CN112569197A - Vitamin D3 composition and preparation method and application thereof - Google Patents
Vitamin D3 composition and preparation method and application thereof Download PDFInfo
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- CN112569197A CN112569197A CN202011564764.5A CN202011564764A CN112569197A CN 112569197 A CN112569197 A CN 112569197A CN 202011564764 A CN202011564764 A CN 202011564764A CN 112569197 A CN112569197 A CN 112569197A
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- vitamin
- active layer
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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 62
- 229940021056 vitamin d3 Drugs 0.000 title claims abstract description 62
- 235000005282 vitamin D3 Nutrition 0.000 title claims abstract description 61
- 239000000203 mixture Substances 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title abstract description 18
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 32
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract description 28
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 28
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 28
- 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 28
- 238000005507 spraying Methods 0.000 claims abstract description 25
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims abstract description 17
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 16
- 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 13
- 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 claims abstract description 13
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims abstract description 13
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims abstract description 13
- 229940068968 polysorbate 80 Drugs 0.000 claims abstract description 13
- 229920000053 polysorbate 80 Polymers 0.000 claims abstract description 13
- 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 13
- 235000010378 sodium ascorbate Nutrition 0.000 claims abstract description 13
- 229960005055 sodium ascorbate Drugs 0.000 claims abstract description 13
- 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 13
- 235000010384 tocopherol Nutrition 0.000 claims abstract description 13
- 239000011732 tocopherol Substances 0.000 claims abstract description 13
- 229960001295 tocopherol Drugs 0.000 claims abstract description 13
- 229930003799 tocopherol Natural products 0.000 claims abstract description 13
- 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 13
- 229910000019 calcium carbonate Inorganic materials 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 11
- 239000011162 core material Substances 0.000 claims abstract description 5
- 239000007921 spray Substances 0.000 claims abstract description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 239000008213 purified water Substances 0.000 claims description 16
- 238000002955 isolation Methods 0.000 claims description 14
- 239000007910 chewable tablet Substances 0.000 claims description 5
- -1 compound calcium carbonate Chemical class 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229940068682 chewable tablet Drugs 0.000 claims description 2
- 239000000454 talc Substances 0.000 claims 2
- 235000012222 talc Nutrition 0.000 claims 2
- 229910052623 talc Inorganic materials 0.000 claims 2
- 230000004888 barrier function Effects 0.000 claims 1
- 239000002245 particle Substances 0.000 abstract description 10
- 238000005516 engineering process Methods 0.000 abstract description 9
- 239000000725 suspension Substances 0.000 abstract description 7
- 239000000843 powder Substances 0.000 abstract description 6
- 239000011241 protective layer Substances 0.000 abstract description 2
- 239000011248 coating agent Substances 0.000 abstract 1
- 238000000576 coating method Methods 0.000 abstract 1
- 239000010410 layer Substances 0.000 description 48
- 239000000243 solution Substances 0.000 description 20
- 235000010216 calcium carbonate Nutrition 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 239000003826 tablet Substances 0.000 description 8
- 238000007873 sieving Methods 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
- 238000000889 atomisation Methods 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000002156 mixing 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
- 239000000126 substance Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 208000003217 Tetany Diseases 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
- 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
- 208000007442 rickets Diseases 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
- 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
- 229930195725 Mannitol Natural products 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000008468 bone growth Effects 0.000 description 1
- 230000023852 carbohydrate metabolic process Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 208000002925 dental caries Diseases 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 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
- 238000003825 pressing Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound 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
- 238000001694 spray drying Methods 0.000 description 1
- 230000001629 suppression Effects 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
- A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- 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
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a composition for effectively improving the stability of vitamin D3 and a preparation process thereof, belonging to the technical field of pharmacy. The vitamin D3 composition comprises sugar core, hydroxypropyl methylcellulose, tocopherol, sodium ascorbate, polysorbate 80, vitamin D3, talcum powder and magnesium stearate. The preparation process comprises the following steps: spraying a solution comprising hydroxypropyl methylcellulose, tocopherol, sodium ascorbate, polysorbate 80, vitamin D3 onto a sugar core in a fluidized bed apparatus by using a bottom spray technique; the prepared sugar core is sprayed with a suspension containing hydroxypropyl methylcellulose, talcum powder and magnesium stearate to be used as a protective layer. The Wurster coating technology is adopted, so that the stability of vitamin D3 can be improved, the granularity of D3 powder can be effectively improved and is close to that of calcium carbonate particles, and the good content uniformity of subsequent tablets is ensured.
Description
Technical Field
The invention belongs to the technical field of pharmacy, and relates to a composition for effectively improving the stability of vitamin D3 and a preparation process thereof, and the composition is used for preparing compound calcium carbonate chewable tablets.
Background
Molecular structure of vitamin D3:
molecular formula C27H44O，Mr384.64，CAS No:67-97-0
Chemical name of 9, 10-ring-opening cholest-5, 7,10(19) -triene-3 beta-alcohol
Vitamin D3(Vitamin D3), also known as cholecalciferol, is the most important 1 form of the Vitamin D family and primarily regulates calcium and phosphorus metabolism in the body. Vitamin D3 is obtained by converting 7-dehydrocholesterol in skin by ultraviolet irradiation. Vitamin D3 is the natural form of vitamin D, but is not a biologically active form thereof. It can be used for treating rickets, osteomalacia, tetany and finger tetany in infants, rickets with dental caries. Meanwhile, the biological functions of the vitamin D3 are wide: regulating calcium and phosphorus metabolism, and improving calcium and phosphorus absorption of organism; promoting bone growth; regulate proliferation, differentiation and change of cell biological functions of various tissue cells; exert immune regulation and improve glycometabolism; preventing amino acid loss through the kidney.
Since the unsaturated double bonds at the 5,7 and 10 positions in the structure of vitamin D3 are easily degraded by light, oxygen and heat, a stable vitamin D3 composition needs to be developed.
Chinese patent CN 104686812B discloses a preparation of coated nano-vitamin D3, but the particle size of the prepared vitamin D3 is too small to be mixed uniformly with other excipients, and the requirement of mixing uniformity cannot be met.
Chinese patent CN 107156456A discloses a composition including cyclodextrin and vitamin D3, but the dosage of ethanol organic solvent in the preparation process is large, so that the composition is not suitable for being prepared into a pharmaceutical preparation.
Chinese patent CN 106214468A discloses a composition of vitamin D3, which is prepared by mixing an oil phase and a water phase and then performing a spray drying process. But the preparation process is more complicated and has higher requirements on experimental equipment.
In view of the above problems, the vitamin D3 composition prepared by the invention can not only improve the stability of vitamin D3, but also has a relatively simple preparation process, and more importantly, can effectively improve the particle size of D3 powder, which is close to the particle size of calcium carbonate particles, and ensures that the content uniformity of subsequent tablets is good.
Disclosure of Invention
The invention aims to provide a composition for effectively improving the stability of vitamin D3 and a preparation process thereof, and the composition is used for preparing compound calcium carbonate chewable tablets.
In order to achieve the above objects, there is provided a composition for effectively improving the stability of vitamin D3 and a process for preparing the same, the formulation comprising: sugar core, hydroxypropyl methylcellulose, tocopherol, sodium ascorbate, polysorbate 80, vitamin D3, talcum powder and magnesium stearate.
The invention provides a vitamin D3 composition, which comprises an active layer and an isolation layer, wherein the active layer comprises a sugar core, vitamin D3, hydroxypropyl methyl cellulose, polysorbate 80, tocopherol and sodium ascorbate, and the isolation layer comprises the active layer sugar core, hydroxypropyl methyl cellulose, talcum powder and magnesium stearate.
The vitamin D3 composition comprises the following components in percentage by mass:
active layer:
isolation layer:
5-15% of hydroxypropyl methyl cellulose
1 to 10 percent of talcum powder
0.25 to 2 percent of magnesium stearate
The active layer is prepared by preparing solution from vitamin D3, hydroxypropyl methylcellulose, polysorbate 80, tocopherol, sodium ascorbate and purified water, and spraying the solution onto the sugar core with the sugar core as carrier.
The isolating layer is prepared by preparing hydroxypropyl methylcellulose, talcum powder, magnesium stearate and purified water into a solution, taking the active layer sugar core as a carrier, and spraying the solution onto the active layer sugar core.
The diameter of the sugar core is 0.1-0.35 mm.
The viscosity of the hydroxypropyl methylcellulose is 2-8 mPa. (apparent viscosity of 2% aqueous solution at 20 ℃).
The invention provides a preparation method of the vitamin D3 composition, which comprises the steps of preparing an active layer and an isolation layer.
The preparation of the active layer comprises the steps of preparing a solution from vitamin D3, hydroxypropyl methylcellulose, polysorbate 80, tocopherol, sodium ascorbate and purified water, taking the sugar core as a carrier, and spraying the solution onto the sugar core in a fluidized bed device by using a bottom spraying technology to obtain the active layer sugar core.
The preparation of the isolation layer comprises preparing hydroxypropyl methylcellulose, talcum powder, magnesium stearate and purified water into a solution, taking the active layer sugar core as a carrier, and spraying the solution onto the active layer sugar core in a fluidized bed device by using a bottom spraying technology. The isolation layer is the protective layer, and isolated oxygen, moisture and illumination protect vitamin D3's stability, when the suppression simultaneously is tabletted, avoid the active layer to be destroyed.
The invention provides a preparation process of the composition, which comprises the following steps: the active layer is prepared by preparing vitamin D3, hydroxypropyl methylcellulose, polysorbate 80, tocopherol, sodium ascorbate, and purified water into a solution, and spraying the solution onto a sugar core in a fluidized bed apparatus by using bottom spray (Wurster) technique with the sugar core as a carrier. The isolating layer is prepared by preparing hydroxypropyl methylcellulose, pulvis Talci, magnesium stearate, and purified water into solution, spraying the solution onto the active layer sugar core in fluidized bed device by using bottom spray (Wurster) technique with active layer sugar core as carrier.
The invention provides application of the vitamin D3 composition in preparing compound calcium carbonate D3 chewable tablets.
The vitamin D3 composition prepared by the invention can improve the stability of vitamin D3, has a simple preparation process, can improve the stability of vitamin D3, can effectively improve the granularity of D3 powder, is close to that of calcium carbonate particles, and ensures good content uniformity of subsequent tablets.
Detailed Description
To better illustrate the objects, technical solutions and advantages of the present invention, the technical solutions of the present invention are described in further detail below with reference to specific embodiments.
Example 1
Active layer
The invention provides a composition for effectively improving the stability of vitamin D3, which comprises the following components in parts by weight:
active layer
Insulating layer
The process comprises the following steps:
preparation of vitamin D3 solution: dissolving hydroxypropyl methylcellulose in purified water, adding polysorbate 80, stirring, adding antioxidant tocopherol and sodium ascorbate, adding vitamin D3, and stirring.
Placing a blank sugar core with the granularity of 0.1-0.15 mm in a fluidized bed, spraying a vitamin D3 solution into the fluidized bed by adopting a bottom spraying (Wurster) technology, wherein the atomizing pressure is 2bar, the air inlet temperature is 80 ℃, the air outlet temperature is 45 ℃, and an active layer component is formed on the surface of the sugar core. Drying, and sieving with 80 mesh sieve to obtain active layer sugar core.
Suspension: dissolving hydroxypropyl methylcellulose in purified water, adding pulvis Talci and magnesium stearate, and stirring. Placing the active layer sugar core in a fluidized bed, spraying the suspension into the fluidized bed by adopting a bottom spraying (Wurster) technology, wherein the atomization pressure is 2bar, the air inlet temperature is 80 ℃, the air exhaust temperature is 50 ℃, and an isolation layer is formed on the surface of the active layer sugar core to form vitamin D3 powder.
Example 2
Active layer
The invention provides a composition for effectively improving the stability of vitamin D3, which comprises the following components in parts by weight:
active layer
Insulating layer
The process comprises the following steps:
preparation of vitamin D3 solution: dissolving hydroxypropyl methylcellulose in purified water, adding polysorbate 80, stirring, adding antioxidant tocopherol and sodium ascorbate, adding vitamin D3, and stirring.
Placing a blank sugar core with the granularity of 0.1-0.15 mm in a fluidized bed, spraying a vitamin D3 solution into the fluidized bed by adopting a bottom spraying (Wurster) technology, wherein the atomizing pressure is 2bar, the air inlet temperature is 80 ℃, the air outlet temperature is 45 ℃, and an active layer component is formed on the surface of the sugar core. Drying, and sieving with 80 mesh sieve to obtain active layer sugar core.
Suspension: dissolving hydroxypropyl methylcellulose in purified water, adding pulvis Talci and magnesium stearate, and stirring. Placing the active layer sugar core in a fluidized bed, spraying the suspension into the fluidized bed by adopting a bottom spraying (Wurster) technology, wherein the atomization pressure is 2bar, the air inlet temperature is 80 ℃, the air exhaust temperature is 50 ℃, and an isolation layer is formed on the surface of the active layer sugar core to form vitamin D3 powder.
Example 3
Active layer
The invention provides a composition for effectively improving the stability of vitamin D3, which comprises the following components in parts by weight:
active layer
Insulating layer
The process comprises the following steps:
preparation of vitamin D3 solution: dissolving hydroxypropyl methylcellulose in purified water, adding polysorbate 80, stirring, adding antioxidant tocopherol and sodium ascorbate, adding vitamin D3, and stirring.
Placing a blank sugar core with the granularity of 0.1-0.15 mm in a fluidized bed, spraying a vitamin D3 solution into the fluidized bed by adopting a bottom spraying (Wurster) technology, wherein the atomizing pressure is 2bar, the air inlet temperature is 80 ℃, the air outlet temperature is 45 ℃, and an active layer component is formed on the surface of the sugar core. Drying, and sieving with 80 mesh sieve to obtain active layer sugar core.
Suspension: dissolving hydroxypropyl methylcellulose in purified water, adding pulvis Talci and magnesium stearate, and stirring. Placing the active layer sugar core in a fluidized bed, spraying the suspension into the fluidized bed by adopting a bottom spraying (Wurster) technology, wherein the atomization pressure is 2bar, the air inlet temperature is 80 ℃, the air exhaust temperature is 50 ℃, and an isolation layer is formed on the surface of the active layer sugar core to form vitamin D3 powder.
Experimental example 1 vitamin D3 stability test
The stability tests of the vitamin D3 powder prepared in examples 1 to 3 and the commercially available D3 powder showed that the contents of the vitamin D3 powder prepared in examples 1 to 3 and the commercially available D3 powder were not significantly changed, and the degradation tendency of the relevant substances in examples 1 to 3 was significantly reduced compared with that of the commercially available D3 powder.
Experimental example 2 tablet
Content uniformity
Three production scale samples (batch: 4 ten thousand tablets) were prepared and compared in quality with the commercial calqi D. Preparing calcium carbonate particles by excipient calcium carbonate, mannitol and polyvidone, sieving wet particles with a 20-mesh sieve, crushing dry particles with a granulator to obtain calcium carbonate particles with the mesh diameter of 1.0mm, mixing with the essence and magnesium stearate in the embodiment 1, and pressing into tablets.
According to 0941 of the four general rules of the 2020 edition of Chinese pharmacopoeia, content uniformity detection is carried out, and results show that the content uniformity of three batches of the self-made samples is superior to CallQi, and the content uniformity meets the requirement that A +2.2S is less than or equal to 15 and meets the regulation.
| Batch number | Calqi D | 190301 | 190302 | 190303 |
| Average content (%) | 117.7 | 100.5 | 99.9 | 100.1 |
| 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 |
Stability of
The stability test is carried out on the self-made tablet and the commercially available calqi D, and the results show that the contents of the self-made tablet and the commercially available calqi D are not obviously changed, and the degradation tendency of related substances of the self-made tablet is greatly reduced compared with that of the commercially available calqi D.
In conclusion, according to the analysis of the long-term stability result of 12 months, the vitamin D3 powder and the compound calcium carbonate D3 chewable tablet have good product quality.
Claims (10)
1. A vitamin D3 composition, which is characterized by comprising two parts, namely an active layer and an isolation layer, wherein the active layer comprises a sugar core, vitamin D3, hydroxypropyl methyl cellulose, polysorbate 80, tocopherol and sodium ascorbate, and the isolation layer comprises hydroxypropyl methyl cellulose, talcum powder and magnesium stearate.
2. The vitamin D3 composition according to claim 1, wherein the composition comprises, by mass:
active layer:
isolation layer:
5-15% of hydroxypropyl methyl cellulose
1 to 10 percent of talcum powder
0.25-2% of magnesium stearate.
3. The vitamin D3 composition according to claim 1 or 2, wherein the active layer is prepared by preparing vitamin D3, hydroxypropyl methylcellulose, polysorbate 80, tocopherol, sodium ascorbate, and purified water into a solution, and spraying the solution onto a sugar core with the sugar core as a carrier.
4. The vitamin D3 composition according to claim 1 or 2, wherein the isolation layer is prepared by preparing a solution of hydroxypropyl methylcellulose, talc, magnesium stearate, and purified water, and spraying the solution onto the active layer sugar core with the active layer sugar core as a carrier.
5. The vitamin D3 composition of claim 1 or 2, wherein the sugar core has a diameter of 0.1-0.35 mm.
6. The vitamin D3 composition according to claim 1 or 2, wherein the hydroxypropyl methylcellulose has a viscosity of 2-8 mPa s.
7. A process for preparing a vitamin D3 composition according to any one of claims 1 to 6, comprising preparing an active layer and a barrier layer.
8. The method of claim 7, wherein the preparing of the active layer comprises preparing a solution of vitamin D3, hydroxypropyl methylcellulose, polysorbate 80, tocopherol, sodium ascorbate, and purified water, and spraying the solution onto the sugar core in a fluidized bed apparatus using a bottom spray technique using a sugar core as a carrier to obtain the active layer sugar core.
9. The process of claim 7, wherein the isolation layer is prepared by preparing a solution of hydroxypropylmethylcellulose, talc, magnesium stearate, purified water, and spraying the solution onto the active layer cores in a fluidized bed apparatus using a bottom spray technique with the active layer cores as a carrier.
10. The vitamin D3 composition of any one of claims 1-6, for use in preparing a compound calcium carbonate D3 chewable tablet.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113476458A (en) * | 2021-08-19 | 2021-10-08 | 山东达因海洋生物制药股份有限公司 | Vitamin D3 compound and preparation method and application thereof |
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| US20100158998A1 (en) * | 2008-12-23 | 2010-06-24 | Michael Fox | Formulations comprising vitamin d or derivatives thereof |
| US20120207825A1 (en) * | 2009-09-17 | 2012-08-16 | Sunilendu Bhushan Roy | Pharmaceutical compositions for reducing alcohol-induced dose dumping |
| CN108969496A (en) * | 2018-09-07 | 2018-12-11 | 江苏恒丰强生物技术有限公司 | A kind of pet benazepril hydrochloride chewable tablets and preparation method thereof |
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| US20100158998A1 (en) * | 2008-12-23 | 2010-06-24 | Michael Fox | Formulations comprising vitamin d or derivatives thereof |
| US20120207825A1 (en) * | 2009-09-17 | 2012-08-16 | Sunilendu Bhushan Roy | Pharmaceutical compositions for reducing alcohol-induced dose dumping |
| CN108969496A (en) * | 2018-09-07 | 2018-12-11 | 江苏恒丰强生物技术有限公司 | A kind of pet benazepril hydrochloride chewable tablets and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113476458A (en) * | 2021-08-19 | 2021-10-08 | 山东达因海洋生物制药股份有限公司 | Vitamin D3 compound and preparation method and application thereof |
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