TR2021019695A2 - A TABLET FORMULATION CONTAINING MICRONIZED BENIDIPINE - Google Patents
A TABLET FORMULATION CONTAINING MICRONIZED BENIDIPINEInfo
- Publication number
- TR2021019695A2 TR2021019695A2 TR2021/019695 TR2021019695A2 TR 2021019695 A2 TR2021019695 A2 TR 2021019695A2 TR 2021/019695 TR2021/019695 TR 2021/019695 TR 2021019695 A2 TR2021019695 A2 TR 2021019695A2
- Authority
- TR
- Turkey
- Prior art keywords
- film
- coated tablet
- benidipine
- sodium
- tablet according
- Prior art date
Links
- 229960004916 benidipine Drugs 0.000 title claims abstract description 49
- QZVNQOLPLYWLHQ-ZEQKJWHPSA-N benidipine Chemical compound C1([C@H]2C(=C(C)NC(C)=C2C(=O)OC)C(=O)O[C@H]2CN(CC=3C=CC=CC=3)CCC2)=CC=CC([N+]([O-])=O)=C1 QZVNQOLPLYWLHQ-ZEQKJWHPSA-N 0.000 title claims abstract description 48
- 239000007916 tablet composition Substances 0.000 title description 2
- 239000000203 mixture Substances 0.000 claims abstract description 40
- 239000007941 film coated tablet Substances 0.000 claims abstract description 36
- 238000009472 formulation Methods 0.000 claims abstract description 21
- 239000002245 particle Substances 0.000 claims abstract description 20
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 239000012458 free base Substances 0.000 claims abstract description 12
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 10
- 238000000034 method Methods 0.000 claims abstract description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 18
- 229960001021 lactose monohydrate Drugs 0.000 claims description 14
- 239000011248 coating agent Substances 0.000 claims description 13
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.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 WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 claims description 12
- 239000008187 granular material Substances 0.000 claims description 12
- 239000000945 filler Substances 0.000 claims description 11
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 11
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 11
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 11
- 229920000881 Modified starch Polymers 0.000 claims description 10
- 239000011230 binding agent Substances 0.000 claims description 10
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 10
- 238000000576 coating method Methods 0.000 claims description 10
- 239000003826 tablet Substances 0.000 claims description 10
- 235000019359 magnesium stearate Nutrition 0.000 claims description 9
- 238000002156 mixing Methods 0.000 claims description 8
- 239000002202 Polyethylene glycol Substances 0.000 claims description 7
- 229920001223 polyethylene glycol Polymers 0.000 claims description 7
- 238000007873 sieving Methods 0.000 claims description 7
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 6
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 6
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 6
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 6
- 229940105329 carboxymethylcellulose Drugs 0.000 claims description 6
- 239000007884 disintegrant Substances 0.000 claims description 6
- 239000000314 lubricant Substances 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 229920002472 Starch Polymers 0.000 claims description 5
- 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 5
- 229930006000 Sucrose Natural products 0.000 claims description 5
- 235000010443 alginic acid Nutrition 0.000 claims description 5
- 229920000615 alginic acid Polymers 0.000 claims description 5
- 238000005469 granulation Methods 0.000 claims description 5
- 230000003179 granulation Effects 0.000 claims description 5
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 5
- 239000000463 material Substances 0.000 claims description 5
- 229940032147 starch Drugs 0.000 claims description 5
- 239000008107 starch Substances 0.000 claims description 5
- 235000019698 starch Nutrition 0.000 claims description 5
- 239000005720 sucrose Substances 0.000 claims description 5
- 229960004793 sucrose Drugs 0.000 claims description 5
- 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
- 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 4
- 229930195725 Mannitol Natural products 0.000 claims description 4
- 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 4
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 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
- 229960001631 carbomer Drugs 0.000 claims description 4
- 238000001035 drying Methods 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
- 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
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 4
- 239000000594 mannitol Substances 0.000 claims description 4
- 235000010355 mannitol Nutrition 0.000 claims description 4
- 229920001282 polysaccharide Polymers 0.000 claims description 4
- 239000005017 polysaccharide Substances 0.000 claims description 4
- 150000004804 polysaccharides Chemical class 0.000 claims description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 4
- 238000003825 pressing Methods 0.000 claims description 4
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 4
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 4
- 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 3
- 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 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 3
- 229940072056 alginate Drugs 0.000 claims description 3
- 239000011575 calcium Substances 0.000 claims description 3
- 239000002270 dispersing agent Substances 0.000 claims description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 3
- 229960001375 lactose Drugs 0.000 claims description 3
- 239000008101 lactose Substances 0.000 claims description 3
- 229920000193 polymethacrylate Polymers 0.000 claims description 3
- 235000010413 sodium alginate Nutrition 0.000 claims description 3
- 239000000661 sodium alginate Substances 0.000 claims description 3
- 229940005550 sodium alginate Drugs 0.000 claims description 3
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 2
- 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
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
- 229920002261 Corn starch Polymers 0.000 claims description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- 235000019739 Dicalciumphosphate Nutrition 0.000 claims description 2
- 229930091371 Fructose Natural products 0.000 claims description 2
- 239000005715 Fructose Substances 0.000 claims description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 2
- 108010010803 Gelatin Proteins 0.000 claims description 2
- 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 2
- 229920002907 Guar gum Polymers 0.000 claims description 2
- 229920002774 Maltodextrin Polymers 0.000 claims description 2
- 239000005913 Maltodextrin Substances 0.000 claims description 2
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 claims description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
- 229920001100 Polydextrose Polymers 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- 239000000783 alginic acid Substances 0.000 claims description 2
- 229960001126 alginic acid Drugs 0.000 claims description 2
- 150000004781 alginic acids Chemical class 0.000 claims description 2
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 2
- 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 2
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims description 2
- 229910052791 calcium Inorganic materials 0.000 claims description 2
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- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 2
- -1 dextrates Chemical compound 0.000 claims description 2
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- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 claims description 2
- 229940038472 dicalcium phosphate Drugs 0.000 claims description 2
- 229910000390 dicalcium phosphate Inorganic materials 0.000 claims description 2
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 claims description 2
- RRPFCKLVOUENJB-UHFFFAOYSA-L disodium;2-aminoacetic acid;carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O.NCC(O)=O RRPFCKLVOUENJB-UHFFFAOYSA-L 0.000 claims description 2
- 229960000878 docusate sodium Drugs 0.000 claims description 2
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- 239000000832 lactitol Substances 0.000 claims description 2
- 235000010448 lactitol Nutrition 0.000 claims description 2
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 claims description 2
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- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 claims description 2
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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 2
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Abstract
Mevcut buluş, serbest baz formunda veya farmasötik olarak kabul edilebilir tuzlar formunda benidipin ve farmasötik olarak kabul edilebilir en az bir eksipiyan içeren bir film kaplı tabletle ilgili olup, özelliği benidipinin, 50 µm'den küçük bir d (0.9) partikül boyutuna sahip olmasıdır. Ayrıca formülasyon, etkili bir proses kullanılarak elde edilir.The present invention relates to a film-coated tablet comprising Benidipine in free base form or in the form of pharmaceutically acceptable salts and at least one pharmaceutically acceptable excipient, characterized in that the Benidipine has a particle size d (0.9) of less than 50 µm. Moreover, the formulation is obtained using an efficient process.
Description
TARIFNAME MIKRONIZE BENIDIPIN IÇEREN BIR TABLET FORMÜLASYONU Bulusun Alani Mevcut bulus, serbest baz formunda veya farmasötik olarak kabul edilebilir tuzlar formunda benidipin ve farmasötik olarak kabul edilebilir en az bir eksipiyan içeren bir film kapli tablet ile ilgili olup. burada benidipinin d (0.9) partikül boyutu 50 pm'den küçüktür. Ayrica formülasyon, etkili bir islem kullanilarak elde edilir. Bulusun Geçmisi Benidipin, 1,4-dihidro-2,ö-dimetil-4-(3-nitrofeniI)-3,5-piridin-dikarboksilik asit metil 1- (fenilmetil)-3-piperidinil ester hidroklorür formülüne sahiptir. Anti-hipertansif ve anti-anginal etkilere sahip sentetik bir dihidropiridin türevidir. Üçlü L-, T- ve N tipi kalsiyum kanal blokeridir. Bahsedilen üç Ca kanalini da inhibe edebilen tek kalsiyum antagonistidir. Ayrica benidipin hücre zari ile yüksek afiniteye sahiptir, vasküler seçicilige ve böbrek koruyucu etkiye sahiptir. Bu nedenle hipertansiyon ve renal parankimal hipertansiyon ve anjina tedavisi için ideal, güvenli ve etkili bir ajandir. Benidipin, asagidaki Formül l kimyasal yapisina sahiptir. Formül l: Benidipin Benidipin, BCS siniflandirmasinda sinif li bir ilaçtir, yani suda az çözünürdür. Az çözünür ilaçlar için, çözünme, emilim hizi sinirlayici prosestir ve genellikle biyoyararlanimini etkileyen en önemli faktördür. Formik asitte çok çözünür, dimetilformamidde serbestçe çözünür, metanol veya etanolde çözünür, asetik anhidritte az çözünürdür. Ayrica, benidipin HCI, formülasyonda düsük miktarlarda bulunur, bu nedenle eksipiyanlarin asiri kullanimi ve aralarindaki uyumsuzluklar sikistirilabilirligi olumsuz etkileyebilir. Problem ayrica akiskanliga ve içerik tekdüzeligine de neden olabilir. Benidipin ilk olarak EP63365 82 basvurusu ile açiklanmistir. Bu bulusta, yukarida bahsedilen bu problemlerin üstesinden gelmek için, 50 um'den küçük bir d (0.9) partikül boyutuna sahip, serbest baz formunda veya farmasötik olarak kabul edilebilir tuzlar formunda benidipin içeren bir film kapli tablet saglanmaktadir. Ayrica film kapli tablet, basit ve uygun maliyetli yöntem olan standart teknikler kullanilarak gelistirilmistir. Bulusun Ayrintili Açiklamasi Mevcut bulusun esas amaci, benidipinin neden oldugu problemleri ortadan kaldirmak ve ilgili önceki teknige ilave avantajlar getirmektir. Mevcut bulusun baska bir amaci, istenen çözünme profilini saglayan bir formülasyonda 50 um'den küçük bir d (0.9) partikül boyutuna sahip benidipin ve farmasötik olarak kabul edilebilir en az bir eksipiyan içeren bir film kapli tablet saglamaktir. Mevcut bulusun baska bir amaci, akiskanlik, sikistirilabilirlik ve içerik tekdüzeligi gibi mükemmel farmakoteknik özellikler ile karakterize edilen bir formülasyon saglamaktir. Mevcut bulusun bir baska amaci, istenen çözünmeye ve istenen stabiliteye sahip olan benidipin içeren bir film kapli tablet formülasyonunun hazirlanmasi için etkili bir proses elde etmektir. Serbest baz formundaki veya asagidaki partikül boyutlarina sahip farmasötik olarak kabul edilebilir tuzlar formundaki benidipinin, formülasyon için önemli oldugunu bulduk. Bu özellikle çözünme özelliklerini olumlu yönde etkiler Elde edilen tabletler istenen çözünme profiline sahiptir. Burada kullanildigi sekliyle, "partikül boyutu", lazer kirinim yöntemi (yani, malvern analizi) gibi geleneksel olarak kabul edilen herhangi bir yöntemle test edildiginde kümülatif hacim boyutu dagilimi anlamina gelir. d (0.9) terimi, partiküllerin hacimce %90'inin daha ince oldugu boyutu ifade eder. d (0.5) terimi, partiküllerin hacimce %50'sinin daha ince oldugu boyutu ifade eder. Bulusun bir düzenlemesine göre, bir film kapli tablet, serbest baz formunda veya farmasötik olarak kabul edilebilir tuzlar formunda benidipin ve farmasötik olarak kabul edilebilir en az bir eksipiyan içerir, burada benidipin, 50 pm'den küçük bir d (0.9) partikül boyutuna sahiptir. Mevcut bulusun bu düzenlemesine göre, serbest baz formundaki veya farmasötik olarak kabul edilebilir tuzlar formundaki benidipin, 35 pm'den küçük, tercihen 25 pm'den küçük, tercihen 18 pm'den küçük bir d (0.9) partikül boyutuna sahiptir. Mevcut bulusun bu düzenlemesine göre, serbest baz formundaki veya farmasötik olarak kabul edilebilir tuzlar formundaki benidipin, 3 um ile 18 um arasinda bir d (0.9) partikül boyutuna sahiptir. Mevcut bulusun bu düzenlemesine göre, serbest baz formundaki veya farmasötik olarak kabul edilebilir tuzlar formundaki benidipin, 30 pm'den küçük, tercihen 25 um'den küçük, tercihen 20 um'den küçük, tercihen tercihen 15 um'den küçük, tercihen 10 um'den küçük bir (:1 (0.5) partikül boyutuna sahiptir. Mevcut bulusun bu düzenlemesine göre, serbest baz formundaki veya farmasötik olarak kabul edilebilir tuzlar formundaki benidipin, 1 um ile 10 um arasinda bir d (0.5) partikül boyutuna sahiptir. Mevcut bulusun bu düzenlemesine göre, benidipin, benidipin hidroklorür formunda bulunmaktadir. Mevcut bulusun bir düzenlemesine göre, benidipin hidroklorür miktari toplam formülasyonda agirlikça %1 .O ile %10.0 arasindadir. Tercihen toplam formülasyonda agirlikça %1.0 ile %60 arasindadir. Bulusun bir düzenlemesine göre, bir film kapli tablet, dolgu maddeleri, baglayicilar, dagiticilar, farmasötik olarak kabul edilebilir en az bir eksipiyan içerir. Benidipin HCI, formülasyonda düsük miktarlarda bulunur, bu nedenle eksipiyanlarin asiri kullanimi ve aralarindaki uyumsuzluklar sikistirilabilirligi olumsuz yönde etkileyebilir. Problem ayrica akiskanliga ve içerik tekdüzeligine de neden olabilir. Sasirtici bir sekilde, film kapli tablet en az bir uygun dolgu maddesi ile hazirlandiginda, istenen akiskanlik, sikistirilabilirlik ve içerik tekdüzeliginin gözlemlendigi bulunmustur. Uygun dolgu maddeleri, laktoz monohidrat, mikrokristal selüloz, laktoz, mannitol, spreyle kurutulmus mannitol, nisasta, dekstroz, sakaroz, fruktoz, maltoz, sorbitol, ksilitol, inorganik tuzlar, kalsiyum tuzlari, polisakkaritler, dikalsiyum fosfat, sodyum klorür, dekstratlar, laktitol, sukroz -maltodekstrin karisimi, trehaloz, sodyum karbonat, sodyum bikarbonat, kalsiyum karbonat veya bunlarin karisimlarini içeren gruptan seçilir. Mevcut bulusun bir düzenlemesine göre dolgu maddesi laktoz monohidrattir. Mevcut bulusun bir düzenlemesine göre, dolgu maddelerinin miktari toplam formülasyonda agirlikça %70.0 ile %88.0 arasindadir. Tercihen toplam formülasyonda agirlikça %74.0 ile ve içerik tekdüzeligini saglar. Uygun baglayicilar, polivinilpirolidon, sodyum karboksimetil selüloz, polietilen glikol, polivinil alkol, dogal zamklar, sukroz, sodyum aljinat, hidroksipropil metil selüloz, hidroksipropil selüloz, karboksi metil selüloz, metil selüloz, jelatin, karagenan, guar zamki, karbomer, polimetakrilatlar, metakrilat polimerler, aljinat, alginik asit, ksantan zamki, hyaluronik asit, polisakaritler, karbomer, poloksamer, poliakrilamid, polioksietilen-alkil eter, polidekstroz, polietilen oksit veya bunlarin karisimlarindan olusan gruptan seçilir. Mevcut bulusun bir düzenlemesine göre, baglayici polivinilpirolidondur. Mevcut bulusun bir düzenlemesine göre, baglayicilarin miktari toplam formülasyonda agirlikça veya %30 ile %80 arasindadir. Uygun dagiticilar, prejelatinize nisasta, krospovidon, kroskarmeloz sodyum, nisasta, düsük ikameli hidroksipropil selüloz, sodyum karboksimetil selüloz, kalsiyum karboksimetil selüloz, karboksimetil selüloz, dokusat sodyum, düsük ikameli hidroksipropil selüloz, sodyum aljinat, misir nisastasi, sodyum nisasta glikolat, sodyum glisin karbonat veya bunlarin karisimlarini içeren gruptan seçilir. Mevcut bulusun bir düzenlemesine göre dagitici, prejelatinize nisastadir. Mevcut bulusun bir düzenlemesine göre, dagiticilarin miktari toplam formülasyonda agirlikça Uygun lubrikantlari'glidantlar, magnezyum stearat, sodyum stearil fumarat, talk, kolloidal silikon dioksit, misir, kalsiyum stearat, çinko stearat, sodyum klorat, magnezyum lauril sülfat, sodyum oleat, sodyum asetat, sodyum benzoat, stearik asit, fumarik asit, gliseril palmito sülfat veya bunlarin karisimlarindan olusan gruptan seçilir. Mevcut bulusun bir düzenlemesine göre Iubrikant/glidant, magnezyum stearattir. Mevcut bulusun bir düzenlemesine göre, Iubrikant/glidantin miktari toplam formülasyonda agirlikça %0.1 ile %30 arasindadir. Tercihen toplam formülasyonda agirlikça %05 ile %20 arasindadir. Uygun kaplama maddeleri, polimetakrilatlar, hidroksil propil metil selüloz, Iaktoz monohidrat, talk, hidroksipropil selüloz, polivinil alkol (PVA), polietilen glikol (PEG), talk, gliserin, polivinil alkol-polietilen glikol kopolimerleri (Kollicoat® IR), etilselüloz dispersiyonlari (Surelease®), polivinilpirolidon, polivinilpirolidon-vinil asetat kopolimeri (PVP-VA), ponceau, demir oksit, pigmentler, boyalar, titanyum dioksit, triasetin, boyar maddeler veya bunlarin karisimlarindan olusan gruptan seçilir. Mevcut bulusun bir düzenlemesine göre kaplama maddeleri, hidroksipropil metilselüloz, talk, titanyum dioksit, polietilen glikoldur. Mevcut bulusun bir düzenlemesine göre, kaplama maddeleri Iaktoz monohidrat, hidroksipropil metilselüloz, titanyum dioksit, polietilen glikol, sari demir oksit, triasetin, ponceau, FD&C Mavi'dir. Mevcut bulusun bir düzenlemesine göre, kaplama maddelerinin miktari toplam formülasyonda agirlikça %10 ila 5.0'tir. Mevcut bulusun bir düzenlemesine göre, serbest baz formunda veya farmasötik olarak kabul edilebilir tuzlar formunda benidipin içeren film kapli tablet, 20 N ile 70 N arasinda bir sertlige sahiptir. Bu, yüksek kimyasal ve mekanik stabilite saglar, dolayisiyla kolay kirilgan degildir, fakat ayni zamanda yüksek çözünme hizi ve kisa dagilma süresi saglar. Eniveka Tablet Hardness Tester ile sertlik testi yapilmistir. Mevcut bulusun bir düzenlemesine göre, film kapli tablet sunlari içerir; - 50 pm'den küçük d90 partikül boyutuna sahip Benidipin hidroklorür - Laktoz monohidrat - Polivinilpirolidon Mevcut bulusun bir düzenlemesine göre, film kapli tablet sunlari içerir; 7 50 pm'den küçük d90 partikül boyutuna sahip Benidipin hidroklorür I Laktoz monohidrat - Prejelatinize nisasta - Polivinilpirolidon 7 Magnezyum stearat Mevcut bulusun bir düzenlemesine göre, film kapli tablet bir yas granülasyon yöntemi kullanilarak elde edilir, bu nedenle basit ve düsük maliyetli bir üretim yöntemi kullanilmistir. Yas granülasyon prosesi ayrismayi etkili bir sekilde önler, böylece iyi çözünme ve dagilma özellikleri elde edebilir. Proseste, en az bir baglayici ve bir solvent (tercihen su) ile bir granülasyon solüsyonu hazirlandiginda, istenen içerik tekdüzeliginin saglandigi gözlemlenmistir. Özellikle küçük miktarlarda benidipin kullaniminin neden oldugu problem, uygun eksipiyanlar ve basamaklar içeren yas granülasyon ile önlenmistir. Bulusun bu düzenlemesine göre, benidipin içeren film kapli tablet hazirlanmasina yönelik bir proses, asagidaki adimlari içerir: a) 50 um'den küçük d90 partikül boyutuna sahip benidipin hidroklorür, en az bir dolgu maddesi ve en az bir dagiticinin karistirilmasi ve ardindan elenmesi, En az bir baglayicinin suda çözdürülmesi, Adim (a)'daki karisimin, adim (b)'deki granülasyon solüsyonu ile granüle edilmesi,. Yas granülün elenmesi ve yas granülün akiskan yatakli kurutucuda kurutulmasi, Kuru granülün elenmesi, f) En az bir Iubrikant/glidantin ilave edilmesi ve ardindan karistirilmasi, g) Hazirlanan karisimin basilarak tablet haline getirilmesi, h) Bu tabletlerin kaplama maddeleri ile kaplanmasi. Bulusun bir düzenlemesine göre, benidipin içeren film kapli tablet hazirlanmasina yönelik bir proses, asagidaki adimlari içerir: a) Benidipin hidroklorür, Iaktoz monohidrat ve prejelatinize nisastanin karistirilmasi ve ardindan elenmesi, ) Polivinilpirolidonun suda çözdürülmesi, ) Adim (a)'daki karisimin, adim (b)'deki granülasyon solüsyonu ile granüle edilmesi, d) Yas granülün elenmesi ve yas granülün akiskan yatakli kurutucuda kurutulmasi, ) Kuru granülün elenmesi, f) Magnezyum stearat ilave edilerek karistirilmasi, g) Hazirlanan karisimin basilarak tablet haline getirilmesi, h) Bu tabletlerin kaplama maddeleri ile kaplanmasi. Örnek 1: Film kapli tablet Bilesenler Miktar (toplam formülasyonun agirlikça (50 um'den küçük d90 partikül 1.0 - 10.0 boyutuna sahip) mikronize benidipin hidroklorür Laktoz monohidrat 70.0 - 88.0 Prejelatinize nisasta 3.0 - 15.0 Polivinilpirolidon K-30 2.0 - 15.0 Magnezyum stearat 0.1 - 3.0 Film kaplama 1.0 - 5.0 TOPLAM 100 Örnek 2: Film kapli tablet Bilesenler Miktar (toplam formülasyonun agirlikça Benidipin hidroklorür 2.0 Laktoz monohidrat 81.5 Prejelatinize nisasta 7.5 Polivinilpirolidon K-30 5.0 Magnezyum stearat 1.0 Film kaplama - Titanyum dioksit(E 171] % 18.15 30 o Talk (E553bl % 5.45 0 Makrogol (PEG 4000]% 3.85 TOPLAM Örnek 3: Film kapli tablet Bilesenler Miktar (toplam formülasyonun agirlikça Benidipin hidroklorür 4.0 Laktoz monohidrat 79.5 Prejelatinize nisasta 7.5 Polivinilpirolidon K-30 5.0 Magnezyum stearat 1.0 Film kaplama o Laktoz m0nohidrat% 21.00 0 Titanyum dioksit % 24.25 i PEG 3000 Toz % 8.00 0 Sari demir oksit %0. 737 30 i Triasetin %63.00 0 Ponceau 4R %0.011 0 FD&C Mavi No 2 %0002 TOPLAM 100 Örnek 1 veya 2 veya 3 için bir proses sunlari içerir; a) Benidipin hidroklorür, laktoz monohidrat ve preielatinize nisastanin karistirilmasi ve ardindan elenmesi, e) Kuru granülün elenmesi, Polivinilpirolidonun suda çözdürülmesi, Adim (a)'daki karisimin. adim (b)'deki granülasyon solüsyonu ile granüle edilmesi, Yas granülün elenmesi ve yas granülün akiskan yatakli kurutucuda kurutulmasi, f) Magnezyum stearat ilave edilerek karistirilmasi, g) Hazirlanan karisimin basilarak tablet haline getirilmesi, h) Bu tabletlerin kaplama maddeleri ile kaplanmasi. TR TR TR DESCRIPTION A TABLET FORMULATION CONTAINING MICRONIZED BENIDIPIN Field of the Invention The present invention relates to a film-coated tablet containing Benidipine in free base form or in the form of pharmaceutically acceptable salts and at least one pharmaceutically acceptable excipient. where the particle size d (0.9) of Benidipine is less than 50 pm. Moreover, the formulation is obtained using an effective process. Background of the Invention Benidipine has the formula 1,4-dihydro-2,o-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid methyl 1-(phenylmethyl)-3-piperidinyl ester hydrochloride. It is a synthetic dihydropyridine derivative with anti-hypertensive and anti-anginal effects. It is a triple L-, T- and N-type calcium channel blocker. It is the only calcium antagonist that can inhibit all three Ca channels mentioned. Additionally, Benidipine has a high affinity with the cell membrane, has vascular selectivity and a renal protective effect. Therefore, it is an ideal, safe and effective agent for the treatment of hypertension and renal parenchymal hypertension and angina. Benidipine has the following Formula I chemical structure. Formula 1: Benidipine Benidipine is a classified drug in the BCS classification, meaning it is slightly soluble in water. For poorly soluble drugs, dissolution is the rate-limiting process of absorption and is often the most important factor affecting bioavailability. It is very soluble in formic acid, freely soluble in dimethylformamide, soluble in methanol or ethanol, slightly soluble in acetic anhydride. Additionally, Benidipine HCl is present in low amounts in the formulation, so excessive use of excipients and incompatibilities between them can negatively affect compressibility. The problem can also cause fluidity and content monotony. Benidipine was first disclosed in application EP63365 82. In this invention, to overcome these above-mentioned problems, a film-coated tablet containing Benidipine in the form of free base or in the form of pharmaceutically acceptable salts with a particle size d (0.9) of less than 50 µm is provided. Moreover, the film-coated tablet was developed using standard techniques, which is a simple and cost-effective method. Detailed Description of the Invention The main purpose of the present invention is to eliminate the problems caused by benidipine and to bring additional advantages to the relevant prior art. It is another object of the present invention to provide a film-coated tablet comprising Benidipine having a particle size d (0.9) of less than 50 µm and at least one pharmaceutically acceptable excipient in a formulation that provides the desired dissolution profile. Another object of the present invention is to provide a formulation characterized by excellent pharmacotechnical properties such as flowability, compressibility and content uniformity. Another object of the present invention is to obtain an effective process for preparing a film-coated tablet formulation containing Benidipine having the desired dissolution and desired stability. We have found that Benidipine in its free base form or in the form of pharmaceutically acceptable salts with particle sizes below is important for the formulation. This particularly positively affects the dissolution properties. The resulting tablets have the desired dissolution profile. As used herein, "particle size" means the cumulative volume size distribution when tested by any conventionally accepted method, such as the laser diffraction method (i.e., malvern analysis). The term d (0.9) refers to the size at which 90% of the particles by volume are finer. The term d (0.5) refers to the size at which 50% of the particles are finer by volume. According to one embodiment of the invention, a film-coated tablet comprises Benidipine in free base form or in the form of pharmaceutically acceptable salts and at least one pharmaceutically acceptable excipient, wherein Benidipine has a particle size d (0.9) of less than 50 pm. According to this embodiment of the present invention, Benidipine in free base form or in the form of pharmaceutically acceptable salts has a particle size d (0.9) of less than 35 pm, preferably less than 25 pm, preferably less than 18 pm. According to this embodiment of the present invention, Benidipine in its free base form or in the form of pharmaceutically acceptable salts has a particle size d (0.9) between 3 µm and 18 µm. According to this embodiment of the present invention, Benidipine in its free base form or in the form of pharmaceutically acceptable salts has a size of less than 30 µm, preferably less than 25 µm, preferably less than 20 µm, preferably less than 15 µm, preferably 10 µm. According to this embodiment of the present invention, Benidipine in its free base form or in the form of pharmaceutically acceptable salts has a particle size d (0.5) between 1 µm and 10 µm. According to this embodiment of the present invention Accordingly, Benidipine is present in the form of Benidipine hydrochloride. According to one embodiment of the present invention, the amount of Benidipine hydrochloride is between 1.0% and 10.0% by weight of the total formulation. According to one embodiment of the invention, it is a film-coated tablet. , fillers, binders, disintegrants, contains at least one pharmaceutically acceptable excipient. Benidipine HCl is present in low amounts in the formulation, therefore excessive use of excipients and incompatibilities between them may adversely affect compressibility. The problem can also cause fluidity and content monotony. Surprisingly, it has been found that when the film-coated tablet is prepared with at least one suitable filler, the desired fluidity, compressibility and content uniformity are observed. Suitable fillers are lactose monohydrate, microcrystalline cellulose, lactose, mannitol, spray-dried mannitol, starch, dextrose, sucrose, fructose, maltose, sorbitol, xylitol, inorganic salts, calcium salts, polysaccharides, dicalcium phosphate, sodium chloride, dextrates, lactitol, The sucrose-maltodextrin mixture is selected from the group consisting of trehalose, sodium carbonate, sodium bicarbonate, calcium carbonate, or mixtures thereof. According to one embodiment of the present invention, the filler is lactose monohydrate. According to one embodiment of the present invention, the amount of fillers is between 70.0% and 88.0% by weight in the total formulation. Preferably at 74.0% by weight in the total formulation and ensures content uniformity. Suitable binders include polyvinylpyrrolidone, sodium carboxymethyl cellulose, polyethylene glycol, polyvinyl alcohol, natural gums, sucrose, sodium alginate, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, carboxy methyl cellulose, methyl cellulose, gelatin, carrageenan, guar gum, carbomer, polymethacrylates, methacrylate polymers. , alginate, alginic acid, xanthan gum, hyaluronic acid, polysaccharides, carbomer, poloxamer, polyacrylamide, polyoxyethylene-alkyl ether, polydextrose, polyethylene oxide, or mixtures thereof. According to one embodiment of the present invention, the binder is polyvinylpyrrolidone. According to one embodiment of the present invention, the amount of binders is between 30% and 80% by weight in the total formulation. Suitable disintegrants are pregelatinized starch, crospovidone, croscarmellose sodium, starch, low substituted hydroxypropyl cellulose, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, carboxymethyl cellulose, docusate sodium, low substituted hydroxypropyl cellulose, sodium alginate, corn starch, sodium starch glycolate, sodium glycine carbonate or mixtures thereof. According to one embodiment of the present invention, the disintegrant is pregelatinized starch. According to one embodiment of the present invention, the amount of dispersants by weight in the total formulation. Suitable lubricants include glidants, magnesium stearate, sodium stearyl fumarate, talc, colloidal silicon dioxide, corn, calcium stearate, zinc stearate, sodium chlorate, magnesium lauryl sulfate, sodium oleate, sodium acetate, selected from the group consisting of sodium benzoate, stearic acid, fumaric acid, glyceryl palmito sulfate, or mixtures thereof. According to one embodiment of the present invention, the lubricant/glidant is magnesium stearate. According to one embodiment of the present invention, the amount of lubricant/glidantin is between 0.1% and 30% by weight in the total formulation. Preferably it is between 05% and 20% by weight in the total formulation. Suitable coating materials are polymethacrylates, hydroxyl propyl methyl cellulose, lactose monohydrate, talc, hydroxypropyl cellulose, polyvinyl alcohol (PVA), polyethylene glycol (PEG), talc, glycerin, polyvinyl alcohol-polyethylene glycol copolymers (Kollicoat® IR), ethylcellulose dispersions ( Surelease®), polyvinylpyrrolidone, polyvinylpyrrolidone-vinyl acetate copolymer (PVP-VA), ponceau, iron oxide, pigments, dyes, titanium dioxide, triacetin, dyestuffs, or mixtures thereof. According to an embodiment of the present invention, the coating materials are hydroxypropyl methylcellulose, talc, titanium dioxide, polyethylene glycol. According to one embodiment of the present invention, the coating agents are Iactose monohydrate, hydroxypropyl methylcellulose, titanium dioxide, polyethylene glycol, yellow iron oxide, triacetin, ponceau, FD&C Blue. According to one embodiment of the present invention, the amount of coating agents is 10 to 5.0% by weight in the total formulation. According to one embodiment of the present invention, the film-coated tablet containing Benidipine in its free base form or in the form of pharmaceutically acceptable salts has a hardness between 20 N and 70 N. This ensures high chemical and mechanical stability, so it is not easily brittle, but also provides a high dissolution rate and short dispersion time. Hardness test was performed with Eniveka Tablet Hardness Tester. According to one embodiment of the present invention, the film-coated tablet includes; - Benidipine hydrochloride with d90 particle size less than 50 pm - Lactose monohydrate - Polyvinylpyrrolidone According to an embodiment of the present invention, the film-coated tablet contains; 7 Benidipine hydrochloride I with d90 particle size less than 50 pm Lactose monohydrate - Pregelatinized starch - Polyvinylpyrrolidone 7 Magnesium stearate According to an embodiment of the present invention, the film-coated tablet is obtained using a wet granulation method, therefore a simple and low-cost production method has been used. . The wet granulation process effectively prevents segregation, so it can achieve good dissolution and dispersion properties. In the process, it has been observed that when a granulation solution is prepared with at least one binder and a solvent (preferably water), the desired content uniformity is achieved. The problem caused by the use of Benidipine, especially in small amounts, has been prevented by wet granulation with appropriate excipients and steps. According to this embodiment of the invention, a process for preparing film-coated tablets containing Benidipine includes the following steps: a) mixing and subsequent sieving of Benidipine hydrochloride with a d90 particle size of less than 50 µm, at least one filler and at least one dispersant, At least dissolving a binder in water, granulating the mixture in step (a) with the granulation solution in step (b), Sifting the wet granule and drying the wet granule in a fluidized bed dryer, Sieving the dry granule, f) Adding at least one lubricant/glidantin and then mixing, g) Turning the prepared mixture into tablets by pressing, h) Coating these tablets with coating materials. According to one embodiment of the invention, a process for preparing film-coated tablets containing Benidipine includes the following steps: a) Mixing and then sieving Benidipine hydrochloride, Lactose monohydrate and pregelatinized starch, ) Dissolving polyvinylpyrrolidone in water, ) Dissolving the mixture in step (a), step ( b) Granulating with the granulation solution in above, d) Sifting the wet granule and drying the wet granule in a fluidized bed dryer, ) Sifting the dry granule, f) Mixing by adding magnesium stearate, g) Turning the prepared mixture into tablets by pressing, h) Coating these tablets coating with substances. Example 1: Film-coated tablet Components Quantity (by weight of the total formulation (d90 particle size less than 50 µm 1.0 - 10.0) micronized Benidipine hydrochloride Lactose monohydrate 70.0 - 88.0 Pregelatinized starch 3.0 - 15.0 Polyvinylpyrrolidone K-30 2.0 - 15.0 Magnesium stearate 0.1 - 3.0 Film-coated 1.0 - 5.0 TOTAL 100 Example 2: Film-coated tablet Components Quantity (by weight of the total formulation Benidipine hydrochloride 2.0 Lactose monohydrate 81.5 Pregelatinized starch 7.5 Polyvinylpyrrolidone K-30 5.0 Magnesium stearate 1.0 Film-coating - Titanium dioxide(E 171%) 18.15 30 o'clock Talc (E553bl 5.45% 0 Macrogol (PEG 4000] 3.85% TOTAL Example 3: Film-coated tablet Components Quantity (by weight of total formulation Benidipine hydrochloride 4.0 Lactose monohydrate 79.5 Pregelatinized starch 7.5 Polyvinylpyrrolidone K-30 5.0 Magnesium stearate 1.0 Film coating o Lactose m0nohydrate 21.00% 0 Titanium dioxide 24.25% i PEG 3000 Powder 8.00% 0 Yellow iron oxide 0.737 30% i Triacetin 63.00% 0 Ponceau 4R 0.011% 0 FD&C Blue No 2 0002% TOTAL 100 A process for Example 1 or 2 or 3 includes; a) Mixing and then sieving Benidipine hydrochloride, lactose monohydrate and preeilatinized starch, e) Sieving the dry granule, Dissolving the polyvinylpyrrolidone in water, The mixture in step (a). Granulating with the granulation solution in step (b), Sifting the wet granule and drying the wet granule in a fluidized bed dryer, f) Adding magnesium stearate and mixing, g) Turning the prepared mixture into tablets by pressing, h) Coating these tablets with coating materials. TR TR TR
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/TR2022/051468 WO2023113744A2 (en) | 2021-12-13 | 2022-12-10 | A tablet formulation comprising micronized benidipine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TR2021019695A2 true TR2021019695A2 (en) | 2023-06-21 |
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