JP2002179559A - Thin-layer sugar-coated tablet and method for producing the same - Google Patents
Thin-layer sugar-coated tablet and method for producing the sameInfo
- Publication number
- JP2002179559A JP2002179559A JP2001300501A JP2001300501A JP2002179559A JP 2002179559 A JP2002179559 A JP 2002179559A JP 2001300501 A JP2001300501 A JP 2001300501A JP 2001300501 A JP2001300501 A JP 2001300501A JP 2002179559 A JP2002179559 A JP 2002179559A
- Authority
- JP
- Japan
- Prior art keywords
- sugar
- thin
- layer
- coated
- coated tablet
- 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- Withdrawn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
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- 239000007940 sugar coated tablet Substances 0.000 title claims abstract description 54
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 11
- 239000003826 tablet Substances 0.000 claims abstract description 100
- 238000009495 sugar coating Methods 0.000 claims abstract description 44
- 239000007788 liquid Substances 0.000 claims abstract description 23
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- 229940009714 erythritol Drugs 0.000 claims abstract description 13
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- 239000011230 binding agent Substances 0.000 claims abstract description 12
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- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- YKZPPPNXRZHVGX-PXYKVGKMSA-L dipotassium;(2s)-2-aminobutanedioate;hydron;hydrate Chemical compound [H+].[H+].O.[K+].[K+].[O-]C(=O)[C@@H](N)CC([O-])=O.[O-]C(=O)[C@@H](N)CC([O-])=O YKZPPPNXRZHVGX-PXYKVGKMSA-L 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000010642 eucalyptus oil Substances 0.000 description 1
- 229940044949 eucalyptus oil Drugs 0.000 description 1
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 description 1
- 229960001596 famotidine Drugs 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000010643 fennel seed oil Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000008369 fruit flavor Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229940014259 gelatin Drugs 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229950002441 glucurolactone Drugs 0.000 description 1
- 229950004542 glucuronamide Drugs 0.000 description 1
- 238000009499 grossing Methods 0.000 description 1
- 229960002146 guaifenesin Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001341 hydroxy propyl starch Substances 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
- 229960000991 ketoprofen Drugs 0.000 description 1
- 239000010501 lemon oil Substances 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 229960001983 magnesium aspartate Drugs 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- RXMQCXCANMAVIO-CEOVSRFSSA-L magnesium;(2s)-2-amino-4-hydroxy-4-oxobutanoate Chemical compound [H+].[H+].[Mg+2].[O-]C(=O)[C@@H](N)CC([O-])=O.[O-]C(=O)[C@@H](N)CC([O-])=O RXMQCXCANMAVIO-CEOVSRFSSA-L 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 229960005321 mecobalamin Drugs 0.000 description 1
- 229960005042 mequitazine Drugs 0.000 description 1
- JEWJRMKHSMTXPP-BYFNXCQMSA-M methylcobalamin Chemical compound C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O JEWJRMKHSMTXPP-BYFNXCQMSA-M 0.000 description 1
- 235000007672 methylcobalamin Nutrition 0.000 description 1
- 239000011585 methylcobalamin Substances 0.000 description 1
- 229940051020 methylephedrine hydrochloride Drugs 0.000 description 1
- 239000008368 mint flavor Substances 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- GFEGEDUIIYDMOX-BMJUYKDLSA-N n-[(4-amino-2-methylpyrimidin-5-yl)methyl]-n-[(z)-3-[[(z)-2-[(4-amino-2-methylpyrimidin-5-yl)methyl-formylamino]-5-hydroxypent-2-en-3-yl]disulfanyl]-5-hydroxypent-2-en-2-yl]formamide Chemical compound C=1N=C(C)N=C(N)C=1CN(C=O)C(\C)=C(CCO)/SSC(/CCO)=C(/C)N(C=O)CC1=CN=C(C)N=C1N GFEGEDUIIYDMOX-BMJUYKDLSA-N 0.000 description 1
- PLPRGLOFPNJOTN-UHFFFAOYSA-N narcotine Natural products COc1ccc2C(OC(=O)c2c1OC)C3Cc4c(CN3C)cc5OCOc5c4OC PLPRGLOFPNJOTN-UHFFFAOYSA-N 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 229960005010 orotic acid Drugs 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 229960001190 pheniramine Drugs 0.000 description 1
- 229960002305 phenylpropanolamine hydrochloride Drugs 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 229940068988 potassium aspartate Drugs 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 235000019814 powdered cellulose Nutrition 0.000 description 1
- 229920003124 powdered cellulose Polymers 0.000 description 1
- 229940088417 precipitated calcium carbonate Drugs 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- 235000007682 pyridoxal 5'-phosphate Nutrition 0.000 description 1
- 239000011589 pyridoxal 5'-phosphate Substances 0.000 description 1
- 229960001327 pyridoxal phosphate Drugs 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 239000010666 rose oil Substances 0.000 description 1
- 235000019719 rose oil Nutrition 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000021309 simple sugar Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- GQTHJBOWLPZUOI-FJXQXJEOSA-M sodium D-pantothenate Chemical compound [Na+].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O GQTHJBOWLPZUOI-FJXQXJEOSA-M 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 235000010378 sodium ascorbate Nutrition 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 229940068459 sodium pantothenate Drugs 0.000 description 1
- AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 description 1
- 229940084026 sodium valproate Drugs 0.000 description 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 239000000892 thaumatin Substances 0.000 description 1
- 235000010436 thaumatin Nutrition 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- 229960001385 thiamine disulfide Drugs 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 description 1
- 229960001661 ursodiol Drugs 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、薄層糖衣錠および
その製造方法に関する。さらに詳しくは、不快な臭いの
マスキングおよびウイスカーの防止、高水分で分解する
薬物の安定化、製剤の小型化、製造時間の短縮を可能に
するための薄層の糖衣を施した薄層糖衣錠およびその製
造方法に関する。The present invention relates to a thin-layer dragee and a method for producing the same. More specifically, a thin dragee coated with a thin dragee to enable masking of unpleasant odors and prevention of whiskers, stabilization of drugs that decompose with high moisture, downsizing of preparations, and shortening of production time, and It relates to the manufacturing method.
【０００２】[0002]
【従来の技術】従来の糖衣錠は、一般に、素錠に対し、
ショ糖液からなる糖衣液を用いて、素錠重量の７０〜１
１０％の糖衣を施すことによって製造していた。このよ
うに、被覆量が多いことと被膜が結晶性物質であるショ
糖からなるため、従来の糖衣には、不快な臭いをマス
キングできる、ウイスカーの発生を防止できるという
利点があった。しかし、同時に、製剤の大型化、製
造時間の長期化、製剤の高水分化（平衡相対湿度（Ｅ
ＲＨ）６０％程度）による、薬物の経時的な安定性の悪
化という欠点があった。2. Description of the Related Art Conventional dragees are generally
Using sugar coating liquid consisting of sucrose liquid, the weight of uncoated tablets is 70-1.
It was produced by applying a 10% sugar coating. As described above, since the coating amount is large and the coating is made of sucrose, which is a crystalline substance, the conventional sugar coating has an advantage that an unpleasant odor can be masked and generation of whiskers can be prevented. However, at the same time, the formulation becomes larger, the production time becomes longer, and the formulation becomes more water-soluble (equilibrium relative humidity (E
RH) (about 60%).
【０００３】一方、ヒドロキシプロピルメチルセルロー
ス（ＨＰＭＣ）を固形分中に５０％以上含むフィルムコ
ーティングは、コーティング液の固形分濃度が２０％以
下であり、粘性も低いので、１０００μｍ以下の液滴に
してコーティングすることができる。このため、素錠に
対して素錠重量の３〜５％という少ない量でも十分に素
錠表面を均一にコーティングすることができる。したが
って、従来の糖衣の欠点である〜をもたない。しか
し、ＨＰＭＣは非結晶性物質であり、被膜の透過性が高
いので、ＨＰＭＣフィルム錠は、従来の糖衣の利点であ
るおよびをもたない。ＨＰＭＣのフィルムコーティ
ング液に乳糖、マンニトール等の糖質を添加することも
あるが、これらを添加しても、ＨＰＭＣが主体であるた
め、従来の糖衣の利点であるおよびをもつことはな
かった。On the other hand, a film coating containing 50% or more of hydroxypropylmethylcellulose (HPMC) in a solid content has a solid content concentration of 20% or less and a low viscosity. can do. Therefore, the surface of the uncoated tablet can be sufficiently coated uniformly with a small amount of 3 to 5% of the uncoated tablet weight. Therefore, it does not have the disadvantages of the conventional sugar coating. However, HPMC film tablets have and do not have the advantages of conventional sugar coatings, because HPMC is an amorphous substance and the permeability of the coating is high. In some cases, saccharides such as lactose and mannitol are added to the HPMC film coating solution. However, even if these are added, HPMC is mainly used, and thus, there is no advantage of the conventional sugar coating.
【０００４】さらに、従来の糖衣より被覆量を減らした
薄層糖衣錠の製造方法が特開昭６２−５９１０号や特開
平１１−１１６４６７号において開示されているが、こ
れらは、糖衣層中の糖をショ糖に限定しており、シュガ
ーレス化の薄層糖衣錠を興じするものではない。また、
特開平１１−１１６４６７号では、ヒドロキシプロピル
セルロース（ＨＰＣ）またはヒドロキシプロピルメチル
セルロース（ＨＰＭＣ）を主成分とするフィルムコーテ
ィング液を糖衣層の表面にさらに被覆するという煩雑な
方法が記載されている。しかしながら、これらは、不快
な臭いのマスキング、ウイスカーの発生の防止、製剤の
低水分化を目的にしておらず、錠剤の小型化のみを目的
とした薄層糖衣錠であった。Further, Japanese Patent Application Laid-Open Nos. 62-5910 and 11-116467 disclose a method for producing a thin-layer sugar-coated tablet having a coating amount smaller than that of a conventional sugar-coating. Is limited to sucrose, and does not encourage sugar-less thin-layer dragees. Also,
JP-A-11-116467 describes a complicated method of further coating the surface of a sugar coating layer with a film coating solution containing hydroxypropylcellulose (HPC) or hydroxypropylmethylcellulose (HPMC) as a main component. However, these are thin-layer sugar-coated tablets which are not intended for masking unpleasant odor, preventing whisker generation, and reducing the water content of the preparation, but only for miniaturization of tablets.
【０００５】[0005]
【発明が解決しようとする課題】本発明の目的は、不快
な臭いのマスキングおよびウイスカーの発生の防止に有
用で、シュガーレス化が可能であり、かつ、製造時間も
短く、錠剤の小型化が可能で、錠剤の低水分化（平衡相
対湿度（ＥＲＨ）４０％以下）による高水分で分解する
薬物の安定化が可能な薄層糖衣錠の製造方法およびその
薄層糖衣錠を提供することにある。SUMMARY OF THE INVENTION An object of the present invention is to prevent unpleasant odors from being masked and to prevent whiskers from being generated. It is an object of the present invention to provide a method for producing a thin-layer dragee capable of stabilizing a drug that decomposes with high moisture by reducing the water content of the tablet (equilibrium relative humidity (ERH) is 40% or less) and to provide the thin-layer dragee.
【０００６】[0006]
【課題を解決するための手段】本発明者らは、上記の目
的を達成するために鋭意検討した結果、糖質、賦形剤お
よび結合剤を含む糖衣液を用いれば、素錠重量の５〜６
０％の糖衣を被覆することにより、不快な臭いのマスキ
ングおよびウイスカー発生の防止ができること、また、
糖質として糖アルコールを使用することが可能であり、
これにより、シュガーレス化ができることを見出した。
また、発明者らは、不快な臭いを有する薬物としてＬ−
システインを素錠に配合する場合、水または有機溶媒で
造粒せず、そのまま混合工程で配合し、素錠を製するこ
とにより、驚くべきことに、不快な臭いを低減すること
を見出した。さらに、粒子径１００μｍ以下のものの割
合が５０％以下のものを用いると、より不快な臭いが低
減されることも見出した。このような、Ｌ−システイン
を配合する素錠を本発明の方法によって薄層糖衣で被覆
することによって、不快な臭いが全くしない糖衣錠を製
造することができることも見出した。さらに、本発明の
薄層糖衣錠は、従来の糖衣に比べて、錠剤の小型化が可
能であり、製造時間も短く、さらに、錠剤を低水分化
（平衡相対湿度（ＥＲＨ）４０％以下）できるため、高
水分で分解する薬物の安定性も従来の糖衣より良好とな
ることも見出した。本発明は、これらの知見に基づいて
完成したものである。Means for Solving the Problems The inventors of the present invention have conducted intensive studies to achieve the above object, and as a result, the use of a sugar coating solution containing a carbohydrate, an excipient and a binder has resulted in a weight loss of 5% for an uncoated tablet. ~ 6
By coating the sugar coating of 0%, masking of unpleasant odor and prevention of whisker generation can be achieved.
It is possible to use sugar alcohols as sugars,
As a result, it has been found that it is possible to make a sugar-less product.
In addition, the present inventors have reported that L-
When cysteine is blended in plain tablets, it was surprisingly found that unpleasant odor was reduced by blending in a mixing step without granulation with water or an organic solvent and producing plain tablets. Furthermore, it was also found that when the ratio of particles having a particle size of 100 μm or less was 50% or less, more unpleasant odor was reduced. It has also been found that by coating such uncoated tablets containing L-cysteine with a thin-layer sugar coating by the method of the present invention, a sugar-coated tablet free of any unpleasant odor can be produced. Furthermore, the thin-layer sugar-coated tablet of the present invention can reduce the size of tablets, shorten the production time, and reduce the water content of the tablets (equilibrium relative humidity (ERH) 40% or less) as compared with conventional sugar-coated tablets. Therefore, it has also been found that the stability of a drug that decomposes at high moisture becomes better than that of a conventional sugar coating. The present invention has been completed based on these findings.
【０００７】すなわち、本発明は、（１） 素錠重量の
５〜６０％の、糖質、賦形剤および結合剤を含む糖衣層
を有する薄層糖衣錠、（２） 糖質が、糖および糖アル
コールからなる群から選択される１種以上の糖質である
上記（１）記載の薄層糖衣錠、（３） 糖がショ糖およ
びトレハロース、糖アルコールが、エリスリトール、マ
ンニトール、ソルビトール、キシリトール、トレハロー
ス、マルチトール、粉末還元麦芽糖水飴および還元乳糖
からなる群から選択される１種以上のものである上記
（２）記載の薄層糖衣錠、（４） 糖アルコールがエリ
スリトールである上記（２）記載の薄層糖衣錠、（５）
不快な臭いを有する薬物を配合した素錠を用いた上記
（１）〜（４）いずれか１項記載の薄層糖衣錠、（６）
不快な臭いを有する薬物が、Ｌ−システインおよびビ
タミンＢ1類からなる群から選択される１種以上のもの
である上記（５）記載の薄層糖衣錠、（７） Ｌ−シス
テインを水または有機溶媒で造粒せず、そのまま混合工
程で配合し、製した素錠を用いた上記（５）記載の薄層
糖衣錠。（８） 薬物が、粒子径１００μｍ以下の粒子
の含有割合が５０％以下のＬ−システインである上記
（６）記載の薄層糖衣錠、（９） 薬物が、塩酸チアミ
ン、硝酸チアミンおよび塩酸フルスルチアミン等からな
る群から選択されるビタミンＢ1類である上記（６）記
載の薄層糖衣錠、（１０） 高水分で分解する薬物を配
合した素錠を用いた上記（１）〜（４）いずれか１項記
載の薄層糖衣錠、（１１） 高水分で分解する薬物がＬ
−システイン、ビタミンＢ類、ビタミンＣ類、ビタミン
Ｅ類、パントテン酸カルシウムおよびビオチンからなる
群から選択される１種以上のものである上記（１０）記
載の薄層糖衣錠、（１２） ウイスカーを発生する薬物
を配合した素錠を用いた上記（１）〜（４）いずれか１
項記載の薄層糖衣錠、（１３） ウイスカーを発生する
薬物がイブプロフェン、カフェイン、無水カフェイン、
エテンザミドおよびイソプロピルアンチピリンからなる
群から選択される１種以上のものである上記（１２）記
載の薄層糖衣錠、（１４） シュガーレス化した糖衣錠
である上記（１）〜（１３）いずれか１項記載の薄層糖
衣錠、（１５） 下掛けを有する糖衣錠である上記
（１）〜（１４）いずれか１項記載の薄層糖衣錠、（１
６） さらに、糖衣層に薬物を含む上記（１）〜（１
５）いずれか１項記載の薄層糖衣錠、（１７） 平衡相
対湿度４０％以下である上記（１）〜（１６）いずれか
１項記載の薄層糖衣錠、（１８） 素錠に対し、糖質、
賦形剤および結合剤を含む糖衣液を手がけし、および／
または０．１〜１０００μｍの液滴として噴霧して、素
錠重量の５〜６０％の糖衣を施すことを特徴とする薄層
糖衣錠の製造方法、および（１９） 液滴を噴霧する上
記（１８）記載の薄層糖衣錠の製造方法を提供するもの
である。That is, the present invention relates to (1) a thin-layer dragee having a dragee layer containing a carbohydrate, an excipient and a binder in an amount of 5 to 60% of the weight of the uncoated tablet; (1) the sugar-coated tablet according to the above (1), wherein the sugar is at least one saccharide selected from the group consisting of sugar alcohols; (3) the sugar is sucrose and trehalose; and the sugar alcohol is erythritol, mannitol, sorbitol, xylitol, trehalose. Thin-layer sugar-coated tablet according to the above (2), which is at least one selected from the group consisting of maltitol, powdered reduced maltose starch syrup and reduced lactose; (4) the above-mentioned (2), wherein the sugar alcohol is erythritol Thin dragee, (5)
The thin-layer sugar-coated tablet according to any one of the above (1) to (4), which uses an uncoated tablet containing a drug having an unpleasant odor, (6)
Drug having an unpleasant odor, is one or more selected from the group consisting of L- cysteine and vitamin B 1 class above (5), wherein the thin layer dragees, (7) L- cysteine water or an organic The thin-layer sugar-coated tablet according to the above (5), wherein the uncoated tablet is produced by directly mixing in a mixing step without granulation with a solvent. (8) The thin-layer dragee according to the above (6), wherein the drug is L-cysteine having a content ratio of particles having a particle size of 100 μm or less of 50% or less, (9) the drug is thiamine hydrochloride, thiamine nitrate and fursulfur hydrochloride. a vitamin B 1 class selected from the group consisting of thiamine or the like above (6), wherein the thin layer dragees, above using uncoated tablets containing a combination of drugs degrade at (10) high moisture (1) to (4) The thin-layer sugar-coated tablet according to any one of (11), wherein the drug that decomposes at high moisture is L
-The thin-layer dragee according to the above (10), which is one or more selected from the group consisting of cysteine, vitamins B, vitamins C, vitamins E, calcium pantothenate and biotin; Any one of the above (1) to (4) using an uncoated tablet containing
(13) The drug that generates whiskers is ibuprofen, caffeine, anhydrous caffeine,
The thin-layer sugar-coated tablet according to the above (12), which is at least one selected from the group consisting of etensamide and isopropylantipyrine, and (14) the sugar-coated sugar-coated tablet according to any one of the above (1) to (13). (15) The thin-layer dragee according to any one of the above (1) to (14), which is a dragee having an undergarment.
6) Furthermore, the above-mentioned (1) to (1) wherein the sugar coating layer contains a drug.
5) The thin-coated sugar-coated tablet according to any one of (1) to (16), wherein the equilibrium relative humidity is 40% or less; quality,
Handle sugar coatings containing excipients and binders, and / or
Alternatively, a method for producing a thin-layer sugar-coated tablet characterized by spraying as a droplet of 0.1 to 1000 μm and applying sugar coating of 5 to 60% of the weight of the uncoated tablet, and (19) spraying the droplet (18) )).
【０００８】[0008]
【発明の実施の形態】本発明における薄層糖衣錠の糖衣
層形成のための糖衣液に用いられる糖質としては、ショ
糖（精製白糖、白糖）、果糖、ブドウ糖、乳糖、トレハ
ロースのような単糖類、二糖類、エリスリトール、マン
ニトール、ソルビトール、キシリトール、マルチトー
ル、粉末還元麦芽糖水飴、還元乳糖のような糖アルコー
ル等が挙げられる。シュガーレス化には糖アルコールが
好ましく、特に、後に記載する、素錠への糖衣液の噴霧
により糖衣錠を製造する場合は、エリスリトールが好ま
しい。糖衣液中の糖質の量は、糖衣液中の固形分として
１０〜９９％（重量％、以下同じ）、好ましくは、２０
〜９５％である。BEST MODE FOR CARRYING OUT THE INVENTION Carbohydrates used in a sugar coating solution for forming a sugar-coating layer of a thin-layer sugar-coated tablet of the present invention include simple sugars such as sucrose (purified sucrose, sucrose), fructose, glucose, lactose and trehalose. Examples include saccharides, disaccharides, erythritol, mannitol, sorbitol, xylitol, maltitol, powdered reduced maltose syrup, and sugar alcohols such as reduced lactose. Sugarless is preferably used for sugar-less treatment. Particularly, when a sugar-coated tablet is produced by spraying a sugar-coated solution onto an uncoated tablet as described later, erythritol is preferred. The amount of carbohydrate in the sugar coating liquid is 10 to 99% (% by weight, hereinafter the same) as solid content in the sugar coating liquid, preferably 20%.
~ 95%.
【０００９】糖衣液に用いられる賦形剤としては、タル
ク、沈降炭酸カルシウム、リン酸一水素カルシウム、リ
ン酸水素カルシウム、リン酸水素ナトリウム、リン酸二
カリウム、リン酸二水素カリウム、リン酸二水素カルシ
ウム、リン酸二水素ナトリウム、硫酸カルシウム、乳酸
カルシウム、酸化チタン、カオリン、含水二酸化ケイ
素、合成ケイ酸アルミニウム、合成ヒドロサイト、乾燥
水酸化アルミニウム、炭酸マグネシウム、酸化マグネシ
ウム、軽質無水ケイ酸、ステアリン酸マグネシウム、ス
テアリン酸カルシウム、ショ糖脂肪酸エステル、クロス
ポビドン、カルメロース、クロスカルメロースナトリウ
ム、カルメロースカルシウム、カルメロースナトリウ
ム、カルボキシメチルエチルセルロース、カルボキシス
ターチナトリウム等が挙げられる。糖衣液中の賦形剤の
量は、糖衣液中の固形分として０．０１〜６０％、好ま
しくは０．１〜５０％である。[0009] Excipients used in sugar coating liquids include talc, precipitated calcium carbonate, calcium monohydrogen phosphate, calcium hydrogen phosphate, sodium hydrogen phosphate, dipotassium phosphate, potassium dihydrogen phosphate, dihydrogen phosphate. Calcium hydrogen, sodium dihydrogen phosphate, calcium sulfate, calcium lactate, titanium oxide, kaolin, hydrous silicon dioxide, synthetic aluminum silicate, synthetic hydrosite, dried aluminum hydroxide, magnesium carbonate, magnesium oxide, light anhydrous silicic acid, stearin Magnesium salt, calcium stearate, sucrose fatty acid ester, crospovidone, carmellose, croscarmellose sodium, carmellose calcium, carmellose sodium, carboxymethylethylcellulose, carboxystarch sodium, etc. It is below. The amount of the excipient in the sugar coating liquid is 0.01 to 60%, preferably 0.1 to 50%, as a solid content in the sugar coating liquid.
【００１０】糖衣液に用いられる結合剤としては、アラ
ビアゴム末、プルラン、ヒドロキシプロピルセルロース
（ＨＰＣ）、ヒドロキシプロピルメチルセルロース２２
０８（ＨＰＭＣ２２０８）、ヒドロキシプロピルメチル
セルロース２９０６（ＨＰＭＣ２９０６）、ヒドロキシ
プロピルメチルセルロース２９１０（ＨＰＭＣ２９１
０）、メチルセルロース（ＭＣ）、ヒドロキシエチルセ
ルロース（ＨＥＣ）、結晶セルロース、粉末セルロー
ス、低置換度ヒドロキシプロピルセルロース、デキスト
リン、トウモロコシデンプン、アルファー化デンプン、
部分アルファー化デンプン、ヒドロキシプロピルスター
チ、ポリビニルピロリドン（ＰＶＰ）、カルボキシビニ
ルポリマー、ポリビニルアルコール（ＰＶＡ）、結晶セ
ルロース・カルメロースナトリウム、ゼラチン、キサン
タンガム、トラガント、トラガント末、マクロゴール２
００、マクロゴール３００、マクロゴール４００、マク
ロゴール６００、マクロゴール１０００、マクロゴール
１５００、マクロゴール１５４０、マクロゴール４００
０、マクロゴール６０００、マクロゴール２００００、
ポリオキシエチレン［１０５］ポリオキシプロピレン
［５］グリコール等が挙げられる。The binder used in the sugar coating liquid includes gum arabic powder, pullulan, hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose 22
08 (HPMC2208), hydroxypropylmethylcellulose 2906 (HPMC2906), hydroxypropylmethylcellulose 2910 (HPMC291
0), methylcellulose (MC), hydroxyethylcellulose (HEC), crystalline cellulose, powdered cellulose, low-substituted hydroxypropylcellulose, dextrin, corn starch, pregelatinized starch,
Partially pregelatinized starch, hydroxypropyl starch, polyvinylpyrrolidone (PVP), carboxyvinyl polymer, polyvinyl alcohol (PVA), crystalline cellulose carmellose sodium, gelatin, xanthan gum, tragacanth, tragacanth powder, macrogol 2
00, macro goal 300, macro goal 400, macro goal 600, macro goal 1000, macro goal 1500, macro goal 1540, macro goal 400
0, Macrogol 6000, Macrogol 20,000,
And polyoxyethylene [105] polyoxypropylene [5] glycol.
【００１１】結晶セルロースを結合剤として用いる場合
は、平均粒子径６０μｍ以下のグレードのものを用いる
のが好ましい。具体的には、アビセルＰＨ−Ｆ２０、ア
ビセルＰＨ−Ｍ２５、アビセルＰＨ−Ｍ１５、アビセル
ＰＨ−Ｍ８、アビセルＰＨ−１０１、セオラスＫＧ−８
０１、セオラスＫＧ−８０２（旭化成）が好ましい。本
発明で用いられる糖衣液中の結合剤の量は、糖衣液中の
固形分として０．１〜６０％、好ましくは１〜５０％で
ある。When crystalline cellulose is used as the binder, it is preferable to use a grade having an average particle diameter of 60 μm or less. Specifically, Avicel PH-F20, Avicel PH-M25, Avicel PH-M15, Avicel PH-M8, Avicel PH-101, Theolus KG-8
01, CEOLUS KG-802 (Asahi Kasei) is preferred. The amount of the binder in the sugar coating liquid used in the present invention is 0.1 to 60%, preferably 1 to 50%, as a solid content in the sugar coating liquid.
【００１２】素錠に配合する薬物としては、特に、不快
な臭いを有する薬物、高水分で分解する薬物、ウイスカ
ーを発生する薬物を用いることができる。本発明で素錠
に用いられる不快な臭いを有する薬物としては、Ｌ−シ
ステインや、塩酸チアミン、硝酸チアミンおよび塩酸フ
ルスルチアミン等からなる群から選択されるビタミンＢ
1類等が挙げられる。Ｌ−システインの場合、水または
有機溶媒で造粒せず、そのまま混合工程で配合し、素錠
を製すると、不快な臭いが低減されたＬ−システイン配
合素錠を製造できる。また、粒子径が１００μｍ以下の
ものの含有割合が５０％以下、好ましくは３０％以下の
ものを配合しても、不快な臭いが低減されたＬ−システ
イン配合素錠を製造でき、両者を併用した場合は、さら
に不快な臭いが低減されたＬ−システイン配合素錠を製
造できる。Ｌ−システインは圧縮成形性が悪いが、セル
ロース誘導体（例えば、結晶セルロース、低置換度ヒド
ロキシプロピルセルロース等）の配合により改善され
る。また、打錠時の杵面への粉末の付着（スティッキン
グ）は、ステアリン酸マグネシウムを素錠重量に対して
０．３〜３％、好ましくは０．５〜２．５％配合するこ
とにより改善される。[0012] As the drug to be mixed with the uncoated tablet, a drug having an unpleasant odor, a drug which decomposes at high moisture, and a drug which generates whiskers can be used. Drugs having an unpleasant odor used in the plain tablets of the present invention include L-cysteine, vitamin B selected from the group consisting of thiamine hydrochloride, thiamine nitrate, fursultiamine hydrochloride and the like.
Class 1 and the like. In the case of L-cysteine, if it is not granulated with water or an organic solvent, but is blended in the mixing step as it is to produce a plain tablet, an uncomfortable L-cysteine blended tablet with reduced unpleasant odor can be produced. In addition, even when the content of particles having a particle diameter of 100 μm or less is 50% or less, preferably 30% or less, an unpleasant odor-reduced L-cysteine-containing uncoated tablet can be produced, and both are used in combination. In this case, an L-cysteine-containing uncoated tablet with further reduced unpleasant odor can be produced. Although L-cysteine has poor compression moldability, it can be improved by blending a cellulose derivative (eg, crystalline cellulose, low-substituted hydroxypropylcellulose, etc.). In addition, the sticking of powder to the punch surface during tableting is improved by adding 0.3 to 3%, preferably 0.5 to 2.5% of magnesium stearate to the weight of the uncoated tablet. Is done.
【００１３】本発明で素錠に用いられる高水分で分解す
る薬物としては、上記の不快な臭い有する薬物の他、ビ
タミンＢ類（例、塩酸チアミン、硝酸チアミン、硝酸ビ
スチアミン、チアミンジスルフィド、塩酸ジセチアミ
ン、オクトチアミン、ビスイブチアミン、ビスベンチア
ミン、フルスルチアミン、ベンフォチアミン、リボフラ
ビン、リン酸リボフラビンナトリウム、酪酸リボフラビ
ン、塩酸ピリドキシン、リン酸ピリドキサール、シアノ
コバラミン、酢酸ヒドロキソコバラミン、メコバラミン
等）、ビタミンＣ類（例、アスコルビン酸、アスコルビ
ン酸カルシウム、アスコルビン酸ナトリウム等）、ビタ
ミンＥ類（例、酢酸ｄｌ−α−トコフェロール、酢酸ｄ
−α−トコフェロール、コハク酸ｄ−α−トコフェロー
ル、コハク酸ｄｌ−α−トコフェロール、コハク酸ｄ−
α−トコフェロールカルシウム等）が挙げられる。さら
に、パントテン酸カルシウム、パントテン酸カルシウム
タイプＳ、ビオチン、ニコチン酸アミド、ニコチン酸、
パントテン酸ナトリウム、葉酸、Ｌ−システイン、Ｌ−
塩酸システイン、オロチン酸、ガンマ−オリザノール、
ウルソデオキシコール酸、グルクロノラクトン、グルク
ロン酸アミド、アスパラギン酸カリウム、アスパラギン
酸マグネシウム、アスピリン、アセトアミノフェン、エ
テンザミド、イブプロフェン、ケトプロフェン、インド
メタシン、シメチジン、ファモチジン、イソプロピルア
ンチピリン、塩酸ジフェンヒドラミン、ｄ−マレイン酸
クロルフェニラミン、ｄｌ−マレイン酸クロルフェニラ
ミン、メキタジン、フマル酸クレマスチン、塩酸クロペ
ラスチン、塩酸フェニルプロパノールアミン、臭化水素
酸デキストロメトルファン、リン酸コデイン、リン酸ジ
ヒドロコデイン、塩酸ノスカピン、ノスカピン、ｄｌ−
塩酸メチルエフェドリン、グアイフェネシン、塩化リゾ
チーム等が挙げられる。[0013] The drug which decomposes at high moisture used in the uncoated tablet of the present invention includes, in addition to the drug having an unpleasant odor, vitamins B (eg, thiamine hydrochloride, thiamine nitrate, bisthiamine nitrate, thiamine disulfide, disetiamine hydrochloride) Octoctiamine, bisbutiamine, bisbenthamine, fursultiamine, benfotiamine, riboflavin, sodium riboflavin phosphate, riboflavin butyrate, pyridoxine hydrochloride, pyridoxal phosphate, cyanocobalamin, hydroxocobalamin acetate, mecobalamin, etc.), vitamin Cs (Eg, ascorbic acid, calcium ascorbate, sodium ascorbate, etc.), vitamin Es (eg, dl-α-tocopherol acetate, d acetate)
-Α-tocopherol, d-α-tocopherol succinate, dl-α-tocopherol succinate, d-succinate
α-tocopherol calcium, etc.). Further, calcium pantothenate, calcium pantothenate type S, biotin, nicotinamide, nicotinic acid,
Sodium pantothenate, folic acid, L-cysteine, L-
Cysteine hydrochloride, orotic acid, gamma-oryzanol,
Ursodeoxycholic acid, glucuronolactone, glucuronamide, potassium aspartate, magnesium aspartate, aspirin, acetaminophen, etenzazamide, ibuprofen, ketoprofen, indomethacin, cimetidine, famotidine, isopropylantipyrine, diphenhydramine hydrochloride, d-chlore maleate Pheniramine, dl-chlorpheniramine maleate, mequitazine, clemastine fumarate, cloperastine hydrochloride, phenylpropanolamine hydrochloride, dextromethorphan hydrobromide, codeine phosphate, dihydrocodeine phosphate, noscapine hydrochloride, noscapine, dl-
Examples include methylephedrine hydrochloride, guaifenesin, lysozyme chloride and the like.
【００１４】本発明で素錠に用いられるウイスカーを発
生する薬物としては、イブプロフェン、カフェイン、無
水カフェイン、エテンザミド、イソプロピルアンチピリ
ン、サリチル酸、カルバマゼピン、バルプロ酸ナトリウ
ム、１−メントール、ｄｌ−メントール等が挙げられ
る。上記した薬物は、素錠中に単独で、あるいは２種以
上を併用して配合される。Examples of the whisker-generating drug used in the uncoated tablet of the present invention include ibuprofen, caffeine, anhydrous caffeine, etensamide, isopropylantipyrine, salicylic acid, carbamazepine, sodium valproate, 1-menthol, and dl-menthol. No. The above-mentioned drugs are used alone or in combination of two or more in uncoated tablets.
【００１５】また、本発明により製造される薄層糖衣錠
には、服用性の向上を目的として、糖衣層に香りおよび
味を付与することもでき、例えば、着香剤または香料、
矯味剤を適量、糖衣液に混合することにより付与でき
る。本発明で使用することのできる着香剤または香料と
しては、例えば、ハッカ油、ユーカリ油、ケイヒ油、ウ
イキョウ油、チョウジ油、オレンジ油、レモン油、ロー
ズ油、フルーツフレーバー、ミントフレーバー、ペパー
ミントパウダー、ｄｌ−メントール、ｌ−メントール等
が挙げられる。矯味剤としては、糖、糖アルコール、高
甘味度甘味剤、酸味剤を配合することができる。矯味剤
として本発明で用いられる糖および糖アルコールは、シ
ョ糖、トレハロース、乳糖、マンニトール、ソルビトー
ル、キシリトール、マルチトール、エリスリトール、粉
末還元麦芽糖水飴等が挙げられる。矯味剤として本発明
で用いられる高甘味度甘味剤は、人工的に合成された甘
味剤のうち、その甘味度が砂糖の数倍以上のもの、好ま
しくは約１００倍以上のものをいい、具体的には、例え
ば、アスパルテーム、ステビア、サッカリン、グリチル
リチン二カリウム、ソーマチン、スクラロース、アセス
ルファームＫ等が挙げられる。矯味剤として本発明で用
いられる酸味剤は、クエン酸、リンゴ酸、酒石酸、アス
コルビン酸等が挙げられる。[0015] The thin-layer dragée manufactured by the present invention can also impart a fragrance and taste to the dragee layer for the purpose of improving ingestibility.
It can be provided by mixing an appropriate amount of a flavoring agent with a sugar coating liquid. Flavoring agents or flavors that can be used in the present invention include, for example, mint oil, eucalyptus oil, cauliflower oil, fennel oil, clove oil, orange oil, lemon oil, rose oil, fruit flavor, mint flavor, peppermint powder Dl-menthol, 1-menthol and the like. Sugars, sugar alcohols, high-intensity sweeteners and sour agents can be blended as flavoring agents. The sugar and sugar alcohol used in the present invention as a flavoring agent include sucrose, trehalose, lactose, mannitol, sorbitol, xylitol, maltitol, erythritol, powdered reduced maltose syrup and the like. The high-intensity sweetener used in the present invention as a flavoring agent refers to an artificially synthesized sweetener whose sweetness is several times or more as high as that of sugar, preferably about 100 times or more. Specifically, for example, aspartame, stevia, saccharin, dipotassium glycyrrhizinate, thaumatin, sucralose, acesulfame K and the like can be mentioned. The sour agent used in the present invention as a flavoring agent includes citric acid, malic acid, tartaric acid, ascorbic acid and the like.
【００１６】本発明において糖衣を施す素錠は、常法に
より調製すればよい。例えば、薬物を適当な賦形剤、結
合剤等とともに、混合、造粒後、打錠して調製する。ま
た、常法に従い、素錠に防水膜を施してもよい。In the present invention, uncoated tablets to be sugar-coated may be prepared by a conventional method. For example, a drug is prepared by mixing, granulating, and tableting with a suitable excipient, binder and the like. In addition, a waterproof film may be applied to the uncoated tablet according to an ordinary method.
【００１７】上記のような糖質、賦形剤および結合剤を
上記の割合で精製水中に溶解または懸濁することによ
り、糖衣液を調製する。本発明においては、所望によ
り、素錠に加え、糖衣層中に薬物を含有させてもよく、
特に限定するものではないが、素錠中に配合すると、他
の薬物と相互反応してしまうような薬物は糖衣層中に含
有させることができる。糖衣層とは、下掛け（subcoati
ng）層、中掛け（smoothing)層、上掛け（coloring)
層、艶出し（polishing)層のうちから選択される１つ以
上のそうをいう。上掛け層は着色剤を含むシロップ液を
コーティングすることが多いが、着色剤を含まないシロ
ップ層をコーティングすることもある。シロップ液は糖
衣液と同じような糖質、賦形剤および結合剤を含んでも
よく、また、糖衣液と異なる糖質だけのもの、糖質と結
合剤から成る場合、糖質と賦形剤からなる場合等があ
る。艶出し液としては、カルナウバロウ、白ロウなどの
ワックス類、エタノール、メタノール、ｎ−ヘキサン等
の有機溶媒に溶解または懸濁させた溶液を用いることも
できる。A sugar coating solution is prepared by dissolving or suspending the above-mentioned saccharide, excipient and binder in the above-mentioned ratio in purified water. In the present invention, if desired, in addition to the uncoated tablet, a drug may be contained in the sugar coating layer,
Although not particularly limited, a drug that, when incorporated into an uncoated tablet, interacts with another drug can be contained in the sugar-coated layer. The sugar coating layer is the undercoat (subcoati
ng) layer, middle layer (smoothing) layer, top layer (coloring)
One or more layers selected from a layer, a polishing layer. The top layer is often coated with a syrup containing a colorant, but may also be coated with a syrup layer without a colorant. The syrup solution may contain the same sugars, excipients and binders as the sugar coating solution. Etc. As the polishing liquid, a solution dissolved or suspended in waxes such as carnauba wax and white wax, and organic solvents such as ethanol, methanol and n-hexane can also be used.
【００１８】本発明の薄層糖衣錠を製造するには、常法
に従い、例えば、上記のような糖衣液を手かけにより、
および／または０．１〜１０００μｍの液滴として素錠
に噴霧し、素錠重量の５〜６０％の糖衣を施す。好まし
くは噴霧することにより、短時間で小型の薄層糖衣錠剤
を得ることができる。このとき、必要に応じて、糖衣液
とともに、散布剤も用いることができる。散布剤として
は、タルク、沈降性カルシウム、カオリン、デンプン、
アラビアゴム末、結晶セルロース、ショ糖、トレハロー
ス、エリスリトール、マルチトール、粉末還元麦芽糖水
飴、乳糖、マンイトール等から１種または２種以上を選
択することができる。得られた薄層糖衣錠は、不快な臭
いをマスキングし、ウイスカーの発生を防止する効果を
有し、糖アルコールの使用により、シュガーレス化する
ことができる。また、低水分（平衡相対湿度（ＥＲＨ）
４０％以下）の錠剤が得られるため、高水分で分解する
薬物を安定化することができる。In order to produce the thin-layer sugar-coated tablet of the present invention, for example, the above sugar-coated solution is applied by hand according to a conventional method.
And / or sprayed onto uncoated tablets as droplets of 0.1 to 1000 μm, and sugar-coated at 5 to 60% of the weight of the uncoated tablet. Preferably, by spraying, it is possible to obtain a small thin sugar-coated tablet in a short time. At this time, if necessary, a spraying agent can be used together with the sugar coating liquid. Sprays include talc, precipitated calcium, kaolin, starch,
One or more types can be selected from gum arabic powder, crystalline cellulose, sucrose, trehalose, erythritol, maltitol, powdered reduced maltose syrup, lactose, mannitol and the like. The obtained thin-layer sugar-coated tablet has an effect of masking an unpleasant odor and preventing the generation of whiskers, and can be made sugarless by using a sugar alcohol. In addition, low moisture (equilibrium relative humidity (ERH)
(40% or less), so that a drug that decomposes at high moisture can be stabilized.
【００１９】[0019]
【実施例】以下に実施例を挙げて本発明をさらに詳しく
説明するが、本発明はこれらに限定されるものではな
い。 実施例１ アスコルビン酸１０００ｇ、リボフラビン１２ｇ、コハ
ク酸ｄ−α−トコフェロール（レギュラー粒度品）５０
ｇ、パントテン酸カルシウム タイプＳ ４６．２ｇ、
結晶セルロース（セオラスＫＧ８０１、旭化成）９５．
８ｇ、乳糖９５．８ｇを流動層造粒機（ＦＤ−３ＳＮ、
パウレック）にて、６％ヒドロキシプロピルセルロース
（ＨＰＣ−Ｌ）水溶液９０３．３ｇを噴霧することによ
り、流動層造粒する。その後、整粒機（パワーミル、昭
和化学機械）にて整粒し、整粒末を得た。得られた整粒
末１０８３．２ｇに、Ｌ−システイン（粒子径１００μ
ｍ以下、１５％）１２８ｇ、結晶セルロース（セオラス
ＫＧ８０1、旭化成）１２８ｇ、低置換度ヒドロキシプ
ロピルセルロース（Ｌ−ＨＰＣ（ＬＨ３１）、信越化
学）７２ｇ、特殊ケイ酸カルシウム（フローライトＲ
Ｅ、徳山曹達）７．２ｇ、ステアリン酸マグネシウム２
１．６ｇを混合機（タンブラー混合機、昭和化学機械）
にて混合し、得られた混合末をロータリー式打錠機で、
直径９ｍｍの臼、曲率半径７．５ｍｍのＲ面杵にて、１
錠当たりの重量３００ｍｇ、厚さ４．９ｍｍとなるよう
に製錠し、素錠を得た。素錠６錠当たりの処方を表１に
示す。EXAMPLES The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the present invention is limited thereto. Example 1 1000 g of ascorbic acid, 12 g of riboflavin, d-α-tocopherol succinate (regular particle size product) 50
g, calcium pantothenate type S 46.2 g,
Microcrystalline cellulose (Ceolas KG801, Asahi Kasei) 95.
8 g of lactose and 95.8 g of lactose in a fluidized bed granulator (FD-3SN,
Fluid bed granulation by spraying 903.3 g of a 6% aqueous solution of hydroxypropylcellulose (HPC-L) at Powrex). Thereafter, the resulting mixture was sized using a sizing machine (Power Mill, Showa Chemical Machinery Co., Ltd.) to obtain a sieved powder. To 1083.2 g of the obtained sized powder, L-cysteine (particle size 100 μm) was added.
m, 15%) 128 g, crystalline cellulose (Seolas KG801, Asahi Kasei) 128 g, low-substituted hydroxypropylcellulose (L-HPC (LH31), Shin-Etsu Chemical) 72 g, special calcium silicate (Fluorite R)
E, Soda Tokuyama) 7.2 g, magnesium stearate 2
1.6 g of a mixer (tumbler mixer, Showa Chemical Machinery)
At a rotary tableting machine.
With a 9 mm diameter mortar and an R surface punch with a curvature radius of 7.5 mm, 1
Tablets were manufactured to have a weight per tablet of 300 mg and a thickness of 4.9 mm to obtain uncoated tablets. Table 1 shows the prescription per 6 uncoated tablets.
【００２０】[0020]
【表１】 [Table 1]
【００２１】上記の素錠３００ｇに、精製白糖５４ｇ、
タルク２４ｇ、結晶セルロース（アビセルＰＨ−Ｆ２
０）１０ｇ、アラビアゴム末１２ｇを精製水８３.５ｇ
に溶解、懸濁した糖衣液を用い、ハイコーター（ＨＣＴ
−ＭＩＮＩ、フロイント産業）にて、素錠に対して素錠
重量の１５％量コーティングし、更にその上に、精製白
糖５０ｇ、タルク１８ｇ、酸化チタン１０ｇ、結晶セル
ロース（アビセルＰＨ−Ｆ２０）１０ｇ、アラビアゴム
末１２ｇを精製水８３．５ｇに溶解、懸濁した糖衣液を
用い、素錠に対して素錠重量の２０％量コーティングし
た。続いて、精製白糖９４ｇ、アラビアゴム末６ｇを精
製水８３．５ｇに溶解させたシロップ液を素錠に対して
５％量コーティングし、薄層の糖衣錠を得た。なお、薄
層の糖衣錠に、艶だし液（カルナウバロウ、白ロウを溶
解させたエタノール−ｎ−ヘキサン溶液）を微量、コー
ティングし、艶だしを行った。To 300 g of the uncoated tablet, 54 g of purified sucrose,
24 g of talc, crystalline cellulose (Avicel PH-F2
0) 10g and 12g of gum arabic powder were converted to 83.5g of purified water.
Using a sugar coating solution dissolved and suspended in a high coater (HCT
-MINI, Freund Corporation), coated on the uncoated tablet in an amount of 15% of the weight of the uncoated tablet, and further, 50 g of purified sucrose, 18 g of talc, 10 g of titanium oxide, 10 g of crystalline cellulose (Avicel PH-F20), Using a sugar coating solution obtained by dissolving and suspending 12 g of gum arabic powder in 83.5 g of purified water, the uncoated tablet was coated with 20% of the weight of the uncoated tablet. Subsequently, a syrup solution prepared by dissolving 94 g of purified sucrose and 6 g of gum arabic powder in 83.5 g of purified water was coated on the plain tablet in an amount of 5% to obtain a thin-layer sugar-coated tablet. In addition, a thin layer of sugar-coated tablets was coated with a slight amount of a polish liquid (an ethanol-n-hexane solution in which carnauba wax and white wax were dissolved), and polish was performed.
【００２２】実施例２ 実施例１の素錠３００ｇに、エリスリトール５０ｇ、タ
ルク２８ｇ、結晶セルロース（アビセルＰＨ−Ｆ２０）
１０ｇ、アラビアゴム末１２ｇを精製水１２０ｇに溶
解、懸濁した糖衣液を用い、ハイコーター（ＨＣＴ−Ｍ
ＩＮＩ、フロイント産業）にて、素錠に対して素錠重量
の３５％量コーティングし、更にその上に、エリスリト
ール８９ｇ、アラビアゴム末１０ｇ、マクロゴール６０
００ １ｇを精製水１６０ｇに溶解させた糖衣液を素錠
に対して５％量コーティングし、薄層の糖衣錠を得た。
なお、薄層の糖衣錠に、艶だし液（カルナウバロウ、白
ロウを溶解させたエタノール−ｎ−ヘキサン溶液）を微
量、コーティングし、艶だしを行った。Example 2 To 300 g of the uncoated tablet of Example 1, 50 g of erythritol, 28 g of talc, microcrystalline cellulose (Avicel PH-F20)
Using a sugar coating solution in which 10 g and 12 g of gum arabic powder were dissolved and suspended in 120 g of purified water, a high coater (HCT-M
INI, Freund Corporation) to coat 35% of the weight of the uncoated tablet on the uncoated tablet, and further, 89 g of erythritol, 10 g of acacia powder, Macrogol 60
A sugar coating solution prepared by dissolving 1 g of 001 in 160 g of purified water was coated on the plain tablet in an amount of 5% to obtain a thin-layer sugar-coated tablet.
In addition, a thin layer of sugar-coated tablets was coated with a slight amount of a polish liquid (an ethanol-n-hexane solution in which carnauba wax and white wax were dissolved), and polish was performed.
【００２３】実施例３ アスコルビン酸２７００ｇ、リボフラビン５４ｇ、コハ
ク酸ｄ−α−トコフェロール（レギュラー粒度品）２２
５ｇ、粉末還元麦芽糖水飴３５１ｇ、結晶セルロース
（セオラスＫＧ−８０１、旭化成）２４０．８ｇを流動
層造粒機（ＦＤ−５Ｓ、パウレック）にて、６％ヒドロ
キシプロピルセルロース（ＨＰＣ−Ｌ）水溶液２７００
ｇを噴霧することにより、流動層造粒する。その後、整
粒機（パワーミル、昭和化学機械）にて整粒し、整粒末
を得た。得られた整粒末３３１８ｇに、Ｌ−システイン
６４０ｇ、パントテン酸カルシウム タイプＳ１８４．
８ｇ、結晶セルロース（セオラスＫＧ−８０１、旭化
成）３４５．２ｇ、低置換度ヒドロキシプロピルセルロ
ース（Ｌ−ＨＰＣ（ＬＨ３１）、信越化学）２４０ｇ、
特殊ケイ酸カルシウム（フローライトＲＥ、徳山曹達）
２４ｇ、ステアリン酸マグネシウム４８ｇを混合機（タ
ンブラー混合機、昭和化学機械）にて混合し、得られた
混合末をロータリー式打錠機で、直径８．８ｍｍの臼、
曲率半径７．０ｍｍのＲ面杵にて、１錠当たりの重量３
００ｍｇ、厚さ５．２ｍｍとなるように製錠し、素錠を
得た。上記の素錠３２４０ｇに、ヒドロキシプロピルメ
チルセルロース（ＴＣ−５ＭＷ）１２０ｇを精製水１０
８０ｇに溶解したコーティング液を用い、コーティング
機（ドリアコーター ＤＲＣ−５００、バウレック）に
て、素錠重量に対して２％量コーティングし、更にその
上に、エリスリトール９１８．５ｇ、タルク４８５．３
ｇ、酸化チタン３４．７ｇ、結晶セルロース（アビセル
ＰＨ−Ｆ２０）８６．６ｇ、アラビアゴム末２０７．９
ｇを精製水２８２７ｇに溶解、懸濁したコーティング液
を用い、コーティング機（ドリアコーター ＤＲＣ−５
００、バウレック）にて素錠重量に対して３８％量コー
ティングした。更にその上に、エリスリトール５４０
ｇ、マクロゴール６０００ ６０ｇを精製水９８０ｇに
溶解したコーティング液を用い、コーティング機（ドリ
アコーター ＤＲＣ−５００、バウレック）にて素錠重
量に対して５％量コーティングし、コーティング錠を得
た。なお、該コーティング錠に、艶だし液（カルナウバ
ロウ、白ロウを溶解させたエタノール−ｎ−ヘキサン溶
液）を微量、コーティングし、艶だしを行った。Example 3 2700 g of ascorbic acid, 54 g of riboflavin, d-α-tocopherol succinate (regular particle size product) 22
5 g of powdered reduced maltose starch syrup, 351 g of crystalline cellulose (Seolas KG-801, Asahi Kasei) and 240.8 g of a 6% hydroxypropylcellulose (HPC-L) aqueous solution 2700 in a fluidized bed granulator (FD-5S, Powrex)
g in a fluidized bed by spraying. Thereafter, the resulting mixture was sized using a sizing machine (Power Mill, Showa Chemical Machinery Co., Ltd.) to obtain a sieved powder. To 3318 g of the obtained sized powder, 640 g of L-cysteine and calcium pantothenate type S184.
8 g, crystalline cellulose (Seolas KG-801, Asahi Kasei) 345.2 g, low-substituted hydroxypropyl cellulose (L-HPC (LH31), Shin-Etsu Chemical) 240 g,
Special calcium silicate (Fluorite RE, Tokuyama Soda)
24 g and 48 g of magnesium stearate were mixed with a mixer (tumbler mixer, Showa Chemical Machinery Co., Ltd.), and the obtained mixed powder was milled with a rotary tableting machine to a mill having a diameter of 8.8 mm.
Weight per tablet of 3 with a 7.0 mm radius R-punch
Tablets were made to give 00 mg and a thickness of 5.2 mm to obtain uncoated tablets. To 3240 g of the above uncoated tablet, 120 g of hydroxypropyl methylcellulose (TC-5MW) was added to purified water 10
Using a coating solution dissolved in 80 g, a coating machine (Doria Coater DRC-500, Baurek) was used to coat 2% of the weight of the uncoated tablet, and 918.5 g of erythritol and 485.3 of talc were further coated thereon.
g, titanium oxide 34.7 g, crystalline cellulose (Avicel PH-F20) 86.6 g, gum arabic powder 207.9
g was dissolved and suspended in 2827 g of purified water, and a coating machine (Doria Coater DRC-5) was used.
00, Baurec) in an amount of 38% based on the weight of the uncoated tablet. In addition, erythritol 540
g and Macrogol 6000 (60 g) were dissolved in 980 g of purified water, and coated with a coating machine (Doria Coater DRC-500, Baurek) in an amount of 5% based on the weight of the uncoated tablet to obtain a coated tablet. In addition, the coated tablets were coated with a slight amount of a polishing liquid (an ethanol-n-hexane solution in which carnauba wax and white wax were dissolved) to perform polishing.
【００２４】比較例１ アスコルビン酸１０００ｇ、リボフラビン１２ｇ、コハ
ク酸ｄ−α−トコフェロール（レギュラー粒度品）５０
ｇ、パントテン酸カルシウム タイプＳ ４６．２ｇ、
Ｌ−システイン（粒子径１００μｍ以下６０％）１６０
ｇ、結晶セルロース（セオラスＫＧ８０１、旭化成）９
５.８ｇ、乳糖９５．８ｇを流動層造粒機（ＦＤ−３Ｓ
Ｎ、パウレック）にて、６％ヒドロキシプロピルセルロ
ース（ＨＰＣ−Ｌ）水溶液９０３．３ｇを噴霧すること
により、流動層造粒した。その後、整粒機（パワーミ
ル、昭和化学機械）にて、整粒し、整粒末を得た。 得
られた整粒末１２１１．２ｇに、結晶セルロース（セオ
ラスＫＧ８０１、旭化成）１２８ｇ、低置換度ヒドロキ
シプロピルセルロース（Ｌ−ＨＰＣ（ＬＨ３１）、信越
化学）７２ｇ、特殊ケイ酸カルシウム（フローライトＲ
Ｅ、エーザイ）７.２ｇ、ステアリン酸マグネシウム２
１．６ｇを混合機（タンブラー混合機、昭和化学機械）
にて混合し、得られた混合末をロータリー式打錠機で、
直径９ｍｍの臼、曲率半径７．５ｍｍのＲ面杵にて、１
錠当たりの重量３００ｍｇ、厚さ４．９ｍｍとなるよう
に製錠し、素錠を得た。素錠６錠当たりの処方は表１と
同じである。上記の素錠３００ｇに、ハイコーター（Ｈ
ＣＴ−ＭＩＮＩ、フロイント産業）を用い、ヒドロキシ
プロピルメチルセルロース２９１０（ＴＣ−５ＭＷ）４
５ｇ、マクロゴール６０００ ９ｇ、酸化チタン ６ｇ
を精製水４０１．５ｇに溶解させた水溶液を素錠に対し
て、５％量コーティングしたフィルム錠を得た。Comparative Example 1 1000 g of ascorbic acid, 12 g of riboflavin, d-α-tocopherol succinate (regular particle size product) 50
g, calcium pantothenate type S 46.2 g,
L-cysteine (particle size: 100% or less 60%) 160
g, crystalline cellulose (Ceolas KG801, Asahi Kasei) 9
5.8 g of lactose and 95.8 g of lactose were mixed with a fluid bed granulator (FD-3S).
N, Powrex), 903.3 g of a 6% aqueous solution of hydroxypropylcellulose (HPC-L) was sprayed to perform fluidized bed granulation. Thereafter, the resulting mixture was sized using a sizing machine (Power Mill, Showa Chemical Machinery Co., Ltd.) to obtain a sieved powder. To 1211.2 g of the obtained sized powder, 128 g of crystalline cellulose (Seolas KG801, Asahi Kasei), 72 g of low-substituted hydroxypropylcellulose (L-HPC (LH31), Shin-Etsu Chemical), special calcium silicate (Flolite R)
E, Eisai) 7.2 g, magnesium stearate 2
1.6 g of a mixer (tumbler mixer, Showa Chemical Machinery)
At a rotary tableting machine.
With a 9 mm diameter mortar and an R surface punch with a curvature radius of 7.5 mm, 1
Tablets were manufactured to have a weight per tablet of 300 mg and a thickness of 4.9 mm to obtain uncoated tablets. The prescription per 6 uncoated tablets is the same as in Table 1. 300 g of the above uncoated tablets are coated with a high coater (H
CT-MINI, Freund Corporation) and hydroxypropyl methylcellulose 2910 (TC-5MW) 4
5g, Macrogol 6000 9g, Titanium oxide 6g
Was dissolved in 401.5 g of purified water to obtain a film tablet coated with 5% of the uncoated tablet.
【００２５】Ｌ−システイン由来の不快臭の評価 実施例１、実施例２および比較例１の錠剤について、Ｌ
−システイン由来の不快臭を、５名のパネラーによる官
能試験によって評価した。結果を表２に示す。 Evaluation of Unpleasant Odor Derived from L-Cysteine The tablets of Example 1, Example 2 and Comparative Example 1
-The unpleasant odor derived from cysteine was evaluated by a sensory test by 5 panelists. Table 2 shows the results.
【００２６】[0026]
【表２】 −：Ｌ−システイン由来の不快臭が全くない ±：Ｌ−システイン由来の不快臭がほとんどない ＋：Ｌ−システイン由来の不快臭がある ＋＋：Ｌ−システイン由来の不快臭が強くある ＋＋＋：Ｌ−システイン由来の不快臭が著しく強くある[Table 2] -: No unpleasant odor derived from L-cysteine at all ±: Almost no unpleasant odor derived from L-cysteine +: Unpleasant odor derived from L-cysteine ++: Strong unpleasant odor derived from L-cysteine +++: L -Extremely strong unpleasant odor derived from cysteine
【００２７】実施例１、２および３の薄層糖衣錠は、不
快臭が全くなく、本発明により、不快な臭いが低減され
たＬ−システイン配合錠剤を製造することができた。The thin-layer sugar-coated tablets of Examples 1, 2 and 3 had no unpleasant odor, and according to the present invention, L-cysteine-containing tablets with reduced unpleasant odor could be produced.
【００２８】比較例２ １２インチオニオンパン装着した糖衣機（ＮＯ１６−
Ｄ、菊水製作所）にて、実施例１の素錠９９０ｇに、表
３に示す組成の糖衣液と表４に示す組成の散布剤を用
い、素錠に対して、素錠重量の６０％量のサブコーティ
ングを施し、更にその上に、表３に示す組成の糖衣液の
みを用い、素錠重量の２６％量のスムーズコーティング
を施した。続いて、精製白糖１００ｇを精製水５０ｇに
溶解させたシロップ夜を素錠に対して、１４％量のシロ
ップコーティングを施し、糖衣錠を得た。次いで、糖衣
錠に、艶だし液（カルナウバロウ、白ロウを溶解させた
エタノール・ｎ−へキサン溶液）を微量、コーティング
し、艶だしを行った。Comparative Example 2 A sugar-coating machine equipped with a 12-inch union pan (NO16-
D, Kikusui Seisakusho), to 990 g of the uncoated tablet of Example 1, a sugar coating liquid having the composition shown in Table 3 and a spraying agent having the composition shown in Table 4 were used. And a smooth coating of 26% of the uncoated tablet weight was further applied thereon using only the sugar coating liquid having the composition shown in Table 3. Subsequently, a syrup night obtained by dissolving 100 g of purified sucrose in 50 g of purified water was coated on a plain tablet in a syrup amount of 14% to obtain a sugar-coated tablet. Next, the sugar-coated tablets were coated with a slight amount of a polish liquid (an ethanol / n-hexane solution in which carnauba wax and white wax were dissolved), and polish was performed.
【００２９】[0029]
【表３】 [Table 3]
【００３０】[0030]
【表４】 [Table 4]
【００３１】糖衣錠中の薬物の安定化の評価 本発明によって低水分化することにより、糖衣錠中の薬
物を安定化できることを確認するために、実施例２と比
較例２の錠剤の水分と５０℃１ヶ月保存品のパントテン
酸カルシウムの残存率を比較した。 試験方法 試料溶液調製法 試料粉末［パントテン酸カルシウム（Ｃ18Ｈ32ＣａＮ2
Ｏ10）約０．０１ｇに対応する量］を精密に量り、０．
０５ｍｏｌ／Ｌリン酸二水素アンモニウム溶液を正確に
１００ｍＬ加える。２０分間激しく振り混ぜ抽出した
後、遠心分離し、上澄み液を孔径０．４５μｍのフィル
ターでろ過し、ろ液を試料溶液とする。 標準溶液調整法 パントテン酸カルシウム（タイプＳ）［パントテン酸カ
ルシウム（Ｃ18Ｈ32ＣａＮ2Ｏ10）約０．０１ｇに対応
する量］を精密に量り、０．０５ｍｏｌ／Ｌリン酸二水
素アンモニウム溶液を加えて溶かし、正確に１００ｍＬ
として標準溶液とする。 ＨＰＬＣ条件 検出器：紫外吸光光度計（測定波長：２１０ｎｍ） カラム：ＹＭＣ−ＰａｃｋＯＤＳＡＭ−３０２（１５ｃ
ｍ×４．６ｍｍＩＤ．） カラム温度：２５℃付近の一定温度 移動相：０．０５ｍｏｌ／リン酸二水素アンモニウム溶
液（ｐＨ３．５）＊１／メタノール混液（１９：１） 流量：毎分約１．０ｍＬ 注入量：２０μＬ ＊１：リン酸二水素アンモニウム５．７５ｇを水に溶か
し１０００ｍＬとした後、薄めたリン酸（１→１０）を
加えてｐＨ３．５に調整する。結果を表５に示す。 Evaluation of Stabilization of Drug in Dragees In order to confirm that the drug in the dragees can be stabilized by reducing the water content according to the present invention, the water content of the tablets of Example 2 and Comparative Example 2 was measured at 50 ° C. The residual ratio of calcium pantothenate of the one-month storage product was compared. Test method Sample solution preparation method Sample powder [calcium pantothenate (C 18 H 32 CaN 2
O 10 ) in an amount corresponding to about 0.01 g].
Add exactly 100 mL of the 05 mol / L ammonium dihydrogen phosphate solution. After vigorously shaking and extracting for 20 minutes, the mixture is centrifuged, and the supernatant is filtered through a filter having a pore size of 0.45 μm, and the filtrate is used as a sample solution. Standard solution preparation method Calculate calcium pantothenate (type S) [amount corresponding to about 0.01 g of calcium pantothenate (C 18 H 32 CaN 2 O 10 )] accurately, and add 0.05 mol / L ammonium dihydrogen phosphate solution. And dissolve, add exactly 100 mL
As the standard solution. HPLC conditions Detector: UV absorption photometer (measuring wavelength: 210 nm) Column: YMC-PackODSAM-302 (15c
mx 4.6 mm ID. Column temperature: constant temperature around 25 ° C. Mobile phase: 0.05 mol / ammonium dihydrogen phosphate solution (pH 3.5) * 1 / Methanol mixture (19: 1) Flow rate: about 1.0 mL per minute Injection volume: 20 μL * 1: Dissolve 5.75 g of ammonium dihydrogen phosphate in water to make 1000 mL, and adjust the pH to 3.5 by adding diluted phosphoric acid (1 → 10). Table 5 shows the results.
【００３２】[0032]
【表５】 比較例２の糖衣錠は、水分が高いが、実施例２の薄層糖
衣錠は、低水分化することができた。そのため、比較例
２の糖衣錠中のパントテン酸カルシウムの安定性は悪か
ったが、実施例２の薄層糖衣錠中のパントテン酸カルシ
ウムの安定性はよかった。本発明により、糖衣錠を低水
分化することができ、高水分で分解する薬物の安定性を
向上させることができた。[Table 5] The sugar-coated tablet of Comparative Example 2 had a high water content, whereas the thin-layer dragee of Example 2 was able to reduce the water content. Therefore, the stability of calcium pantothenate in the sugar-coated tablet of Comparative Example 2 was poor, but the stability of calcium pantothenate in the thin-layer sugar-coated tablet of Example 2 was good. INDUSTRIAL APPLICABILITY According to the present invention, sugar-coated tablets can be reduced in water content, and the stability of a drug that decomposes at high water content can be improved.
【００３３】実施例４ コハク酸トコフェロールカルシウム５１７．９ｇ、塩酸
ピリドキシン５００ｇ、ガンマ−オリザノール５０ｇ、
軽質無水ケイ酸（サイリシア３２０）７７．２５ｇ、結
晶セルロース（アビセルＰＨ１０１）２１０．８５ｇを
６％ヒドロキシプロピルセルロース（ＨＰＣ−Ｌ）水溶
液１１５０ｇを用いて、流動層造粒機（ＦＤ−３ＳＮ、
パウレック）にて、造粒、乾燥した。得られた造粒末を
整粒機（パワーミル、昭和化学機械）にて整粒した。こ
の整粒末をＥ群整粒末とする。一方、塩酸フルスルチア
ミン５４５．８ｇ、結晶セルロース（アビセルＰＨ１０
１）1７９．８６５ｇを流動層造粒機（ＦＤ−３ＳＮ、
パウレック）にて、６％ヒドロキシプロピルセルロース
（ＨＰＣ−Ｌ）水溶液２７５ｇを噴霧することにより、
流動層造粒する。なお、ＨＰＣ−Ｌ水溶液を噴霧する前
に、酢酸ヒドロキソコバラミン７．８３５ｇ、を７％水
溶液として噴霧した。得られた造粒末を整粒機（パワー
ミル、昭和化学機械）にて整粒し、整粒末を得た。この
整粒末をＴ群整粒末とする。Ｅ群整粒末５７０ｇ、Ｔ群
整粒末３００ｇに、軽質無水ケイ酸（サイリシア３２
０）１１．１ｇ、結晶セルロース（アビセルＰＨ１０
１）１３７．３ｇ、低置換度ヒドロキシプロピルセルロ
ース（Ｌ‐ＨＰＣ（ＬＨ３１））８３．４ｇ、ステアリ
ン酸マグネシウム８．２ｇを混合機（タンブラー混合
機、昭和化学機械）にて混合し、得られた混合末をロー
タリー式打錠機で、直径８ｍｍの臼、曲率半径６．５ｍ
ｍのＲ面杵にて、１錠当たりの重量１８５ｍｇ、厚さ
４．２５ｍｍとなるように製錠し、素錠を得た。素錠３
錠当たりの処方を表６に示す。Example 4 517.9 g of tocopherol calcium succinate, 500 g of pyridoxine hydrochloride, 50 g of gamma-oryzanol,
Using fluidized bed granulator (FD-3SN, 77.25 g of light anhydrous silicic acid (Sylysia 320) and 210.85 g of crystalline cellulose (Avicel PH101) using 1150 g of 6% hydroxypropylcellulose (HPC-L) aqueous solution.
(Powrex) and granulated and dried. The obtained granulated powder was sized by a sizing machine (Power Mill, Showa Chemical Machinery). This sized powder is referred to as Group E sized powder. On the other hand, 545.8 g of fursultiamine hydrochloride, crystalline cellulose (Avicel PH10)
1) 179.865 g of a fluidized bed granulator (FD-3SN,
By spraying 275 g of a 6% aqueous solution of hydroxypropylcellulose (HPC-L)
Fluid bed granulation. Before spraying the HPC-L aqueous solution, 7.835 g of hydroxocobalamin acetate was sprayed as a 7% aqueous solution. The obtained granulated powder was sized using a sizing machine (Power Mill, Showa Chemical Machinery) to obtain a sized powder. This sized powder is referred to as a T-group sized powder. Add 570 g of sized powder of Group E and 300 g of sized powder of Group T to light anhydrous silicic acid (Sylysia 32
0) 11.1 g, crystalline cellulose (Avicel PH10
1) 137.3 g, 83.4 g of low-substituted hydroxypropylcellulose (L-HPC (LH31)) and 8.2 g of magnesium stearate were mixed with a mixer (tumbler mixer, Showa Chemical Machinery) to obtain a mixture. Using a rotary tableting machine, the mixed powder was milled with a diameter of 8 mm and radius of curvature 6.5 m.
The tablets were made with an m-side R-face punch so as to have a weight of 185 mg per tablet and a thickness of 4.25 mm to obtain uncoated tablets. Plain tablet 3
Table 6 shows the formulation per tablet.
【００３４】[0034]
【表６】 [Table 6]
【００３５】上記の素錠３００ｇに実施例１と同じ糖衣
液処方、コーティング量の薄層糖衣を施した。 比較例３ 実施例４の素錠３００ｇに、ハイコーター（ＨＣＴ−Ｍ
ＩＮＩ、フロイント産業）を用い、ヒドロキシプロピル
メチルセルロース２９１０（ＴＣ−５ＭＷ）４５ｇ、マ
クロゴール６０００ ９ｇ、酸化チタン ６ｇを精製水
４０１．５ｇに溶解させた水溶液を素錠に対して５％量
コーティングしたフィルム錠を得た。The above-mentioned uncoated tablets (300 g) were coated with a thin-layer sugar coating having the same sugar coating composition and coating amount as in Example 1. Comparative Example 3 To 300 g of the uncoated tablet of Example 4, a high coater (HCT-M
(INI, Freund Corp.), a film prepared by coating an aqueous solution prepared by dissolving 45 g of hydroxypropylmethylcellulose 2910 (TC-5MW), 9 g of macrogol 6000 g, and 6 g of titanium oxide in 401.5 g of purified water, based on plain tablets in an amount of 5%. I got a tablet.
【００３６】塩酸フルスルチアミン由来の不快臭の評価 実施例４および比較例３の錠剤について、塩酸フルスル
チアミン由来の不快臭を、５名のパネラーによる官能試
験によって評価した。結果を表７に示す。 Evaluation of unpleasant odor derived from fursultiamine hydrochloride The unpleasant odor derived from fursultiamine hydrochloride was evaluated for the tablets of Example 4 and Comparative Example 3 by a sensory test by five panelists. Table 7 shows the results.
【００３７】[0037]
【表７】 [Table 7]
【００３８】実施例５ イブプロフェン９００ｇ、乳糖９４０ｇ、結晶セルロー
ス（アビセルＰＨ１０１、旭化成）７００ｇを流動層造
粒機（ＦＤ−３ＳＮ、パウレック）にて、６％ヒドロキ
シプロピルセルロース（ＨＰＣ−Ｌ）水溶液１３３４ｇ
を噴霧することにより、流動層造粒した。その後、整粒
機（パワーミル、昭和化学機械）にて整粒し、整粒末を
得た。得られた整粒末１３５０ｇに、結晶セルロース
（アビセルＰＨ１０１、旭化成）２１４．２ｇ、クロス
カルメロースナトリウム（アクジゾル、旭化成）８２．
５ｇ、ステアリン酸マグネシウム３．３ｇを混合機（タ
ンブラー混合機、昭和化学機械）にて混合し、得られた
混合末をロータリー式打錠機で、直径８．５ｍｍの臼、
曲率半径６ｍｍのＲ面杵にて、１錠当たりの重量２７５
ｍｇ、厚さ４．８ｍｍとなるように製錠し、素錠を得
た。上記の素錠３００ｇに、精製白糖５４ｇ、タルク２
４ｇ、結晶セルロース（アビセルＰＨ−Ｆ２０）１０
ｇ、アラビアゴム末 １２ｇを精製水８３．５ｇに溶
解、懸濁した糖衣液を用い、ハイコーター（ＨＣＴ−２
０、フロイント産業）にて、素錠に対して素錠重量の３
５％量コーティングした。続いて、精製白糖９４ｇ、ア
ラビアゴム末６ｇを精製水８３．５ｇに溶解させたシロ
ップ液を素錠に対して、５％量コーティングし、薄層の
糖衣錠を得た。なお、薄層の糖衣錠に、艶だし液（カル
ナウバロウ、白ロウを溶解させたエタノール・ｎ−ヘキ
サン溶液）を微量、コーティングし、艶だしを行った。Example 5 900 g of ibuprofen, 940 g of lactose, and 700 g of crystalline cellulose (Avicel PH101, Asahi Kasei) were mixed with 1334 g of a 6% aqueous solution of hydroxypropylcellulose (HPC-L) in a fluidized bed granulator (FD-3SN, Powrex).
Was sprayed to obtain a fluidized bed granulation. Thereafter, the resulting mixture was sized using a sizing machine (Power Mill, Showa Chemical Machinery Co., Ltd.) to obtain a sieved powder. To 1350 g of the obtained sized powder, 214.2 g of crystalline cellulose (Avicel PH101, Asahi Kasei) and croscarmellose sodium (Acdizol, Asahi Kasei)
5 g and 3.3 g of magnesium stearate were mixed with a mixer (tumbler mixer, Showa Chemical Machinery Co., Ltd.), and the obtained mixed powder was mixed with a rotary tableting machine using a mill having a diameter of 8.5 mm.
Weight per tablet 275 with an R-face punch with a radius of curvature of 6 mm
mg and 4.8 mm in thickness to obtain a tablet. To 300 g of the above uncoated tablet, 54 g of purified sucrose, talc 2
4 g, crystalline cellulose (Avicel PH-F20) 10
g, gum arabic powder 12 g was dissolved and dissolved in 83.5 g of purified water.
0, Freund's industry).
5% coating. Subsequently, a syrup solution obtained by dissolving 94 g of purified sucrose and 6 g of gum arabic powder in 83.5 g of purified water was coated on the uncoated tablet in an amount of 5% to obtain a thin-layer sugar-coated tablet. In addition, a thin layer of sugar-coated tablets was coated with a slight amount of a polish liquid (an ethanol / n-hexane solution in which carnauba wax and white wax were dissolved) to perform polish.
【００３９】比較例４ 実施例５の素錠３００ｇに、ハイコーター（ＨＣＴ‐Ｍ
ＩＮＩ、フロイント産業）を用い、ヒドロキシプロピル
メチルセルロース２９１０（ＴＣ−５ＭＷ）２７ｇ、乳
糖２４ｇ、酸化チタン９ｇを精製水２４０ｇに溶解させ
た水溶液を素錠に対して、５％量コーティングしたフィ
ルム錠を得た。Comparative Example 4 300 g of the uncoated tablet of Example 5 was added to a high coater (HCT-M
INI, Freund Sangyo) to obtain a film tablet coated with an aqueous solution obtained by dissolving 27 g of hydroxypropylmethylcellulose 2910 (TC-5MW), 24 g of lactose, and 9 g of titanium oxide in 240 g of purified water, based on an uncoated tablet. Was.
【００４０】ウイスカーの発生度合いの評価法 実施例５および比較例４の錠剤を用いて、ウイスカーの
発生度合いを評価した。錠剤からのウイスカーの発生度
合いの試験は、６Ｋのガラス瓶に錠剤を１００錠入れ、
密栓で５０℃１ヶ月保存し、ウイスカーの発生によるガ
ラス瓶のくもりの度合いを肉眼で観察することによって
評価した。ガラス瓶のくもりの程度が大きい程、ウイス
カーの発生が大きいことを示す。結果を表８に示す。 Evaluation method of whisker generation degree Using the tablets of Example 5 and Comparative Example 4, the whisker generation degree was evaluated. To test the degree of whisker generation from tablets, put 100 tablets in a 6K glass bottle,
The glass bottle was stored in a sealed stopper at 50 ° C. for 1 month, and the degree of cloudiness of the glass bottle due to the generation of whiskers was evaluated by observing it with the naked eye. The higher the degree of cloudiness of the glass bottle, the greater the occurrence of whiskers. Table 8 shows the results.
【００４１】[0041]
【表８】 −：ガラス瓶のくもりが全くない ±：ガラス瓶のくもりがほとんどない ＋：ガラス瓶のくもりがある ＋＋：ガラス瓶のくもりが強くある ＋＋＋：ガラス瓶のくもりが著しく強くある[Table 8] −: There is no clouding in the glass bottle ±: There is almost no clouding in the glass bottle +: There is clouding in the glass bottle ++: The clouding in the glass bottle is strong +++: The clouding in the glass bottle is extremely strong
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.7 識別記号 ＦＩ テーマコート゛(参考） Ａ６１Ｋ 31/375 Ａ６１Ｋ 31/375 31/4188 31/4188 31/51 31/51 31/525 31/525 47/10 47/10 47/26 47/26 47/36 47/36 Ａ６１Ｐ 3/02 Ａ６１Ｐ 3/02 １０５ １０５ 29/00 29/00 Ｆターム(参考） 4C076 AA43 BB01 CC03 CC04 CC21 CC24 DD38 DD67 FF26 FF52 GG16 4C086 AA01 AA02 BC83 MA03 MA05 MA35 MA52 NA09 ZC25 4C206 AA01 AA02 DA24 JA58 MA03 MA05 MA55 MA72 NA09 ZB11 ZC21 ──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. 7 Identification symbol FI Theme coat ゛ (Reference) A61K 31/375 A61K 31/375 31/4188 31/4188 31/51 31/51 31/525 31/525 47 / 10 47/10 47/26 47/26 47/36 47/36 A61P 3/02 A61P 3/02 105 105 29/00 29/00 F term (reference) 4C076 AA43 BB01 CC03 CC04 CC21 CC24 DD38 DD67 FF26 FF52 GG16 4C086 AA01 AA02 BC83 MA03 MA05 MA35 MA52 NA09 ZC25 4C206 AA01 AA02 DA24 JA58 MA03 MA05 MA55 MA72 NA09 ZB11 ZC21
Claims (19)
および結合剤を含む糖衣層を有する薄層糖衣錠。1. A thin-coated sugar-coated tablet having a sugar-coated layer containing 5 to 60% of the weight of the uncoated tablet and containing a carbohydrate, an excipient and a binder.
群から選択される１種以上の糖質である請求項１記載の
薄層糖衣錠。2. The thin-layer sugar-coated tablet according to claim 1, wherein the sugar is at least one kind of sugar selected from the group consisting of sugar and sugar alcohol.
コールが、エリスリトール、マンニトール、ソルビトー
ル、キシリトール、マルチトール、粉末還元麦芽糖水飴
および還元乳糖からなる群から選択される１種以上のも
のである請求項２記載の薄層糖衣錠。3. The sugar is sucrose and trehalose, and the sugar alcohol is at least one selected from the group consisting of erythritol, mannitol, sorbitol, xylitol, maltitol, powdered reduced maltose syrup and reduced lactose. 2. The thin-layer sugar-coated tablet according to 2.
求項２記載の薄層糖衣錠。4. The thin-coated sugar-coated tablet according to claim 2, wherein the sugar alcohol is erythritol.
を用いた請求項１〜４いずれか１項記載の薄層糖衣錠。5. The thin-layer sugar-coated tablet according to any one of claims 1 to 4, wherein an uncoated tablet containing a drug having an unpleasant odor is used.
インおよびビタミンＢ1類からなる群から選択される１
種以上のものである請求項５記載の薄層糖衣錠。6. 1 drug having an unpleasant smell, which is selected from the group consisting of L- cysteine and vitamin B 1 class
6. The thin-layer sugar-coated tablet according to claim 5, which is of at least one kind.
粒せず、そのまま混合工程で配合し、製した素錠を用い
た請求項５記載の薄層糖衣錠。7. The thin-layer sugar-coated tablet according to claim 5, wherein L-cysteine is not granulated with water or an organic solvent, but is blended as it is in the mixing step, and used as a plain tablet.
含有割合が５０％以下のＬ−システインである請求項６
記載の薄層糖衣錠。8. The drug is L-cysteine having a content ratio of particles having a particle diameter of 100 μm or less of 50% or less.
The thin-layer sugar-coated tablet according to the above.
よび塩酸フルスルチアミン等からなる群から選択される
ビタミンＢ1類である請求項６記載の薄層糖衣錠。9. drugs, thiamine hydrochloride, thin layer dragee claim 6 wherein the vitamin B 1 class selected from the group consisting of thiamin nitrate and fursultiamine hydrochloride and the like.
を用いた請求項１〜４いずれか１項記載の薄層糖衣錠。10. The thin-layer sugar-coated tablet according to any one of claims 1 to 4, wherein an uncoated tablet containing a drug that decomposes at high moisture is used.
ン、ビタミンＢ類、ビタミンＣ類、ビタミンＥ類、パン
トテン酸カルシウムおよびビオチンからなる群から選択
される１種以上のものである請求項１０記載の薄層糖衣
錠。11. The drug that decomposes at high moisture is at least one selected from the group consisting of L-cysteine, vitamin Bs, vitamin Cs, vitamin Es, calcium pantothenate, and biotin. The thin-layer sugar-coated tablet according to the above.
素錠を用いた請求項１〜４いずれか１項記載の薄層糖衣
錠。12. The thin-layer sugar-coated tablet according to any one of claims 1 to 4, wherein an uncoated tablet containing a whisker-generating drug is used.
フェン、カフェイン、無水カフェイン、エテンザミドお
よびイソプロピルアンチピリンからなる群から選択され
る１種以上のものである請求項１２記載の薄層糖衣錠。13. The thin-layer dragee according to claim 12, wherein the whisker-generating drug is at least one selected from the group consisting of ibuprofen, caffeine, anhydrous caffeine, etensamide and isopropylantipyrine.
項１〜１３いずれか１項記載の薄層糖衣錠。14. The thin-layer sugar-coated tablet according to any one of claims 1 to 13, which is a sugar-less sugar-coated tablet.
〜１４いずれか１項記載の薄層糖衣錠。15. A sugar-coated tablet having an underlay.
The thin-layer sugar-coated tablet according to any one of claims 14 to 14.
〜１５いずれか１項記載の薄層糖衣錠。16. The composition according to claim 1, further comprising a drug in the sugar coating layer.
The thin-layer sugar-coated tablet according to any one of claims 15 to 15.
１〜１６いずれか１項記載の薄層糖衣錠。17. The thin-layer sugar-coated tablet according to claim 1, which has an equilibrium relative humidity of 40% or less.
剤を含む糖衣液を手がけし、および／または０．１〜１
０００μｍの液滴として噴霧して、素錠重量の５〜６０
％の糖衣を施すことを特徴とする薄層糖衣錠の製造方
法。18. An uncoated tablet is coated with a sugar coating liquid containing a carbohydrate, an excipient and a binder, and / or 0.1 to 1%.
Sprayed as droplets of 000 μm, and
% Sugar-coated tablets.
糖衣錠の製造方法。19. The method for producing a thin-layer sugar-coated tablet according to claim 18, wherein droplets are sprayed.
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| JP2004099543A (en) * | 2002-09-10 | 2004-04-02 | Taisho Pharmaceut Co Ltd | Dragees |
| JP2004161700A (en) * | 2002-11-14 | 2004-06-10 | Kobayashi Pharmaceut Co Ltd | Composition in which bitterness and odor of cysteines are reduced |
| JP2004161701A (en) * | 2002-11-14 | 2004-06-10 | Kobayashi Pharmaceut Co Ltd | Composition with reduced bitterness and odor of cysteines |
| WO2005029980A1 (en) * | 2003-09-26 | 2005-04-07 | Kobayashi Pharmaceutical Co., Ltd. | Composition with relieved unpleasant odor or taste of cysteines |
| JP2005298528A (en) * | 2005-07-14 | 2005-10-27 | Kobayashi Pharmaceut Co Ltd | Composition with reduced unpleasant odor or taste of cysteines |
| JP2005298373A (en) * | 2004-04-08 | 2005-10-27 | Kyowa Hakko Kogyo Co Ltd | Sugar-coated tablets containing water-absorbing amino acids |
| WO2006095819A1 (en) | 2005-03-10 | 2006-09-14 | Taisho Pharmaceutical Co., Ltd. | Sugar-coated pill |
| JP2006256961A (en) * | 2004-02-27 | 2006-09-28 | Dainippon Sumitomo Pharma Co Ltd | Dragees |
| JP2006328001A (en) * | 2005-05-27 | 2006-12-07 | Ss Pharmaceut Co Ltd | Formulation for oral administration |
| WO2006132360A1 (en) * | 2005-06-10 | 2006-12-14 | Takeda Pharmaceutical Company Limited | Sugar-coated tablet |
| JP2007053952A (en) * | 2005-08-24 | 2007-03-08 | Towa Chem Ind Co Ltd | Hard coating layer, hard coating product and manufacturing method thereof |
| JP2007191474A (en) * | 2005-12-20 | 2007-08-02 | Takeda Chem Ind Ltd | Colored dragees |
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| JP2008201711A (en) * | 2007-02-20 | 2008-09-04 | Ss Pharmaceut Co Ltd | Solid formulation with reduced cysteine odor |
| JP2008260778A (en) * | 2008-06-06 | 2008-10-30 | Kyoto Pharmaceutical Industries Ltd | Film coated tablets |
| WO2010018614A1 (en) * | 2008-08-11 | 2010-02-18 | 味の素株式会社 | Hydrophilic amino acid-containing preparation having improved taste |
| JP5038541B1 (en) * | 2012-03-22 | 2012-10-03 | 秋山錠剤株式会社 | Dragee manufacturing method |
| KR101364561B1 (en) * | 2006-01-16 | 2014-02-18 | 에스에스 세야쿠 가부시키 가이샤 | Compression molded preparation |
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| WO2017078024A1 (en) * | 2015-11-02 | 2017-05-11 | 三菱商事フードテック株式会社 | Method for accelerating sugar coating formation for forming sugar coating composed of sugar alcohol with calcium lactate |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS625910A (en) * | 1985-07-02 | 1987-01-12 | Shin Etsu Chem Co Ltd | Method for producing thin sugar-coated tablets |
| JPH01135716A (en) * | 1987-11-20 | 1989-05-29 | Takeda Chem Ind Ltd | Sugar-coated layer of sucrose and formation thereof |
| JPH0925245A (en) * | 1995-07-13 | 1997-01-28 | Mitsubishi Chem Corp | Dragee and dragees |
-
2001
- 2001-09-28 JP JP2001300501A patent/JP2002179559A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS625910A (en) * | 1985-07-02 | 1987-01-12 | Shin Etsu Chem Co Ltd | Method for producing thin sugar-coated tablets |
| JPH01135716A (en) * | 1987-11-20 | 1989-05-29 | Takeda Chem Ind Ltd | Sugar-coated layer of sucrose and formation thereof |
| JPH0925245A (en) * | 1995-07-13 | 1997-01-28 | Mitsubishi Chem Corp | Dragee and dragees |
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