GB2569119A - An aqueous beverage containing microencapsulated food supplement - Google Patents
An aqueous beverage containing microencapsulated food supplement Download PDFInfo
- Publication number
- GB2569119A GB2569119A GB1720230.0A GB201720230A GB2569119A GB 2569119 A GB2569119 A GB 2569119A GB 201720230 A GB201720230 A GB 201720230A GB 2569119 A GB2569119 A GB 2569119A
- Authority
- GB
- United Kingdom
- Prior art keywords
- polymer
- vitamin
- core
- microcapsules
- eudragit
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 235000013361 beverage Nutrition 0.000 title claims abstract description 73
- 235000015872 dietary supplement Nutrition 0.000 title claims description 41
- 229920000642 polymer Polymers 0.000 claims abstract description 109
- 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 claims abstract description 92
- 229930003316 Vitamin D Natural products 0.000 claims abstract description 72
- 235000019166 vitamin D Nutrition 0.000 claims abstract description 72
- 239000011710 vitamin D Substances 0.000 claims abstract description 72
- 150000003710 vitamin D derivatives Chemical class 0.000 claims abstract description 72
- 229940046008 vitamin d Drugs 0.000 claims abstract description 72
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 62
- 239000003094 microcapsule Substances 0.000 claims abstract description 53
- 239000002253 acid Substances 0.000 claims abstract description 32
- 238000000034 method Methods 0.000 claims abstract description 30
- 229920003134 Eudragit® polymer Polymers 0.000 claims abstract description 25
- 239000011248 coating agent Substances 0.000 claims abstract description 22
- 238000000576 coating method Methods 0.000 claims abstract description 22
- 239000013543 active substance Substances 0.000 claims abstract description 18
- 229920001661 Chitosan Polymers 0.000 claims abstract description 17
- 239000001856 Ethyl cellulose Substances 0.000 claims abstract description 15
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229920001249 ethyl cellulose Polymers 0.000 claims abstract description 15
- 235000019325 ethyl cellulose Nutrition 0.000 claims abstract description 15
- 241000124008 Mammalia Species 0.000 claims abstract description 8
- 206010047626 Vitamin D Deficiency Diseases 0.000 claims abstract description 6
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 239000000725 suspension Substances 0.000 claims abstract description 3
- 239000007788 liquid Substances 0.000 claims description 29
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical group COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims description 23
- 239000012530 fluid Substances 0.000 claims description 19
- 238000001035 drying Methods 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- 235000020124 milk-based beverage Nutrition 0.000 claims description 5
- 235000012206 bottled water Nutrition 0.000 claims description 4
- 238000005507 spraying Methods 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- 239000007921 spray Substances 0.000 claims description 2
- 229920003137 Eudragit® S polymer Polymers 0.000 abstract description 10
- 235000013336 milk Nutrition 0.000 abstract description 8
- 239000008267 milk Substances 0.000 abstract description 8
- 210000004080 milk Anatomy 0.000 abstract description 8
- 229920003136 Eudragit® L polymer Polymers 0.000 abstract description 4
- 239000011859 microparticle Substances 0.000 description 47
- 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 description 25
- 235000005282 vitamin D3 Nutrition 0.000 description 20
- 239000011647 vitamin D3 Substances 0.000 description 20
- 229940021056 vitamin d3 Drugs 0.000 description 20
- 239000000047 product Substances 0.000 description 18
- 235000013305 food Nutrition 0.000 description 16
- 239000006185 dispersion Substances 0.000 description 14
- 230000009469 supplementation Effects 0.000 description 13
- 239000000203 mixture Substances 0.000 description 11
- 238000001694 spray drying Methods 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- -1 fatty acid ester Chemical class 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 239000002245 particle Substances 0.000 description 8
- 229940088594 vitamin Drugs 0.000 description 8
- 229930003231 vitamin Natural products 0.000 description 8
- 235000013343 vitamin Nutrition 0.000 description 8
- 239000011782 vitamin Substances 0.000 description 8
- 230000015556 catabolic process Effects 0.000 description 7
- 239000008367 deionised water Substances 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 229910052500 inorganic mineral Inorganic materials 0.000 description 7
- 238000011068 loading method Methods 0.000 description 7
- 239000011707 mineral Substances 0.000 description 7
- 235000010755 mineral Nutrition 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 238000006731 degradation reaction Methods 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 230000002496 gastric effect Effects 0.000 description 6
- 239000002105 nanoparticle Substances 0.000 description 6
- 238000013268 sustained release Methods 0.000 description 6
- 239000012730 sustained-release form Substances 0.000 description 6
- 229920003148 Eudragit® E polymer Polymers 0.000 description 5
- VBVAVBCYMYWNOU-UHFFFAOYSA-N coumarin 6 Chemical compound C1=CC=C2SC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 VBVAVBCYMYWNOU-UHFFFAOYSA-N 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- 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 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 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 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 210000000988 bone and bone Anatomy 0.000 description 4
- NEDGUIRITORSKL-UHFFFAOYSA-N butyl 2-methylprop-2-enoate;2-(dimethylamino)ethyl 2-methylprop-2-enoate;methyl 2-methylprop-2-enoate Chemical compound COC(=O)C(C)=C.CCCCOC(=O)C(C)=C.CN(C)CCOC(=O)C(C)=C NEDGUIRITORSKL-UHFFFAOYSA-N 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 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 4
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000005538 encapsulation Methods 0.000 description 4
- 229960002061 ergocalciferol Drugs 0.000 description 4
- 150000004665 fatty acids Chemical class 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 208000007442 rickets Diseases 0.000 description 4
- 235000001892 vitamin D2 Nutrition 0.000 description 4
- 239000011653 vitamin D2 Substances 0.000 description 4
- 150000003722 vitamin derivatives Chemical class 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 241000283086 Equidae Species 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 235000014171 carbonated beverage Nutrition 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- KPHWPUGNDIVLNH-UHFFFAOYSA-M diclofenac sodium Chemical compound [Na+].[O-]C(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl KPHWPUGNDIVLNH-UHFFFAOYSA-M 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 229940093499 ethyl acetate Drugs 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 239000003925 fat Substances 0.000 description 3
- 235000019197 fats Nutrition 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 3
- 229940117841 methacrylic acid copolymer Drugs 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 208000005368 osteomalacia Diseases 0.000 description 3
- 239000006041 probiotic Substances 0.000 description 3
- 235000018291 probiotics Nutrition 0.000 description 3
- 210000000813 small intestine Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 230000036561 sun exposure Effects 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 230000000007 visual effect Effects 0.000 description 3
- LLQHSBBZNDXTIV-UHFFFAOYSA-N 6-[5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-4,5-dihydro-1,2-oxazol-3-yl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC1CC(=NO1)C1=CC2=C(NC(O2)=O)C=C1 LLQHSBBZNDXTIV-UHFFFAOYSA-N 0.000 description 2
- 229920002126 Acrylic acid copolymer Polymers 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- NEAPKZHDYMQZCB-UHFFFAOYSA-N N-[2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]ethyl]-2-oxo-3H-1,3-benzoxazole-6-carboxamide Chemical compound C1CN(CCN1CCNC(=O)C2=CC3=C(C=C2)NC(=O)O3)C4=CN=C(N=C4)NC5CC6=CC=CC=C6C5 NEAPKZHDYMQZCB-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 229920002301 cellulose acetate Polymers 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 229960000956 coumarin Drugs 0.000 description 2
- 235000001671 coumarin Nutrition 0.000 description 2
- 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 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 235000018823 dietary intake Nutrition 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 235000013350 formula milk Nutrition 0.000 description 2
- 235000020189 fortified milk Nutrition 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000011785 micronutrient Substances 0.000 description 2
- 235000013369 micronutrients Nutrition 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 238000005191 phase separation Methods 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 235000013406 prebiotics Nutrition 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000000527 sonication Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 238000007669 thermal treatment Methods 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- 235000019155 vitamin A Nutrition 0.000 description 2
- 239000011719 vitamin A Substances 0.000 description 2
- 235000008924 yoghurt drink Nutrition 0.000 description 2
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 241000282421 Canidae Species 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 229920008347 Cellulose acetate propionate Polymers 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000282994 Cervidae Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-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
- 241001649081 Dina Species 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 229920003141 Eudragit® S 100 Polymers 0.000 description 1
- 241000282818 Giraffidae Species 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 241000282320 Panthera leo Species 0.000 description 1
- 241000282376 Panthera tigris Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 241000282405 Pongo abelii Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 229930003448 Vitamin K Natural products 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 229920002494 Zein Polymers 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- IYKJEILNJZQJPU-UHFFFAOYSA-N acetic acid;butanedioic acid Chemical compound CC(O)=O.OC(=O)CCC(O)=O IYKJEILNJZQJPU-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229920006243 acrylic copolymer Polymers 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000008468 bone growth Effects 0.000 description 1
- 230000010072 bone remodeling Effects 0.000 description 1
- 235000020535 bottled fortified water Nutrition 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 229940057779 calci-chew Drugs 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007771 core particle Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000019007 dietary guidelines Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 208000035475 disorder Diseases 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
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020774 essential nutrients Nutrition 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 235000020988 fatty fish Nutrition 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 229940013317 fish oils Drugs 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 235000008216 herbs Nutrition 0.000 description 1
- 239000013029 homogenous suspension Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 229920000639 hydroxypropylmethylcellulose acetate succinate Polymers 0.000 description 1
- 230000003116 impacting effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 235000015122 lemonade Nutrition 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 235000013310 margarine Nutrition 0.000 description 1
- 239000003264 margarine Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 235000018343 nutrient deficiency Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000020665 omega-6 fatty acid Nutrition 0.000 description 1
- 229940033080 omega-6 fatty acid Drugs 0.000 description 1
- 229940098462 oral drops Drugs 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 238000005453 pelletization Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 235000013570 smoothie Nutrition 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 235000011496 sports drink Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000037072 sun protection Effects 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 125000005591 trimellitate group Chemical group 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 235000015192 vegetable juice Nutrition 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 235000019168 vitamin K Nutrition 0.000 description 1
- 239000011712 vitamin K Substances 0.000 description 1
- 150000003721 vitamin K derivatives Chemical class 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940046010 vitamin k Drugs 0.000 description 1
- 235000020812 vitamin status Nutrition 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 235000008939 whole milk Nutrition 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 239000005019 zein Substances 0.000 description 1
- 229940093612 zein Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/15—Vitamins
- A23L33/155—Vitamins A or D
-
- 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
- A61K31/592—9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Food Science & Technology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Epidemiology (AREA)
- Nutrition Science (AREA)
- Mycology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Preparation (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
An aqueous beverage comprises a suspension of microcapsules, the microcapsules comprising a core comprising an active agent disposed within a first polymer, and an outer coating encapsulating the core and comprising a second polymer, wherein the first polymer is acid stable and water soluble, the second polymer is water stable and/or acid soluble, and the active agent is unstable in one or more of light, water and acid. The active agent may be Vitamin D and the beverage may be water or milk-based. The first polymer may beselected from EUDRAGIT ® L or EUDRAGIT ® S and the second polymer may be selected from EUDRAGIT ® E, chitosan, or ethyl cellulose. The beverage is preferably provided in a transparent polymer bottle. A method of making an aqueous beverage comprising encapsulated active agent, and a method of preventing vitamin D deficiency in mammals is also claimed.
Description
An aqueous beverage containing microencapsulated food supplement
Field of the Invention
The present invention relates to a beverage comprising microencapsulated food supplements, and in particular microencapsulated Vitamin D. Also contemplated are methods of making aqueous beverages comprising microencapsulated food supplements such as vitamins, minerals or other food supplements.
Background to the Invention
Vitamin D is a naturally occurring vitamin which is fat soluble. It consists of 2 major forms;
Vitamin D2 (ergocalciferol) and Vitamin D3 (cholecalciferol)[1j. Vitamin D3 is the form which is synthesised by human and is the form recommended for supplementation. Vitamin D3 is found naturally in a limited number of foods such as fatty fish, fish oils and in small amounts in cheese and egg yolk. It is mainly photosynthesized in humans by the action of ultraviolet B radiation from the sun. Vitamin D is an essential nutrient to human health. It promotes intestinal absorption of minerals such as calcium and phosphorus from the diet to enable normal bone mineralisation, allow bone growth and remodelling [1], Insufficient vitamin D will result in thin, brittle and misshapen bones which under extreme deficiencies can result in Rickets in children and osteomalacia in adults, while severe deficiencies can lead to osteoporosis in adults. Evidence suggest poor vitamin D levels across the various age groups and in particular infants, pregnant women and elderly. This is more pronounced in the northern countries including Ireland, where sun exposure is limited and as sun exposure is a cause of melanoma, sun protection is recommended, or where cultural dress requirements prevents sun exposure. There is in addition growing literature which suggests that low plasma levels of vitamin D may contribute to a number of chronic diseases such as hypertension, cardiovascular disease, diabetes mellitus (type 1 diabetes), certain inflammatory and autoimmune diseases and some forms of cancer [1-4], Many countries have therefore revised their dietary guidelines for Vitamin D3 and deveoped plans for food fortification or supplementation. In Ireland, The Food and Safety
Authority of Ireland (FSAI) issued recommendations for a national policy on Vitamin D supplementation for infants as cases of rickets re-emerged in infants. Studies have shown that dietary intakes of vitamin D in irish adults, adolescents, children and pregnant women fall below 5 mcg per day resulting in poor Vitamin D levels [5], The FSAI recommendation that infants from birth to 12 months should be supplemented with 5mcg of Vitamin D daily. This recommendation was subsequently endorsed by the Department of Health and Children, and the Health Service Executive (HSE).
The recommended daily allowance (RDA) as published by the Food and Nutrition Board, Institute of Medicine, National Academies of Sciences, US, in 2010, is 600 IU (15mcg) for those 1-70 years of age and pregnant or breastfeeding women, and 800 IU (20mcg) for those over 71 years of age [2], The RDA in Europe is lower and varies with age groups and countries. It ranges from 0-10, with 10 mcg (400 IU) being most common RDA, Table 1, [6], In 2013, Norway and Italy raised their RDA to 20 and 25 mcg per day respectively. The Food Safety Authority of Ireland (FSAI) has issued recommendation of 5 mcg daily dose for infants 0-12 months although evidence show poor vitamin D levels across the population [5].
A number of countries have policies on supplementation of vitamin D and certain staple foods such as infant formula, milk, cereals, flour, bread, juices, margarine, fats are fortified with vitamin D. Unfortunately, dietary intake levels still fall below RDA. In Europe including Ireland, daily intake of vitamin D in children 1-18 years are well below RDA at 20-80% below. Food fortification and supplementation are an effective method of increasing vitamin D levels across all sectors of the population provided this is regularly consumed. Currently only a few products are fortified. These fortified products do not represent daily intake across all population which limit their effectiveness. A product such as fortified water can lead to an improvement in vitamin status in population. To date this is not an area which has been developed. Water is generally consumed on a daily basis by most age groups and presents an opportunity for addressing this vital supplementation.
The addition of Vitamin D2 and D3 are legally permitted to foods is legally permitted to be added to foods listed in Annex I of Regulation (EC) No 1925/2006 [as amended by Commission Regulation (EC) No. 1170/2009], with no addition being permitted to unprocessed foods or alcoholic beverages.
For a nutrient and/or health claim to be made to consumers, vitamin D concentration in the food product has to be at least 15% (or at least 7.5% for drinks) of the specified EU nutrient reference value (per 100 g) for vitamin D of 5 pg (EC 2011)’
For labeling of Vitamin D supplementation therefore, at least 7.5% for drinks of 5mcg has to be added per 100mls water = 0.375mcg/100 mis
In Ireland, Avonmore super milk contains Vitamin D3 at 5mcg per 250mls serving ( equivalent to 2mcg/100mls or 40% of 5mcg) and Kelloggs Special K contains 2.5mcg per 35 g serving (equivalent to ~7.5mcg/100g or 150% of 5 mcg).
Vitamin D is available as therapeutic supplementation in the following products: Calcichew tablets in combination with Calcium. Dose of Vitamin D3 per tablet = 400IU or 10mcg, to be taken 2 tablets per day. Other similar products are Calvidin®, Osteofos®. Desunin® contains only cholecalciferol at a dose of 20mcg/tablet with recommended daily dose of 1 tablet per day.
Thorens® oral drops containing 10,000 IU or250mcg/ml for infants. 1 drop= 200IU or 5mcg to be administered daily.The formulation of this drop is Vitamin D in olive oil and has a shelf life of 3 years. After opening, it has a shelf life of 6 months.
Vitamin D3 is cholecaliferol. It has a molecular formula of C27H44O and a molecular weight of 384.637. Its molecular structure is shown in figure 1. Its melting point is 82-87°C and its water solubility at 20°C is <0.1g/L (<0.1mg/ml).
The mMolar (384.6mg/1000ml) absorptivity at265nm is 18.2 (Hexane or ethanol). Vitamin D3 is soluble in organic solvents and slightly soluble in oils. Vitamin D3 is prepared from cholesterol extracted from the lanolin of sheep’s wool. Cholesterol is converted to 7dehydrocholesterol then treated with UV light to produce cholecalciferol which is then crystallized. Due to its method of production, Vitamin D3 is of animal origin and hence not suitable for vegetarians and this may need to be addressed depending on the market it is intended for.
The conversion of Vitamin D3 from IU to weight is 40 IU = 1 pg Calciferol [3,6]
Vitamin D3 undergoes oxidation, and is oxidised rapidly when exposed to air. Other external factors which affect its stability are humidity, light, and low pH. In the presence of nitrogen, at RT, stability over 56 days storage was reported [7], figure 2. Storage under controlled conditions of low humidity and under nitrogen is generally recommended for storage of Vitamin D3 raw materials. In addition antioxidants can be added to prevent its oxidation. For use a supplementation in foods, granulation, pelletisation, and microencapsulation appear to be strategies which have been utilised. To protect the molecule from degradation. While Vitamin D3 can withstand Temperatures up to 40oC, it is sensitive to changes in temperature at high humidity levels. Vitamin D3 has been reported to be sensitive to trace metals.[8,9], In comparison, Vitamin D2 has lower stability.
As shown in Table A, when subject to thermal treatment at 72°C for 15 seconds, Vitamin D3 content in pH 3.5 was not statistically significantly reduced. In pH 6.6 buffer, a small drop in content of <6% was observed.
Table A. Impact of thermal treatment on Vitamin D content in pH 3.5 and pH 6.6 buffer
VtiamtB 1> eanienf
and pH ef baffcr | 72X | rrtefliloii % | ||
Mean ± | Range | Meaii ± 811 | ||
Vitamin Eh, pH 3.5 | ·$39 < | ± ri.46 | 97.54% | |
Vttamm D>, pH 3.5 | 16.70 ± | 0.62 | 15.74 ± 0.46 | 94.2339 |
Vitamin Eh, pH 6.6 | 16.79 ± | 0.38 | 15.51 ± 0.20 | 92.32% |
Vitisnm pH 6 6 | 16.05 ± | {J 62 | 15.28 ± 0.77 | 96 15% |
Due to its sensitivity to oxygen, light and humidity, microencapsulation of vitamin D is carried using a number of formulation strategies including spray drying. Shi et al 2002 encapsulated Vitamin D2 in chitosan (CS) microcores by spray drying first to produce cores which were further encapsulated by coating with ethyl cellulose using a phase separation/precipitation method. This resulted in microparticles of size 2-20um depending on the chitosan concentration. The Vitamin D3 loading efficiency using these processed was > 86% and the microcapsules showed sustained release of Vitamin D for up to 12 hours[13], Luo et al 2012 encapsulated Vitamin D3 at 7.5% w/w loading into Zein (Z) nanoparticles (NPs) by phase separation. Subsequently, these were coated with carboxymethyl chitosan (CMCS) at Z/CMCS ratios of 1:1, 1:2 and 2:1 and hardened by calcium ions. Nanoparticles of size 100-200nm were formed showing an encapsulation efficiency (EE) of 50-88%. The uncoated NPs showing lowest encapsulation efficiency and coated NPs at Z/CMCS ratio of 1:2 and hardened with CMCS/Ca ratio of 20:1 showing the highest loading of 88%. The coated NPs showed sustained release properties of Vitamin D 3 where only -50% of drug was released after day 8 [14],
It is an object of the invention to provide an aqueous beverage containing Vitamin Dina stabilised and protected form, which is protected during storage from degradation due to light and humidity, and from acid in the stomach, and which is released in the small intestine.
Summary of the Invention
The present invention addresses the need for an aqueous beverage comprising stabilised and protected Vitamin D which is released in the small intestine. The Vitamin D is provided in a microencapsulated form using 3-fluid nozzle spray drying, which provides, in a single step, microcapsules having a core containing Vitamin D (or a different environmentally sensitive agent) disposed in a first polymer, and a coating encapsulating the core comprising a second polymer. The outer coat of the microcapsule comprises a polymer (second polymer) that is water insoluble, and thus stable in an aqueous beverage. The outer coat may be acid soluble (i.e. EUDRAGIT E) enabling the outer coat to degrade in the low PH of the stomach, exposing the acid stable and inner core (first polymer). This embodiment is suitable when the beverage has an alkaline pH (i.e. some mineral waters). In some embodiments, the outer coat (second polymer) is a sustained release polymer (i.e. Ethylcellulose, EUDRAGIT RS, RL or RE) that is water insoluble. The inner core (first polymer) is acid stable but water soluble, so that it survives gastric transit without breakdown, thereby protecting the Vitamin D from acid, and will only break down once the core has passed into the small intestine where the higher pH and aqueous conditions allow the core to break down releasing the Vitamin D at its target location. Various polymers may be employed as the first and second polymers, as described below. The microcapsules may be dispersed in water at levels of about 0.01% (w/vw) without unduly affecting the clarity of the water, and Vitamin D may be incorporated into the microcapsules at a loading of 0.1% of the microcapsules (w/w), which allows incorporation of 5-up to 10 mcg Vitamin D per 100 mis of beverage. For other beverages for which clarity is not an issue, higher amounts of microcapsules may be dispersed in the beverage. The invention is particularly applicable for beverages containing Vitamin D, but may be applied to other food supplements such as vitamins and minerals, probiotics, prebiotics, fatty acids and micronutrients.
According to a first aspect of the present invention, there is provided an aqueous beverage typically comprising a suspension of microcapsules, the microcapsules comprising a core comprising a food supplement disposed within a first polymer, and an outer coating encapsulating the core and comprising a second polymer, wherein the first polymer is acid stable and water soluble, and the second polymer is water stable and optionally acid soluble and wherein the food supplement is stabilised and protected within the microcapsule.
According to a second aspect of the present invention, there is provided a microcapsule comprising a core comprising an food supplement disposed within a first polymer, and an outer coating encapsulating the core and comprising a second polymer, wherein the first polymer is acid stable and water soluble, and the second polymer is water stable and optionally acid soluble, and wherein the food supplement is stabilised and protected within the microcapsule.
In one embodiment, the food supplement is sensitive to acid, light, heat or water degradation. In one embodiment, the food supplement is sensitive to acid and water degradation. In one embodiment, the food supplement is sensitive to acid, light and water degradation. One example is Vitamin D, which degrades in the presence of acid, light and water. Other examples include Vitamin A, E and K. Probiotics, amino acids, Omega-3, Omega-6 fatty acids.
In one embodiment, the aqueous beverage is water. In another embodiment, the aqueous beverage is milk or a milk product. In one embodiment, the beverage is a nutritional supplement drink. In one embodiment, the aqueous beverage is a sports drink. In one embodiment, the aqueous beverage is a carbonated beverage in which case the second polymer will be stable at the pH of the beverage but unstable at gastric pH. Carbonated beverages have a lower pH than non-carbonated beverages. The second polymer will be dependent on pH and lipophilicity of the beverage.
In one embodiment, the aqueous beverage comprises about 0.0001% to about 0.01% microcapsules (w/w). In one embodiment, the aqueous beverage comprises about 0.001% to about 0.005% microcapsules (w/w). Higher levels may be incorporated for beverages which are not clear, for example 0.1-10% (w/w).
In one embodiment, the microcapsules comprise about 0.05 to about 10 % food supplement (w/w). In one embodiment, the microcapsules comprise about 0.05 to about 0. 5% food supplement (w/w). In one embodiment, the microcapsules comprise about 0.1% food supplement (w/w). The content will be dependant on the dose of the food supplement to be incorporated.
In one embodiment, the aqueous beverage comprises 0.5 to 10 pg food supplement per 100 ml of aqueous beverage(w/w). In one embodiment, the aqueous beverage comprises about 1 to about 5pg food supplement per 100 ml of aqueous beverage (w/w).
. In one embodiment, the aqueous beverage has a volume of 10-1000, 10-500, or100-500 mis, for example about 100, 200, 300, 400 or 500 mis. In one embodiment, the aqueous beverage has a volume of about 500 mis and comprises about 1 to about 50 pg, about 5 to about 25 pg, of food supplement, for example Vitamin D.
In one embodiment, the first polymer is stable in aqueous solution at a pH of less than 5, typically stable at a pH of 1-2, and soluble in aqueous solution at a pH of above 5, for example 5-7 or 6-7.
In one embodiment, the second polymer is stable in aqueous solution at a pH above 5, for example 5-7 or 6-7, and soluble in an aqueous solution at a pH below 5, for example 1-2.
In one embodiment, the second polymer comprises a sustained release polymer (i.e. ethyl cellulose or EUDRAGIT RS, RL or RE.
In one embodiment, the first polymer is an enteric polymer, for example EUDRAGIT L, S or LD.
In one embodiment, the second polymer is selected from chitosan, or ethyl cellulose or a derivative thereof.
In one embodiment, the microcapsules have an average particle diameter of 0.1 to 200 pm. In one embodiment, microcapsules have an average particle diameter of 0.8 to 50 pm.
In one embodiment, microcapsules have an average particle diameter of 1 to 25 pm.
The invention also provides a packaged product comprising an aqueous beverage of the invention contained within a sealed package, for example a bottle or carton. In one embodiment, the bottle is a transparent bottle, for example a transparent glass or polymeric bottle.
In a further aspect, the invention provides a method of making microcapsules comprising the steps of:
providing a core-forming liquid stream comprising a food supplement and a first polymer, in which the food supplement is typically unstable in one or more of light, water and acid, providing a coating-forming liquid stream comprising a second polymer, providing a 3-fluid nozzle arrangement having an outer nozzle disposed concentrically about a core nozzle, simultaneously spraying the core-forming fluid stream from the core nozzle and the coating-forming fluid stream from the outer nozzle to produce microcapsules having a core comprising the food supplement disposed with the first polymer and a coating encapsulating the core comprising the second polymer, and solidifying the microcapsules upon formation in a drying chamber, wherein the first polymer is typically acid stable and water soluble, and the second polymer is typically water stable and optionally acid soluble.
In a further aspect, the invention provides a method of making an aqueous beverage (for example an aqueous beverage of the invention), comprising the steps of:
providing a core-forming liquid stream comprising a food supplement and a first polymer, in which the food supplement is unstable in one or more of light, water and acid, providing a coating-forming liquid stream comprising a second polymer, providing a 3-fluid nozzle arrangement having an outer nozzle disposed concentrically about a core nozzle, simultaneously spraying the core-forming fluid stream from the core nozzle and the coating-forming fluid stream from the outer nozzle to produce microcapsules having a core comprising the food supplementdisposed with the first polymer and a coating encapsulating the core comprising the second polymer, solidifying the microcapsules upon formation in a drying chamber, and adding the microcapsules to an aqueous liquid to form the aqueous beverage, wherein the first polymer is typically acid stable and water soluble, and the second polymer is typically water stable and optionally acid soluble.
In one embodiment, the core-forming liquid stream comprises 0.5% to 10% total solids (w/v) and the coating forming liquid stream comprises 1% to 20% total solids (w/v).
In one embodiment, the method employs a spray-dryer, in which the inlet temperature for the core and coating forming liquid streams is 70-140°C, preferably 80-105°C, and the outlet temperature for the core and coating forming liquid streams is 40-85°C, preferably 45-65°C. The specific temperatures employed for the inlet and outlet temperatures for the core and coating fluid streams is dependent on the solvents employed, and may be varied according to the circumstances as determined by a person skilled in the art.
In one embodiment, in which the aqueous beverage is sealed in a container, for example a transparent container. In one embodiment, the container is a bottle or carton, preferably a transparent polymeric bottle.
In another aspect, the invention provides a method of maintaining adequate Vitamin D intake in a mammal, comprising a step of administering an aqueous beverage of the invention to the individual, in which the beverage typically comprises 5 to 25mg Vitamin D.
In another aspect, the invention provides a non-therapeutic method of preventing Vitamin D deficiency in a mammal, comprising a step of administering an aqueous beverage of the invention to the individual, in which the beverage typically comprises 5 to 25mg Vitamin D.
In one embodiment of the method of the invention, the aqueous beverage is administered to the mammal once a day.
The invention also provides an aqueous beverage of the invention, for use in a method of treating a disease or condition characterised by Vitamin D deficiency, in which the method comprises a step of administering the aqueous beverage to the individual, and in which the beverage typically comprises 5 to 25mg Vitamin D.
Other aspects and preferred embodiments of the invention are defined and described in the other claims set out below.
Brief Description of the Figures
Figure 1. Drug release from ethylcellulose single walled microparticles using a surrogate drug, sodium diclofenac (DFS) of water solubility of 50mg/ml. Solubility of Vitamin D in water is < 0.1mg/ml.
Figure 2. Illustration of method of making microcapsules using 3-nozzle spray drying as described in EP
Figure 3. Microparticles prepared as per table 2 above in order of formulations listed.
Figure 4. Dispersion of Chitosan microparticles in Ballygowan water (1 +2) and in deionised water (3)
Figure 5. Dispersions of Eudragit L and S microparticles in deionised water at a concentration of 25mg/m
Figure 6. Dispersion of core (Eudragit E), coat(Eudragit S)and Double walled Eudragit E/S microparticles in deionised water (A and B) and in deionised water (C).
Detailed Description of the Invention
All publications, patents, patent applications and other references mentioned herein are hereby incorporated by reference in their entireties for all purposes as if each individual publication, patent or patent application were specifically and individually indicated to be incorporated by reference and the content thereof recited in full.
Definitions and general preferences
Where used herein and unless specifically indicated otherwise, the following terms are intended to have the following meanings in addition to any broader (or narrower) meanings the terms might enjoy in the art:
Unless otherwise required by context, the use herein of the singular is to be read to include the plural and vice versa. The term a or an used in relation to an entity is to be read to refer to one or more of that entity. As such, the terms a (or an), one or more, and at least one are used interchangeably herein.
As used herein, the term comprise, or variations thereof such as comprises or comprising, are to be read to indicate the inclusion of any recited integer (e.g. a feature, element, characteristic, property, method/process step or limitation) or group of integers (e.g. features, element, characteristics, properties, method/process steps or limitations) but not the exclusion of any other integer or group of integers. Thus, as used herein the term comprising is inclusive or open-ended and does not exclude additional, unrecited integers or method/process steps.
As used herein, the term “disease” is used to define any abnormal condition that impairs physiological function and is associated with specific symptoms. The term is used broadly to encompass any disorder, illness, abnormality, pathology, sickness, condition or syndrome in which physiological function is impaired irrespective of the nature of the aetiology (or indeed whether the aetiological basis for the disease is established). It therefore encompasses conditions arising from infection, trauma, injury, surgery, radiological ablation, poisoning or nutritional deficiencies.
As used herein, the term treatment or treating refers to an intervention (e.g. the administration of an agent to a subject) which cures, ameliorates or lessens the symptoms of a disease or removes (or lessens the impact of) its cause(s) (for example, the reduction in accumulation of pathological levels of lysosomal enzymes). In this case, the term is used synonymously with the term “therapy”.
Additionally, the terms treatment or treating refers to an intervention (e.g. the administration of an agent to a subject) which prevents or delays the onset or progression of a disease or reduces (or eradicates) its incidence within a treated population. In this case, the term treatment is used synonymously with the term “prophylaxis”.
As used herein, an effective amount or a therapeutically effective amount of a food supplementdefines an amount that can be administered to a subject without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio, but one that is sufficient to provide the desired effect, e.g. provide adequate amounts of Vitamin D to a subject. The amount will vary from subject to subject, depending on the age and general condition of the individual and other factors. Thus, while it is not possible to specify an exact effective amount, those skilled in the art will be able to determine an appropriate effective amount in any individual case using routine experimentation and background general knowledge.
In the context of effective amounts as defined above, the term subject (which is to be read to include individual, animal, consumer or mammal where context permits) defines any subject, particularly a mammalian subject, for whom supplementation isrequired. Mammalian subjects include, but are not limited to, humans, domestic animals, farm animals, zoo animals, sport animals, pet animals such as dogs, cats, guinea pigs, rabbits, rats, mice, horses, cattle, cows; primates such as apes, monkeys, orangutans, and chimpanzees; canids such as dogs and wolves; felids such as cats, lions, and tigers; equids such as horses, donkeys, and zebras; food animals such as cows, pigs, and sheep; ungulates such as deer and giraffes; and rodents such as mice, rats, hamsters and guinea pigs. In preferred embodiments, the subject is a human.
As used herein, the term “Vitamin D deficiency” refers to a situation where an individuals’ average daily intake of Vitamin D is less than the recommended daily intake for the country concerned. If it is not corrected, it can lead to abnormal bone mineralisation and growth, and thin, brittle or misshapen bones. In more extreme cases it can lead to Rickets in children, osteomalacia in adults, and severe deficiency can lead to osteoporosis in adults. It has also been implicated in many other chronic diseases, including hypertension, cardiovascular disease, diabetes meiltus, Type II diabetes, and certain inflammatory and autoimmune diseases (i.e. asthma in children), and some forms of cancer. The term “disease or condition characterised by Vitamin D deficiency” should be understood to mean Osteoporoisis, Osteomalacia, and Rickets.
As used herein, the term “aqueous beverage” refers to a drink for mammals, especially humans, which contains water and microcapsules where the microcapsules are suspended in the water. Typically, the beverage contains at least 50%, 60%, 70%, 80%, 90%, 95% or 99% water (v/v). In one embodiment, the aqueous beverage is water, for example mineral water, which may be still, sparkling or flavoured. In one embodiment, the aqueous beverage is milk or a milk product, for example added protein milk drink, fortified milk, yoghurt drink. In one embodiment, the aqueous beverage is a carbonated sugary drink such as cola or lemonade. In one embodiment, the aqueous beverage is a smoothie, or fruitor vegetable juice. In one embodiment, the aqueous beverage comprises 1% to 5% microcapsules (w/w). In one embodiment, the aqueous beverage comprises 0.001% to 0.005% food supplement (w/w). In one embodiment, the aqueous beverage comprises 11000 pg, 1-100 pg, 1-50 pg, or 5-25 pg of food supplement, typically Vitamin D. In one embodiment, the aqueous beverage has a volume of 10-1000, 10-500, or100-500 mis, for example about 100, 200, 300, 400 or 500 mis. In one embodiment, the aqueous beverage has a volume of about 500 mis and comprises 5-25 pg of food supplement (i.e. Vitamin D).
As used herein, the term “microcapsule” refers to a micron-size particle that has a core comprising a food supplement disposed within a first polymer and a coat comprising a second polymer encapsulating the core. In one embodiment, the microcapsules have an average particle diameter of 0.1 to 200 pm. In one embodiment, microcapsules have an average particle diameter of 0.8 to 50 pm. In one embodiment, microcapsules have an average particle diameter of 1 to 25 pm. The size of the microcapsules is measured by a Malvern Mastersizer Model 2000 fitted with the Scirocco 2000(A) attachment for dry powder analysis. The microcapsules are typically produced by 3-fluid nozzle spray drying techniques, described previously in EP2097072, in which a core-forming fluid comprising food supplement and a first polymer is sprayed through the central nozzle and simultaneously an outer coat forming fluid comprising a second polymer is sprayed through an outer concentric nozzle to form microdroplets which are then dried in a drying chamber. This produces microcapsules with an inner core of food supplement dispersed throughout a matrix of first polymer, and an outer coat of the second polymer. The microcapsule is typically water stable, and is capable of protecting the active agent during gastric transit and ileal release. In one embodiment, the core comprises a matrix formed of first polymer and food supplement dispersed throughout the core (polynuclear). In another embodiment, the core is mono-nuclear, and comprises food supplement in the centre surrounded by a coating of first polymer. In one embodiment, the core or coating comprises an additional component selected from: a lipid component (for example a fatty acid, fatty acid ester, hydrogenated oil, solid fat or oil, or wax); an inorganic component; a pharmaceutical excipient selected from a disintegrant, binder, plasticizer, fragrance, sweetening agent (natural or synthetic), lubricant, colourant, stabilizer, surfactant; or an additional active agent which may be a pharmaceutically active agent.
As used herein, the term “food supplement” (or “nutritional supplement”) refers to agents that are consumed by humans and mammals as a supplement to a normal diet and which are intended to have a biologically beneficial effect. The term includes vitamins, minerals, lipids and lipid components such as fatty acids, amino acids (including branch-chain amino acids and essential amino acids), proteins, probiotics, prebiotics, herbs, botanicals, plant extracts, microalgae, and other micronutrients. In one embodiment, the food supplement is sensitive to degradation in water and/or light, for example the fat-soluble vitamins A, D E and K, and fatty acids.
As used herein, the term “first polymer” refers to a polymer that is acid stable and water soluble. The term “acid stable” means that the polymer is stable (i.e. Insoluble in acidic pH) or in simulated gastric conditions. The term “water soluble” means that the polymer dissolves in deionised water at pH 6-7 at ambient temperature. Examples of the first polymer is an enteric polymer, for example a (meth)acrylic copolymer such as methacrylic acid copolymer L (i.e. EUDRAGIT L from Evonik Industries), methacrylic acid copolymer LD (i.e. EUDRAGIT LD from Evonik Industries), methacrylic acid copolymer S (i.e. EUDRAGIT S from Evonik Industries), or a cellulose derivative such as hydroxypropylmethyl cellulose acetate succinate, hydroxypropylmethyl cellulose phthalate, hydroxymethylethyl cellulose phthalate, carboxymethylethyl cellulose, cellulose acetate propionate, cellulose acetate phthalate, cellulose acetate succinate, cellulose acetate trimellitate, and methyl cellulose phthalate. The core may comprise more than one first polymer, for example a mixture of 2, 3, 4 or 5 first polymers. In one embodiment, the core consists essentially of first polymer and food supplement.
As used herein, the term “second polymer” refers to a polymer that is water stable and optionally acid soluble. The term “acid soluble” means that the polymer is not acid stable. The term “water stable” means that the polymer is not water soluble (i.e. water insoluble). Examples of the second polymer include polymers such as gastric polymers (water stable and acid soluble) and sustained release polymers. Examples of sustained release polymers suitable for use in the present invention include water insoluble cellulose derivatives such as ethyl cellulose, water insoluble acrylic acid copolymers such as an ethyl acrylate methyl methacrylate-chlorotrimethylammonium ethyl methacrylate copolymer (i.e. EUDRAGIT RS and EUDRAGIT RL, both from Evonik Industries), an ethyl acrylate methyl methacrylate copolymer (i.e. EUDRAGIT NE from Evonik Industries). Examples of gastric polymers include polyvinyl derivatives such as polyvinyl acetal diethylaminoacetate, (meth)acrylic acid copolymers such as methyl methacrylate-butyl methacrylatedimethylaminoethyl methacrylate copolymer (EUDRAGIT E from Evonik Industries). The coat may comprise more than one second polymer, for example a mixture of 2, 3, 4 or 5 second polymers. In one embodiment, the coat consists essentially of second polymer. In one embodiment, the coat comprises active agent.
As used herein, the term “core forming liquid stream” refers to a liquid composition comprising first polymer, food supplementand solvent. In one embodiment, the coreforming liquid stream comprises 0.5% to 30%, 0.5% to 20%, or 0.5% to 10% first polymer (w/v). In one embodiment, the core-forming liquid stream comprises 0.5% to 3%, or about1%, first polymer (w/v). In one embodiment, the core-forming liquid stream comprises 0.001% to 10%, 0.005% to 5%, 0.01% to 1% or 0.01% to 0.1% food supplement. In one embodiment, the solvent is selected from water and an organic solvent depending on polymer properties.and commercially available form. A number of polymers are now available as aqueous dispersions and may be used for this process
As used herein, the term “coating forming liquid stream” refers to a liquid composition comprising second polymer. In one embodiment, and the coating forming liquid stream comprises 0.1% to 30%, 1% to 20%, 1% to 15%, 1% to 10%, 2% to 20%, 2% to 15%, 2% to 10%, 1% to 5%, or about 1%, 2%, 3%, 4% or 5% second polymer (w/v). In one embodiment, the solvent is selected from water and an organic solvent depending on polymer properties.and commercially available form. A number of polymers are now available as aqueous dispersions and may be used for this process. Generally, the solvent is an organic solvent.
As used herein, the term “organic solvent” includes alcohols (i.e. ethanol, propanol, isoproponal, etc), hydrocarbons (i.e. n-hexan, cyclohexane, etc), halogenated alkanes (i.e. dichloromethane, chloroform, trichloroethane, carbon tetrachloride, etc), ketones, (i.e. acetone, methyl ethyl ketone, etc), esters (ethyl acetate, etc), ethers, nitriles (i.e. acetonitrile, etc), etc. Preferred solvents for the core forming fluid stream include ethanol, isopropyl alcohol, ethylacetate, acetone, water. Preferred solvents for the coating forming fluid stream include ethanol, isopropyl alcohol, ethylacetate, acetone, water.
As used herein, the term “spray drying” refers to a process in which a fluid or combination of fluid is sprayed through a 3-liquid nozzle to form droplets which are dried in a drying chamber. The inlet temperature refers to the temperature of the gas at the entrance of the drying chamber and the outlet temperature refers to the gas temperature at the outlet of the drying chamber. The method of the present invention employs spray drying apparatus and technology described in EP2097072 (“double nozzle spray drying”) having a 3-liquid nozzlefor producing microcapsules have a core of one material and a coat encapsulating the core comprising a different material. A 3-liquid nozzle is a spray-drying nozzle having an outer nozzle (for coating fluid) and an inner core nozzle (for core fluid) disposed concentrically within the outer nozzle.
As used herein, the term “milk drink” refers to a milk-based beverage including whole milk, skimmed milk, fortified milk (fortified with one or more vitamins or minerals), a protein milk (having added protein), or a drinking yoghurt.
Exemplification
The invention will now be described with reference to specific Examples. These are merely exemplary and for illustrative purposes only: they are not intended to be limiting in anyway to the scope of the monopoly claimed or to the invention described. These examples constitute the best mode currently contemplated for practicing the invention.
Formulation strategy: Single polymer/sinqle walled microparticles
Microcapsules were prepared using a fluorescent marker, Coumarin-6, as surrogate Vitamin D.
Table 1 below list the parameters and characteristics of single walled/single polymer microparticles prepared using chitosan, ethylcellulose and Eudragit polymers. The solution was sprayed at a rate of 3 ml/min and at an inlet temperature of 140°C for chitosan and 90100°C for Eudragit microparticles.
Table 1: Spray drying parameters and characteristics of microparticles using a single polymer system
Batch n° (Polymer) | Total solids (% w/v) | T outlet (°C) | % Product Yield | Median Particle size d(5o%) pm |
LPF 01 (chitosan) | 0.5 | 74 | 54.2 | 2.82±0.42 |
LPF 02 (chitosan) | 0.75 | 76 | 61 | 3.39±0.11 |
LPF 03 (chitosan) | 1 | 78 | 73.8 | 3.06±0.09 |
KPF 01 (Ethylcellulose) | 2 | 51 | 53.2 | 11.06+1.56 |
KPF 02 (Ethylcellulose) | 5 | 42 | 44.4 | 8.62±0.06 |
KPF 03 (Ethylcellulose) | 10 | 45 | 46 | 8.5±0.13 |
LPF L1 ( Eudragit L) | 10 (Vitamin D 12.5 mg) | 41 | 59.9 | 13.98±0.39 |
LPF S1 (Eudragit S) | 6 (Vitamin D 12.5mg) | 38 | 63.0 | 10.27±0.25 |
LPF S1 (Eudragit S) | 6 (Vitamin D 12.5mg) | 45 (inlet 95°C) | 71.7 | 16.16±0.87 |
LPF S1 (Eudragit S) | 6 (Vitamin D 12.5mg) | 42 (inlet 90oC) | 93.3 | 19.66±0.84 |
Microencapsulation and testing of Vitamin D
From the results in Table 1, all polymers selected successfully produced microparticles with a high product yield of 44-93%. Microparticles were in the fine particle size range, ranging from 2-20microns, a size which is suitable for dispersion into liquids. Decreasing the inlet temperature, the temperature at which microencapsulation takes place from 100°C to 95°C, resulted in an increase in product yield and an increase in product flow properties was observed at 95°C.
Examination of microparticle load per bottle, mixing potential and visual clarity of simulated final product
Various microparticles weights were calculated to give increasing dose of vitamin D per bottle of 5, 12.5 and 25mcg Vitamin D per 500mls bottle. At a calculated Vitamin D loading of 0.1% w/w of microparticles, this corresponds to a microparticle weight of 5, 12.5 and 25 mg per bottle. When added to Ballygowan water, chitosan microparticles were found to disperse and suspend easily. Clarity of the water marginally decreased with increasing weight of microparticles. On prolonged storage of >6 weeks, no visual change was observed. At the Vitamin D loading of 0.1% w/w identified, this represents a suitable product volume for adding to bottled water without impacting on visual quality of the final product.
Demonstration of encapsulation of Vitamin D was carried out using a fluorescent marker, Coumarin-6, which has similar water solubility as Vitamin D.
Release of ‘Vitamin D’ from microparticles.
Due to the very low solubility of coumarin-6, levels of coumarin-6 released are too low to be measurable. This would be expected to be similar for Vitamin D at the same loading of 0.1% w/w as the solubility of vitamin D is comparable to that of Coumarin-6. Using sodium diclofenac as a model drug with a h water solubility of 500-fold higher compared to vitamin D, we demonstrated that when microencapsulated as single walled microparticles, using ethylcellulose, its release in water was significantly slowed (figure 1).
Based on these data and the solubility of vitamin D, it can be assumed that the release of Vitamin D from similar single walled microparticles will be significantly slower probably to negligible levels over time. The release is expected to be further slowed or prevented in presence of a second polymer coat.
Encapsulation of Vitamin D in double walled microparticles
Double walled microparticles were prepared using 2 polymers and a 3-nozzle spraying apparatus as described in EP2097072 (Royal College of Surgeons in Ireland) and illustrated in Figure 2.
Using this technology, Vitamin D was protected in the core (Fig.2) using Eudragit S polymer which is soluble at human intestinal pH of 5+. A second feed line, simultaneously coat the vitamin D core particles using Eudragit E polymer which is soluble in human stomach pH 1-2 but not at higher pHs and hence would be insoluble at the pHs of bottled water 5+.
The formulation and process parameters used and the characteristics of the microparticles obtained are shown in Table 2 below. Microparticles were successfully produced at increasing polymer concentration and core to coat ratios. Figure 2 shows the microparticles prepared using the core solution only and the 3 double-walled microparticles. The reduction in intensity of coumarin (core) can be seen when microparticles are double walled. The median size (D 50%) of the microparticles was small and in the range of 8-11.5 microns. Product yield was low characteristic of small batches as 20 mis of solutions were spray dried.
Table 2. Formulation parameters for EUDRAGIT E100Z EUDRAGIT S100 microparticles using RCSI’s double microencapsulation technology.
Bate h n° | Total solid s (% w/v) | Coat (Eudragi t E) % w/v | Core (Eudragit S+ Vit D + coumarin) % w/v | T inlet (°C) | T outlet (°C) | Feed Flow Rate (ml/min) | % Product Yield |
LPF CR1 | 1 | 0 | 1 | 90 | 52 | 2 (1:1) | 27.8 |
LPF E12 S | 18 | 12 | 6 | 90 | 56 | 2 (1:1) | 13.93 |
LPF ES9 0 | 4 | 3 | 1 | 90 | 58 | 2 (1:1) | 24.4 |
LPF ES9 5 | 4 | 3 | 1 | 95 | 57 | 3 (1.5:1.5) | 29.4 |
Figure 4 shows microparticles prepared as per Table 2 above in order of formulations listed.
Stability evaluation of microparticles
a) Dispersion of single walled mciroparticles in deionised water pl-16-7
Dispersion of chitosan microparticles in deionised water at a microparticle concentration of 100mg/ml was difficult. At a lower concentration of 10mg/ml, dispersion of microparticles into a homogenous suspension was observed (figure 4 below). Eudragit L & S microparticles suspended less readily and required sonication to accelerate dispersion. At a microparticle concentration of 25mg/ml. Homogenous dispersions were formed which stayed stable for a period of 4 weeks at room temperature (Figure 5).
b) Eudragit E and & S double walled microparticles
Eudragit E and S double walled microparticles suspended similarly to Eudragit single walled microparticles and required sonication to accelerate dispersion at25mg/ml. Homogenous dispersions were formed which stayed stable for a period of 3-4 weeks at room temperature. Figure 6 shows the dispersions formed at 25mg/ml for core microparticles and double walled microparticles.
Summary
The invention preparing suitable microparticles containing Vitamin D for supplementation in bottled water and other beverages. The microparticles produced were shown to encapsulate Vitamin D and with the process used, greater than 90% of the Vitamin D can be encapsulated. Other characteristics are listed below:
5· Microparticles produced showed good product yield which can be greater as batch sizes is increased, a characteristic of the spray drying process • Microparticles produced are in fine sie range and and suitable for adding to water without affecting clarity at the product volumes calculated to give predetermined supplementation dose of 5-25mcg per 500mls.
10· Process conditions can be refined to give free flowing powders suitable for further processing as liquid, semisolids or solid products. Microparticles produced may be suitable for supplementation in other beverages although the polymers used may need to be altered depending on product specifications.
Equivalents
The foregoing description details presently preferred embodiments of the present invention.
Numerous modifications and variations in practice thereof are expected to occur to those skilled in the art upon consideration of these descriptions. Those modifications and variations are intended to be encompassed within the claims appended hereto.
Claims (15)
1. An aqueous beverage comprising a suspension of microcapsules, the microcapsules comprising a core comprising a food supplement disposed within a first polymer, and an outer coating encapsulating the core and comprising a second polymer, wherein the first polymer is acid stable and water soluble, the second polymer is water stable and/or acid soluble, and the active agent is unstable in one or more of light, water and acid.
2. An aqueous beverage according to Claim 1, in which the food supplement is Vitamin D.
3. An aqueous beverage according to Claim 1 or 2, selected from water or a milk drink.
4. An aqueous beverage according to any preceding Claim, comprising about 0.0005% to 0.01% microcapsules (w/w), and in which the microcapsules comprise about 0.05% to 10% active agent (w/w).
4. An aqueous beverage according to any preceding Claim, comprising about 0.001% to 0.005% microcapsules (w/w), and in which the microcapsules comprise about 0.05% to 0.5% active agent (w/w).
5. An aqueous beverage according to any preceding Claim, in which the first polymer is selected from EUDRAGIT L or EUDRAGIT S and the second polymer is selected from EUDRAGIT E, chitosan, or ethyl cellulose.
6. An aqueous beverage according to Claim 1 which is a milk drink or water, in which the active agent is Vitamin D, comprising about 0.0005% to 0.01% microcapsules (w/w), and in which the microcapsules comprise about 0.05% to 0.5% active agent (w/w), and in which the first polymer is selected from EUDRAGIT L or EUDRAGIT S and the second polymer is selected from EUDRAGIT E, chitosan, or ethyl cellulose.
7. A bottled beverage comprising an aqueous beverage of any of Claim 1 to 6 contained within a sealed transparent polymer bottle.
8. A bottled water according to Claim 7 in which the active agent is Vitamin D.
9. A method of making an aqueous beverage, comprising the steps of:
providing a core-forming liquid stream comprising an active agent and a first polymer, in which the active agent is unstable in one or more of light, water and acid, providing a coating-forming liquid stream comprising a second polymer, providing a two-spray nozzle arrangement having an outer nozzle disposed concentrically about a core nozzle, simultaneously spraying the core-forming fluid stream from the core nozzle and the coating-forming fluid stream from the outer nozzle to produce microcapsules having a core comprising an active agent disposed with the first polymer and a coating encapsulating the core comprising the second polymer, solidifying the microcapsules upon formation in a drying chamber, and adding the microcapsules to an aqueous liquid to form the aqueous beverage.
10. A method according to Claim 9 in which the active agent is Vitamin D.
11. A method according to Claim 9 or 10, in which the core-forming liquid stream comprises 0.5% to 10% total solids (w/v) and the coating forming liquid stream comprises 1% to 20% total solids (w/v).
12. A method according to any of Claims 9 to 11, that employs a spray-dryer, in which the inlet temperature for the core and coating forming liquid streams is 80-140°C and the outlet temperature for the core and coating forming liquid streams is 45-80°C.
13. A method according to any of Claims 9 to 12, in which the first polymer is selected from EUDRAGIT L or EUDRAGIT S and the second polymer is selected from EUDRAGIT E, chitosan, or ethyl cellulose.
14. A method according to any of Claims 9 to 13, in which the aqueous beverage is bottled in a transparent polymeric bottle.
15. A non-therapeutic method of preventing Vitamin D deficiency in a mammal, comprising a step of administering an aqueous beverage of any of Claims 1 to 9 to the individual, in which the beverage comprises about 5 to 25mg Vitamin D.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB1720230.0A GB2569119A (en) | 2017-12-05 | 2017-12-05 | An aqueous beverage containing microencapsulated food supplement |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB1720230.0A GB2569119A (en) | 2017-12-05 | 2017-12-05 | An aqueous beverage containing microencapsulated food supplement |
Publications (2)
Publication Number | Publication Date |
---|---|
GB201720230D0 GB201720230D0 (en) | 2018-01-17 |
GB2569119A true GB2569119A (en) | 2019-06-12 |
Family
ID=60950326
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB1720230.0A Withdrawn GB2569119A (en) | 2017-12-05 | 2017-12-05 | An aqueous beverage containing microencapsulated food supplement |
Country Status (1)
Country | Link |
---|---|
GB (1) | GB2569119A (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2021053603A1 (en) * | 2019-09-18 | 2021-03-25 | Wet Holdings (Global) Limited | Drink beverages |
CN116616449A (en) * | 2023-06-05 | 2023-08-22 | 浙江索契壹营养科技有限公司 | Beverage with high calcium and vitamin D stably loaded by acidic antibacterial system and preparation method thereof |
EP4114201A4 (en) * | 2020-03-02 | 2023-08-23 | Nuversys Ltd. | A stable food-grade microcapsule for the delivery of unstable and food-incompatible active ingredients to food products |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1991019486A1 (en) * | 1990-06-14 | 1991-12-26 | Kalmo Enterprises, Inc. | Stable aqueous drug suspensions |
EP1897544A1 (en) * | 2006-09-05 | 2008-03-12 | Holger Lars Hermann | Opioid agonist and antagonist combinations |
WO2014044794A2 (en) * | 2012-09-21 | 2014-03-27 | Ferring Bv | Pharmaceutical composition |
-
2017
- 2017-12-05 GB GB1720230.0A patent/GB2569119A/en not_active Withdrawn
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1991019486A1 (en) * | 1990-06-14 | 1991-12-26 | Kalmo Enterprises, Inc. | Stable aqueous drug suspensions |
EP1897544A1 (en) * | 2006-09-05 | 2008-03-12 | Holger Lars Hermann | Opioid agonist and antagonist combinations |
WO2014044794A2 (en) * | 2012-09-21 | 2014-03-27 | Ferring Bv | Pharmaceutical composition |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2021053603A1 (en) * | 2019-09-18 | 2021-03-25 | Wet Holdings (Global) Limited | Drink beverages |
EP4114201A4 (en) * | 2020-03-02 | 2023-08-23 | Nuversys Ltd. | A stable food-grade microcapsule for the delivery of unstable and food-incompatible active ingredients to food products |
CN116616449A (en) * | 2023-06-05 | 2023-08-22 | 浙江索契壹营养科技有限公司 | Beverage with high calcium and vitamin D stably loaded by acidic antibacterial system and preparation method thereof |
Also Published As
Publication number | Publication date |
---|---|
GB201720230D0 (en) | 2018-01-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Reque et al. | Encapsulation of probiotics and nutraceuticals: Applications in functional food industry | |
Ge et al. | Nanocomplexes composed of chitosan derivatives and β-Lactoglobulin as a carrier for anthocyanins: Preparation, stability and bioavailability in vitro | |
Liu et al. | Co-encapsulation systems for delivery of bioactive ingredients | |
JP5352235B2 (en) | Superabsorbent oral composition containing oxidized coenzyme Q10 | |
Jampilek et al. | Potential of nanonutraceuticals in increasing immunity | |
Li et al. | Microencapsulation of vitamins, minerals, and nutraceuticals for food applications | |
AU2018100110A4 (en) | Ubiquinone And Ubiquinol Compositions, And Methods Relating Thereto | |
de Abreu Figueiredo et al. | Microencapsulation by spray chilling in the food industry: Opportunities, challenges, and innovations | |
KR20190026648A (en) | Compositions and methods for selective gastrointestinal tract delivery | |
US20180000743A1 (en) | Modified Alginate Hydrogels for Therapeutic Agents, their Preparation and Methods Thereof | |
GB2569119A (en) | An aqueous beverage containing microencapsulated food supplement | |
Lee | Strategic design of delivery systems for nutraceuticals | |
CN106455667A (en) | Formulation of fat-soluble vitamin | |
EP2605756A2 (en) | Functional food compositions and methods | |
Bodade et al. | Microencapsulation of bioactive compounds and enzymes for therapeutic applications | |
US20230248808A1 (en) | Joint Health Composition and Use Thereof in Healthy Mammals | |
Carlan et al. | Innovation and improvement in food fortification: Microencapsulation of vitamin B2 and B3 by a spray-drying method and evaluation of the simulated release profiles | |
US11173127B2 (en) | Potato protein nanoparticles | |
Mohite et al. | Encapsulation Techniques for De-livery of Bioactive Compounds in Milk and Dairy Products-A Review | |
US20240066041A1 (en) | Microparticles containing stabilized cbd oil, and methods for the production thereof | |
Saha et al. | Review of methods for encapsulation of nutraceutical compounds | |
WO2022006200A1 (en) | Dietary composition and method | |
Mar et al. | A Prospective Review on the Encapsulation of Bioactive Compounds | |
Abbasi et al. | A Critical Review on the Bioavailability Promotion of the Food Bioactive Compounds: Nano Lipid Carriers Perspective | |
Rong et al. | Superabsorbent polysaccharide hydrogels as nutrient carriers |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |