WO2019004984A2 - A pharmaceutical formulation comprising cholecalciferol - Google Patents
A pharmaceutical formulation comprising cholecalciferol Download PDFInfo
- Publication number
- WO2019004984A2 WO2019004984A2 PCT/TR2018/050236 TR2018050236W WO2019004984A2 WO 2019004984 A2 WO2019004984 A2 WO 2019004984A2 TR 2018050236 W TR2018050236 W TR 2018050236W WO 2019004984 A2 WO2019004984 A2 WO 2019004984A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- vitamin
- pharmaceutical formulation
- cholecalciferol
- chewable tablet
- tablet form
- Prior art date
Links
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 title claims abstract description 50
- 239000011647 vitamin D3 Substances 0.000 title claims abstract description 49
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 title claims abstract description 44
- 235000005282 vitamin D3 Nutrition 0.000 title claims abstract description 25
- 229940021056 vitamin d3 Drugs 0.000 title claims abstract description 25
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 15
- 239000007910 chewable tablet Substances 0.000 claims abstract description 24
- 229940068682 chewable tablet Drugs 0.000 claims abstract description 22
- 239000003826 tablet Substances 0.000 claims abstract description 15
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 10
- 239000013543 active substance Substances 0.000 claims abstract description 9
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 10
- 239000000796 flavoring agent Substances 0.000 claims description 6
- 235000019634 flavors Nutrition 0.000 claims description 6
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 claims description 5
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 5
- 229930195725 Mannitol Natural products 0.000 claims description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 5
- 235000019359 magnesium stearate Nutrition 0.000 claims description 5
- 239000000594 mannitol Substances 0.000 claims description 5
- 235000010355 mannitol Nutrition 0.000 claims description 5
- 229940085605 saccharin sodium Drugs 0.000 claims description 5
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 4
- 239000011230 binding agent Substances 0.000 claims description 4
- 239000008119 colloidal silica Substances 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 239000000314 lubricant Substances 0.000 claims description 4
- 239000008368 mint flavor Substances 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- 229940069328 povidone Drugs 0.000 claims description 4
- 239000008122 artificial sweetener Substances 0.000 claims description 3
- 235000021311 artificial sweeteners Nutrition 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims 1
- 230000007812 deficiency Effects 0.000 claims 1
- 229930003316 Vitamin D Natural products 0.000 description 19
- 235000019166 vitamin D Nutrition 0.000 description 19
- 239000011710 vitamin D Substances 0.000 description 19
- 229940046008 vitamin d Drugs 0.000 description 19
- 150000003710 vitamin D derivatives Chemical class 0.000 description 18
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 13
- 229910000019 calcium carbonate Inorganic materials 0.000 description 7
- 239000000825 pharmaceutical preparation Substances 0.000 description 7
- 229940127557 pharmaceutical product Drugs 0.000 description 7
- 229940088594 vitamin Drugs 0.000 description 7
- 239000011782 vitamin Substances 0.000 description 7
- 229930003231 vitamin Natural products 0.000 description 6
- 235000013343 vitamin Nutrition 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- 150000003722 vitamin derivatives Chemical class 0.000 description 5
- 235000015872 dietary supplement Nutrition 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 206010047626 Vitamin D Deficiency Diseases 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930182558 Sterol Natural products 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 150000003432 sterols Chemical class 0.000 description 2
- 235000003702 sterols Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000011653 vitamin D2 Substances 0.000 description 2
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 229910002012 Aerosil® Inorganic materials 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
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- UCTLRSWJYQTBFZ-UHFFFAOYSA-N Dehydrocholesterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)CCCC(C)C)CCC33)C)C3=CC=C21 UCTLRSWJYQTBFZ-UHFFFAOYSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 229920003081 Povidone K 30 Polymers 0.000 description 1
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 1
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 description 1
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 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
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- MECHNRXZTMCUDQ-UHFFFAOYSA-N Vitamin D2 Natural products C1CCC2(C)C(C(C)C=CC(C)C(C)C)CCC2C1=CC=C1CC(O)CCC1=C MECHNRXZTMCUDQ-UHFFFAOYSA-N 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- -1 calcium carbonate vitamin D Chemical class 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229940032446 cholecalciferol chewable tablet Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000013345 egg yolk Nutrition 0.000 description 1
- 210000002969 egg yolk Anatomy 0.000 description 1
- 229960002061 ergocalciferol Drugs 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000006539 genistein Nutrition 0.000 description 1
- 229940045109 genistein Drugs 0.000 description 1
- TZBJGXHYKVUXJN-UHFFFAOYSA-N genistein Natural products C1=CC(O)=CC=C1C1=COC2=CC(O)=CC(O)=C2C1=O TZBJGXHYKVUXJN-UHFFFAOYSA-N 0.000 description 1
- ZCOLJUOHXJRHDI-CMWLGVBASA-N genistein 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 ZCOLJUOHXJRHDI-CMWLGVBASA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 229940098462 oral drops Drugs 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 235000005875 quercetin Nutrition 0.000 description 1
- 229960001285 quercetin Drugs 0.000 description 1
- 235000021283 resveratrol Nutrition 0.000 description 1
- 229940016667 resveratrol Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000000475 sunscreen effect Effects 0.000 description 1
- 239000000516 sunscreening agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000001892 vitamin D2 Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
Definitions
- the invention is related to a pharmaceutical formulation in chewable tablet form comprising cholecalciferol in order to supply the need of vitamin D 3 .
- Vitamin D deficiency or insufficiency causes diseases such as common cancer, cardiovascular, metabolic syndrome, infectious, autoimmune and osteoporosis.
- Vitamin D is necessary for osteogenesis and balance of the minerals of calcium and phosphorus.
- Vitamin D may be taken with diet as ergocalciferol (vitamin D 2 ) which is present in plants and as cholecalciferol (vitamin D 3 ) which is present in animal tissues.
- Vitamin D takes place among fat soluble vitamins and at the same time it is a group of sterol which is hormone and hormone precursor because it can be synthesized as endogeny in proper biological medium.
- the most important sterols which belongs to vitamin D family is vitamin D 3 , namely, cholecalciferol.
- vitamin D especially vitamin D 3
- cholecalciferol namely vitamin D 3 in certain amounts or percentages.
- Pharmaceutically acceptable forms may be in tablets, film coated tablets, chewable tablets, oral drops.
- Vitamin D 3 is in combination with calcium carbonate in the said document.
- a vitamin D calcium chewable tablet and production method thereof are mentioned.
- the amount of vitamin D 3 by weight is quite low in the chewable tablet mentioned in the said document.
- a chewable tablet with the composition of calcium carbonate vitamin D and preparation method thereof are mentioned. In the said document, it is mentioned that this tablet comprises starch, sucrose and pure water beside calcium carbonate and vitamin D. Vitamin D 3 is not the only active agent and its amount in the tablet is quite low in the document.
- vitamin D is in the amount of 400 IU to 10,000 IU in the said food supplement and the food supplement comprises 10 mg to 250 mg of genistein, 30 mg to 1000 mg of resveratrol, 40 mg to 1000 mg of quercetin in addition to vitamin D.
- the food supplement is in the forms of capsule, tablet, dragee, powder, chewable like gum or granule.
- a pharmaceutical form comprising only vitamin D 3 is not given in the document.
- the aim of the invention is to carry out an easy to use pharmaceutical product which provides that the active agent cholecalciferol is taken in high dose to meet the need for vitamin D 3 .
- the pharmaceutical product developed for this aim doses of cholecalciferol change in the range of 600 IU and 3000 IU.
- the pharmaceutical product developed is in chewable tablet form.
- the most important advantage of chewable tablets is being easy to use due to the fact that patients do not have to keep water with them. Therefore; chewable tablet forms provide higher patient comfort than other tablet forms.
- the disclosed pharmaceutical product comprises an active agent cholecalciferol as a vitamin D 3 source and at least one excipient.
- the pharmaceutical product comprises cholecalciferol in the range of 600 IU and 3000 IU in a unit tablet.
- the product obtained from the disclosed pharmaceutical formulation is in a pharmaceutical product form which user can use quite easily.
- the pharmaceutical product is in tablet form in the preferred embodiment of the invention.
- the preferred form is chewable tablet in this embodiment.
- the amount of the active agent cholecalciferol in the said product is in the range of 600 IU and 3000 IU in a unit tablet in an embodiment of the invention. In another embodiment of the invention, the amount of cholecalciferol is inthe range of 1000 IU and 3000 IU in a unit tablet. In another preferred embodiment of the invention, the amount of cholecalciferol is 1000 IU in a unit tablet.
- Diluents mannitol
- binders povidone
- flavorants mint flavor
- lubricants magnesium stearate
- artificial sweeteners sacharin sodium
- glidants colloidal silica
- the formulation comprises 50 mg to 1000 mg of mannitol by weight as the diluent, 5 mg to 50 mg of povidone by weight as the binder, 0,1 mg to 15 mg of colloidal silica by weight as the glidant, 0,15 mg to 1,0 mg of saccharin sodium by weight as the artificial sweetener, 0,9 mg to 25 mg of flavor preferably mint flavor by weight as the flavorant, 10 mg to 100 mg of magnesium stearate by weight as the lubricant.
- This amount ranges of the excipients given in the invention are for the formulations comprising cholecalciferol in equivalent amount to 600 IU to 3000 IU.
- the disclosed cholecalciferol chewable tablet is prepared by using direct compression method in its production.
- the examples related to the formulations in which the invention is applied are below. The invention is not limited to this examples.
- the amounts of the excipients which may be used in case that cholecalciferol is in doses that are equivalent to 600 IU, 1000 IU, 2000 IU and 3000 IU are given by weight in the example tables below.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention is related to a pharmaceutical formulation in chewable tablet form comprising an active agent cholecalciferol in the range of 600 IU to 3000 IU as a vitamin D3 source and at least one excipient in a unit tablet.
Description
A PHARMACEUTICAL FORMULATION COMPRISING CHOLECALCIFEROL
Related Technical Field of the Invention:
The invention is related to a pharmaceutical formulation in chewable tablet form comprising cholecalciferol in order to supply the need of vitamin D3.
Prior Art:
It is known that vitamin D deficiency or insufficiency causes diseases such as common cancer, cardiovascular, metabolic syndrome, infectious, autoimmune and osteoporosis. Vitamin D is necessary for osteogenesis and balance of the minerals of calcium and phosphorus. Vitamin D may be taken with diet as ergocalciferol (vitamin D2) which is present in plants and as cholecalciferol (vitamin D3) which is present in animal tissues. Vitamin D takes place among fat soluble vitamins and at the same time it is a group of sterol which is hormone and hormone precursor because it can be synthesized as endogeny in proper biological medium. The most important sterols which belongs to vitamin D family is vitamin D3, namely, cholecalciferol. Cholecalciferol is formed significantly from 7-dehydrocholesterol in the skin as a result of photochemical effect of ultraviolet B (UVB) rays of the sun. Therefore, exposing to sun sufficiently prevents vitamin D deficiency. However; although our country is rich in sunlight as a result of its geographical location, nowadays both children and adults may get diseases indicated above because they cannot take vitamin D enough during the day due to various working and education conditions. In addition, vitamin D is present mostly in fishes, livers and egg yolks among foods of animal origin. Even if sunlight and some foods are sources for vitamin D, synthesis of vitamin D in the body decreases or may not be possible in some situations. For example;
• Decreasing synthesis of vitamin D in the skin with elderliness in direct proportion to age,
• Need for sunlight long time especially in winter by people having different skin colors, · Limiting synthesis of vitamin D in the skin due to use of sun screens,
• Preventing absorption of vitamin D from intestines and causing not to convert vitamin D to its active form in some medical problems.
Due to these reasons listed above and so on, it is quite important to use vitamin D, especially vitamin D3, as a vitamin support. In the state of the art, there are products in pharmaceutical or pharmaceutically acceptable forms comprising cholecalciferol namely vitamin D3 in certain amounts or percentages. Pharmaceutically acceptable forms may be in tablets, film coated tablets, chewable tablets, oral drops.
The chemical structure of cholecalciferol is as below:
Formula: The chemical structure of cholecalciferol
In the patent document of CN106420808 (A) in the state of the art, a pharmaceutical compound comprising vitamin D3, calcium carbonate and pharmaceutically acceptable excipients and specifically a preparation method for this compound are mentioned. Vitamin D3 is in combination with calcium carbonate in the said document.
In another patent document of CN 106333961 in the state of the art, a vitamin D calcium chewable tablet and production method thereof are mentioned. There are 1000 gr of calcium carbonate, 0.2 - 0.3 gr of vitamin D3, 225 to 235 gr of milk powder, 190 to 210 gr of sorbitol, 30 to 40 gr of dextrin and 30 to 40 gr of starch in the vitamin C calcium chewable tablet comprising vitamin D in the said document. The amount of vitamin D3 by weight is quite low in the chewable tablet mentioned in the said document.
In another patent document of WO 2016086557 in the state of the art, a chewable tablet with the composition of calcium carbonate vitamin D and preparation method thereof are mentioned. In the said document, it is mentioned that this tablet comprises starch, sucrose and pure water beside calcium carbonate and vitamin D. Vitamin D3 is not the only active agent and its amount in the tablet is quite low in the document.
In another patent document of US 20160089383 in the state of the art, a food supplement is mentioned. It is stated that vitamin D is in the amount of 400 IU to 10,000 IU in the said food supplement and the food supplement comprises 10 mg to 250 mg of genistein, 30 mg to 1000 mg of resveratrol, 40 mg to 1000 mg of quercetin in addition to vitamin D. It is mentioned in the document that the food supplement is in the forms of capsule, tablet, dragee, powder, chewable like gum or granule. However, a pharmaceutical form comprising only vitamin D3 is not given in the document.
In another patent document of CN 103494836 in the state of the art, a composite chewable tablet comprising calcium carbonate and vitamin D3 for children and old people is mentioned. It is indicated in the document that the said tablet consists of calcium carbonate, vitamin D3 and excipients. However, a pharmaceutical form comprising only vitamin D3 is not given in the said document and the amount of vitamin D3 is quite low. In the prior art documents given above, vitamin D3 is not the only active agent in the pharmaceutical forms comprising vitamin D3. In case that a single vitamin source comprising necessary doses is not used, patients have to meet said their vitamin needs from one or more specific-vitamin sources. This causes additional medicine consumption and decreasing adaptation to the vitamin regime. Therefore; patients cannot take the vitamin in the dose for which their bodies need and in one go. Thus, developing a pharmaceutical form which is easy to use and which especially comprises vitamin D3 in high amounts is needed. Therefore; all or significant amount of vitamin D3 for which the body needs may be taken when the pharmaceutical compound is used in one go. In addition, it is important that there are easy to use medicine forms when patients' usage is considered. Therefore; developing forms for this is required. Thus, a pharmaceutical
form which is chewable and comprises high amount of vitamin D3 in a unit tablet has not been developed in the state of the art.
Brief Description of the Invention:
The aim of the invention is to carry out an easy to use pharmaceutical product which provides that the active agent cholecalciferol is taken in high dose to meet the need for vitamin D3.
In the pharmaceutical product developed for this aim, doses of cholecalciferol change in the range of 600 IU and 3000 IU. In addition, the pharmaceutical product developed is in chewable tablet form. The most important advantage of chewable tablets is being easy to use due to the fact that patients do not have to keep water with them. Therefore; chewable tablet forms provide higher patient comfort than other tablet forms.
Detailed Description of the Invention:
The disclosed pharmaceutical product comprises an active agent cholecalciferol as a vitamin D3 source and at least one excipient. In an embodiment of the invention, the pharmaceutical product comprises cholecalciferol in the range of 600 IU and 3000 IU in a unit tablet.
• The product obtained from the disclosed pharmaceutical formulation is in a pharmaceutical product form which user can use quite easily. The pharmaceutical product is in tablet form in the preferred embodiment of the invention. The preferred form is chewable tablet in this embodiment.
The amount of the active agent cholecalciferol in the said product is in the range of 600 IU and 3000 IU in a unit tablet in an embodiment of the invention. In another embodiment of the invention, the amount of cholecalciferol is inthe range of 1000 IU and 3000 IU in a unit tablet. In another preferred embodiment of the invention, the amount of cholecalciferol is 1000 IU in a unit tablet.
In the preparation of chewable tablet from the disclosed formulation, various excipients are used. Diluents (mannitol), binders (povidone), flavorants (mint flavor), lubricants
(magnesium stearate), artificial sweeteners (saccharin sodium) and glidants (colloidal silica) may be counted among excipients that may be used but not limited to these.
The formulation comprises 50 mg to 1000 mg of mannitol by weight as the diluent, 5 mg to 50 mg of povidone by weight as the binder, 0,1 mg to 15 mg of colloidal silica by weight as the glidant, 0,15 mg to 1,0 mg of saccharin sodium by weight as the artificial sweetener, 0,9 mg to 25 mg of flavor preferably mint flavor by weight as the flavorant, 10 mg to 100 mg of magnesium stearate by weight as the lubricant. This amount ranges of the excipients given in the invention are for the formulations comprising cholecalciferol in equivalent amount to 600 IU to 3000 IU.
The disclosed cholecalciferol chewable tablet is prepared by using direct compression method in its production. The examples related to the formulations in which the invention is applied are below. The invention is not limited to this examples. The amounts of the excipients which may be used in case that cholecalciferol is in doses that are equivalent to 600 IU, 1000 IU, 2000 IU and 3000 IU are given by weight in the example tables below.
Example 1;
Example2:
Unit Formula of Cholecalciferol 1000 IU Chewable Tablet
Weight amount in the unit
Ingredients Intended use formula (mg/ ITablet)
Cholecalciferol
equivalent amount to 1000 IU Active agent (Premix)
Mannitol 100 SD 270,35 Diluent
Povidone K-30 6,00 Binder
Aerosil 1,50 Glidant
Saccharin Sodium 0,15 Sweetener (Artificial)
Mint Flavor 0,90 Flavor
Magnesium Stearate 12,00 Lubricant
Example 3:
Example 4:
The invention is not limited with the embodiments disclosed above and a skilled person in the art can perform different embodiments of the invention easily. They should be evaluated within the scope of the invention protection demanded with claims.
Claims
1. A pharmaceutical formulation in chewable tablet form comprising an active agent cholecalciferol as a vitamin D3 source and at least one excipient;
characterized by comprising the active ingredient cholecalciferol in the amount of 600 IU to 3000 IU in a unit tablet.
2. The pharmaceutical formulation in chewable tablet form according to claim 1 characterized by comprising the active agent cholecalciferol in the amount of 1000 IU in the unit tablet.
3. The pharmaceutical formulation in chewable tablet form according to claim 2 characterized by comprising excipients as follows; mannitol as a diluent, povidone as a binder, colloidal silica as a glidant, saccharin sodium as an artificial sweetener, mint flavor as a flavor, magnesium stearate as a lubricant.
4. The pharmaceutical formulation in chewable tablet form according to claim 3 characterized by comprising 50 mg to 1000 mg of mannitol by weight.
5. The pharmaceutical formulation in chewable tablet form according to claim 3 characterized by comprising 5 mg to 50 mg of povidone by weight.
6. The pharmaceutical formulation in chewable tablet form according to claim 3 characterized by comprising 0,1 mg to 15 mg of colloidal silica by weight.
7. The pharmaceutical formulation in chewable tablet form according to claim 3 characterized by comprising 0,15 to 1,0 mg of saccharin sodium by weight.
8. The pharmaceutical formulation in chewable tablet form according to claim 3 characterized by comprising 0,9 mg to 25 mg of flavor by weight.
9. The pharmaceutical formulation in chewable tablet form according to claim 3 characterized by comprising 10 mg to 100 mg of magnesium stearate by weight.
10. The pharmaceutical formulation in chewable tablet form according to any of claims above for use in the treatment of vitamin D3 deficiency.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR201707762 | 2017-05-29 | ||
| TR2017/07762 | 2017-05-29 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2019004984A2 true WO2019004984A2 (en) | 2019-01-03 |
| WO2019004984A3 WO2019004984A3 (en) | 2019-03-07 |
Family
ID=64741744
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/TR2018/050236 WO2019004984A2 (en) | 2017-05-29 | 2018-05-16 | A pharmaceutical formulation comprising cholecalciferol |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2019004984A2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114269349A (en) * | 2019-08-09 | 2022-04-01 | 埃比奥吉恩药物股份公司 | Cholecalciferol for use in the treatment of celiac disease |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2192136B1 (en) * | 2002-01-04 | 2005-03-16 | Italfarmaco, S.A. | PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OR PREVENTION OF OSTEOPOROSIS. |
| ES2255429B1 (en) * | 2004-10-25 | 2007-08-16 | Italfarmaco, S.A. | COMPOSITIONS PHARMACEUTICAL BUCODISPERSABLES. |
| FR2953139B1 (en) * | 2009-11-27 | 2012-04-13 | Servier Lab | PHARMACEUTICAL COMPOSITION COMPRISING STRONTIUM SALT, VITAMIN D AND CYCLODEXTRIN |
-
2018
- 2018-05-16 WO PCT/TR2018/050236 patent/WO2019004984A2/en active Application Filing
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114269349A (en) * | 2019-08-09 | 2022-04-01 | 埃比奥吉恩药物股份公司 | Cholecalciferol for use in the treatment of celiac disease |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2019004984A3 (en) | 2019-03-07 |
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