TR2021005579A2 - FILM COATED TABLET OF VILDAGLIPTIN AND METFORMIN HYDROCHLORIDE - Google Patents
FILM COATED TABLET OF VILDAGLIPTIN AND METFORMIN HYDROCHLORIDEInfo
- Publication number
- TR2021005579A2 TR2021005579A2 TR2021/005579A TR2021005579A TR2021005579A2 TR 2021005579 A2 TR2021005579 A2 TR 2021005579A2 TR 2021/005579 A TR2021/005579 A TR 2021/005579A TR 2021005579 A TR2021005579 A TR 2021005579A TR 2021005579 A2 TR2021005579 A2 TR 2021005579A2
- Authority
- TR
- Turkey
- Prior art keywords
- film
- mixture
- coated tablet
- vildagliptin
- cellulose
- Prior art date
Links
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin hydrochloride Natural products CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 title claims abstract description 46
- 229960001254 vildagliptin Drugs 0.000 title claims abstract description 43
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 title claims abstract description 40
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 title claims abstract description 39
- 239000007941 film coated tablet Substances 0.000 title claims abstract description 27
- 229960004329 metformin hydrochloride Drugs 0.000 title claims abstract description 15
- 239000000203 mixture Substances 0.000 claims abstract description 88
- 239000011230 binding agent Substances 0.000 claims abstract description 20
- 239000003826 tablet Substances 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 14
- 229960003105 metformin Drugs 0.000 claims description 31
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 25
- 238000009472 formulation Methods 0.000 claims description 24
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 18
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 16
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical group [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 13
- 229920001531 copovidone Polymers 0.000 claims description 13
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 13
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 13
- DLRVVLDZNNYCBX-UHFFFAOYSA-N Polydextrose Polymers OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(O)O1 DLRVVLDZNNYCBX-UHFFFAOYSA-N 0.000 claims description 12
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 12
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 12
- 239000000314 lubricant Substances 0.000 claims description 11
- 229920006316 polyvinylpyrrolidine Polymers 0.000 claims description 11
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 9
- 239000002202 Polyethylene glycol Substances 0.000 claims description 9
- 235000019359 magnesium stearate Nutrition 0.000 claims description 9
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 9
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 9
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 9
- 229920001223 polyethylene glycol Polymers 0.000 claims description 9
- 239000000945 filler Substances 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 229920002472 Starch Polymers 0.000 claims description 7
- 239000008107 starch Substances 0.000 claims description 7
- 235000019698 starch Nutrition 0.000 claims description 7
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 6
- 229920001100 Polydextrose Polymers 0.000 claims description 6
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 6
- 235000013856 polydextrose Nutrition 0.000 claims description 6
- 239000001259 polydextrose Substances 0.000 claims description 6
- 229940035035 polydextrose Drugs 0.000 claims description 6
- 229920000193 polymethacrylate Polymers 0.000 claims description 6
- 235000010413 sodium alginate Nutrition 0.000 claims description 6
- 239000000661 sodium alginate Substances 0.000 claims description 6
- 229940005550 sodium alginate Drugs 0.000 claims description 6
- 239000011248 coating agent Substances 0.000 claims description 5
- 238000000576 coating method Methods 0.000 claims description 5
- 229920000609 methyl cellulose Polymers 0.000 claims description 5
- 235000010981 methylcellulose Nutrition 0.000 claims description 5
- 239000001923 methylcellulose Substances 0.000 claims description 5
- 229960002900 methylcellulose Drugs 0.000 claims description 5
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 4
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- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 4
- 229920000881 Modified starch Polymers 0.000 claims description 4
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 229920002125 Sokalan® Polymers 0.000 claims description 4
- 235000010443 alginic acid Nutrition 0.000 claims description 4
- 229920000615 alginic acid Polymers 0.000 claims description 4
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 4
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 4
- 229960001631 carbomer Drugs 0.000 claims description 4
- 235000010418 carrageenan Nutrition 0.000 claims description 4
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- 229940113118 carrageenan Drugs 0.000 claims description 4
- 235000010980 cellulose Nutrition 0.000 claims description 4
- 229920002678 cellulose Polymers 0.000 claims description 4
- 239000001913 cellulose Substances 0.000 claims description 4
- RBLGLDWTCZMLRW-UHFFFAOYSA-K dicalcium;phosphate;dihydrate Chemical compound O.O.[Ca+2].[Ca+2].[O-]P([O-])([O-])=O RBLGLDWTCZMLRW-UHFFFAOYSA-K 0.000 claims description 4
- 239000008273 gelatin Substances 0.000 claims description 4
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- 229940014259 gelatin Drugs 0.000 claims description 4
- 235000019322 gelatine Nutrition 0.000 claims description 4
- 235000011852 gelatine desserts Nutrition 0.000 claims description 4
- 239000008103 glucose Substances 0.000 claims description 4
- 235000010417 guar gum Nutrition 0.000 claims description 4
- 239000000665 guar gum Substances 0.000 claims description 4
- 229960002154 guar gum Drugs 0.000 claims description 4
- 229920002674 hyaluronan Polymers 0.000 claims description 4
- 229960003160 hyaluronic acid Drugs 0.000 claims description 4
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 4
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 4
- 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 description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 229920001277 pectin Polymers 0.000 claims description 4
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- 229960000502 poloxamer Drugs 0.000 claims description 4
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- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims description 4
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 3
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 claims description 3
- 239000001506 calcium phosphate Substances 0.000 claims description 3
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 3
- 235000011010 calcium phosphates Nutrition 0.000 claims description 3
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 3
- 239000008116 calcium stearate Substances 0.000 claims description 3
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- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 3
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- 229940105329 carboxymethylcellulose Drugs 0.000 claims description 3
- -1 dextrates Polymers 0.000 claims description 3
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 3
- 239000001095 magnesium carbonate Substances 0.000 claims description 3
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 3
- 239000000395 magnesium oxide Substances 0.000 claims description 3
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 3
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 3
- 235000002639 sodium chloride Nutrition 0.000 claims description 3
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 3
- BZSXEZOLBIJVQK-UHFFFAOYSA-N 2-methylsulfonylbenzoic acid Chemical compound CS(=O)(=O)C1=CC=CC=C1C(O)=O BZSXEZOLBIJVQK-UHFFFAOYSA-N 0.000 claims description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims description 2
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- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 2
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- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 claims description 2
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- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
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- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
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- KPGABFJTMYCRHJ-YZOKENDUSA-N ammonium alginate Chemical compound [NH4+].[NH4+].O1[C@@H](C([O-])=O)[C@@H](OC)[C@H](O)[C@H](O)[C@@H]1O[C@@H]1[C@@H](C([O-])=O)O[C@@H](O)[C@@H](O)[C@H]1O KPGABFJTMYCRHJ-YZOKENDUSA-N 0.000 claims description 2
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- 229940094522 laponite Drugs 0.000 claims description 2
- XCOBTUNSZUJCDH-UHFFFAOYSA-B lithium magnesium sodium silicate Chemical compound [Li+].[Li+].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Na+].[Na+].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3 XCOBTUNSZUJCDH-UHFFFAOYSA-B 0.000 claims description 2
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Abstract
Mevcut buluş vildagliptin veya vildagliptin HCI, en az bir bağlayıcı ve metformin hidroklorür içerikli bir karışımı içeren bir film kaplı tablet ile ilgilidir; bu sayede söz konusu tablet ile arzu edilen stabilite ve farmakoteknik özelliklerin yanı sıra arzu edilen çözünme profili elde edilmektedir. Mevcut buluş ayrıca basit, hızlı, uygun maliyetli, zamandan tasarruf edilmesini sağlayan ve endüstriyel açıdan elverişli bir film kaplı tablet hazırlama yöntemi ile ilgilidir.The present invention relates to a film-coated tablet comprising vildagliptin or a mixture of vildagliptin HCl, at least one binder and metformin hydrochloride; in this way, the desired dissolution profile is obtained as well as the desired stability and pharmacotechnical properties with the said tablet. The present invention also relates to a simple, fast, cost-effective, time-saving and industrially suitable method of preparing film-coated tablets.
Description
TARFNAME VILDAGLIPTIN VE METFORMIN HIDROKLORÜRÜN FILM KAPLI TABLETI Teknik Alan Mevcut bulus vildagliptin veya vildagliptin HCI, en az bir baglayici ve metformin hidroklorür içerikli bir karisimi içeren bir film kapli tablet ile ilgilidir; bu sayede söz konusu tablet ile arzu edilen stabilite ve farmakoteknik özelliklerin yani sira arzu edilen çözünme profili elde edilmektedir. Mevcut bulus ayrica basit, hizli, uygun maliyetli, zamandan tasarruf edilmesini saglayan ve endüstriyel açidan elverisli bir film kapli tablet hazirlama yöntemi ile ilgilidir. Bulusun Geçmisi Diyabet; degisen salgi, azalan insülin faaliyeti veya bu iki faktörün bir araya gelmesiyle insülin faaliyetinin azaldigi veya yok oldugu, karbonhidrat metabolizmasina iliskin bir grup bozukluktur. Tip 1 ve Tip 2 olmak üzere baslica iki diyabet tipi vardir: Tip 1 diyabetin sebebi, pankreastaki insülin üreten hücrelerin (beta hücrelerinin) zarar görmüs olmasidir. Tip 1 diyabette pankreas yetersiz miktarda insülin üretir veya hiç insülin üretemez, bu nedenle de seker enerji olarak kullanilmak üzere vücut hücrelerine giremez. Tip 1 diyabetli hastalar kan sekerini kontrol etmek için insülin enjeksiyonu kullanmak zorundadir. Tip 2 diyabette ise pankreas insülin üretmesine karsin, ya üretilen insülin miktari yetersizdir ya da insülin islevini yerine getirememektedir. Tip 2 diyabet genelde 40 yasin üzerindeki fazla kilolu insanlarda görülmektedir. Tip 2 diyabet kimi zaman diyet, kilo yönetimi ve egzersiz yoluyla kontrol edilebilir. Bununla birlikte oral yolla alinan glukoz düsürücü ilaçlar veya insülin enjeksiyonlari ile de tedavi edilebilir. Vildagliptin, tip 2 diyabetin (insüline bagimli olmayan diyabet) tedavisinde kullanilmak üzere gelistirilen bir dipeptidil dipeptidaz-IV (DPP-IV) inhibitörüdür. Vildagliptin dipeptidil dipeptidaz- benzeri peptid-1'in (GLP-1) ve glukoza bagimli insülinotropik peptidin (GIP) etkilerini de inhibe eder. Vildagliptinin kimyasal adi (S)-{[(3-hidroksiadamantan-1-iI)amino]asetiI}piroIidin- 2-karbonitril olup kimyasal yapisi asagidaki Formül 1'deki gibidir. Formül 1 Metanol suda ve organik polar çözüoülerde çözünür. Vildagliptin, 50 mg'lik dozaj formlarinda Galvus® markasi altinda satilmaktadir. Seker hastaligina (diabetes mellitus) karsi, özellikle de tip 2 diyabetin tedavisinde kullanilir. Metformin, oral yolla uygulanan biguanid yapisina sahip bir antidiyabetiktir. Metformin hidroklorür beyaz-kirli beyaz arasi kristalin bir bilesiktir ve suda serbestçe çözünürken aseton, eter ve kloroformda neredeyse çözünmez. Önerilen oral metformin dozlari genellikle Tek basina ya da sülfonilüreler, alfa-glukosidaz inhibitörleri ya da insülinle kombinasyon halinde kullanilmaktadir. Metformin hidroklorürün kimyasal adi 1,1-dimetilbiguanid hidroklorür; kimyasal yapisi ise asagida verilen Formül II'deki gibidir. Formül II Vildagliptin ve metformin hidroklorür kombinasyonundan olusan ürün Eucreas® markasiyla seklinde) satilmaktadir. Birlestirilen etkin bilesenlerin farmasötik formülasyonlari ve bunlarin hazirlanmasina yönelik proses EP 1948149 dokümaninda açiklanmaktadir. açiklanmaktadir. Burada açiklanan bir tablet etken maddelerin yani sira bilinen yardimci maddeleri, örnegin dolgu maddelerini, baglayicilari, dagitioilari, Iubrikanlari ve renklendirioileri içerebilmektedir. Lubrikan örnekleri arasinda kolloidal silika, magnezyum trisilikat, nisasta, talk, kalsiyum fosfat, magnezyum stearat, aluminyum stearat, kalsiyum stearat, magnezyum karbonat, magnezyum oksit, polietilen glikol, selüloz ve mikrokristalin selülozdan söz edilmektedir. EP dokümaninda sitagliptin veya vildagliptin etkin maddesi veya bunlarin bir tuzu ile kombinasyon halinde metformin etkin maddesini ve bir Iubrikani (bilesimin toplam agirligina bagli olarak %10'dan daha fazla miktarda) içeren bir farmasötik bilesim açiklanmaktadir. Sözü edilen Iubrikan polietilen glikol veya polietilen glikol ile en az bir diger lubrikanin karisimidir. Metformin HCI ile vildagliptinin her ikisine iliskin bazi yapisal problemler söz konusudur. Çevresel ve fiziki kosullarin etkisiyle vildagliptin de dahil olmak üzere bir çok etkin maddede stabiliteyle ilgili sorunlar ortaya çikmaktadir. Vildagliptin hava ve neme karsi fazlasiyla duyarli bir etkin maddedir. Vildagliptin hava ve neme maruz birakildiginda yapisal olarak bozunmakta ve kimyasal davranis degisiklikleri gelistirmektedir. Gelistirilen vildagliptin ürünlerinin stabilitesi istenen seviyede degildir ve bunlarin raf ömrü kisalmaktadir. Buna ilaveten vildagliptin kendisini içeren formülasyonlarin gelistirilmesinde kullanilan yardimci maddelere karsi da reaktiftir. Bu durum formülasyonda safsizliklarin olusmasina neden olmakta ve istenmeyen bilesenlerin formülasyona dahil edilmesine yol açmaktadir. Ayrica metforminin sikistirilabilirligi de yetersizdir. Tüm bunlar göz önünde bulunduruldugunda vildagliptin ve metformin HCI içeren bir formülasyon olusturulmasinin ne denli zor oldugu görülecektir. Mevcut bulusta vildagliptin veya vildagliptin HCI, metformin hidroklorürü içeren bir karisim (sözü edilen karisimdaki metformin HCI miktari agirlik bakimindan %920 ve %97.0 oranindadir) ve en az bir baglayiciyi içeren bir film kapli tablet ortaya konulmakta olup bu karisim ayrica baglayicilar, dolgu maddeleri, lubrikanlar veya bunlarin karisimlarini içeren gruptan seçilen en az bir farmasötik olarak kabul edilebilir yardimci maddeyi içermektedir. Yukarida bahsedilen sorunlari ortadan kaldirmak adina belli bir oranda ve seçilen yardimci maddeleri içeren bir film kapli tablet ile bu tableti hazirlamaya yönelik bir proses gelistirilmistir. Bulusun Detayli Açiklamasi Mevcut bulusun esas amaci, yüksek stabiliteli bir tablet seklinde sikistirilabilecek vildagliptin/vildagliptin HCI ve metformin HCI içeren bir tablet ortaya koymaktir. Mevcut bulusun bir diger amaci, metformin HCI ve vildagliptinin olumsuz yapisal özellikleri göz önünde bulundurularak arzu edilen çözünme profili ve sikistirilabilirlige sahip olan bir tablet ortaya konulmasidir. Mevcut bulusun bir düzenlemesine göre film kapli tablet; - Vildagliptin veya vildagliptin HCI, - Metformin hidroklorür içeren bir karisim ve - En az bir baglayiciyi içermekte olup burada; karisimdaki metformin HCl miktari agirlik bakimindan %920 ve %970 oranindadir ve karisim baglayicilar, dolgu maddeleri, Iubrikanlar veya bunlarin karisimlarini içeren gruptan seçilen en az bir farmasötik olarak kabul edilebilir yardimci maddeyi içermektedir. Mevcut bulusun bir düzenlemesine göre, vildagliptin veya vildagliptin HCI miktari toplam formülasyon agirligi bakimindan %20 ile %100 arasindadir. Bu miktar tercihen toplam formülasyon agirligi bakimindan %120 ile %70 veya %30 ile %50 arasindadir. Mevcut bulusun bir düzenlemesine göre, metformin hidroklorür içeren karisimin miktari toplam formülasyon agirligi bakimindan %700 ile %850 arasindadir. Metformin HCI'nin büyük miktarlarda kullanilmasi, formülasyonun hazirlanmasi esnasinda bireysel bilesim birimlerinde etkin maddenin içerik tekdüzeligi bakimindan problemlere yol açabilmektedir. Içerik tekdüzeligi problemleri nedeniyle etkin maddenin bazi yardimci maddelerle etkilesime girme ihtimali söz konusudur. Bu ise içerik tekdüzeliginin, ilacin çözünmesinde önemli bir rol oynadigini göstermektedir. Ayrica fiziksel özellikler bakimindan da metforminin sikistirilabilirligi yetersizdir ve formülasyonun gelistirilmesinde kabul edilebilir mekanik dayanimi olan bir tablet veya kapsülün nasil elde edilecegi önemli bir problem teskil etmektedir. Mevcut bulusta metformin HCI'nin miktari agirlik bakimindan %950 oranindadir (granüle edilmis metforminin Dogrudan Sikistirilabilirlik derecesi %95). Bu sayede arzu edilen içerik tekdüzeligi ve dolayisiyla da arzu edilen çözünme profili elde edilmektedir. Dahasi arzu edilen sikistirilabilirlik ve yüksek fiziksellik saglanmaktadir. Karisim sayesinde, metforminin sikistirilabilirligi düsük olsa dahi ilave proseslere gerek kalmaksizin tablet dogrudan baski yöntemiyle sikistirilabilmektedir. Genel anlamda bir formülasyonda bulunan yardimci maddeler; etkin maddenin çözünürlügü, absorpsiyonu, biyoyararlanimi gibi fizikokimyasal ve farmakokinetik özelliklerini olumlu veya olumsuz etkileyebilmektedir. Bu nedenle bir formülasyon (özellikle de bir karisim) gelistirilirken etkin maddeyle birlikte kullanilacak olan yardimci maddelerin dikkatli ve bilinçli bir sekilde seçilmesi gerekmektedir. Formülasyonlarda etkin maddeler ile yardimci maddeler arasinda fizikokimyasal uyumsuzluk olmamalidir. Karisimdaki uygun dolgu maddesi; mikrokristalin selüloz, susuz Iaktoz, dikalsiyum fosfat dihidrat, amonyum aljinat, kalsiyum karbonat, kalsiyum fosfat, kalsiyum sülfat, selüloz, selüloz asetat, dextratlar, dekstrin, dekstroz, eritritol, estilselüloz, mannitol, magnezyum karbonat, magnezyum oksit, maltodekstrin, polidekstroz, polimetakrilatlar, sodyum aljinat, sodyum klorür, nisasta, seker küreleri, sülfobütileter beta-siklodekstrin, polisorbat 80, ksilitol veya bunlarin karisimlarini içeren gruptan seçilmektedir. Mevcut bulusun bir düzenlemesine göre karisimdaki dolgu maddesi mikrokristalin selülozdür. Karisimdaki uygun baglayici; sodyum karboksimetil selüloz, polivinilpirolidon (K30, K90), sodyum karboksimetil selüloz, polietilen glikol, nisasta, prejelatinize nisasta, sodyum aljinat, hidroksipropil metil selüloz, hidroksipropil selüloz, karboksi metil selüloz, metil selüloz, jelatin, karragenan, guar sakizi, polimetakrilatlar, metakrilat polimerler, hiyalüronik asit, pektin, polisakkaritler, karbomer, poloksamer, poliakrilamid, alüminyum hidroksit, polioksietilen-alkil eter, polidekstroz, polietien oksit veya bunlarin karisimlarini içeren gruptan seçilmektedir. Mevcut bulusun bir düzenlemesine göre karisimdaki baglayici sodyum karboksimetil selüloz veya polivinilpirolidon (K30, K90) veya bunlarin karisimlaridir. Karisimdaki uygun Iubrikanlar; magnezyum stearat, sodyum stearil fumarat, kalsiyum stearat, sodyum klorat, magnezyum loril sülfat, sodyum asetat, sodyum benzoat, polietilen glikol, sodyum Ioril sülfat veya bunlarin karisimlarini içeren gruptan seçilmektedir. Mevcut bulusun bir düzenlemesine göre karisimdaki lubrikan magnezyum stearattir. Mevcut bulusun bir düzenlemesine göre karisim; metformin HCI, mikrokristalin selüloz, sodyum karboksimetil selüloz, polivinilpirolidon K30, polivinilpirolidon K90, magnezyum stearati içermektedir. Bu sayede arzu edilen sikistirilabilirlik ve yüksek fiziksellik saglanmaktadir. Karisim sayesinde, metforminin sikistirilabilirligi düsük olsa dahi ilave proseslere gerek kalmaksizin tablet dogrudan baski yöntemiyle sikistirilabilmektedir. Mevcut bulusun bir düzenlemesine göre, karisimdaki metformin hidroklorür miktari toplam formülasyon agirligi bakimindan %650 ile %820 arasinda, karisimdaki mikrokristalin selüloz miktari toplam formülasyon agirligi bakimindan %01 ile %20 arasinda, karisimdaki sodyum karboksimetil selüloz miktari toplam formülasyon agirligi bakimindan %005 ile %10 arasinda, karisimdaki polivinilpirolidon K30 miktari toplam formülasyon agirligi bakimindan bakimindan %0.1 ile %1.0 arasinda, karisimdaki magnezyum stearat miktari toplam formülasyon agirligi bakimindan %0.1 ile %1.0 arasindadir. Uygun baglayicilar; polivinilpirolidon, sodyum karboksimetil selüloz, polietilen glikol, polivinil alkol, nisasta, prejelatinize nisasta, glukoz, glukoz surubu, dogal sakizlar, sukroz, sodyum aljinat, hidroksipropil metil selüloz, hidroksipropil selüloz, karboksi metil selüloz, metil selüloz, jelatin, karragenan, guar sakizi, karbomer, polimetakrilatlar, metakrilat polimerleri, agar, aljinat, aljinik asit, ksantan sakizi, hiyalüronik asit, pektin, polisakkaritler, poloksamer, poliakrilamid, aluminyum hidroksit, laponit, bentonit, polioksietilen-alkil eter, polidekstroz, polietien oksit veya bunlarin karisimlarini içeren gruptan seçilmektedir. Mevcut bulusun bir düzenlemesine göre, baglayicilarin miktari toplam formülasyon agirligi bakimindan %4.0 ile %250 arasindadir. Mevcut bulusun bir düzenlemesine göre baglayici kopovidon veya polivinilpirolidon veya bunlarin karisimlaridir. Mevcut bulusun bir düzenlemesine göre sasirtici bir sekilde kopovidon kullanilmasinin neme duyarli bir ilaç olan vildagliptin ile hidrojen baglar olusturulmasini sagladigi, bu sayede çözünürlük, çözünme hizi ve stabiliteyi arttirdigi görülmüstür. Mevcut bulusun bir düzenlemesine göre baglayici olarak özellikle kopovidon 8- Ultra kullanilmaktadir. Kopovidon S- Ultranin peroksit orani diger kopovidondan düsük oldugundan arzu edilen stabilitenin saglanmasina yardimci olmaktadir. Mevcut bulusun bir düzenlemesine göre, tablet baglayici olarak kopovidonu içermektedir ve kopovidonun miktari toplam formülasyon agirligi bakimindan %150 ile %250 arasindadir. Mevcut bulusun bir düzenlemesine göre, tablet baglayici olarak kopovidon ve polivinilpirolidonu içermektedir ve kopovidonun miktari toplam formülasyon agirligi bakimindan %20 ile %6.0 arasinda; polivinilpirolidonun miktari toplam formülasyon agirligi bakimindan %2.0 ile %6.0 arasindadir. Mevcut bulusun bir düzenlemesine göre film kapli tablet - Vildagliptin veya vildagliptin HCI, - Metformin hidroklorür içeren bir karisim ve - kopovidon ve/veya polivinilpirolidonu içermekte olup; burada karisimdaki metformin HCI miktari agirlik bakimindan %920 ile %970 arasindadir ve karisim metformin HCI, mikrokristalin selüloz, sodyum karboksimetil selüloz, polivinilpirolidon K30, polivinilpirolidon K90, magnezyum stearati içermektedir. Burada kullanildigi sekliyle 'parçacik boyutu'; lazer kirinimi yöntemi (bir baska ifadeyle Malvern analizi) gibi konvansiyonel olarak kabul görmüs herhangi bir yöntem ile test edilen kümülatif hacim boyut dagilimi anlamina gelmektedir. d (0.9) terimi, hacimce parçaciklarin Mevcut bulusun bu düzenlemesine göre vildagliptin veya vildagliptin HCl'nin parçacik boyutu arasindadir. Mevcut bulusun bu düzenlemesine göre metformin HCI'nin parçacik boyutu 500 um'den Mevcut bulus konusu film kapli tablet, dogrudan baski veya kuru granülasyon gibi teknigin mevcut durumunda iyi bilinen standart teknikler ya da üretim yöntemleri kullanilarak hazirlanabilir. Mevcut bulusun bir düzenlemesine göre film kapli tablet dogrudan baski yöntemi ile elde edilmektedir; bu sayede de basit ve maliyeti düsük bir üretim yöntemi uygulanmis olmaktadir. Ayrica vildagliptin hava ve neme karsi oldukça duyarli oldugu için de bu yöntem avantajlidir, çünkü bu yöntemde yüksek nem söz konusu olmadigi gibi hizli da bir yöntemdir. Mevcut bulusun bir düzenlemesine göre, film kapli tableti hazirlama prosesi ayrica asagidaki adimlari içermektedir: a) Metformin HCI içeren karisimin 1.0 mm'lik bir elekten geçirilmesi, b) Vildagliptin ve kopovidon ve/veya polivinilpirolidonun 0.9 mm'lik bir elekten geçirilmesi ve (a) adimindaki metformin HCI içeren karisimin yarisinin eklenerek karistirilmasi, c) Metformin HCI içeren karisimin diger yarisinin eklenerek karistirilmasi, d) Tablet elde edecek sekilde sikistirilmasi, e) Tabletlerin kaplama ile kaplanmasi. Mevcut bulusun bir düzenlemesine göre, nihai ürünün nem siniri %1 .0'dir. Mevcut bulusun bir düzenlemesine göre, tablet sikistirma prosesi esnasinda tabletlerin nemini azaltmak adina kuru hava besleme ve hava çikisi sistemi uygulanmistir. Ayrica tabletin sikistirilmasindan sonra, kaplama esnasinda uygulanacak olan kuru hava besleme sistemi olusturulmustur ve beslenen havanin nemi %10'un altina indirilmistir. Tablet sikistirma prosesi tamamlanincaya kadar nem emilimini önlemek üzere kurutucu madde kullanilmistir. Kurutucu maddeler IBC ile birlestirilmektedir. Ürünün muhafaza edildigi ve nakledildigi bölgelere kurutucu madde olarak silika jel yerlestirilmistir. Bunun ürünle temas etmemesi saglanmistir. TR TR DESCRIPTION FILM COATED TABLET OF VILDAGLIPTIN AND METFORMIN HYDROCHLORIDE Technical Field The present invention relates to a film-coated tablet containing vildagliptin or a mixture of vildagliptin HCl, at least one binder and metformin hydrochloride; In this way, the desired stability and pharmacotechnical properties as well as the desired dissolution profile are achieved with the tablet in question. The present invention also relates to a film-coated tablet preparation method that is simple, fast, cost-effective, time-saving and industrially convenient. Background of the Invention Diabetes; It is a group of disorders related to carbohydrate metabolism in which insulin action is reduced or absent due to altered secretion, decreased insulin activity, or a combination of these two factors. There are two main types of diabetes, Type 1 and Type 2: The cause of Type 1 diabetes is that the insulin-producing cells (beta cells) in the pancreas are damaged. In type 1 diabetes, the pancreas produces insufficient or no insulin, so sugar cannot enter the body cells to be used as energy. Patients with type 1 diabetes must use insulin injections to control blood sugar. In type 2 diabetes, although the pancreas produces insulin, either the amount of insulin produced is insufficient or insulin cannot perform its function. Type 2 diabetes is generally seen in overweight people over the age of 40. Type 2 diabetes can sometimes be controlled through diet, weight management and exercise. However, it can also be treated with oral glucose-lowering drugs or insulin injections. Vildagliptin is a dipeptidyl dipeptidase-IV (DPP-IV) inhibitor developed for use in the treatment of type 2 diabetes (non-insulin-dependent diabetes). Vildagliptin also inhibits the effects of dipeptidyl dipeptidase-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). The chemical name of vildagliptin is (S)-{[(3-hydroxyadamantan-1-yl)amino]acetyl}pyrrolidine-2-carbonitrile and its chemical structure is as in Formula 1 below. Formula 1 Methanol is soluble in water and organic polar solutions. Vildagliptin is sold under the brand name Galvus® in 50 mg dosage forms. It is used against diabetes mellitus, especially in the treatment of type 2 diabetes. Metformin is an antidiabetic with a biguanide structure that is administered orally. Metformin hydrochloride is a white to off-white crystalline compound that is freely soluble in water and virtually insoluble in acetone, ether and chloroform. Recommended oral doses of metformin are generally used alone or in combination with sulfonylureas, alpha-glucosidase inhibitors, or insulin. The chemical name of metformin hydrochloride is 1,1-dimethylbiguanide hydrochloride; Its chemical structure is as in Formula II given below. The product, which consists of the combination of Formula II Vildagliptin and metformin hydrochloride, is sold under the brand name Eucreas®. Pharmaceutical formulations of the combined active ingredients and the process for their preparation are described in EP 1948149. is explained. A tablet disclosed herein may contain active ingredients as well as known excipients, such as fillers, binders, disintegrants, lubricants and colourants. Examples of lubricants include colloidal silica, magnesium trisilicate, starch, talc, calcium phosphate, magnesium stearate, aluminum stearate, calcium stearate, magnesium carbonate, magnesium oxide, polyethylene glycol, cellulose and microcrystalline cellulose. The EP document discloses a pharmaceutical composition comprising the active ingredient metformin and a lubricant (in an amount of more than 10% based on the total weight of the composition) in combination with the active ingredient sitagliptin or vildagliptin or a salt thereof. Said Lubricant is polyethylene glycol or a mixture of polyethylene glycol and at least one other lubricant. There are some structural problems with both metformin HCl and vildagliptin. Stability-related problems arise with many active substances, including vildagliptin, under the influence of environmental and physical conditions. Vildagliptin is an active substance that is extremely sensitive to air and moisture. Vildagliptin structurally degrades when exposed to air and moisture and develops chemical behavior changes. The stability of the developed vildagliptin products is not at the desired level and their shelf life is shortened. In addition, vildagliptin is reactive to excipients used in the development of formulations containing it. This situation causes impurities to form in the formulation and leads to the inclusion of undesirable components into the formulation. Additionally, the compressibility of metformin is insufficient. Considering all these, it will be seen how difficult it is to create a formulation containing vildagliptin and metformin HCl. The present invention provides a film-coated tablet containing vildagliptin or vildagliptin HCl, a mixture containing metformin hydrochloride (the amount of metformin HCl in said mixture is in the ratio of 920% and 97.0% by weight) and at least one binder, this mixture also containing binders, fillers, lubricants. or mixtures thereof. In order to eliminate the problems mentioned above, a process has been developed to prepare this tablet with a film-coated tablet containing selected excipients in a certain ratio. Detailed Description of the Invention The main aim of the present invention is to provide a tablet containing vildagliptin/vildagliptin HCl and metformin HCl that can be compressed into a high stability tablet. Another aim of the present invention is to produce a tablet with the desired dissolution profile and compressibility, considering the negative structural properties of metformin HCl and vildagliptin. Film-coated tablet according to an embodiment of the present invention; - Vildagliptin or vildagliptin HCl, - A mixture containing metformin hydrochloride and - At least one binder, wherein; The amount of metformin HCl in the mixture is between 920 and 970% by weight, and the mixture contains at least one pharmaceutically acceptable excipient selected from the group consisting of binders, fillers, lubricants, or mixtures thereof. According to an embodiment of the present invention, the amount of vildagliptin or vildagliptin HCl is between 20% and 100% by weight of the total formulation. This amount is preferably between 120% and 70% or 30% and 50% by weight of the total formulation. According to one embodiment of the present invention, the amount of the mixture containing metformin hydrochloride is between 700% and 850% by weight of the total formulation. The use of large amounts of Metformin HCl may cause problems in terms of content uniformity of the active ingredient in individual composition units during the preparation of the formulation. Due to content uniformity problems, there is a possibility that the active substance may interact with some excipients. This shows that content uniformity plays an important role in the dissolution of the drug. In addition, the compressibility of metformin is insufficient in terms of physical properties, and how to obtain a tablet or capsule with acceptable mechanical strength poses an important problem in the development of the formulation. In the present invention, the amount of metformin HCl is 950% by weight (Direct Compressibility of granulated metformin is 95%). In this way, the desired content uniformity and therefore the desired dissolution profile is achieved. Moreover, the desired compressibility and high physicality are achieved. Thanks to the mixture, even if the compressibility of metformin is low, the tablet can be compressed directly by the printing method without the need for additional processes. In general terms, excipients found in a formulation; It may positively or negatively affect the physicochemical and pharmacokinetic properties of the active substance, such as solubility, absorption and bioavailability. For this reason, when developing a formulation (especially a mixture), the auxiliary substances to be used together with the active substance must be carefully and consciously selected. There should be no physicochemical incompatibility between active ingredients and excipients in formulations. Suitable filler in the mixture; microcrystalline cellulose, anhydrous lactose, dicalcium phosphate dihydrate, ammonium alginate, calcium carbonate, calcium phosphate, calcium sulfate, cellulose, cellulose acetate, dextrates, dextrin, dextrose, erythritol, estylcellulose, mannitol, magnesium carbonate, magnesium oxide, maltodextrin, polydextrose, polymethacrylates , sodium alginate, sodium chloride, starch, sugar spheres, sulfobutylether beta-cyclodextrin, polysorbate 80, xylitol, or mixtures thereof. According to one embodiment of the present invention, the filler in the mixture is microcrystalline cellulose. The appropriate binder in the mixture is; sodium carboxymethyl cellulose, polyvinylpyrrolidone (K30, K90), sodium carboxymethyl cellulose, polyethylene glycol, starch, pregelatinized starch, sodium alginate, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, carboxy methyl cellulose, methyl cellulose, gelatin, carrageenan, guar gum, polymethacrylates, methacrylates lat The polymers are selected from the group consisting of hyaluronic acid, pectin, polysaccharides, carbomer, poloxamer, polyacrylamide, aluminum hydroxide, polyoxyethylene-alkyl ether, polydextrose, polyethylene oxide, or mixtures thereof. According to one embodiment of the present invention, the binder in the mixture is sodium carboxymethyl cellulose or polyvinylpyrrolidone (K30, K90) or mixtures thereof. Suitable lubricants in the mixture; is selected from the group consisting of magnesium stearate, sodium stearyl fumarate, calcium stearate, sodium chlorate, magnesium lauryl sulfate, sodium acetate, sodium benzoate, polyethylene glycol, sodium lauryl sulfate, or mixtures thereof. According to one embodiment of the present invention, the lubricant in the mixture is magnesium stearate. The mixture according to an embodiment of the present invention; Contains metformin HCl, microcrystalline cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone K30, polyvinylpyrrolidone K90, magnesium stearate. In this way, the desired compressibility and high physicality are achieved. Thanks to the mixture, even if the compressibility of metformin is low, the tablet can be compressed directly by the printing method without the need for additional processes. According to one embodiment of the present invention, the amount of metformin hydrochloride in the mixture is between 650% and 820% by total formulation weight, the amount of microcrystalline cellulose in the mixture is between 01% and 20% by total formulation weight, the amount of sodium carboxymethyl cellulose in the mixture is between 005% and 10% by total formulation weight. Between, the amount of polyvinylpyrrolidone K30 in the mixture is between 0.1% and 1.0% in terms of total formulation weight, and the amount of magnesium stearate in the mixture is between 0.1% and 1.0% in terms of total formulation weight. Suitable connectors; polyvinylpyrrolidone, sodium carboxymethyl cellulose, polyethylene glycol, polyvinyl alcohol, starch, pregelatinized starch, glucose, glucose syrup, natural gums, sucrose, sodium alginate, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, carboxy methyl cellulose, methyl cellulose, gelatin, carrageenan, guar gum , carbomer, polymethacrylates, methacrylate polymers, agar, alginate, alginic acid, xanthan gum, hyaluronic acid, pectin, polysaccharides, poloxamer, polyacrylamide, aluminum hydroxide, laponite, bentonite, polyoxyethylene-alkyl ether, polydextrose, polyethylene oxide or mixtures thereof. is selected. According to one embodiment of the present invention, the amount of binders is between 4.0% and 250% by weight of the total formulation. According to one embodiment of the present invention, the binder is copovidone or polyvinylpyrrolidone or mixtures thereof. Surprisingly, according to one embodiment of the present invention, it has been observed that the use of copovidone enables the formation of hydrogen bonds with vildagliptin, a moisture-sensitive drug, thus increasing the solubility, dissolution rate and stability. According to an embodiment of the present invention, especially copovidone 8-Ultra is used as a binder. Since the peroxide rate of Kopovidone S- Ultra is lower than other copovidone, it helps to provide the desired stability. According to one embodiment of the present invention, the tablet contains copovidone as a binder and the amount of copovidone is between 150% and 250% by weight of the total formulation. According to an embodiment of the present invention, the tablet contains copovidone and polyvinylpyrrolidone as binders, and the amount of copovidone is between 20% and 6.0% by weight of the total formulation; The amount of polyvinylpyrrolidone is between 2.0% and 6.0% by weight of the total formulation. According to an embodiment of the present invention, the film-coated tablet contains - Vildagliptin or vildagliptin HCl, - a mixture containing metformin hydrochloride and - copovidone and/or polyvinylpyrrolidone; wherein the amount of metformin HCl in the mixture is between 920 and 970% by weight and the mixture contains metformin HCl, microcrystalline cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone K30, polyvinylpyrrolidone K90, magnesium stearate. 'Particle size' as used here; It means the cumulative volume size distribution tested by any conventionally accepted method, such as the laser diffraction method (i.e. Malvern analysis). The term d (0.9) refers to the particle size of vildagliptin or vildagliptin HCl according to this embodiment of the present invention. According to this embodiment of the present invention, the particle size of metformin HCl is from 500 µm. The film-coated tablet of the present invention can be prepared using standard techniques or production methods well known in the state of the art, such as direct printing or dry granulation. According to one embodiment of the present invention, the film-coated tablet is obtained by direct printing method; In this way, a simple and low-cost production method is applied. Moreover, since vildagliptin is very sensitive to air and humidity, this method is advantageous because high humidity is not required in this method and it is a fast method. According to one embodiment of the present invention, the process of preparing the film-coated tablet further includes the following steps: a) passing the mixture containing metformin HCl through a 1.0 mm sieve, b) passing the vildagliptin and copovidone and/or polyvinylpyrrolidone through a 0.9 mm sieve, and (a) Adding half of the mixture containing metformin HCl in step and mixing, c) Adding and mixing the other half of the mixture containing Metformin HCl, d) Compressing to obtain tablets, e) Covering the tablets with coating. According to one embodiment of the present invention, the moisture limit of the final product is 1.0%. According to an embodiment of the present invention, a dry air supply and air outlet system is applied to reduce the moisture of the tablets during the tablet compression process. Additionally, after compressing the tablet, a dry air supply system was created to be applied during coating and the humidity of the supplied air was reduced below 10%. A desiccant was used to prevent moisture absorption until the tablet compression process was completed. Desiccants are combined with IBC. Silica gel was placed as a drying agent in the areas where the product was stored and transported. It is ensured that it does not come into contact with the product. TR TR
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2021/005579A TR2021005579A2 (en) | 2021-03-29 | 2021-03-29 | FILM COATED TABLET OF VILDAGLIPTIN AND METFORMIN HYDROCHLORIDE |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2021/005579A TR2021005579A2 (en) | 2021-03-29 | 2021-03-29 | FILM COATED TABLET OF VILDAGLIPTIN AND METFORMIN HYDROCHLORIDE |
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