AU2021106478A4 - Vitamin D3 Compositions - Google Patents
Vitamin D3 Compositions Download PDFInfo
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- AU2021106478A4 AU2021106478A4 AU2021106478A AU2021106478A AU2021106478A4 AU 2021106478 A4 AU2021106478 A4 AU 2021106478A4 AU 2021106478 A AU2021106478 A AU 2021106478A AU 2021106478 A AU2021106478 A AU 2021106478A AU 2021106478 A4 AU2021106478 A4 AU 2021106478A4
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- Prior art keywords
- vitamin
- sugar core
- hydroxypropyl methylcellulose
- active layer
- detected
- Prior art date
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- 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 69
- 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 63
- 239000011647 vitamin D3 Substances 0.000 title claims abstract description 61
- 229940021056 vitamin d3 Drugs 0.000 title claims abstract description 61
- 235000005282 vitamin D3 Nutrition 0.000 title claims abstract description 60
- 239000000203 mixture Substances 0.000 title claims abstract description 30
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 34
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract description 32
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 32
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 32
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims abstract description 32
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 17
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000005516 engineering process Methods 0.000 claims abstract description 16
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims abstract description 16
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims abstract description 16
- 229920000053 polysorbate 80 Polymers 0.000 claims abstract description 16
- 229940068968 polysorbate 80 Drugs 0.000 claims abstract description 16
- 235000010378 sodium ascorbate Nutrition 0.000 claims abstract description 16
- 229960005055 sodium ascorbate Drugs 0.000 claims abstract description 16
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 claims abstract description 16
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 claims abstract description 16
- 239000000454 talc Substances 0.000 claims abstract description 16
- 229910052623 talc Inorganic materials 0.000 claims abstract description 16
- 235000010384 tocopherol Nutrition 0.000 claims abstract description 16
- 239000011732 tocopherol Substances 0.000 claims abstract description 16
- 229960001295 tocopherol Drugs 0.000 claims abstract description 16
- 229930003799 tocopherol Natural products 0.000 claims abstract description 16
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims abstract description 16
- 235000012222 talc Nutrition 0.000 claims abstract description 8
- 238000005507 spraying Methods 0.000 claims abstract description 6
- 239000000243 solution Substances 0.000 claims description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 21
- 238000002955 isolation Methods 0.000 claims description 17
- 239000008213 purified water Substances 0.000 claims description 14
- 239000007864 aqueous solution Substances 0.000 claims description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 abstract description 25
- 239000002245 particle Substances 0.000 abstract description 18
- 238000002360 preparation method Methods 0.000 abstract description 17
- 229910000019 calcium carbonate Inorganic materials 0.000 abstract description 11
- 239000000843 powder Substances 0.000 abstract description 7
- 239000000725 suspension Substances 0.000 abstract description 7
- 239000011162 core material Substances 0.000 abstract description 4
- 229940057948 magnesium stearate Drugs 0.000 abstract description 2
- 239000011241 protective layer Substances 0.000 abstract description 2
- 229940033134 talc Drugs 0.000 abstract description 2
- 239000010410 layer Substances 0.000 description 48
- 230000007774 longterm Effects 0.000 description 15
- 235000010216 calcium carbonate Nutrition 0.000 description 10
- 239000003826 tablet Substances 0.000 description 9
- 229940057802 caltrate Drugs 0.000 description 7
- 238000000889 atomisation Methods 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000007910 chewable tablet Substances 0.000 description 4
- -1 compound calcium carbonate Chemical class 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000011574 phosphorus Substances 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 238000013112 stability test Methods 0.000 description 3
- XQFJZHAVTPYDIQ-LETJEVNCSA-N (1s)-3-[(e)-2-[(1r,3ar,7ar)-1-[(e,2r,5r)-5,6-dimethylhept-3-en-2-yl]-7a-methyl-1,2,3,3a,6,7-hexahydroinden-4-yl]ethenyl]-4-methylcyclohex-3-en-1-ol Chemical compound C=1([C@@H]2CC[C@@H]([C@]2(CCC=1)C)[C@H](C)/C=C/[C@H](C)C(C)C)\C=C\C1=C(C)CC[C@H](O)C1 XQFJZHAVTPYDIQ-LETJEVNCSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 229930003316 Vitamin D Natural products 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000008827 biological function Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 208000007442 rickets Diseases 0.000 description 2
- BUNBVCKYYMRTNS-UHFFFAOYSA-N tachysterol Natural products C=1CCC2(C)C(C(C)CCC(C)C(C)C)CCC2C=1C=CC1=C(C)CCC(O)C1 BUNBVCKYYMRTNS-UHFFFAOYSA-N 0.000 description 2
- 235000019166 vitamin D Nutrition 0.000 description 2
- 239000011710 vitamin D Substances 0.000 description 2
- 150000003710 vitamin D derivatives Chemical class 0.000 description 2
- 229940046008 vitamin d Drugs 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 208000003217 Tetany Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000008468 bone growth Effects 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 208000002925 dental caries Diseases 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 208000005368 osteomalacia Diseases 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical group O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 238000004513 sizing Methods 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 210000001519 tissue Anatomy 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Nutrition Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Physiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
OF THE DISCLOSURE
The present disclosure provides a composition that can effectively improve the
stability of vitamin D3 and a preparation process thereof, and belongs to the field of
pharmaceutical technology. The composition provided in the present disclosure
comprises a sugar core, hydroxypropyl methylcellulose, tocopherol, sodium ascorbate,
polysorbate 80, vitamin D3, talc, and magnesium stearate. The preparation process is as
follows: preparing a solution containing hydroxypropyl methylcellulose, tocopherol,
sodium ascorbate, polysorbate 80, and vitamin D3, spraying the solution on the sugar
core in a fluidized bed by using Wurster technology; then spraying the prepared sugar
core with a suspension containing hydroxypropyl methylcellulose, talc, and magnesium
stearate as a protective layer. The present disclosure adopts Wurster technology, which
can not only improve the stability of vitamin D3, but also effectively increase the
particle size of D3 powder, the particle size is close to the that of calcium carbonate
particles, ensuring good content uniformity of subsequent tablets.
I (
Description
VITAMIN D3 COMPOSITIONS
[011 The present disclosure belongs to the field of pharmaceutical technology, relates to a composition that can effectively improve the stability of vitamin D3 and a preparation process thereof, and the use for preparing compound calcium carbonate chewable tablets.
[021 Molecular structure of vitamin D3 is as follows: HO
[03]
[04] Molecular formula is C 2 7H 4 4 0, Mr384.64, CAS No: 67-97-0
[05] Chemical name: 9, 10-secocholestr-5, 7, 10 (19)-trien-3-ol, 3-beta
[06] Vitamin D3, also known as cholecalciferol, is the most important form in the vitamin D family, which mainly regulates calcium and phosphorus metabolism in the body. Vitamin D3 is transformed from 7-dehydrogenous cholesterol in the skin by ultraviolet radiation. Vitamin D3 is a natural form of vitamin D, but is not its biologically active form. It is used for rickets, osteomalacia and infantile tetany. It can also be used for prevention and treatment of rickets with caries. At the same time, the biological function of vitamin D3 is relatively wide: regulating calcium and phosphorus metabolism, improving the body's absorption of calcium and phosphorus; promoting bone growth; regulating the proliferation and differentiation of various tissues and cells, and changing the biological functions of cells; exerting immune regulation and improving glucose metabolism; and preventing the loss of amino acids through the kidneys.
[07] In view of the fact that the unsaturated double bonds at positions 5, 7, and 10 in the vitamin D3 structure are easily degraded by light, oxygen, and heat, it is necessary to develop a stable vitamin D3 composition.
[08] Chinese Patent CN 104686812B discloses a preparation method of coated nano-vitamin D3, but the particle size of the vitamin D3 prepared is too small to be uniformly mixed with other excipients, and cannot meet the requirements of mixing uniformity.
[09] Chinese patent application CN 107156456 A discloses an inclusion composition of cyclodextrin and vitamin D3, but the amount of ethanol organic solvent in the preparation process is relatively large, which is not suitable for preparing pharmaceutical preparations.
[10] Chinese patent application CN 1062144468 A discloses a vitamin D3 composition prepared by a mixture of oil phase and water phase, followed by spray drying process. However, the preparation process is cumbersome and requires higher experimental equipment.
[11] In view of the above problems, the vitamin D3 composition prepared by the present disclosure can not only improve the stability of vitamin D3, but also the preparation process is relatively simple. More importantly, it can effectively increase the particle size of D3 powder, which is close to the particle size of calcium carbonate particles, ensuring good content uniformity of subsequent tablet.
[12] The purpose of the present disclosure is to provide a composition that can effectively improve the stability of vitamin D3 and a preparation process thereof, and the use for preparing compound calcium carbonate chewable tablets.
[13] In order to achieve the above object, the present disclosure provides a composition that can effectively improve the stability of vitamin D3 and a preparation process thereof, the composition comprises a sugar core, hydroxypropyl methylcellulose, tocopherol, sodium ascorbate, polysorbate 80, vitamin D3, talc, and magnesium stearate.
[14] The present disclosure provides a vitamin D3 composition, wherein comprising two parts of an active layer and an isolation layer. The active layer includes a sugar core, vitamin D3, hydroxypropyl methylcellulose, polysorbate 80, tocopherol and sodium ascorbate, the isolation layer contains active layer of sugar core, hydroxypropyl methylcellulose, talc, and magnesium stearate.
[15] The vitamin D3 composition comprises the following components by mass percentage:
[16] The active layer:
[17] Sugar core 70-800%
[18] Vitamin D3 0.1-1 %
[19] Hydroxypropyl methylcellulose 5-15 %
[20] Polysorbate 80 1-100%
[21] Tocopherol 0.5-20%
[22] Sodium ascorbate 2-8%
[23] The isolation layer:
[24] Hydroxypropyl methylcellulose 5-15 %
[25] Talc 1-100%
[26] Magnesium stearate 0.25-20%.
[27] The active layer is prepared by preparing a solution of vitamin D3, hydroxypropyl methylcellulose, polysorbate 80, tocopherol, sodium ascorbate, and purified water, using the sugar core as a carrier, and spraying the solution onto the sugar core.
[28] The isolation layer is prepared by preparing a solution of hydroxypropyl methylcellulose, talc, magnesium stearate, and purified water, using the active layer of sugar core as the carrier, and spaying the solution onto the active layer of sugar core.
[29] The sugar core has a diameter of 0.1-0.35 mm.
[30] The viscosity of the hydroxypropyl methylcellulose is 2-8 mPa-s. (apparent viscosity of 2 % aqueous solution at 20°C).
[31] The present disclosure provides a method of preparing a vitamin D3 composition comprising the preparation of an active layer and an isolation layer.
[32] The preparation of the active layer comprises preparing a solution of vitamin D3, hydroxypropyl methylcellulose, polysorbate 80, tocopherol, sodium ascorbate, and purified water, using the sugar core as a carrier, and spraying the solution onto the sugar core on a fluidized bed by using Wurster technology to obtain the active layer of sugar core.
[33] The preparation of the isolation layer includes preparing a solution of hydroxypropyl methylcellulose, talc, magnesium stearate, and purified water, using the active layer of sugar core as the carrier, and spaying the solution onto the active layer of sugar core on the fluidized bed by using Wurster technology. The isolation layer is a protective layer, which can isolate oxygen, moisture, and light, protect the stability of vitamin D3, and prevent the active layer from being damaged when pressed into tablets.
[34] The present disclosure provides a preparation process for the composition: the active layer is prepared by preparing a solution of vitamin D3, hydroxypropyl methylcellulose, polysorbate 80, tocopherol, sodium ascorbate, and purified water, using the sugar core as a carrier, and spraying the solution onto the sugar core on a fluidized bed by using Wurster technology. the isolation layer is prepared by preparing a solution of hydroxypropyl methylcellulose, talc, magnesium stearate, and purified water, using the active layer of sugar core as the carrier, and spaying the solution onto the active layer of sugar core on the fluidized bed by using Wurster technology.
[35] The present disclosure provides a use of a vitamin D3 composition for preparing compound calcium carbonate D3 chewable tablets.
[36] The vitamin D3 composition prepared by the present disclosure can not only improve the stability of vitamin D3, but also has a simple preparation process. It can not only improve the stability of vitamin D3, but also effectively increase the particle size of D3 powder, which is close to the particle size of calcium carbonate particles, ensuring good content uniformity of tablets.
[37] In order to better illustrate the objectives, technical schemes and main points of the present disclosure, the technical schemes of the present disclosure will be further described in detail below in conjunction with specific embodiments.
[38] Example 1
[39] Active layer
[40] The present disclosure provides a composition that can effectively improve the stability of vitamin D3, comprising the following components in parts by weight:
[41] The active layer:
[42] Sugar core 70.5 g
[43] Vitamin D3 0.5 g
[441 Hydroxypropyl methylcellulose 8 g
[45] Polysorbate 80 2 g
[46] Tocopherol 1g
[47] Sodium ascorbate 4 g
[48] Pure water 100 g
[49] The isolation layer:
[50] Hydroxypropyl methylcellulose 8 g
[51] Talc 5 g
[52] Magnesium stearate 1g
[53] Pure water 100 g
[54] Process steps:
[55] Preparation of Vitamin D3 solution: Hydroxypropyl methylcellulose was dissolved in purified water, polysorbate 80 was added thereto, stirred evenly, antioxidant tocopherol and sodium ascorbate were added, then vitamin D3 was added, and the mixture was stirred evenly.
[56] A blank sugar core having a particle size of 0.1-0.15 mm was placed in a fluidized bed, the vitamin D3 solution was sprayed into a fluidized bed by using Wurster technology, the atomization pressure was 2 bar, the inlet air temperature was 80°C, the exhaust air temperature was 45°C, and the active layer was formed on the surface of the sugar core. After drying, they were passed through an 80-mesh sieve to obtain the active layer of sugar core.
[57] Suspension: The hydroxypropyl methylcellulose was dissolved in purified water, talc and magnesium stearate were added, and mixed evenly. The active layer of sugar core was placed in a fluidized bed, the suspension was sprayed into the fluidized bed by using Wurster technology, the atomization pressure was 2 bar, the inlet air temperature was 80°C, the exhaust air temperature was 50°C, the isolation layer was formed on the surface of the active layer of sugar core to form vitamin D3 powder.
[58] Example 2
[59] Active layer
[60] The present disclosure provides a composition that can effectively improve the stability of vitamin D3, comprising the following components in parts by weight:
[61] The active layer:
[62] Sugar core 70.5 g
[63] Vitamin D3 0.5 g
[64] Hydroxypropyl methylcellulose 12 g
[65] Polysorbate 80 2 g
[66] Tocopherol 1g
[67] Sodium ascorbate 4 g
[68] Pure water 100 g
[69] The isolation layer:
[70] Hydroxypropyl methylcellulose 4 g
[71] Talc 5 g
[72] Magnesium stearate 1g
[73] Pure water 100 g
[74] Process steps:
[75] Preparation of Vitamin D3 solution: Hydroxypropyl methylcellulose was dissolved in purified water, polysorbate 80 was added thereto, stirred evenly, antioxidant tocopherol and sodium ascorbate were added, then vitamin D3 was added, and the mixture was stirred evenly.
[76] A blank sugar core having a particle size of 0.1-0.15 mm was placed in a fluidized bed, the vitamin D3 solution was sprayed into a fluidized bed by using Wurster technology, the atomization pressure was 2 bar, the inlet air temperature was 80°C, the exhaust air temperature was 45°C, and the active layer was formed on the surface of the sugar core. After drying, they were passed through an 80-mesh sieve to obtain the active layer of sugar core.
[77] Suspension: The hydroxypropyl methylcellulose was dissolved in purified water, talc and magnesium stearate were added, and mixed evenly. The active layer of sugar core was placed in a fluidized bed, the suspension was sprayed into the fluidized bed by using Wurster technology, the atomization pressure was 2 bar, the inlet air temperature was 80°C, the exhaust air temperature was 50°C, the isolation layer was formed on the surface of the active layer of sugar core to form vitamin D3 powder.
[78] Example 3
[79] Active layer
[80] The present disclosure provides a composition that can effectively improve the stability of vitamin D3, comprising the following components in parts by weight:
[81] The active layer:
[82] Sugar core 70.5 g
[83] Vitamin D3 0.5 g
[84] Hydroxypropyl methylcellulose 4 g
[85] Polysorbate 80 2 g
[86] Tocopherol 1g
[87] Sodium ascorbate 4 g
[88] Pure water 100 g
[89] The isolation layer:
[90] Hydroxypropyl methylcellulose 12 g
[91] Talc 5 g
[92] Magnesium stearate 1g
[93] Pure water 100 g
[94] Process steps:
[95] Preparation of Vitamin D3 solution: Hydroxypropyl methylcellulose was dissolved in purified water, polysorbate 80 was added thereto, stirred evenly, antioxidant tocopherol and sodium ascorbate were added, then vitamin D3 was added, and the mixture was stirred evenly.
[96] A blank sugar core having a particle size of 0.1-0.15 mm was placed in a fluidized bed, the vitamin D3 solution was sprayed into a fluidized bed by using Wurster technology, the atomization pressure was 2 bar, the inlet air temperature was 80°C, the exhaust air temperature was 45°C, and the active layer was formed on the surface of the sugar core. After drying, they were passed through an 80-mesh sieve to obtain the active layer of sugar core.
[97] Suspension: The hydroxypropyl methylcellulose was dissolved in purified water, talc and magnesium stearate were added, and mixed evenly. The active layer of sugar core was placed in a fluidized bed, the suspension was sprayed into the fluidized bed by using Wurster technology, the atomization pressure was 2 bar, the inlet air temperature was 80°C, the exhaust air temperature was 50°C, the isolation layer was formed on the surface of the active layer of sugar core to form vitamin D3 powder.
[98] Experimental Example 1: Stability test of vitamin D3
[99] The vitamin D3 powder in Examples 1-3 and the commercially available D3 powder were subjected to stability test, and the results show that there is no significant change in the content of the vitamin D3 powder prepared in Examples 1-3 and the commercially available D3 powder. However, the degradation trend of related substances in Examples 1-3 is significantly lower than that of the commercially available D3 powder. 1100] commercially vitamin D3 related available D3 subsancs(0o substances ()powder poder Example 1 Example 2 Example 3 (DSM) 0 day 0.12 0.02 0.03 0.04 trans VD3 long-term of12 0.18 0.03 0.05 0.06 months 0 day not detected not detected not detected not detected
EP B long-term of 12 not detected not detected not detected not detected months 0 day not detected not detected not detected not detected
EP C long-term of 12 not detected not detected not detected not detected months 0 day not detected not detected not detected not detected
EP D long-term of 12 not detected not detected not detected not detected months 0 day 0.48 0.08 0.11 0.11 tachysterol long-term 0.83 0.16 _____0.83_0o1120.23 of 12 0.24 months 0 day 0.60 0.10 0.14 0.15 total long-term purities of 12 1.01 0.19 0.28 0.30 months 0 day 101.3 100.8 100.3 101.5 vitamin D3 long-term content of 12 100.8 101.0 100.3 100.9 months
[101] Experimental Example 2: tablets
[102] Content Uniformity
[103] Three batches of production-scale samples (batch: 40,000 pieces) were prepared, and the quality was compared with that of the commercially available Caltrate D. The excipients calcium carbonate, mannitol and povidone were prepared into calcium carbonate particles. The wet particles were passed through a 20-mesh sieve, and the dry particles were passed through a crushing and sizing machine with a sieve aperture of 1.0 mm to obtain calcium carbonate particles, and then calcium carbonate particles were mixed with the vitamin D3 powder in Example 1, flavor and magnesium stearate and compressed into tablets
[104] According to the General Rule 0941 of Chinese Pharmacopoeia (2020 Edition), the content uniformity was tested. The results show that the content uniformity of the three batches of self-made samples is better than that of Caltrate, which satisfies the A
+ 2.2S of less than or equal to 15, and the content uniformity meets the requirements.
[105] batch No. Caltrate D 190301 190302 190303 average content 117.7 100.5 99.9 100.1 (0%)
A 17.3 0.5 0.1 0.1 S (%) 13.7 3.5 3.6 4.0 A+ 2.2S 47.4 8.2 8.0 8.9
[106] Stability
[107] The stability test of the self-made tablets and the commercially available Caltrate D was carried out. The results show that the content of the self-made tablets and the commercially available Caltrate D has no significant changes, and the degradation trend of related substances in the self-made tablets is significantly lower than that of the commercial Caltrate D.
[1081 related substances in Caltrate D 190301 190302 190303 self-made tablets (%) 0 day 0.27 0.02 0.04 0.02 trans VD3 long-term of 12 0.43 0.04 0.05 0.04 months
0 day not detected not detected not detected not detected
EP B long-term of 12 not detected not detected not detected not detected months 0 day not detected not detected not detected not detected
EP C long-term of 12 not detected not detected not detected not detected months 0 day not detected not detected not detected not detected
EP D long-term of 12 not detected not detected not detected not detected months 0 day 0.71 0.08 0.13 0.13 tachysterol long-term of 12 1.23 0.18 0.22 0.22 months 0 day 0.98 0.1 0.17 0.15 total long-term purities of 12 1.66 0.22 0.27 0.26 months 0 day 124.7 100.5 99.9 100.1 vitamin D3 long-term content of 12 123.8 100.5 100.2 99.8 months
[109] In summary, from the analysis of the stability results in the long-term of 12 months, the product quality of the vitamin D3 powder and compound calcium carbonate D3 chewable tablets in the present disclosure is good.
Claims (5)
1. A vitamin D3 composition, wherein comprising an active layer and an isolation layer, the active layer comprises the following components by mass percentage: Sugar core 70-80% Vitamin D3 0.1-1
% Hydroxypropyl methylcellulose 5-15
% Polysorbate 80 1-100% Tocopherol 0.5-20% Sodium ascorbate 2-8% The isolation layer comprises the following components by mass percentage: Hydroxypropyl methylcellulose 5-15
% Talc 1-10% Magnesium stearate 0.25-20%.
2. The vitamin D3 composition according to claim 1, wherein the sugar core has a diameter of 0.1-0.35 mm.
3. The vitamin D3 composition according to claim 1 or 2, wherein in a 2% aqueous solution at 20°C, the viscosity of hydroxypropyl methylcellulose is 1-8 mPa-s.
4. The vitamin D3 composition according to claim 1, wherein the active layer is prepared by preparing a solution of vitamin D3, hydroxypropyl methylcellulose, polysorbate 80, tocopherol, sodium ascorbate, and purified water, using the sugar core as a carrier, and spraying the solution onto the sugar core on a fluidized bed by using Wurster technology to obtain the active layer of sugar core.
5. The vitamin D3 composition according to claim 4, wherein the isolation layer is prepared by preparing a solution of hydroxypropyl methylcellulose, talc, magnesium stearate, and purified water, using the active layer of sugar core as the carrier, and spaying the solution onto the active layer of sugar core on the fluidized bed by using Wurster technology.
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| AU2021106478A AU2021106478A4 (en) | 2021-08-23 | 2021-08-23 | Vitamin D3 Compositions |
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