JPH0526762B2 - - Google Patents
Info
- Publication number
- JPH0526762B2 JPH0526762B2 JP58067649A JP6764983A JPH0526762B2 JP H0526762 B2 JPH0526762 B2 JP H0526762B2 JP 58067649 A JP58067649 A JP 58067649A JP 6764983 A JP6764983 A JP 6764983A JP H0526762 B2 JPH0526762 B2 JP H0526762B2
- Authority
- JP
- Japan
- Prior art keywords
- tablet
- tablets
- disintegrant
- meshes
- glycolate
- 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.)
- Expired - Lifetime
Links
- 239000001913 cellulose Substances 0.000 claims description 11
- 229920002678 cellulose Polymers 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- 239000000843 powder Substances 0.000 claims description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 5
- 229910052791 calcium Inorganic materials 0.000 claims description 5
- 239000011575 calcium Substances 0.000 claims description 5
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 claims description 4
- 125000002057 carboxymethyl group Chemical class [H]OC(=O)C([H])([H])[*] 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 4
- 238000000465 moulding Methods 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims 1
- 239000003826 tablet Substances 0.000 description 20
- 239000007884 disintegrant Substances 0.000 description 12
- 235000010980 cellulose Nutrition 0.000 description 9
- CHRHZFQUDFAQEQ-UHFFFAOYSA-L calcium;2-hydroxyacetate Chemical compound [Ca+2].OCC([O-])=O.OCC([O-])=O CHRHZFQUDFAQEQ-UHFFFAOYSA-L 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 239000002245 particle Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical group O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 description 3
- 239000007916 tablet composition Substances 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 230000001079 digestive effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 238000010298 pulverizing process Methods 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- BXKDSDJJOVIHMX-UHFFFAOYSA-N edrophonium chloride Chemical compound [Cl-].CC[N+](C)(C)C1=CC=CC(O)=C1 BXKDSDJJOVIHMX-UHFFFAOYSA-N 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 239000000449 pharmaceutical disintegrant Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 238000009496 sugar coating process Methods 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Description
本発明は表面状態の改良された錠剤の製造方法
に関するものであり、詳しくは300メツシユ通過
微粉末の繊維素グリコール酸カルシウムを崩壊剤
として添加使用し、賦形することを特徴とする錠
剤の製造方法に関するものである。
固型薬剤は経口摂取後、胃や腸の消化液中で崩
壊し、薬効成分を放出し、胃や腸の壁面から人体
に薬効成分を吸収させるものであるが、取扱い時
は形状が安定して保持されながら、消化液中での
崩壊を充分に行わせるため、多くの場合崩壊剤が
配合使用される。繊維素グリコール酸カルシウム
は医薬用崩壊剤として最も多用されているが、無
味、無臭、白色であつて崩壊性、膨潤倍率、圧縮
成形性などが良好であるなどの利点を有するため
であり、カルボキシメチルセルロースカルシウム
として日本薬局方に収載されECG−505の商品名
(ニチリン化学工業株式会社製造)で市販されて
いる。因みに繊維素グリコール酸カルシウムは
ECG−505の単一グレード商品のみが市販されて
おり、一般的な性質は水中1重量%分散液の媒体
のPHは5〜5.5で、粒度は200メツシユ通過、無水
グルコース単位当たりのカルボキシメチル基の置
換度は0.55〜0.6である。
この水中1%分散液の媒体PHを中和度と呼称す
る。
われわれはさきに無水グルコース単位あたりの
カルボキシメチル基置換度が0.30以上0.80以下の
繊維素グリコール酸カルシウムを崩壊剤として添
加使用する固型薬剤の製造方法において300メツ
シユを通過する微粉末を含有しないものを使用す
ることにより、崩壊性に優れた固型薬剤が得られ
ることを見出し、この事実に基づく発明を特願昭
58−42722号(特開昭59−193815号公報参照)に
特許出願した。
繊維素グリコール酸カルシウムは通常の方法、
例えば特公昭43−7960明細書に示された方法で合
成し乾燥粉砕したものは、かなり広い粒度分布を
有するので篩分して使用する。95%以上が145メ
ツシユを通過する程度に粉砕した場合には300メ
ツシユを通過する微粉末留分が全体の約50%に達
する。特願昭58−42722号に規定した留分のみを
固型製剤の製造に使用するとすれば全体の50%し
か一次的には利用できない。この300メツシユ通
過の微粉末は再湿潤することにより凝集させるこ
とができるので乾燥、粉砕することによつて300
メツシユ不通過の粒度のものを採取することがで
きる。このような再造粒・粉砕の工程は多くとも
3回程度に止めるのが好ましい。湿潤・乾燥・粉
砕の工程を繰り返したものは崩壊性その他錠剤物
性に対して与える影響に殆んど変化がないが若干
着色してくる傾向があるからである。
この発明の発明者等はこの300メツシユ通過の
微粉末の繊維素グリコール酸カルシウムの有効利
用法につき検討した結果、崩壊剤として300メツ
シユ通過の微粉末のみを使用して成型することに
より表面状態の良好な錠剤が得られることを見出
した。
一般に繊維素グリコール酸カルシウムをはじめ
とする繊維素誘導体の錠剤添加剤は、打錠したと
きに表面状態の平滑性を欠くことが指摘されてい
る。このことは裸錠においては外観が劣ることに
なり、糖衣錠においては糖衣工程の作業性が劣る
という傾向を与える。特に崩壊剤は、主薬や賦形
剤その他の成分と予めよく混合しておいて打錠す
る場合のほか、一部を打錠直前に混合することも
行われている。後者の方法は崩壊効果をより高め
る手段として用いられているが、この場合崩壊剤
が比較的錠剤の表面近くに位置することになり、
表面状態に与える影響が大きい。
即ち、300メツシユ通過の微粉末の繊維素グリ
コール酸カルシウムを、通常崩壊剤として配合使
用される量、即ち全組成物に対し3〜10重量%使
用し、打錠したものは粒度の大きい崩壊剤を使用
したものに比べ錠剤表面の平滑性に優れたものが
得られる。
尚本発明の方法は、特願昭58−42722号に述べ
たように、粒度の大きい崩壊剤を用いた場合に比
して崩壊性に与える効果は若干劣る傾向がある。
従つて本発明の方法は、例えば主薬が水溶性薬剤
である場合のように、相対的にそれほど大きな崩
壊性を必要としない錠剤組成物に適した製造方法
である。
以下に実施例をあげて本発明を説明する。
実施例及び比較例
無水グルコース単位あたりのカルボキシメチル
基置換度0.52中和度PH4.9の繊維素グリコール酸
カルシウムを以下の粒度別に篩分した。
The present invention relates to a method for producing tablets with improved surface condition, and more specifically, the present invention relates to a method for producing tablets with improved surface condition, and more specifically, a method for producing tablets characterized by adding and using 300-mesh fine powdered calcium fibrous glycolate as a disintegrant and shaping the tablets. It is about the method. After solid drugs are orally ingested, they disintegrate in the digestive juices of the stomach and intestines, releasing their medicinal ingredients and allowing them to be absorbed into the human body through the walls of the stomach and intestines, but their shape remains stable during handling. In many cases, a disintegrant is used in combination to ensure sufficient disintegration in digestive fluids while retaining water. Calcium glycolate is most commonly used as a pharmaceutical disintegrant because it has advantages such as being tasteless, odorless, white, and having good disintegration properties, swelling ratio, compression moldability, etc. It is listed in the Japanese Pharmacopoeia as methylcellulose calcium and is commercially available under the trade name ECG-505 (manufactured by Nichirin Chemical Industry Co., Ltd.). By the way, cellulose calcium glycolate is
Only a single grade of ECG-505 is commercially available, and the general properties are 1% by weight dispersion in water, medium pH of 5-5.5, particle size passing through 200 meshes, carboxymethyl groups per anhydroglucose unit. The degree of substitution is 0.55-0.6. The medium pH of this 1% dispersion in water is called the degree of neutralization. We have previously developed a method for producing a solid drug that does not contain fine powder that passes through 300 meshes in a method for producing a solid drug that uses cellulose calcium glycolate with a degree of substitution of carboxymethyl groups of 0.30 to 0.80 per anhydroglucose unit as a disintegrant. It was discovered that a solid drug with excellent disintegration properties could be obtained by using
A patent application was filed for No. 58-42722 (see Japanese Unexamined Patent Publication No. 193815/1983). Cellulose calcium glycolate is prepared in the usual way,
For example, the product synthesized by the method shown in Japanese Patent Publication No. 7960/1983, dried and ground, has a fairly wide particle size distribution and is therefore used after being sieved. When pulverized to such an extent that 95% or more passes through 145 meshes, the fine powder fraction that passes through 300 meshes reaches approximately 50% of the total. If only the fraction specified in Japanese Patent Application No. 58-42722 were to be used in the production of solid preparations, only 50% of the total would be available for primary use. This fine powder that has passed through the 300 mesh can be agglomerated by rewetting, so it can be dried and crushed to
It is possible to collect particles with a particle size that does not pass through the mesh. It is preferable that such re-granulation and pulverization steps be carried out no more than three times. This is because tablets subjected to repeated wetting, drying, and pulverizing steps tend to become slightly colored, although there is almost no change in disintegration and other physical properties of the tablet. The inventors of this invention investigated the effective use of this fine powder of cellulose calcium glycolate that passed through 300 meshes, and found that the surface condition could be improved by molding using only the fine powder that passed through 300 meshes as a disintegrant. It has been found that good tablets can be obtained. It has been pointed out that tablet additives of cellulose derivatives, such as cellulose calcium glycolate, generally lack surface smoothness when compressed into tablets. This tends to lead to poor appearance in plain tablets and poor workability in the sugar-coating process in sugar-coated tablets. In particular, disintegrants are mixed well with the main drug, excipients, and other components before tabletting, or a portion of the disintegrant is mixed immediately before tabletting. The latter method is used as a means to further enhance the disintegration effect, but in this case the disintegrant is located relatively close to the surface of the tablet,
It has a large effect on the surface condition. That is, finely powdered calcium cellulose glycolate that passes through 300 meshes is used in the amount normally used as a disintegrant, that is, 3 to 10% by weight based on the total composition, and the tablets are used as a disintegrant with a large particle size. Tablets with superior smoothness on the surface can be obtained compared to those using tablets. As stated in Japanese Patent Application No. 58-42722, the method of the present invention tends to have a slightly inferior effect on disintegration properties compared to the case where a disintegrant with a large particle size is used.
Therefore, the method of the present invention is suitable for producing tablet compositions that do not require relatively high disintegration properties, such as when the main drug is a water-soluble drug. The present invention will be explained below with reference to Examples. Examples and Comparative Examples Cellulose calcium glycolate having a degree of carboxymethyl group substitution per anhydroglucose unit of 0.52 and a degree of neutralization PH of 4.9 was sieved into the following particle sizes.
【表】
上記繊維素グリコール酸カルシウムを崩壊剤と
して使用し、薬効成分としてアスコルビン酸、賦
形剤として微結晶セルロース(アビセルPH101、
旭化成製)及び乳糖、滑沢剤としてタルク及びス
テアリン酸マグネシウムを配合した錠剤を直接打
錠法によつて作製した。錠剤組成及び錠剤条件は
次の通りである。
錠剤組成
アスコルビン酸 50.0
アビヤルPH101 28.0
乳糖 14.0
崩壊剤 5.0
タルク 2.5
ステアリン酸マグネシウム 0.5
100.0重量%
製剤条件;
錠径 12mmφ 厚み 4mm
重量 約700mg 打錠圧 4t
崩壊性;
25mmφ×2mの管中に局方第1液(人工胃液)
を満し水面から錠剤を落して液中を落下させ、完
全に分散するのに要する時間を測定
硬度;
モンサント硬度計使用
表面状態;
径12mmφの錠剤では表面状態が機械計測できな
いので径20mmφの大型錠剤を作成しその白色度を
測定した
大型錠剤 成型条件
重量1.0g 20mmφ×2.5mm(厚み)
テンシロンUTM−1/500(東洋精機)使用
圧縮荷重 4.5tm
表面状態は色差計(スガ試験機)で白色度を
測定 100に近いほど白度が高い
測定結果を第1表に示す[Table] The above cellulose calcium glycolate was used as a disintegrant, ascorbic acid was used as the medicinal ingredient, and microcrystalline cellulose (Avicel PH101,
(manufactured by Asahi Kasei) and lactose, and talc and magnesium stearate as lubricants were prepared by a direct compression method. The tablet composition and tablet conditions are as follows. Tablet composition Ascorbic acid 50.0 Abyal PH101 28.0 Lactose 14.0 Disintegrant 5.0 Talc 2.5 Magnesium stearate 0.5 100.0% by weight Formulation conditions; Tablet diameter 12mmφ Thickness 4mm Weight Approximately 700mg Tablet pressure 4t Disintegration; 1 liquid (artificial gastric juice)
Hardness: Measure the time required for complete dispersion by dropping a tablet from the surface of the water. Surface condition using a Monsanto hardness meter. Since the surface condition cannot be measured mechanically for tablets with a diameter of 12 mmφ, a large one with a diameter of 20 mmφ is used. Large tablets were prepared and their whiteness was measured Molding conditions Weight 1.0g 20mmφ x 2.5mm (thickness) Tensilon UTM-1/500 (Toyo Seiki) used Compression load 4.5tm Surface condition was measured using a color difference meter (Suga Test Instruments) Measure the whiteness. The closer it is to 100, the higher the whiteness. The measurement results are shown in Table 1.
【表】【table】
【表】
た。
[Table]
Claims (1)
ル基置換度が0.30以上0.80以下の繊維素グルコー
ル酸カルシウムを配合し、加圧成型して得る錠剤
の製法において、繊維素グリコール酸カルシウム
が300メツシユを通過する微粉末のみからなるも
のを使用することを特徴とする錠剤の製法。1. A fine powder in which calcium cellulose glycolate passes through 300 meshes in a tablet manufacturing method obtained by blending calcium cellulose glycolate with a degree of substitution of carboxymethyl groups per anhydrous glycose unit of 0.30 or more and less than 0.80 and press-molding it. A method for manufacturing a tablet, characterized in that it uses a tablet consisting of:
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP6764983A JPS59193815A (en) | 1983-04-15 | 1983-04-15 | Preparation of tablet |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP6764983A JPS59193815A (en) | 1983-04-15 | 1983-04-15 | Preparation of tablet |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS59193815A JPS59193815A (en) | 1984-11-02 |
JPH0526762B2 true JPH0526762B2 (en) | 1993-04-19 |
Family
ID=13351077
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP6764983A Granted JPS59193815A (en) | 1983-04-15 | 1983-04-15 | Preparation of tablet |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS59193815A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9121414B2 (en) | 2010-11-05 | 2015-09-01 | Gentherm Incorporated | Low-profile blowers and methods |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4734285A (en) * | 1985-10-28 | 1988-03-29 | The Dow Chemical Company | Sustained release compositions |
US4704285A (en) * | 1985-11-18 | 1987-11-03 | The Dow Chemical Company | Sustained release compositions comprising hydroxypropyl cellulose ethers |
JP2680602B2 (en) * | 1987-04-24 | 1997-11-19 | 第一製薬株式会社 | Sustained-release tablets |
JP4698000B2 (en) * | 2000-06-27 | 2011-06-08 | 旭化成ケミカルズ株式会社 | Easily water-soluble drug-containing tablets |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5247914A (en) * | 1975-10-11 | 1977-04-16 | Lilly Industries Ltd | Tablet and its prepation |
JPS57155310A (en) * | 1981-03-20 | 1982-09-25 | Sumitomo Metal Ind Ltd | Removal of slag |
JPS59176217A (en) * | 1983-03-28 | 1984-10-05 | Daicel Chem Ind Ltd | Powder composition for solid pharmaceutical preparation |
-
1983
- 1983-04-15 JP JP6764983A patent/JPS59193815A/en active Granted
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5247914A (en) * | 1975-10-11 | 1977-04-16 | Lilly Industries Ltd | Tablet and its prepation |
JPS57155310A (en) * | 1981-03-20 | 1982-09-25 | Sumitomo Metal Ind Ltd | Removal of slag |
JPS59176217A (en) * | 1983-03-28 | 1984-10-05 | Daicel Chem Ind Ltd | Powder composition for solid pharmaceutical preparation |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9121414B2 (en) | 2010-11-05 | 2015-09-01 | Gentherm Incorporated | Low-profile blowers and methods |
Also Published As
Publication number | Publication date |
---|---|
JPS59193815A (en) | 1984-11-02 |
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