WO2022098320A1 - Topical pharmaceutical compositions containing minoxidil and relevant excipients - Google Patents
Topical pharmaceutical compositions containing minoxidil and relevant excipients Download PDFInfo
- Publication number
- WO2022098320A1 WO2022098320A1 PCT/TR2020/051063 TR2020051063W WO2022098320A1 WO 2022098320 A1 WO2022098320 A1 WO 2022098320A1 TR 2020051063 W TR2020051063 W TR 2020051063W WO 2022098320 A1 WO2022098320 A1 WO 2022098320A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- minoxidil
- topical pharmaceutical
- pharmaceutical composition
- topical
- composition according
- Prior art date
Links
- ZFMITUMMTDLWHR-UHFFFAOYSA-N Minoxidil Chemical compound NC1=[N+]([O-])C(N)=CC(N2CCCCC2)=N1 ZFMITUMMTDLWHR-UHFFFAOYSA-N 0.000 title claims abstract description 62
- 229960003632 minoxidil Drugs 0.000 title claims abstract description 54
- 239000000546 pharmaceutical excipient Substances 0.000 title claims abstract description 22
- 239000012049 topical pharmaceutical composition Substances 0.000 title claims description 17
- 201000004384 Alopecia Diseases 0.000 claims abstract description 32
- 230000000699 topical effect Effects 0.000 claims abstract description 19
- 230000003676 hair loss Effects 0.000 claims abstract description 14
- 201000002996 androgenic alopecia Diseases 0.000 claims abstract description 13
- 208000024963 hair loss Diseases 0.000 claims abstract description 9
- 230000006641 stabilisation Effects 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 45
- 239000000499 gel Substances 0.000 claims description 25
- 239000003349 gelling agent Substances 0.000 claims description 23
- 229920001577 copolymer Polymers 0.000 claims description 12
- OMIGHNLMNHATMP-UHFFFAOYSA-N 2-hydroxyethyl prop-2-enoate Chemical compound OCCOC(=O)C=C OMIGHNLMNHATMP-UHFFFAOYSA-N 0.000 claims description 7
- 229940104261 taurate Drugs 0.000 claims description 6
- 239000002552 dosage form Substances 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 239000006210 lotion Substances 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 3
- FWFUWXVFYKCSQA-UHFFFAOYSA-M sodium;2-methyl-2-(prop-2-enoylamino)propane-1-sulfonate Chemical compound [Na+].[O-]S(=O)(=O)CC(C)(C)NC(=O)C=C FWFUWXVFYKCSQA-UHFFFAOYSA-M 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 9
- 238000002360 preparation method Methods 0.000 abstract description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 238000004519 manufacturing process Methods 0.000 description 9
- 239000003814 drug Substances 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 235000019441 ethanol Nutrition 0.000 description 7
- 239000012535 impurity Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 229940042129 topical gel Drugs 0.000 description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- -1 cinnamaldehyde glycerol acetal Chemical class 0.000 description 6
- 239000008252 pharmaceutical gel Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 231100000360 alopecia Toxicity 0.000 description 5
- 229920002125 Sokalan® Polymers 0.000 description 4
- 206010068168 androgenetic alopecia Diseases 0.000 description 4
- 238000009792 diffusion process Methods 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 3
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229940041616 menthol Drugs 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 241000195940 Bryophyta Species 0.000 description 2
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 235000019568 aromas Nutrition 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- RRAFCDWBNXTKKO-UHFFFAOYSA-N eugenol Chemical compound COC1=CC(CC=C)=CC=C1O RRAFCDWBNXTKKO-UHFFFAOYSA-N 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 230000003779 hair growth Effects 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 235000011929 mousse Nutrition 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000003658 preventing hair loss Effects 0.000 description 2
- 229960004063 propylene glycol Drugs 0.000 description 2
- 235000013772 propylene glycol Nutrition 0.000 description 2
- 239000002453 shampoo Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000008719 thickening Effects 0.000 description 2
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 description 2
- RUVINXPYWBROJD-ONEGZZNKSA-N trans-anethole Chemical compound COC1=CC=C(\C=C\C)C=C1 RUVINXPYWBROJD-ONEGZZNKSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- XUKUURHRXDUEBC-SXOMAYOGSA-N (3s,5r)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-SXOMAYOGSA-N 0.000 description 1
- WEEGYLXZBRQIMU-UHFFFAOYSA-N 1,8-cineole Natural products C1CC2CCC1(C)OC2(C)C WEEGYLXZBRQIMU-UHFFFAOYSA-N 0.000 description 1
- OEYNWAWWSZUGDU-UHFFFAOYSA-N 1-methoxypropane-1,2-diol Chemical compound COC(O)C(C)O OEYNWAWWSZUGDU-UHFFFAOYSA-N 0.000 description 1
- JVTIXNMXDLQEJE-UHFFFAOYSA-N 2-decanoyloxypropyl decanoate 2-octanoyloxypropyl octanoate Chemical compound C(CCCCCCC)(=O)OCC(C)OC(CCCCCCC)=O.C(=O)(CCCCCCCCC)OCC(C)OC(=O)CCCCCCCCC JVTIXNMXDLQEJE-UHFFFAOYSA-N 0.000 description 1
- AZSNMRSAGSSBNP-UHFFFAOYSA-N 22,23-dihydroavermectin B1a Natural products C1CC(C)C(C(C)CC)OC21OC(CC=C(C)C(OC1OC(C)C(OC3OC(C)C(O)C(OC)C3)C(OC)C1)C(C)C=CC=C1C3(C(C(=O)O4)C=C(C)C(O)C3OC1)O)CC4C2 AZSNMRSAGSSBNP-UHFFFAOYSA-N 0.000 description 1
- OZJPLYNZGCXSJM-UHFFFAOYSA-N 5-valerolactone Chemical compound O=C1CCCCO1 OZJPLYNZGCXSJM-UHFFFAOYSA-N 0.000 description 1
- SPBDXSGPUHCETR-JFUDTMANSA-N 8883yp2r6d Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O[C@@H]([C@@H](C)CC4)C(C)C)O3)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1C[C@H](C)[C@@H]([C@@H](C)CC)O[C@@]21O[C@H](C\C=C(C)\[C@@H](O[C@@H]1O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C1)[C@@H](C)\C=C\C=C/1[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\1)O)C[C@H]4C2 SPBDXSGPUHCETR-JFUDTMANSA-N 0.000 description 1
- NEEKVKZFYBQFGT-BTJKTKAUSA-N 9-amino-1,2,3,4-tetrahydroacridin-1-ol;(z)-but-2-enedioic acid Chemical compound OC(=O)\C=C/C(O)=O.C1=CC=C2C(N)=C(C(O)CCC3)C3=NC2=C1 NEEKVKZFYBQFGT-BTJKTKAUSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- NPBVQXIMTZKSBA-UHFFFAOYSA-N Chavibetol Natural products COC1=CC=C(CC=C)C=C1O NPBVQXIMTZKSBA-UHFFFAOYSA-N 0.000 description 1
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 1
- YASYEJJMZJALEJ-UHFFFAOYSA-N Citric acid monohydrate Chemical compound O.OC(=O)CC(O)(C(O)=O)CC(O)=O YASYEJJMZJALEJ-UHFFFAOYSA-N 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- WEEGYLXZBRQIMU-WAAGHKOSSA-N Eucalyptol Chemical compound C1C[C@H]2CC[C@]1(C)OC2(C)C WEEGYLXZBRQIMU-WAAGHKOSSA-N 0.000 description 1
- 239000005770 Eugenol Substances 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 235000019501 Lemon oil Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 235000011203 Origanum Nutrition 0.000 description 1
- 240000000783 Origanum majorana Species 0.000 description 1
- 241000288049 Perdix perdix Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- UVMRYBDEERADNV-UHFFFAOYSA-N Pseudoeugenol Natural products COC1=CC(C(C)=C)=CC=C1O UVMRYBDEERADNV-UHFFFAOYSA-N 0.000 description 1
- 235000001537 Ribes X gardonianum Nutrition 0.000 description 1
- 235000001535 Ribes X utile Nutrition 0.000 description 1
- 235000016919 Ribes petraeum Nutrition 0.000 description 1
- 244000281247 Ribes rubrum Species 0.000 description 1
- 235000002355 Ribes spicatum Nutrition 0.000 description 1
- 235000017276 Salvia Nutrition 0.000 description 1
- 240000007164 Salvia officinalis Species 0.000 description 1
- 239000005844 Thymol Substances 0.000 description 1
- 244000290333 Vanilla fragrans Species 0.000 description 1
- 235000009499 Vanilla fragrans Nutrition 0.000 description 1
- 235000012036 Vanilla tahitensis Nutrition 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 239000002535 acidifier Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- UZFLPKAIBPNNCA-BQYQJAHWSA-N alpha-ionone Chemical compound CC(=O)\C=C\C1C(C)=CCCC1(C)C UZFLPKAIBPNNCA-BQYQJAHWSA-N 0.000 description 1
- UZFLPKAIBPNNCA-UHFFFAOYSA-N alpha-ionone Natural products CC(=O)C=CC1C(C)=CCCC1(C)C UZFLPKAIBPNNCA-UHFFFAOYSA-N 0.000 description 1
- 229940011037 anethole Drugs 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 229940057971 butane Drugs 0.000 description 1
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 229940075510 carbopol 981 Drugs 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229960005233 cineole Drugs 0.000 description 1
- 235000017803 cinnamon Nutrition 0.000 description 1
- 229960002303 citric acid monohydrate Drugs 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000010642 eucalyptus oil Substances 0.000 description 1
- 229940044949 eucalyptus oil Drugs 0.000 description 1
- 239000001902 eugenia caryophyllata l. bud oil Substances 0.000 description 1
- 229960002217 eugenol Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- 230000003450 growing effect Effects 0.000 description 1
- 229940124563 hair growth stimulant Drugs 0.000 description 1
- 230000003719 hair strength Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000001282 iso-butane Substances 0.000 description 1
- 235000013847 iso-butane Nutrition 0.000 description 1
- 229940035415 isobutane Drugs 0.000 description 1
- 229960002418 ivermectin Drugs 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 239000010501 lemon oil Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000003273 male-pattern hair loss Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 206010051747 multiple endocrine neoplasia Diseases 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 239000007908 nanoemulsion Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 229940096978 oral tablet Drugs 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- RUVINXPYWBROJD-UHFFFAOYSA-N para-methoxyphenyl Natural products COC1=CC=C(C=CC)C=C1 RUVINXPYWBROJD-UHFFFAOYSA-N 0.000 description 1
- 239000010663 parsley oil Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 231100000435 percutaneous penetration Toxicity 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 235000013849 propane Nutrition 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
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- 239000000725 suspension Substances 0.000 description 1
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- 229960000790 thymol Drugs 0.000 description 1
- 230000008467 tissue growth Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
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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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
Definitions
- the present invention relates to the preparation of pharmaceutical compositions comprising minoxidil; and also relevant excipients, useful for the topical treatment (regrowth) of androgenic alopecia in males and females and stabilisation of hair loss in patients with androgenic alopecia.
- Androgenetic alopecia is a common form of hair loss in both men and women.
- Alopecia, or hair loss, in its various forms is an ongoing problem effects humankind. Men, women and children can all suffer from disease of alopecia, The reasons can be of one, or a combination of different factors including genetic factors, hormonal factors, surgery, trauma, chemotherapy, aging, certain drug side effects and stress.
- Minoxidil is one of topical active ingredient used for alopecia treatment. It is a medication used for the treatment of male-pattern hair loss and also high blood pressure. It is effective in helping promote hair growth in people with androgenic alopecia regardless of sex.
- Minoxidil is available as a generic medication by prescription in oral tablet form and over the counter as a topical gel, liquid or foam.
- Minoxidil has a chemical name as 2-Imino-6-(l-piperidinyl)-l,2-dihydro-4-pyrimidinamine 3 -oxide and its chemical structure is shown in the Figure I.
- Minoxidil has molecular weight of 209.248 g/mol, is a white or almost white crystalline powder.
- FIG. 1 Minoxidil
- One of the existing drug comprising minoxidil in topical product is Regaine marketed by Johnson & Johnson. This product is available in the form of foam and solution for men and also women. It is used to treat baldness or Androgenetic alopecia’s long-term, hair loss prevention and hair growth.
- Regaine includes butane, butylated hydroxytoluene, cetyl alcohol, citric acid mono hydrate, glycerin, isobutane, lactic acid, polysorbate 60, propane, stearyl alcohol and water.
- Present invention relates to a topical pharmaceutical composition
- a topical pharmaceutical composition comprising; a) 0,1 to 5,0 % by weight of minoxidil, b) a gelling agent, c) one or more pharmaceutically acceptable excipients.
- Present invention relates to a topical pharmaceutical composition
- a topical pharmaceutical composition comprising; a) 5,0 % by weight of minoxidil, b) a gelling agent, c) one or more pharmaceutically acceptable excipients.
- Present invention relates to a topical pharmaceutical composition
- a topical pharmaceutical composition comprising; a) 5,0 % by weight of minoxidil, b) Hydroxyethyl Acrylate / Sodium Dimethyl Acryloyl Taurate Copolymer as a gelling agent, c) one or more pharmaceutically acceptable excipients.
- the present invention also relates to a process for preparing a topical pharmaceutical gel composition and uses of the composition.
- Minoxidil particularly has many advantages for the treatment of hair loss or baldness. Active ingredient of minoxidil has been used to treat of alopecia for many years.
- Minoxidil is a wellknown pharmaceutical active ingredient for treatment of androgenic alopecia and it is proven with many clinical studies.
- the hair loss may be related to alopecia disease for men and/or women.
- Related indications may include weakening of hair strength, loss of hair colour and the like.
- Minoxidil is a pharmaceutically active ingredient having several indications including use as a hair growth stimulant.
- composition of the present invention is also useful for preventing hair loss and thinning hair.
- Minoxidil is externally applied then it shows excellent hair-fostering and hair growing effects. Minoxidil’s property of hair restorer is accepted prevalently.
- Minoxidil has poor solubility in water and ethanol and pharmaceutical preparations currently marketed only contain with a percentage of minoxidil that is, below 5%.
- the invention provides a topical composition containing the composition that is suitable for administering to mammalian skin, such as human skin.
- such topical composition contains an effective amount of (i) the composition, and (ii) a pharmaceutically acceptable carrier.
- the dosage form of the minoxidil containing composition for external use is not particularly limited.
- the dosage form is preferably a gel, a lotion, or a liquid.
- the present inventions provide pharmaceutical compositions comprising minoxidil and relevant excipients, characterized by i) to control / program the release of the active ingredient according to desired therapeutical needs such as hair loss or baldness, ii) a simple and competitive manufacturing process to achieve effect of hair restorer in medically.
- Present invention relates to a specific topical pharmaceutical gel composition
- a specific topical pharmaceutical gel composition comprises a) 0,1 to 5,0 % by weight of minoxidil, b) a gelling agent, c) one or more pharmaceutically acceptable excipients.
- Present invention relates to a specific topical pharmaceutical gel composition
- a specific topical pharmaceutical gel composition comprises a) 5,0 % by weight of minoxidil, b) a gelling agent, c) one or more pharmaceutically acceptable excipients.
- the weight ratio of minoxidil is between 0,1 to 5,0 % (w/w) in topical gel composition. In one embodiment of the invention, the weight ratio of minoxidil is 2,0 % (w/w) in topical gel composition.
- the weight ratio of minoxidil is 5,0 % (w/w) in topical gel composition.
- Gelling agents are commonly used for topical gel compositions. Gelling agents has selfgelling and thickening properties and also the ability to emulsify oily phases, which make it easy to use in the formulation of gels and o/w emulsion gels.
- gelling agents can be selected from polymers or copolymers. Some copolymers are used as a gelling agent for topical pharmaceutical or cosmetic products. Because of their structure and characteristics, it is very useful for topical products.
- Sepineo Derm is a brand of Seppic that is used as a gelling agent and in copolymer structure.
- Structure of Sepineo Derm is a copolymer of hydroxyethyl acrylate and sodium acryloyl dimethyl taurate.
- Seppic - manufacturer of Sepineo Derm it is a ready-to-use polymer in powder form with thickening, stabilizing and texturizing properties.
- Sepineo Derm has some advantages in manufacturing process. Firstly, it is preneutralised powder and therefore does not require a neutralisation step before use. Also, it is dispersible in aqueous or fatty phases and can be mixed equally well in a hot or cold process. Additionally, it is UV resistant, allowing the use of transparent or clear packaging without compromising the formula’s stability.
- compositions according to the invention may also comprise gelling agents ranging from 0.1 to 3% by weight relative to the total weight of the composition.
- compositions of the invention preferentially contain from 0.1 to 3%, and preferably from 0.8 to 1.4%, of gelling agent, more preferably 1.1 %.
- present invention relates to a specific topical pharmaceutical gel composition
- a specific topical pharmaceutical gel composition comprises a) 5,0 % by weight of minoxidil, b) 1,1 % by weight of gelling agent, c) one or more pharmaceutically acceptable excipients.
- present invention relates to a specific topical pharmaceutical gel composition
- a specific topical pharmaceutical gel composition comprises a) 5,0 % by weight of minoxidil, b) 1,1 % by weight of copolymer of hydroxy ethyl acrylate and sodium acryloyl dimethyl taurate, c) one or more pharmaceutically acceptable excipients.
- the invention also relates to a process for preparing a topical pharmaceutical gel compositions as described above, comprising the steps of: a) Adding: Ethanol, distilled water and propylene glycole b) Mixing: Minoxidil c) Mixing: Gelling agent d) Mixing: Menthol and ethanol e) Made up volume with ethanol e) Filling f) Packaging.
- the present invention provides pharmaceutical composition
- minoxidil characterized by a) Simple and also competitive manufacturing process, b) Enhanced patient compliance and convenience, c) The product is administered easily and quickly, d) A dose can be removed with out contamination of materials, e) Eower dose of drug can be used and hence minimize adverse and side effects, f) Medication can be delivered directly to the affected area in a desired form, g) Irritation produced by the mechanical application of topical medication is reduced or eliminated.
- the present invention shows well physical properties depends on its solubility characteristics in appropriate excipients for topical compositions. It shows good properties to provide basic physical stability.
- the success of a dermotological drug depends on the ability of the drug to penetrate through skin in sufficient quantities to achieve the desired therapeutic effect.
- the present invention provides to increase the rate of percutaneous penetration, thereby shortening the time period in which the active agents can show their effect.
- the components of the pharmaceutical composition according to the present invention are brought together into a gel for topical administration according to standard practice and procedures well known to one of ordinary skill in the art using conventional composition and manufacturing techniques.
- the present invention relates a composition comprising minoxidil as an active ingredient for external use, and also relates to a minoxidil composition, which is clear and viscous, is inhibited from dripping, and has a good comfort of use.
- the invention provides pharmaceutical composition comprising minoxidil as an active agent, process of preparation thereof and method of using the same.
- the invention provides a topical pharmaceutical composition comprising effective amount of minoxidil as an active agent and process of preparation thereof.
- the invention provides method to treating one or more dermatological conditions such as androgenic alopecia, baldness or hair loss and the like, by applying topical pharmaceutical composition of minoxidil onto the the affected skin area of a subject in need of such treatment.
- composition of the invention can be packed into suitable containers such as bottle, tube, pouch, or suitable container.
- the topical gel composition of minoxidil comprises one or more pharmaceutically acceptable excipient(s).
- Pharmaceutically acceptable excipients comprise, but are not limited to, gelling agents, polymers, aromas, emollients, solvents, pH adjusting agents, preservatives, fragrances, stabilizers, penetration enhancers, moisturizers, and mixtures thereof.
- Gelling agents can be selected from the group, but are not limited to, carbomer, Carbopol 981, Carbopol ETD 2020, Carbopol 980, Carbopol Ultrez 10 NF and Pemulen TRI, Hydroxyethyl Aery late/S odium Dimethyl Acryloyl Taurate Copolymer (such as Sepineo Derm) or the family of modified starches or mixtures thereof.
- the preferred gelling agent is Hydroxyethyl Aery late/S odium Dimethyl Acryloyl Taurate Copolymer.
- Solvents/cosolvents can be selected from the group, but not limited to, ethanol, ethyl alcohol, polyethylene glycol, propylene glycol, isopropyl alcohol, distilled water and other materials known to one of ordinary skill in the art and mixtures thereof.
- the preferred solvents are ethanol, propylene glycol and distilled water.
- Aromas can be selected from the group, but are not limited to, natural aroma oil (e.g. peppermint oil, partridge currant oil, clove bud oil, parsley oil, eucalyptus oil, lemon oil, orange oil, etc.), menthol, mentane, anethole, methyl salicylate, eucalyptol, cinnamon, 1- methyl acetate, salvia, eugenol, oxanone, alpha-ionone, marjoram, lemon, orange, propenyl guaethol acetyl, sinnamon, vanilla, thymol, linaolol, cinnamaldehyde glycerol acetal, N- substituted p-menthane-3-carboxyamide, 3,1- methoxy propane 1,2-diol.and other materials known to one of ordinary skill in the art and mixtures thereof.
- the preferred aroma is menthol.
- the term “treating” or “treatment” means the alleviation or elimination of symptoms, cure, prevention, or inhibition of a disease or medical condition, or improvement of tissue growth/healing or cosmetic conditions.
- the topical composition may be any form suitable for application to the skin or an animal or human.
- the forms may include gels, solutions, lotions, ointments, mousses, foams, sprays, aerosols, shampoos, creams, pastes or other topical composition forms known in the art.
- the topical compositions may be made into a wide variety of products that include but are not limited to leave-on products (such as lotions, creams, gels, sticks, sprays, and ointments), hair products (such as shampoos, conditioners, sprays, and mousses) and the like.
- leave-on products such as lotions, creams, gels, sticks, sprays, and ointments
- hair products such as shampoos, conditioners, sprays, and mousses
- These product types may contain any of several pharmaceutically acceptable carrier forms including, but not limited to solutions, suspensions, emulsions such as microemulsions and nanoemulsions, gels, and solids carrier forms.
- Other product forms can be formulated by those of ordinary skill in the art.
- pharmaceutically acceptable means molecular entities and compositions that are of sufficient purity and quality for use in the formulation of a composition or medicament of the present invention.
- “Pharmaceutically acceptable excipients” are components that are added to the pharmaceutical formula tion other than the active ingredient ivermectin. Excipients may be added to facilitate manufacture, enhance stability, enhance product characteristics, enhance skin penetration, enhance patient acceptability etc.
- Pharmaceutically acceptable excipients includes, but not limited to, one or more filler, gelling agent, surfactant, humectant, pH modifier, chelating agent, acidifying agent, viscosity enhance, solvent, vehicle, oily vehicle, color, preservative, suspending agent, dispersing agent, and any other excipient known to the art for making pharmaceutical formulation.
- reference product means Regaine product comprising minoxidil 5% from Johnson & Johnson Limited, UK with an expiry date 07/2021.
- test product means Minoxidil Gel product comprising minoxidil 5% from Pharmactive, Turkey with an expiry date 08/2021.
- Example for gel composition comprising minoxidil is below.
- Figure 1 Manufacturing flowchart for pharmaceutical composition comprising minoxidil topical gel. Franz diffusion study
- a Franz diffusion cell system is used as an apparatus for transdermal permeation test, which used a dialyses membrane has receptor media (20/80 Ethanole/water) with 0,45 pm PTFE filter. Samples were collected from the receptor compartment at scheduled time points of 0,5 hour, 1 hour, 2 hours, 3 hours, 4 hours and 5 hours. 1 mL of the sample was collected and analyzed to determine a 5 hour cumulative permeation amount (pg/cm2) for the percutaneous absorption preparation containing minoxidil. The results are presented in Table 1.
- Table 1 Franz diffusion study results of test product, reference product (Regaine) and competitor product (Tugain Gel)
- the percutaneous absorption preparations using test product shows a skin permeation equivalent to or higher than the competitor product (Tugain Gel).
- Viscosity results of test product and competitor product are shown in Table 2.
- Table 3 Initial pH results of present invention for test product, reference product (Regaine) and competitor product (Tugain Gel)
- Test product product > (Impurities) (Minoxidil gel) (Tugain Gel) s ’
- test product has advantages for impurities comparing to competitor product.
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Abstract
The present invention relates to the preparation of pharmaceutical compositions comprising minoxidil; and also relevant excipients, useful for the topical treatment (regrowth) of androgenic alopecia in males and females and stabilisation of hair loss in patients with androgenic alopecia.
Description
TOPICAL PHARMACEUTICAL COMPOSITIONS CONTAINING MINOXIDIL AND RELEVANT EXCIPIENTS
Field of invention
The present invention relates to the preparation of pharmaceutical compositions comprising minoxidil; and also relevant excipients, useful for the topical treatment (regrowth) of androgenic alopecia in males and females and stabilisation of hair loss in patients with androgenic alopecia.
Background of the invention
Androgenetic alopecia is a common form of hair loss in both men and women. Alopecia, or hair loss, in its various forms is an ongoing problem effects humankind. Men, women and children can all suffer from disease of alopecia, The reasons can be of one, or a combination of different factors including genetic factors, hormonal factors, surgery, trauma, chemotherapy, aging, certain drug side effects and stress.
Minoxidil is one of topical active ingredient used for alopecia treatment. It is a medication used for the treatment of male-pattern hair loss and also high blood pressure. It is effective in helping promote hair growth in people with androgenic alopecia regardless of sex.
Minoxidil is available as a generic medication by prescription in oral tablet form and over the counter as a topical gel, liquid or foam.
Minoxidil, has a chemical name as 2-Imino-6-(l-piperidinyl)-l,2-dihydro-4-pyrimidinamine 3 -oxide and its chemical structure is shown in the Figure I. Minoxidil has molecular weight of 209.248 g/mol, is a white or almost white crystalline powder.
Figure 1: Minoxidil
One of the existing drug comprising minoxidil in topical product is Regaine marketed by Johnson & Johnson. This product is available in the form of foam and solution for men and also women. It is used to treat baldness or Androgenetic alopecia’s long-term, hair loss prevention and hair growth. Regaine includes butane, butylated hydroxytoluene, cetyl alcohol, citric acid mono hydrate, glycerin, isobutane, lactic acid, polysorbate 60, propane, stearyl alcohol and water.
Summary of the invention
Present invention relates to a topical pharmaceutical composition comprising; a) 0,1 to 5,0 % by weight of minoxidil, b) a gelling agent, c) one or more pharmaceutically acceptable excipients.
Present invention relates to a topical pharmaceutical composition comprising; a) 5,0 % by weight of minoxidil, b) a gelling agent, c) one or more pharmaceutically acceptable excipients.
Present invention relates to a topical pharmaceutical composition comprising; a) 5,0 % by weight of minoxidil, b) Hydroxyethyl Acrylate / Sodium Dimethyl Acryloyl Taurate Copolymer as a gelling agent, c) one or more pharmaceutically acceptable excipients.
The present invention also relates to a process for preparing a topical pharmaceutical gel composition and uses of the composition.
Detailed description of the invention
Minoxidil particularly has many advantages for the treatment of hair loss or baldness. Active ingredient of minoxidil has been used to treat of alopecia for many years.
Minoxidil is a wellknown pharmaceutical active ingredient for treatment of androgenic alopecia and it is proven with many clinical studies.
Genetic and environmental factors play a major role in causing androgenetic alopecia. Although researchers are studying risk factors that may contribute to this condition, most of these factors still remain unknown.
Investigations continue to understand the connection between androgenetic alopecia and other medical diseases, such as coronary heart disease and prostate cancer in men and polycystic ovary syndrome in women.
The hair loss may be related to alopecia disease for men and/or women. Related indications may include weakening of hair strength, loss of hair colour and the like.
Minoxidil is a pharmaceutically active ingredient having several indications including use as a hair growth stimulant.
The composition of the present invention is also useful for preventing hair loss and thinning hair.
Minoxidil is externally applied then it shows excellent hair-fostering and hair growing effects. Minoxidil’s property of hair restorer is accepted prevalently.
In the market, there are many minoxidil pharmaceutical products including OTC with different dosage forms such as foam, solution or gel.
Minoxidil has poor solubility in water and ethanol and pharmaceutical preparations currently marketed only contain with a percentage of minoxidil that is, below 5%.
In one embodiment, the invention provides a topical composition containing the composition that is suitable for administering to mammalian skin, such as human skin.
In one embodiment, such topical composition contains an effective amount of (i) the composition, and (ii) a pharmaceutically acceptable carrier.
The dosage form of the minoxidil containing composition for external use is not particularly limited. The dosage form is preferably a gel, a lotion, or a liquid.
The present inventions provide pharmaceutical compositions comprising minoxidil and relevant excipients, characterized by i) to control / program the release of the active ingredient according to desired therapeutical needs such as hair loss or baldness, ii) a simple and competitive manufacturing process to achieve effect of hair restorer in medically.
Present invention relates to a specific topical pharmaceutical gel composition comprises a) 0,1 to 5,0 % by weight of minoxidil, b) a gelling agent, c) one or more pharmaceutically acceptable excipients.
Present invention relates to a specific topical pharmaceutical gel composition comprises a) 5,0 % by weight of minoxidil, b) a gelling agent, c) one or more pharmaceutically acceptable excipients.
In one embodiment of the invention, the weight ratio of minoxidil is between 0,1 to 5,0 % (w/w) in topical gel composition.
In one embodiment of the invention, the weight ratio of minoxidil is 2,0 % (w/w) in topical gel composition.
In one embodiment of the invention, the weight ratio of minoxidil is 5,0 % (w/w) in topical gel composition.
Gelling agents are commonly used for topical gel compositions. Gelling agents has selfgelling and thickening properties and also the ability to emulsify oily phases, which make it easy to use in the formulation of gels and o/w emulsion gels.
In one embodiment, gelling agents can be selected from polymers or copolymers. Some copolymers are used as a gelling agent for topical pharmaceutical or cosmetic products. Because of their structure and characteristics, it is very useful for topical products.
Sepineo Derm is a brand of Seppic that is used as a gelling agent and in copolymer structure. Structure of Sepineo Derm is a copolymer of hydroxyethyl acrylate and sodium acryloyl dimethyl taurate.
According to Seppic - manufacturer of Sepineo Derm, it is a ready-to-use polymer in powder form with thickening, stabilizing and texturizing properties.
Using Sepineo Derm has some advantages in manufacturing process. Firstly, it is preneutralised powder and therefore does not require a neutralisation step before use. Also, it is dispersible in aqueous or fatty phases and can be mixed equally well in a hot or cold process. Additionally, it is UV resistant, allowing the use of transparent or clear packaging without compromising the formula’s stability.
The compositions according to the invention may also comprise gelling agents ranging from 0.1 to 3% by weight relative to the total weight of the composition.
Preferably the compositions of the invention preferentially contain from 0.1 to 3%, and preferably from 0.8 to 1.4%, of gelling agent, more preferably 1.1 %.
In one embodiment, present invention relates to a specific topical pharmaceutical gel composition comprises a) 5,0 % by weight of minoxidil, b) 1,1 % by weight of gelling agent, c) one or more pharmaceutically acceptable excipients.
In one embodiment, present invention relates to a specific topical pharmaceutical gel composition comprises a) 5,0 % by weight of minoxidil, b) 1,1 % by weight of copolymer of hydroxy ethyl acrylate and sodium acryloyl dimethyl taurate, c) one or more pharmaceutically acceptable excipients.
The invention also relates to a process for preparing a topical pharmaceutical gel compositions as described above, comprising the steps of: a) Adding: Ethanol, distilled water and propylene glycole b) Mixing: Minoxidil c) Mixing: Gelling agent d) Mixing: Menthol and ethanol e) Made up volume with ethanol e) Filling f) Packaging.
It is found that when present invention of minoxidil gel composition, is prepared with a gelling agent such as Hydroxy ethyl Acrylate / Sodium Dimethyl Acryloyl Taurate Copolymer, Franz diffusion results were satisfy. (Table 1)
Advantages
The present invention provides pharmaceutical composition comprising minoxidil characterized by a) Simple and also competitive manufacturing process, b) Enhanced patient compliance and convenience, c) The product is administered easily and quickly, d) A dose can be removed with out contamination of materials, e) Eower dose of drug can be used and hence minimize adverse and side effects, f) Medication can be delivered directly to the affected area in a desired form, g) Irritation produced by the mechanical application of topical medication is reduced or eliminated.
The present invention shows well physical properties depends on its solubility characteristics in appropriate excipients for topical compositions. It shows good properties to provide basic physical stability.
The success of a dermotological drug depends on the ability of the drug to penetrate through skin in sufficient quantities to achieve the desired therapeutic effect. The present invention provides to increase the rate of percutaneous penetration, thereby shortening the time period in which the active agents can show their effect.
In one aspect, the components of the pharmaceutical composition according to the present invention are brought together into a gel for topical administration according to standard practice and procedures well known to one of ordinary skill in the art using conventional composition and manufacturing techniques.
Another object is to provide improved manufacturing processes which is simple, cost- effective and time saving for preparing the topical compositions of minoxidil.
The present invention relates a composition comprising minoxidil as an active ingredient for external use, and also relates to a minoxidil composition, which is clear and viscous, is inhibited from dripping, and has a good comfort of use.
In an embodiment, the invention provides pharmaceutical composition comprising minoxidil as an active agent, process of preparation thereof and method of using the same.
In an embodiment, the invention provides a topical pharmaceutical composition comprising effective amount of minoxidil as an active agent and process of preparation thereof.
In an embodiment, the invention provides method to treating one or more dermatological conditions such as androgenic alopecia, baldness or hair loss and the like, by applying topical pharmaceutical composition of minoxidil onto the the affected skin area of a subject in need of such treatment.
The composition of the invention can be packed into suitable containers such as bottle, tube, pouch, or suitable container.
The topical gel composition of minoxidil comprises one or more pharmaceutically acceptable excipient(s). Pharmaceutically acceptable excipients comprise, but are not limited to, gelling agents, polymers, aromas, emollients, solvents, pH adjusting agents, preservatives, fragrances, stabilizers, penetration enhancers, moisturizers, and mixtures thereof.
Gelling agents can be selected from the group, but are not limited to, carbomer, Carbopol 981, Carbopol ETD 2020, Carbopol 980, Carbopol Ultrez 10 NF and Pemulen TRI, Hydroxyethyl Aery late/S odium Dimethyl Acryloyl Taurate Copolymer (such as Sepineo Derm) or the family of modified starches or mixtures thereof. The preferred gelling agent is Hydroxyethyl Aery late/S odium Dimethyl Acryloyl Taurate Copolymer.
Solvents/cosolvents can be selected from the group, but not limited to, ethanol, ethyl alcohol, polyethylene glycol, propylene glycol, isopropyl alcohol, distilled water and other materials known to one of ordinary skill in the art and mixtures thereof. The preferred solvents are ethanol, propylene glycol and distilled water.
Aromas can be selected from the group, but are not limited to, natural aroma oil (e.g. peppermint oil, partridge currant oil, clove bud oil, parsley oil, eucalyptus oil, lemon oil, orange oil, etc.), menthol, mentane, anethole, methyl salicylate, eucalyptol, cinnamon, 1- methyl acetate, salvia, eugenol, oxanone, alpha-ionone, marjoram, lemon, orange, propenyl guaethol acetyl, sinnamon, vanilla, thymol, linaolol, cinnamaldehyde glycerol acetal, N- substituted p-menthane-3-carboxyamide, 3,1- methoxy propane 1,2-diol.and other materials known to one of ordinary skill in the art and mixtures thereof. The preferred aroma is menthol.
As used herein, the term "treating" or "treatment" means the alleviation or elimination of symptoms, cure, prevention, or inhibition of a disease or medical condition, or improvement of tissue growth/healing or cosmetic conditions.
The topical composition may be any form suitable for application to the skin or an animal or human. The forms may include gels, solutions, lotions, ointments, mousses, foams, sprays, aerosols, shampoos, creams, pastes or other topical composition forms known in the art.
The topical compositions may be made into a wide variety of products that include but are not limited to leave-on products (such as lotions, creams, gels, sticks, sprays, and ointments), hair products (such as shampoos, conditioners, sprays, and mousses) and the like. These product types may contain any of several pharmaceutically acceptable carrier forms including, but not limited to solutions, suspensions, emulsions such as microemulsions and nanoemulsions, gels, and solids carrier forms. Other product forms can be formulated by those of ordinary skill in the art.
The term “pharmaceutically acceptable” means molecular entities and compositions that are of sufficient purity and quality for use in the formulation of a composition or medicament of the present invention.
“Pharmaceutically acceptable excipients” are components that are added to the pharmaceutical formula tion other than the active ingredient ivermectin. Excipients may be added to facilitate manufacture, enhance stability, enhance product characteristics, enhance skin penetration, enhance patient acceptability etc. Pharmaceutically acceptable excipients includes, but not limited to, one or more filler, gelling agent, surfactant, humectant, pH modifier, chelating agent, acidifying agent, viscosity enhance, solvent, vehicle, oily vehicle, color, preservative, suspending agent, dispersing agent, and any other excipient known to the art for making pharmaceutical formulation.
The term “reference product” means Regaine product comprising minoxidil 5% from Johnson & Johnson Limited, UK with an expiry date 07/2021.
The term “competitor product” means Tugain Gel product comprising minoxidil 5% from CiplaMed, India with an expiry date 04/2021.
The term “test product” means Minoxidil Gel product comprising minoxidil 5% from Pharmactive, Turkey with an expiry date 08/2021.
Example for gel composition comprising minoxidil is below.
Example: Minoxidil Gel Composition
Figure 1: Manufacturing flowchart for pharmaceutical composition comprising minoxidil topical gel.
Franz diffusion study
A Franz diffusion cell system is used as an apparatus for transdermal permeation test, which used a dialyses membrane has receptor media (20/80 Ethanole/water) with 0,45 pm PTFE filter. Samples were collected from the receptor compartment at scheduled time points of 0,5 hour, 1 hour, 2 hours, 3 hours, 4 hours and 5 hours. 1 mL of the sample was collected and analyzed to determine a 5 hour cumulative permeation amount (pg/cm2) for the percutaneous absorption preparation containing minoxidil. The results are presented in Table 1.
Table 1: Franz diffusion study results of test product, reference product (Regaine) and competitor product (Tugain Gel)
Time (h)
As can be seen from Table 1, the percutaneous absorption preparations using test product shows a skin permeation equivalent to or higher than the competitor product (Tugain Gel).
Viscosity results of test product and competitor product (Tugain Gel) are shown in Table 2.
Table 2: Analysis results of viscosity for test product and competitor (Tugain Gel)
Table 3: Initial pH results of present invention for test product, reference product (Regaine) and competitor product (Tugain Gel)
„ „ Competitor
Reference Initial results . _ . . product Test product product (Regaine) (Tugain Gel) pH 8,37 7,51 8,60
There is no significient changes were observed for initial pH values of the test product, reference product (Regaine) and competitor product (Tugain Gel). (Table 3)
Table 4: Impurity results of present invention for test product, reference product (Regaine) and competitor product (Tugain Gel) (Initial)
Competitor
Related Substances , Test product product > (Impurities) (Minoxidil gel) (Tugain Gel) s ’
Impurity A 051 04
Impurity B Not detected Not detected
Impurity E 0,03 Not detected
The Biggest Unidentified Impurity Not detected 0,02
Total Impurity 0,54 0,05
According to table 4, test product has advantages for impurities comparing to competitor product.
Claims
1. A topical pharmaceutical composition comprising; a) 0,1 to 5,0 % by weight of minoxidil, b) a gelling agent, and c) one or more pharmaceutically acceptable excipients.
2. The topical pharmaceutical composition according to claim 1, wherein the weight ratio of minoxidil is 2,0 % (w/w).
3. The topical pharmaceutical composition according to claim 1, wherein the weight ratio of minoxidil is 5,0 % (w/w).
4. The topical pharmaceutical composition according to any of the proceeding claims, wherein said composition comprises 0,8 - 1,4 % w/w of Hydroxy ethyl Acrylate / Sodium Dimethyl Acryloyl Taurate Copolymer as a gelling agent.
5. The topical pharmaceutical composition according to any of the proceeding claims, wherein said composition comprises 1,1 % w/w of Hydroxy ethyl Acrylate / Sodium Dimethyl Acryloyl Taurate Copolymer as a gelling agent.
6. The topical pharmaceutical composition according to claim 1, wherein one or more pharmaceutically acceptable excipient is selected from solvent and aroma.
7. The topical pharmaceutical composition according to any of the preceding claims, comprises; a) 5,0 % by weight of minoxidil, b) 1,1 % by weight of copolymer of hydroxy ethyl acrylate and sodium acryloyl dimethyl taurate as a gelling agent, and c) one or more pharmaceutically acceptable excipients.
8. The topical pharmaceutical composition according to any of the preceding claims, wherein the dosage form of the composition is gel, lotion or liquid.
9. The topical pharmaceutical composition according to any of the preceding claims, wherein the dosage form of the composition is gel. 0. The topical pharmaceutical composition according to any of the preceding claims, for use in the topical treatment (regrowth) of androgenic alopecia in males and females and stabilisation of hair loss in patients with androgenic alopecia.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/TR2020/051063 WO2022098320A1 (en) | 2020-11-09 | 2020-11-09 | Topical pharmaceutical compositions containing minoxidil and relevant excipients |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/TR2020/051063 WO2022098320A1 (en) | 2020-11-09 | 2020-11-09 | Topical pharmaceutical compositions containing minoxidil and relevant excipients |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2022098320A1 true WO2022098320A1 (en) | 2022-05-12 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/TR2020/051063 WO2022098320A1 (en) | 2020-11-09 | 2020-11-09 | Topical pharmaceutical compositions containing minoxidil and relevant excipients |
Country Status (1)
| Country | Link |
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| WO (1) | WO2022098320A1 (en) |
Citations (3)
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|---|---|---|---|---|
| US20120196843A1 (en) * | 2003-08-22 | 2012-08-02 | L'oreal | Compositions containing topical-active agents and pentyleneglycol |
| US20170312206A1 (en) * | 2016-04-29 | 2017-11-02 | The Procter & Gamble Company | Method of treating a hair disorder with n-hydroxypyridinones |
| US20190282538A1 (en) * | 2016-09-30 | 2019-09-19 | Aurobindo Pharma Ltd | Pharmaceutical Composition of Ivermectin and Process for Preparation thereof |
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2020
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120196843A1 (en) * | 2003-08-22 | 2012-08-02 | L'oreal | Compositions containing topical-active agents and pentyleneglycol |
| US20170312206A1 (en) * | 2016-04-29 | 2017-11-02 | The Procter & Gamble Company | Method of treating a hair disorder with n-hydroxypyridinones |
| US20190282538A1 (en) * | 2016-09-30 | 2019-09-19 | Aurobindo Pharma Ltd | Pharmaceutical Composition of Ivermectin and Process for Preparation thereof |
Non-Patent Citations (4)
| Title |
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| "SEPINEO™ D.E.R.M", SEPPIC.COM, 25 January 2017 (2017-01-25), Retrieved from the Internet <URL:https://www.seppic.com/en/sepineo-derm> [retrieved on 20210822] * |
| KUMAR PAWAN, SINGH SHAILENDRA, HANDA VANDANA, KATHURIA HIMANSHU: "Oleic Acid Nanovesicles of Minoxidil for Enhanced Follicular Delivery", MEDICINES, vol. 5, no. 3, 14 September 2018 (2018-09-14), pages 103, XP055938608, DOI: 10.3390/medicines5030103 * |
| M SREENIVASA REDDY, S MUTALIK, G VEERABHADRA RAO: "Preparation and evaluation of minoxidil gels for topical application in alopecia", INDIAN JOURNAL OF PHARMACEUTICAL SCIENCES, MEDKNOW PUBLICATIONS PVT LTD., IN, vol. 68, no. 4, 1 July 2006 (2006-07-01), IN , pages 432 - 436, XP002753664, ISSN: 0250-474X, DOI: 10.4103/0250-474X.27813 * |
| SINGH SHAILENDRA KUMAR, KUMAR PAWAN, JINDAL DEEPAK KUMAR, HANDA VANDANA, BILONIA JYOTI: "Formulation and Evaluation of Minoxidil Gel Using Acrylamide/Sodium Acryloyldimethyl taurate copolymer for Alopecia areata", INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES AND DRUG RESEARCH, vol. 10, no. 01, 15 January 2018 (2018-01-15), pages 1 - 6, XP055938607, DOI: 10.25004/IJPSDR.2018.100101 * |
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