active agent is selected from the group consisting of human and animal hypnotics, sedatives, psychic energizers, tranquilizers, anticonvulsants, muscle relaxants, antiparkinson agents, analgesics, antiinflammatories, anesthetics, muscle contractants, anti-microbials, anti-malarials, hormonal agents, contraceptive agents, sympathomimetries, diuretics, parasiticides, neoplastics, hypoglycemics, opthalmics, electrolytes and diagnostic agents.
34. A drug dispenser substantially as herein described with reference to the accompanying drawings. "-3 APR t'90 oo-.fi r P w u l" JO
35. A drug dispenser according to claim 1 substantially as herein described or exemplified. ALZA CORPORATION By Their attorneys HE^RY HUGHES LIMITED 'JVVCUi
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US6690587A | 1987-06-25 | 1987-06-25 |
Publications (1)
Publication Number | Publication Date |
---|---|
NZ225058A true NZ225058A (en) | 1990-11-27 |
Family
ID=22072483
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NZ225058A NZ225058A (en) | 1987-06-25 | 1988-06-17 | Drug dispenser containing discrete drug units |
Country Status (9)
Country | Link |
---|---|
JP (1) | JP2732530B2 (en) |
AU (1) | AU602221B2 (en) |
CA (1) | CA1301572C (en) |
DE (1) | DE3821424C2 (en) |
ES (1) | ES2009014A6 (en) |
FR (1) | FR2617045B1 (en) |
GB (1) | GB2206046B (en) |
IT (1) | IT1219401B (en) |
NZ (1) | NZ225058A (en) |
Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5342624A (en) * | 1989-02-16 | 1994-08-30 | British Technology Group Ltd. | Dispensing device |
US6200600B1 (en) * | 1989-02-16 | 2001-03-13 | Btg International Limited | Controlled delay release device |
WO1990012567A1 (en) * | 1989-04-21 | 1990-11-01 | Moskovsky Avtomobilestroitelny Institut (Vtuz-Zil) | Device for controlled dosing of active substances into an operative medium |
US5474784A (en) * | 1990-03-02 | 1995-12-12 | British Technology Group Limited | Dispensing device |
GB9004702D0 (en) * | 1990-03-02 | 1990-04-25 | Polysystems Limited | Dispensing device |
US5017381A (en) * | 1990-05-02 | 1991-05-21 | Alza Corporation | Multi-unit pulsatile delivery system |
US5156850A (en) * | 1990-08-31 | 1992-10-20 | Alza Corporation | Dosage form for time-varying patterns of drug delivery |
US6440457B1 (en) | 1993-05-27 | 2002-08-27 | Alza Corporation | Method of administering antidepressant dosage form |
DE4342091A1 (en) * | 1993-12-09 | 1995-06-14 | Asta Medica Ag | Products for the application of initially high doses of Cetrorelix and manufacture of a combination pack for use in the treatment of diseases |
US5980508A (en) * | 1994-06-22 | 1999-11-09 | Controlled Release Technologies Pty Ltd | Controlled release device and method |
WO1998006380A2 (en) * | 1996-08-16 | 1998-02-19 | Alza Corporation | Dosage form for providing ascending dose of drug |
US6919373B1 (en) | 1996-11-12 | 2005-07-19 | Alza Corporation | Methods and devices for providing prolonged drug therapy |
KR101045144B1 (en) * | 2000-10-30 | 2011-06-30 | 유로-셀티크 소시에떼 아노뉨 | Controlled release hydrocodone formulations |
US20110104214A1 (en) | 2004-04-15 | 2011-05-05 | Purdue Pharma L.P. | Once-a-day oxycodone formulations |
US20050232995A1 (en) | 2002-07-29 | 2005-10-20 | Yam Nyomi V | Methods and dosage forms for controlled delivery of paliperidone and risperidone |
JP4824601B2 (en) * | 2007-02-22 | 2011-11-30 | 富士工業株式会社 | Tip protection cover for guided swing paddle |
JP4824602B2 (en) * | 2007-02-22 | 2011-11-30 | 富士工業株式会社 | Tip protection cover for guided swing paddle |
LT2512581T (en) * | 2009-12-17 | 2021-03-25 | Taris Biomedical Llc | Implantable device with intravesical tolerability |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4350271A (en) * | 1980-08-22 | 1982-09-21 | Alza Corporation | Water absorbing fluid dispenser |
US4449983A (en) * | 1982-03-22 | 1984-05-22 | Alza Corporation | Simultaneous delivery of two drugs from unit delivery device |
US4576604A (en) * | 1983-03-04 | 1986-03-18 | Alza Corporation | Osmotic system with instant drug availability |
AU2815684A (en) * | 1983-03-31 | 1984-10-25 | English Glass Company Limited, The | Multi-dose syringe and cannulae therefor |
US4692336A (en) * | 1984-03-19 | 1987-09-08 | Alza Corporation | Self controlled release device for administering beneficial agent to recipient |
ES8800043A1 (en) * | 1985-08-16 | 1987-10-16 | Alza Corp | Osmotic dispenser |
US4675174A (en) * | 1985-08-16 | 1987-06-23 | Alza Corporation | Veterinary dispenser delivering beneficial agent by gas power generated in situ |
US5011692A (en) * | 1985-12-28 | 1991-04-30 | Sumitomo Pharmaceuticals Company, Limited | Sustained pulsewise release pharmaceutical preparation |
US4723958A (en) * | 1986-05-23 | 1988-02-09 | Merck & Co., Inc. | Pulsatile drug delivery system |
-
1988
- 1988-06-15 GB GB8814220A patent/GB2206046B/en not_active Expired - Lifetime
- 1988-06-17 NZ NZ225058A patent/NZ225058A/en unknown
- 1988-06-20 AU AU18169/88A patent/AU602221B2/en not_active Expired
- 1988-06-23 ES ES8801959A patent/ES2009014A6/en not_active Expired
- 1988-06-24 CA CA000570389A patent/CA1301572C/en not_active Expired - Lifetime
- 1988-06-24 IT IT67602/88A patent/IT1219401B/en active
- 1988-06-24 DE DE3821424A patent/DE3821424C2/en not_active Expired - Lifetime
- 1988-06-24 JP JP63156609A patent/JP2732530B2/en not_active Expired - Lifetime
- 1988-06-27 FR FR888808592A patent/FR2617045B1/en not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
---|---|
IT1219401B (en) | 1990-05-11 |
JPS6452457A (en) | 1989-02-28 |
DE3821424C2 (en) | 1997-02-20 |
GB2206046B (en) | 1991-04-03 |
GB8814220D0 (en) | 1988-07-20 |
CA1301572C (en) | 1992-05-26 |
IT8867602A0 (en) | 1988-06-24 |
AU1816988A (en) | 1989-01-05 |
FR2617045A1 (en) | 1988-12-30 |
FR2617045B1 (en) | 1991-09-13 |
AU602221B2 (en) | 1990-10-04 |
GB2206046A (en) | 1988-12-29 |
ES2009014A6 (en) | 1989-08-16 |
JP2732530B2 (en) | 1998-03-30 |
DE3821424A1 (en) | 1989-01-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US4874388A (en) | Multi-layer delivery system | |
US5023088A (en) | Multi-unit delivery system | |
US5110597A (en) | Multi-unit delivery system | |
US5391381A (en) | Dispenser capable of delivering plurality of drug units | |
US5340590A (en) | Delivery system with bilayer osmotic engine | |
US4957494A (en) | Multi-layer delivery system | |
US5499979A (en) | Delivery system comprising kinetic forces | |
US5236689A (en) | Multi-unit delivery system | |
AU602221B2 (en) | Multi-unit delivery system | |
US4627850A (en) | Osmotic capsule | |
EP0482075B1 (en) | Oral osmotic device with hydrogel driving member | |
AU645315B2 (en) | Osmotic dosage system for liquid drug delivery | |
US5776493A (en) | Oral osmotic device for delivery of nystatin with hydrogel driving member | |
CA1222950A (en) | Osmotic device with dual thermodynamic activity | |
US4326525A (en) | Osmotic device that improves delivery properties of agent in situ | |
EP0300623B1 (en) | Dispenser with movable matrix comprising a plurality of tiny pills | |
EP0040899A2 (en) | Method of delivering drug with aid of effervescent activity generated in environment of use | |
AU2199400A (en) | Conversion of liquid filled gelatin capsules into controlled release systems by multiple coatings | |
US4743247A (en) | Process for manufacturing dosage form | |
WO2006007351A2 (en) | Squeeze controlled oral dosage form | |
US4484921A (en) | Theophylline therapy utilizing osmotic delivery | |
US4439195A (en) | Theophylline therapy |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
RENW | Renewal (renewal fees accepted) |