JPH04346929A - Bromocriptine mesylate preparation having stability to light - Google Patents
Bromocriptine mesylate preparation having stability to lightInfo
- Publication number
- JPH04346929A JPH04346929A JP21815791A JP21815791A JPH04346929A JP H04346929 A JPH04346929 A JP H04346929A JP 21815791 A JP21815791 A JP 21815791A JP 21815791 A JP21815791 A JP 21815791A JP H04346929 A JPH04346929 A JP H04346929A
- Authority
- JP
- Japan
- Prior art keywords
- iron sesquioxide
- bromocriptine mesylate
- active ingredient
- preparation
- tablets
- 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.)
- Pending
Links
- OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 title claims abstract description 34
- 229960002802 bromocriptine Drugs 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 claims abstract description 33
- YOBAEOGBNPPUQV-UHFFFAOYSA-N iron;trihydrate Chemical compound O.O.O.[Fe].[Fe] YOBAEOGBNPPUQV-UHFFFAOYSA-N 0.000 claims abstract description 29
- 239000011248 coating agent Substances 0.000 claims abstract description 9
- 239000004480 active ingredient Substances 0.000 claims abstract description 7
- 239000007909 solid dosage form Substances 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims description 8
- 238000000576 coating method Methods 0.000 abstract description 7
- 239000008186 active pharmaceutical agent Substances 0.000 abstract description 4
- 239000003086 colorant Substances 0.000 abstract description 4
- 229940088679 drug related substance Drugs 0.000 abstract description 4
- 238000000354 decomposition reaction Methods 0.000 abstract description 3
- 208000018737 Parkinson disease Diseases 0.000 abstract 1
- 208000011580 syndromic disease Diseases 0.000 abstract 1
- 239000003826 tablet Substances 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 8
- 229930006000 Sucrose Natural products 0.000 description 8
- 229920002678 cellulose Polymers 0.000 description 8
- 239000001913 cellulose Substances 0.000 description 8
- 235000014113 dietary fatty acids Nutrition 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000000194 fatty acid Substances 0.000 description 8
- 229930195729 fatty acid Natural products 0.000 description 8
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 8
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 8
- 239000005720 sucrose Substances 0.000 description 8
- -1 sucrose fatty acid ester Chemical class 0.000 description 8
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 229960003511 macrogol Drugs 0.000 description 6
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 5
- 239000011230 binding agent Substances 0.000 description 5
- 239000001768 carboxy methyl cellulose Substances 0.000 description 5
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 5
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 239000000049 pigment Substances 0.000 description 5
- 238000001035 drying Methods 0.000 description 4
- 239000007941 film coated tablet Substances 0.000 description 4
- 229940031705 hydroxypropyl methylcellulose 2910 Drugs 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 238000004806 packaging method and process Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 229910052742 iron Inorganic materials 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 230000000087 stabilizing effect Effects 0.000 description 3
- 206010000599 Acromegaly Diseases 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 239000007888 film coating Substances 0.000 description 2
- 238000009501 film coating Methods 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 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 description 2
- 235000013980 iron oxide Nutrition 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229940127557 pharmaceutical product Drugs 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229940098778 Dopamine receptor agonist Drugs 0.000 description 1
- 208000001287 Galactorrhea Diseases 0.000 description 1
- 206010017600 Galactorrhoea Diseases 0.000 description 1
- 206010018265 Gigantism Diseases 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 229930182559 Natural dye Natural products 0.000 description 1
- 208000011707 Ovulation disease Diseases 0.000 description 1
- 206010034010 Parkinsonism Diseases 0.000 description 1
- 208000007913 Pituitary Neoplasms Diseases 0.000 description 1
- 201000005746 Pituitary adenoma Diseases 0.000 description 1
- 208000015875 Pituitary gigantism Diseases 0.000 description 1
- 206010061538 Pituitary tumour benign Diseases 0.000 description 1
- 102100024819 Prolactin Human genes 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- 210000004198 anterior pituitary gland Anatomy 0.000 description 1
- 230000000648 anti-parkinson Effects 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
- 210000000750 endocrine system Anatomy 0.000 description 1
- 229960003133 ergot alkaloid Drugs 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- VBMVTYDPPZVILR-UHFFFAOYSA-N iron(2+);oxygen(2-) Chemical class [O-2].[Fe+2] VBMVTYDPPZVILR-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000000978 natural dye Substances 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 208000021310 pituitary gland adenoma Diseases 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
【０００１】0001
【技術分野】本発明は、光安定性が改善されたメシル酸
ブロモクリプチン製剤に関するものである。TECHNICAL FIELD The present invention relates to a bromocriptine mesylate formulation with improved photostability.
【０００２】0002
【背景技術】メシル酸ブロモクリプチンは、麦角アルカ
ロイド由来の化学物質の誘導体で、持続的なドーパミン
受容体作動効果を有し、内分泌系に対しては下垂体前葉
からのプロラクチン分泌を特異的に抑制し、末端肥大症
患者において異常に上昇した成長ホルモン分泌を抑制す
るため、産褥性乳汁分泌の抑制や乳汁漏出症、高プロラ
クチン血性***障害、高プロラクチン血性下垂体腺腫、
末端肥大症、下垂体性巨人症の治療用医薬として、また
、中枢神経系に対しては黒質線状体のドーパミン神経に
作用して抗パーキンソン作用を有するため、パーキンソ
ン症候群などの治療用医薬として広く使用されている薬
物である。[Background technology] Bromocriptine mesylate is a derivative of a chemical substance derived from ergot alkaloids, and has a sustained dopamine receptor agonist effect.On the endocrine system, it specifically suppresses prolactin secretion from the anterior pituitary gland. , to suppress abnormally elevated growth hormone secretion in patients with acromegaly, suppressing puerperal milk secretion, galactorrhea, hyperprolactinemic ovulation disorder, hyperprolactinemic pituitary adenoma,
It is used as a drug for the treatment of acromegaly and pituitary gigantism, and also for the treatment of Parkinson's syndrome as it has an antiparkinsonian effect on the central nervous system by acting on dopamine neurons in the nigrostriatal body. It is a widely used drug.
【０００３】しかし、メシル酸ブロモクリプチンは、光
に対し不安定であるため徐々に着色、分解するという欠
点を有し、市販されているメシル酸ブロモクリプチン製
剤においては、メシル酸ブロモクリプチンに賦形剤など
を加えて打錠するという通常の製法により調製した錠剤
を、遮光性のあるＰＴＰ包装やアルミピロ包装にして製
品としている現状にある。このような製剤にあっては、
保管中の薬物の分解により主薬含量が低下するという欠
点があり、また、包装から服用に必要な量の製剤を取り
出した後の残分について遮光保存するために何らかの処
置を行わなければならないなど管理上の問題も存在する
。[0003] However, bromocriptine mesylate has the disadvantage that it is unstable to light and gradually discolors and decomposes, and commercially available bromocriptine mesylate preparations do not contain excipients or the like in bromocriptine mesylate. Currently, tablets prepared by the usual method of tablet compression are packaged in light-shielding PTP packaging or aluminum pyropackaging. In such preparations,
There is a drawback that the active ingredient content decreases due to decomposition of the drug during storage, and additionally, after the amount of preparation required for administration is removed from the packaging, some kind of treatment must be taken to protect the remaining drug from light. The above problem also exists.
【０００４】0004
【発明の開示】本発明者らは、上記の問題点を解決する
ため種々検討した結果、メシル酸ブロモクリプチンを含
有する固型剤形の薬剤物質を黄色三二酸化鉄および（ま
たは）三二酸化鉄を含む被覆剤で被覆することによって
、変色やメシル酸ブロモクリプチンの分解が抑制され、
極めて安定性に優れたメシル酸ブロモクリプチン製剤が
得られることを見出した。すなわち、本発明は、メシル
酸ブロモクリプチンを有効成分として含有する固型剤形
の薬剤物質を黄色三二酸化鉄および（または）三二酸化
鉄を含む被覆剤で被覆したことを特徴とする製剤を提供
するものである。DISCLOSURE OF THE INVENTION As a result of various studies to solve the above-mentioned problems, the present inventors have determined that a solid dosage form of a pharmaceutical substance containing bromocriptine mesylate can be prepared by adding yellow iron sesquioxide and/or iron sesquioxide. By coating with a coating agent containing bromocriptine mesylate, discoloration and decomposition of bromocriptine mesylate are suppressed.
It has been found that a bromocriptine mesylate formulation with extremely excellent stability can be obtained. That is, the present invention provides a preparation characterized in that a solid dosage form drug substance containing bromocriptine mesylate as an active ingredient is coated with a coating agent containing yellow iron sesquioxide and/or iron sesquioxide. It is something.
【０００５】一般に薬剤製品については、主薬を光や空
気から遮断するため、あるいは外観に美しさを与えて商
品価値を高めるなどの目的でタール色素、レーキ色素、
天然色素あるいは顔料などの種々の着色剤を含有させた
被覆剤が用いられている。[0005] In general, pharmaceutical products use tar pigments, lake pigments,
Coatings containing various coloring agents such as natural dyes or pigments are used.
【０００６】しかしながら、これまで、メシル酸ブロモ
クリプチン製剤については、これらの着色剤が用いられ
た例はなく、また、薬剤に対し、従来、使用可能とされ
ている着色剤がすべてメシル酸ブロモクリプチンの安定
化に対し、効果を発揮し得るものとはいえず、また、タ
ール色素などの場合で言えば、アレルギー発現の副作用
なども考えなければならないのが通常である。However, to date, there have been no cases where these colorants have been used for bromocriptine mesylate preparations, and all of the colorants that have hitherto been available for use in pharmaceuticals are based on the stability of bromocriptine mesylate. However, in the case of tar pigments, side effects such as allergic reactions must also be considered.
【０００７】本発明にかかる製剤の被覆剤中に添加され
る黄色三二酸化鉄（Ｆｅ２Ｏ３・Ｈ２Ｏ）および三二酸
化鉄（Ｆｅ２Ｏ３）は、天然に産する着色顔料であって
、食添および局外規にも収載され、その安定性が確認さ
れ、副作用などの問題は全く存在しない物質である。[0007] Yellow iron sesquioxide (Fe2O3.H2O) and iron sesquioxide (Fe2O3) added to the coating material of the preparation according to the present invention are naturally occurring coloring pigments that are used as food additives and non-governmental regulations. It is a substance that has been listed in Japan, and its stability has been confirmed, and there are no problems such as side effects.
【０００８】次に、本発明を詳細に説明する。本発明に
かかる製剤に関しては、黄色三二酸化鉄および（または
）三二酸化鉄の添加量は、製剤の単位表面積当たり酸化
鉄として、０．１ｍｇ／ｃｍ２〜５ｍｇ／ｃｍ２、好ま
しくは０．２ｍｇ／ｃｍ２〜５ｍｇ／ｃｍ２である。
０．１ｍｇ／ｃｍ２以下の添加量ではメシル酸ブロモク
リプチンの安定化効果が充分でなく、また、５ｍｇ／ｃ
ｍ２を超える添加量は、それによりさらに安定化効果の
向上は見られないので、その添加量は、上記の０．１ｍ
ｇ／ｃｍ２〜５ｍｇ／ｃｍ２の添加量の範囲から、適宜
設定されて用いられる。Next, the present invention will be explained in detail. Regarding the preparation according to the present invention, the amount of yellow iron sesquioxide and/or iron sesquioxide added is 0.1 mg/cm2 to 5 mg/cm2, preferably 0.2 mg/cm2 as iron oxide per unit surface area of the preparation. ~5 mg/cm2. If the amount added is less than 0.1 mg/cm2, the stabilizing effect of bromocriptine mesylate will not be sufficient;
If the amount added exceeds 0.1 m2, no further improvement in the stabilizing effect will be observed.
The amount to be added is set as appropriate from the range of g/cm2 to 5 mg/cm2.
【０００９】また、黄色三二酸化鉄および三二酸化鉄は
、それぞれ単独の使用によっても所期の安定化効果は得
られるが、両酸化鉄を併用する場合には黄色から赤色へ
と遮光波長域が広がるためより効果的である。上記の黄
色三二酸化鉄および三二酸化鉄は、所要量のメシル酸ブ
ロモクリプチンと賦形剤、結合剤などの添加剤と共に錠
剤、丸剤、顆粒剤あるいはカプセル剤などの固型剤形の
薬剤物質の被覆剤中に添加される。最終製剤製品を製造
する際の被覆剤の被覆方法については、特に特定はされ
ず、慣用の被覆方法によるのが通常である。以下に、本
発明にかかる製剤に関し、錠剤を例にとり、その実施例
、比較例並びに実験例を掲げ、本発明を、さらに詳細に
説明する。[0009] In addition, yellow iron sesquioxide and iron sesquioxide can achieve the desired stabilizing effect even when used alone, but when both iron oxides are used together, the light-shielding wavelength range changes from yellow to red. It is more effective because it spreads. The above-mentioned yellow iron sesquioxide and iron sesquioxide are used together with the required amount of bromocriptine mesylate and additives such as excipients and binders to form a drug substance in a solid dosage form such as a tablet, pill, granule or capsule. Added to coatings. The coating method for producing the final pharmaceutical product is not particularly specified, and a conventional coating method is usually used. In the following, the present invention will be explained in more detail with respect to the formulation according to the present invention, taking tablets as an example and presenting Examples, Comparative Examples, and Experimental Examples.
【００１０】実施例１
下記の処方により錠剤を調製する。
（処 方） フィルム錠
メシル酸ブロモクリプチン
２．８７ｍｇ
（ブロモクリプチンとして２．５０ｍｇ）
結晶セルロース
１１６．３３ｍ
ｇ ヒドロキシプロピルセルロース
１．００ｍｇ
カルボキシメチルセルロース
２０．００ｍｇ シ
ョ糖脂肪酸エステル
９．８０ｍｇ
ヒドロキシプロピルメチルセルロース２９１０
７．９０ｍｇ マクロゴール６０
００
１．７４ｍｇ 黄色三二酸化
鉄
０．１８ｍｇ三二酸
化鉄
０．
１８ｍｇ 合 計
１６０．００ｍｇExample 1 Tablets are prepared according to the following formulation. (Prescription) Film tablet Bromocriptine mesylate
2.87mg
(2.50mg as bromocriptine)
crystalline cellulose
116.33m
g Hydroxypropylcellulose
1.00mg
carboxymethylcellulose
20.00mg sucrose fatty acid ester
9.80mg
Hydroxypropyl methylcellulose 2910
7.90mg macrogol 60
00
1.74mg yellow iron sesquioxide
0.18mg iron sesquioxide
0.
18mg total
160.00mg
【００１１】（調製方法）メ
シル酸ブロモクリプチン２８．７ｇに結晶セルロース１
１６３．３ｇおよびカルボキシメチルセルロース２００
ｇを加えて混合した後、局方エタノール１９０ｇにヒド
ロキシプロピルセルロース１０ｇを溶解した結合剤を加
え、バーチカルグラニュレーター（パウレック社製）お
よびフローコーター（フロイント産業製）で造粒する。
この造粒物を乾燥後、ショ糖脂肪酸エステル９８ｇを添
加混合し、ロータリー式打錠機（畑鐵工所製ＨＴ−Ｐ２
２）で１００００錠の錠剤を調製する。この錠剤に局方
エタノール７４５ｇ、ジクロロメタン７４５ｇ、ヒドロ
キシプロピルメチルセルロース２９１０ ７９ｇ、マ
クロゴール６０００ １．７４ｇ、黄色三二酸化鐵１
．８ｇ、三二酸化鉄１．８ｇからなる被覆剤をハイコー
ター（フロイント産業製）を用いて１錠あたり１０ｍｇ
（フィルム厚、約０．０８ｍｍ）のフィルムコーティン
グを施し、フィルムコーティング錠を調製する。(Preparation method) 28.7 g of bromocriptine mesylate and 1 part of crystalline cellulose
163.3g and carboxymethylcellulose 200g
After mixing, a binder prepared by dissolving 10 g of hydroxypropyl cellulose in 190 g of pharmacopoeial ethanol is added, and the mixture is granulated using a vertical granulator (manufactured by Powrex) and a flow coater (manufactured by Freund Sangyo). After drying the granules, 98 g of sucrose fatty acid ester was added and mixed, and
2) Prepare 10,000 tablets. This tablet contains 745 g of pharmacopoeial ethanol, 745 g of dichloromethane, 79 g of hydroxypropyl methyl cellulose, 1.74 g of macrogol 6000, and 1 yellow iron sesquioxide.
．． 8g of iron sesquioxide and 1.8g of iron sesquioxide per tablet using Hi-Coater (manufactured by Freund Sangyo).
(film thickness, approximately 0.08 mm) to prepare film-coated tablets.
【００１２】実施例２
下記の処方により錠剤を調製する。
（処 方） フィルム錠
メシル酸ブロモクリプチン
２．８７ｍｇ
（ブロモクリプチンとして２．５０ｍｇ）
結晶セルロース
１１６．３３ｍ
ｇ ヒドロキシプロピルセルロース
１．００ｍｇ
カルボキシメチルセルロース
２０．００ｍｇ シ
ョ糖脂肪酸エステル
９．８０ｍｇ
ヒドロキシプロピルメチルセルロース２９１０
７．９０ｍｇ マクロゴール６０
００
１．７４ｍｇ黄色三二酸化鉄
０．３６ｍｇ
合 計
１６０
．００ｍｇExample 2 Tablets are prepared according to the following formulation. (Prescription) Film tablet Bromocriptine mesylate
2.87mg
(2.50mg as bromocriptine)
crystalline cellulose
116.33m
g Hydroxypropylcellulose
1.00mg
carboxymethylcellulose
20.00mg sucrose fatty acid ester
9.80mg
Hydroxypropyl methylcellulose 2910
7.90mg macrogol 60
00
1.74mg yellow iron sesquioxide
0.36mg
total
160
．． 00mg
【００１３】（調製方法）メシル酸ブロモク
リプチン２８．７ｇに結晶セルロース１１６３．３ｇお
よびカルボキシメチルセルロース２００ｇを加えて混合
した後、局方エタノール１９０ｇにヒドロキシプロピル
セルロース１０ｇを溶解した結合剤を加え、バーチカル
グラニュレーター（パウレック社製）およびフローコー
ター（フロイント産業製）で造粒する。この造粒物を乾
燥後、ショ糖脂肪酸エステル９８ｇを添加混合し、ロー
タリー式打錠機（畑鐵工所製ＨＴ−Ｐ２２）で１０００
０錠の錠剤を調製する。この錠剤に局方エタノール７４
５ｇ、ジクロロメタン７４５ｇ、ヒドロキシプロピルメ
チルセルロース２９１０ ７９ｇ、マクロゴール６０
００ １．７４ｇ、黄色三二酸化鉄３．６ｇ、からな
る被覆剤をハイコーター（フロイント産業製）を用いて
１錠あたり１０ｍｇ（フィルム厚、約０．０８ｍｍ）の
フイルムコーティングを施し、フィルムコーティング錠
を調製する。(Preparation method) After adding and mixing 1163.3 g of crystalline cellulose and 200 g of carboxymethyl cellulose to 28.7 g of bromocriptine mesylate, a binder prepared by dissolving 10 g of hydroxypropyl cellulose in 190 g of pharmacopoeial ethanol was added, and a vertical granulator was added. (manufactured by Powrex) and a flow coater (manufactured by Freund Sangyo). After drying the granules, 98 g of sucrose fatty acid ester was added and mixed, and a rotary tablet machine (HT-P22 manufactured by Hata Iron Works) was used to
Prepare 0 tablets. This tablet contains ethanol 74 in the pharmacopoeia.
5g, dichloromethane 745g, hydroxypropyl methylcellulose 2910 79g, macrogol 60
00 1.74g and yellow iron sesquioxide 3.6g were coated with a film coating of 10mg (film thickness, approximately 0.08mm) per tablet using a Hi-Coater (manufactured by Freund Sangyo) to form film-coated tablets. Prepare.
【００１４】実施例３
下記の処方により錠剤を調製する。
（処 方） フィルム錠
メシル酸ブロモクリプチン
２．８７ｍｇ
（ブロモクリプチンとして２．５０ｍｇ）
結晶セルロース
１１６．３３ｍ
ｇ ヒドロキシプロピルセルロース
１．００ｍｇ
カルボキシメチルセルロース
２０．００ｍｇ シ
ョ糖脂肪酸エステル
９．８０ｍｇ
ヒドロキシプロピルメチルセルロース２９１０
７．９０ｍｇ マクロゴール６０
００
１．７４ｍｇ三二酸化鉄
０．３６ｍｇ
合 計
１
６０．００ｍｇExample 3 Tablets are prepared according to the following formulation. (Prescription) Film tablet Bromocriptine mesylate
2.87mg
(2.50mg as bromocriptine)
crystalline cellulose
116.33m
g Hydroxypropylcellulose
1.00mg
carboxymethylcellulose
20.00mg sucrose fatty acid ester
9.80mg
Hydroxypropyl methylcellulose 2910
7.90mg macrogol 60
00
1.74mg iron sesquioxide
0.36mg
total
1
60.00mg
【００１５】（調製方法）メシル酸ブロ
モクリプチン２８．７ｇに結晶セルロース１１６３．３
ｇおよびカルボキシメチルセルロース２００ｇを加えて
混合した後、局方エタノール１９０ｇにヒドロキシプロ
ピルセルロース１０ｇを溶解した結合剤を加え、バーチ
カルグラニュレーター（パウレック社製）およびフロー
コーター（フロイント産業製）で造粒する。この造粒物
を乾燥後、ショ糖脂肪酸エステル９８ｇを添加混合し、
ロータリー式打錠機（畑鐵工所製ＨＴ−Ｐ２２）で１０
０００錠の錠剤を調製する。この錠剤に局方エタノール
７４５ｇ、ジクロロメタン７４５ｇ、ヒドロキシプロピ
ルメチルセルロース２９１０ ７９ｇ、マクロゴール
６０００ １．７４ｇ、三二酸化鉄３．６ｇからなる
被覆剤をハイコーター（フロイント産業製）を用いて１
錠あたり１０ｍｇ（フィルム厚、約０．０８ｍｍ）のフ
ィルムコーテイングを施し、フイルムコーティング錠を
調製する。(Preparation method) 28.7 g of bromocriptine mesylate and 1163.3 g of crystalline cellulose
After adding and mixing 10 g of hydroxypropyl cellulose in 190 g of pharmacopoeial ethanol, a binder is added and granulated using a vertical granulator (manufactured by Powrex) and a flow coater (manufactured by Freund Sangyo). After drying this granulated material, 98 g of sucrose fatty acid ester was added and mixed,
10 with a rotary tablet press (HT-P22 manufactured by Hata Iron Works)
000 tablets are prepared. A coating agent consisting of 745 g of pharmacopoeial ethanol, 745 g of dichloromethane, 79 g of hydroxypropyl methyl cellulose, 1.74 g of macrogol 6000, and 3.6 g of iron sesquioxide was applied to the tablets using a Hi-coater (manufactured by Freund Sangyo).
A film coating of 10 mg (film thickness, about 0.08 mm) is applied to each tablet to prepare a film-coated tablet.
【００１６】比較例１
下記の処方により錠剤を調製する。
（処 方） 裸錠
メシル酸ブロモクリプチン
２．８７ｍｇ
（ブロモクリプチンとして２．５０ｍｇ）
結晶セルロース
１１６．３３ｍ
ｇ ヒドロキシプロピルセルロース
１．００ｍｇ
ヒドロキシメチルセルロース
２０．００ｍｇショ糖
脂肪酸エステル
９．８０ｍｇ
合 計
１
５０．００ｍｇComparative Example 1 Tablets are prepared according to the following formulation. (Prescription) Plain tablet Bromocriptine mesylate
2.87mg
(2.50mg as bromocriptine)
crystalline cellulose
116.33m
g Hydroxypropylcellulose
1.00mg
hydroxymethylcellulose
20.00mg sucrose fatty acid ester
9.80mg
total
1
50.00mg
【００１７】（調製方法）メシル酸ブロ
モクリプチン２８．７ｇに結晶セルロース１１６３．３
ｇおよびカルボキシメチルセルロース２００ｇを加えて
混合した後、局方エタノール１９０ｇにヒドロキシプロ
ピルセルロース１０ｇを溶解した結合剤を加え、バーチ
カルグラニュレーター（パウレック社製）およびフロー
コーター（フロイント産業製）で造粒する。この造粒物
を乾燥後、ショ糖脂肪酸エステル９８ｇを添加混合し、
ロータリー式打錠機（畑鐵工所製ＨＴ−Ｐ２２）で１０
０００錠の錠剤を調製する。(Preparation method) 28.7 g of bromocriptine mesylate and 1163.3 g of crystalline cellulose
After adding and mixing 10 g of hydroxypropyl cellulose in 190 g of pharmacopoeial ethanol, a binder is added and granulated using a vertical granulator (manufactured by Powrex) and a flow coater (manufactured by Freund Sangyo). After drying this granulated material, 98 g of sucrose fatty acid ester was added and mixed,
10 with a rotary tablet press (HT-P22 manufactured by Hata Iron Works)
000 tablets are prepared.
【００１８】実験例
実施例１および比較例１の錠剤について以下の方法で光
に対する安定性試験を行った。Experimental Examples The tablets of Example 1 and Comparative Example 1 were tested for stability against light in the following manner.
【００１９】１） 検 体 ■実施例１の錠剤（フイルム錠） ■比較例１の錠剤（裸錠）1) Examination body ■Tablet of Example 1 (film tablet) ■Tablets of Comparative Example 1 (naked tablets)
【００２０】２） 波長選択用フィルター■短波長フ
ィルター ＵＶ−Ｄ３３Ｓ■中波長フィルター Ｂ
−４８Ｓ
■長波長フイルター Ｏ−５４
■全波長フィルター ＵＶ−２２（ベースのフィルタ
ーとして用いる）2) Wavelength selection filter - Short wavelength filter UV-D33S - Medium wavelength filter B
-48S ■Long wavelength filter O-54 ■Full wavelength filter UV-22 (used as a base filter)
【００２１】３） 露光試験
照射光源として陽光ランプ（東芝電材製４００Ｗ．Ｄ４
００）を用い、光源の直下約６０ｃｍに直径１０ｃｍ、
高さ約２ｃｍのシャーレを置き試料を並べた。シャーレ
の５ｃｍ位上部には、各フィルターを置き短波長、中波
長、長波長のみを通過させて波長依存性を確認した。上
記■のフィルターは照射光源の熱の影響をみるためのブ
ランクテストのためのものである。3) A sunlight lamp (400W.D4 manufactured by Toshiba Denzai Co., Ltd.) was used as the exposure test irradiation light source.
00), a diameter of 10 cm, approximately 60 cm directly below the light source,
A petri dish with a height of about 2 cm was placed and the samples were arranged. Each filter was placed about 5 cm above the Petri dish to allow only short, medium, and long wavelengths to pass through to confirm wavelength dependence. The filter ① above is for a blank test to see the effect of heat from the irradiation light source.
【００２２】４） 照射期間 上記の方法により７日および１５日間照射した。4) Irradiation period Irradiation was performed for 7 and 15 days using the method described above.
【００２３】５） 測定項目および定量法■性状（色
）
比較例１の裸錠は錠剤表面について、また、実施例１の
フィルム錠は、フィルムを剥いだ素錠表面について観察
した。
■定量法
経時的に照射した試料錠をメタノールで抽出し、試料錠
中のメシル酸ブロモクリプチン量を高速液体クロマトグ
ラフ法により求めた。5) Measurement Items and Assay Method ■Properties (Color) The plain tablets of Comparative Example 1 were observed on the tablet surface, and the film tablets of Example 1 were observed on the surface of the uncoated tablet from which the film was removed. ■Quantitative method Sample tablets irradiated over time were extracted with methanol, and the amount of bromocriptine mesylate in the sample tablets was determined by high performance liquid chromatography.
【００２４】（測定条件）検出波長：３００ｎｍカラム
：オクタデシルシリル化シリカゲルを充填したカラム
カラム温度：５０°付近の一定温度
移動相：アセトニトリル・０．０１Ｍ炭酸アンモニウム
液混液（７：３）(Measurement conditions) Detection wavelength: 300 nm Column: Column packed with octadecylsilylated silica gel Column temperature: Constant temperature around 50° Mobile phase: Acetonitrile/0.01M ammonium carbonate liquid mixture (7:3)
【００２５】６） 測定結果
実施例１のフィルムコーティング錠は後掲の表−１に示
すとおりであり、性状では、フイルム面の変化は１５日
後にもみられず、フィルムを剥いだ素錠部表面のみ着色
傾向がみられたが、裸錠に比べるとかなり抑制されてい
た。含量についても残存率は１０１．３％、９８．４％
、９９．０％で低下傾向は、ほとんどみられなかった。
これに対し、比較例１の裸錠では後掲の表−２に示すと
おり、長波長は、照射１５日後で性状に変化はなく、含
量も残存率で１００．３％と安定であったが、中波長お
よび短波長では、表面が白色から、まだらに濃褐色とな
っていた。含量についても残存率でそれぞれ８３．２％
、８９．３％と大きな低下が認められた。6) Measurement Results The film-coated tablet of Example 1 is as shown in Table 1 below, and in terms of properties, no change was observed on the film surface even after 15 days, and the surface of the plain tablet after the film was peeled off. Although there was a tendency for coloration to occur, this was considerably suppressed compared to the plain tablets. Regarding the content, the residual rate is 101.3% and 98.4%.
, 99.0%, with almost no downward trend observed. On the other hand, in the case of the plain tablet of Comparative Example 1, as shown in Table 2 below, there was no change in the long wavelength properties after 15 days of irradiation, and the content was stable with a residual rate of 100.3%. At medium and short wavelengths, the surface changed from white to dark brown in spots. Regarding the content, the residual rate was 83.2%.
, a large decrease of 89.3% was observed.
【００２６】[0026]
【発明の効果】後掲の表−１および表−２の結果から明
らかなように、本発明にかかる製剤については、光安定
性の改善効果が顕著に認められた。この効果により、現
在ＰＴＰ包装などがなされて提供されているメシル酸ブ
ロモクリプチン製剤が、包装容器から取り出された際に
、光によって変色したり、主薬含量が低下するという問
題も解消され、臨床の場でまた患者が服用の際にも取り
扱いやすいメシル酸ブロモクリプチン製剤が提供される
。Effects of the Invention As is clear from the results shown in Tables 1 and 2 below, the formulation according to the present invention had a remarkable effect of improving photostability. This effect eliminates the problem that bromocriptine mesylate preparations, which are currently provided in PTP packaging, discolor due to light or decrease in active drug content when taken out of the packaging container, and can be used in clinical settings. Also provided is a bromocriptine mesylate formulation that is easy for patients to handle when taking it.
【００２７】[0027]
【表１】[Table 1]
【００２８】[0028]
【表２】[Table 2]
Claims (1)
として含有する固型剤形の薬剤物質を、黄色三二酸化鉄
および（または）三二酸化鉄を含む被覆剤で被覆したこ
とを特徴とする製剤。1. A preparation comprising a pharmaceutical substance in solid dosage form containing bromocriptine mesylate as an active ingredient and coated with a coating agent containing yellow iron sesquioxide and/or iron sesquioxide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21815791A JPH04346929A (en) | 1991-05-22 | 1991-05-22 | Bromocriptine mesylate preparation having stability to light |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21815791A JPH04346929A (en) | 1991-05-22 | 1991-05-22 | Bromocriptine mesylate preparation having stability to light |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH04346929A true JPH04346929A (en) | 1992-12-02 |
Family
ID=16715536
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP21815791A Pending JPH04346929A (en) | 1991-05-22 | 1991-05-22 | Bromocriptine mesylate preparation having stability to light |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH04346929A (en) |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997039752A1 (en) * | 1996-04-24 | 1997-10-30 | Shionogi & Co., Ltd. | Sertindole preparation and process for the production thereof |
| WO2001010466A1 (en) * | 1999-08-04 | 2001-02-15 | Yamanouchi Pharmaceutical Co., Ltd. | Stable medicinal compositions for oral use |
| US6562375B1 (en) | 1999-08-04 | 2003-05-13 | Yamanouchi Pharmaceuticals, Co., Ltd. | Stable pharmaceutical composition for oral use |
| JP2005263790A (en) * | 2004-02-20 | 2005-09-29 | Eisai Co Ltd | Medicinal preparation containing warfarin potassium and method for producing the same |
| JP2006524230A (en) * | 2003-04-24 | 2006-10-26 | ヤゴテック アーゲー | Tablet with colored core |
| WO2007065448A1 (en) * | 2005-09-08 | 2007-06-14 | H. Lundbeck A/S | Stable solid formulation of sertindole |
| WO2010087462A1 (en) * | 2009-01-29 | 2010-08-05 | 大日本住友製薬株式会社 | Orally disintegrating tablet having inner core |
| JP2011126906A (en) * | 2004-02-20 | 2011-06-30 | Eisai R & D Management Co Ltd | Medicinal preparation containing warfarin potassium and method for producing the same |
| JP2012062327A (en) * | 2011-12-26 | 2012-03-29 | Dainippon Sumitomo Pharma Co Ltd | Composition with improved light stability |
| CN105640901A (en) * | 2014-11-10 | 2016-06-08 | 匈牙利吉瑞大药厂 | Method for preparing bromocriptine mesylate tablets by virtue of novel production process and application of method |
| US9652620B2 (en) | 2014-01-08 | 2017-05-16 | Kabushiki Kaisha Toshiba | Quantum communication device, quantum communication method, and computer program product |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6268860A (en) * | 1985-09-10 | 1987-03-28 | バイエル・アクチエンゲゼルシヤフト | Gelatin-containing beta-carotene |
-
1991
- 1991-05-22 JP JP21815791A patent/JPH04346929A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6268860A (en) * | 1985-09-10 | 1987-03-28 | バイエル・アクチエンゲゼルシヤフト | Gelatin-containing beta-carotene |
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997039752A1 (en) * | 1996-04-24 | 1997-10-30 | Shionogi & Co., Ltd. | Sertindole preparation and process for the production thereof |
| WO2001010466A1 (en) * | 1999-08-04 | 2001-02-15 | Yamanouchi Pharmaceutical Co., Ltd. | Stable medicinal compositions for oral use |
| US6562375B1 (en) | 1999-08-04 | 2003-05-13 | Yamanouchi Pharmaceuticals, Co., Ltd. | Stable pharmaceutical composition for oral use |
| JP2006524230A (en) * | 2003-04-24 | 2006-10-26 | ヤゴテック アーゲー | Tablet with colored core |
| JP4908200B2 (en) * | 2003-04-24 | 2012-04-04 | ヤゴテック アーゲー | Tablet with colored core |
| JP2011126906A (en) * | 2004-02-20 | 2011-06-30 | Eisai R & D Management Co Ltd | Medicinal preparation containing warfarin potassium and method for producing the same |
| JP2005263790A (en) * | 2004-02-20 | 2005-09-29 | Eisai Co Ltd | Medicinal preparation containing warfarin potassium and method for producing the same |
| EA013167B1 (en) * | 2005-09-08 | 2010-02-26 | Х. Лундбекк А/С | Stable solid formulation of sertindole |
| WO2007065448A1 (en) * | 2005-09-08 | 2007-06-14 | H. Lundbeck A/S | Stable solid formulation of sertindole |
| WO2010087462A1 (en) * | 2009-01-29 | 2010-08-05 | 大日本住友製薬株式会社 | Orally disintegrating tablet having inner core |
| CN102300563A (en) * | 2009-01-29 | 2011-12-28 | 大日本住友制药株式会社 | Orally disintegrating tablet having inner core |
| JP5591128B2 (en) * | 2009-01-29 | 2014-09-17 | 大日本住友製薬株式会社 | Orally disintegrating tablet with inner core |
| JP2012062327A (en) * | 2011-12-26 | 2012-03-29 | Dainippon Sumitomo Pharma Co Ltd | Composition with improved light stability |
| US9652620B2 (en) | 2014-01-08 | 2017-05-16 | Kabushiki Kaisha Toshiba | Quantum communication device, quantum communication method, and computer program product |
| CN105640901A (en) * | 2014-11-10 | 2016-06-08 | 匈牙利吉瑞大药厂 | Method for preparing bromocriptine mesylate tablets by virtue of novel production process and application of method |
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