JP2000239186A - Disintegrator for tablet - Google Patents
Disintegrator for tabletInfo
- Publication number
- JP2000239186A JP2000239186A JP3872899A JP3872899A JP2000239186A JP 2000239186 A JP2000239186 A JP 2000239186A JP 3872899 A JP3872899 A JP 3872899A JP 3872899 A JP3872899 A JP 3872899A JP 2000239186 A JP2000239186 A JP 2000239186A
- Authority
- JP
- Japan
- Prior art keywords
- degree
- cmc
- etherification
- tablets
- 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.)
- Granted
Links
- 238000006266 etherification reaction Methods 0.000 claims abstract description 24
- 230000003647 oxidation Effects 0.000 claims abstract description 13
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 13
- 239000001768 carboxy methyl cellulose Substances 0.000 claims abstract description 10
- 239000002245 particle Substances 0.000 claims abstract description 7
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims abstract description 5
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims abstract description 5
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims abstract description 4
- 239000011734 sodium Substances 0.000 claims description 31
- 239000007884 disintegrant Substances 0.000 claims description 8
- 239000000843 powder Substances 0.000 claims description 6
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 5
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 5
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 238000000465 moulding Methods 0.000 abstract description 5
- 239000011812 mixed powder Substances 0.000 abstract 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- 238000003756 stirring Methods 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
- 229940105329 carboxymethylcellulose Drugs 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 210000000936 intestine Anatomy 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
- KJFMBFZCATUALV-UHFFFAOYSA-N phenolphthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2C(=O)O1 KJFMBFZCATUALV-UHFFFAOYSA-N 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 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
- 239000002253 acid Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000001079 digestive effect Effects 0.000 description 2
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 238000012030 stroop test Methods 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000002932 luster Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000007885 tablet disintegrant Substances 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Compositions Of Macromolecular Compounds (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、錠剤用崩壊剤とし
て用いる特定のカルボキシメチルセルロースナトリウム
（以降、ＣＭＣ−Ｎａとする）に関する。TECHNICAL FIELD The present invention relates to a specific sodium carboxymethylcellulose (hereinafter referred to as CMC-Na) used as a disintegrant for tablets.
【０００２】[0002]
【従来の技術】従来加圧成形した錠剤に使用する崩壊剤
としては、カルボキシメチルセルロースカルシウム、デ
ンプン、グアーガム、ＣＭＣ−Ｎａ、アラビアガム、Ｐ
ＶＡなどが使用されている。2. Description of the Related Art Disintegrants conventionally used for tablets formed by compression include carboxymethylcellulose calcium, starch, guar gum, CMC-Na, gum arabic,
VA and the like are used.
【０００３】これらのなかでも、従来の錠剤に使用する
崩壊剤に多く使用されているのは、カルボキシメチルセ
ルロースカルシウムであった。カルボキシメチルセルロ
ースカルシウムは、無味、無臭、白色であって、崩壊
性、膨潤倍率、圧縮成形性などが良好であるとの利点に
よるものである。[0003] Among these, calcium carboxymethylcellulose has been widely used in disintegrants used in conventional tablets. This is because calcium carboxymethylcellulose is tasteless, odorless, and white, and has good disintegration, swelling ratio, compression moldability, and the like.
【０００４】固形錠剤は経口摂取後、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、取り扱い時は形状
が安定して保持されながら、消化液中での崩壊を充分に
行わせることが必要である。[0004] Solid tablets disintegrate in the digestive juices of the stomach and intestines after oral ingestion, release medicinal ingredients, and allow the human body to absorb the medicinal ingredients from the walls of the stomach and intestine. It is necessary to sufficiently disintegrate in the digestive juice while keeping it stable.
【０００５】[0005]
【発明が解決しようとする課題】しかし、この２つの機
能は、うらはらの関係にあり、双方両立の崩壊剤は見つ
けにくく、どちらかの機能が充分に達成されないという
問題点があった。前述のカルボキシメチルセルロースカ
ルシウムにおいても同様で、崩壊性は良好であるが、形
状安定性に難があった。However, the two functions are in a backlash relationship, and it is difficult to find a disintegrant compatible with both functions, and there has been a problem that either function cannot be sufficiently achieved. The same applies to the above-mentioned calcium carboxymethylcellulose, and the disintegration is good, but the shape stability is difficult.
【０００６】[0006]
【課題を解決するための手段】そこで、従来の崩壊剤と
いう概念にこだわらず、粘結剤の機能改質をすることに
着目し、特定範囲のＣＭＣ−Ｎａを限定使用することを
考え、本発明を完成するにいたった。Accordingly, the present invention is not limited to the conventional concept of a disintegrant, but focuses on modifying the function of a binder, and considers the limited use of a specific range of CMC-Na. The invention has been completed.
【０００７】すなわち、本発明は、（ａ）エーテル化度
０．２〜０．５、酸化度０．０１〜０．２のＣＭＣ−Ｎ
ａと、（ｂ）エーテル化度０．８〜２．０のＣＭＣ−Ｎ
ａを、（ａ）：（ｂ）＝１０：９０〜５０：５０（重量
比）の割合で混合してなる粉末粒度が１７７μｍ以下で
ある錠剤用崩壊剤に関する。That is, the present invention relates to (a) CMC-N having a degree of etherification of 0.2 to 0.5 and a degree of oxidation of 0.01 to 0.2.
a, and (b) CMC-N having a degree of etherification of 0.8 to 2.0.
a): (b) = 10: 90 to 50:50 (weight ratio) and a powder disintegrant having a particle size of 177 μm or less.
【０００８】[0008]
【発明の実施の形態】本発明は、（ａ）エーテル化度
０．２〜０．５、酸化度０．０１〜０．２のＣＭＣ−Ｎ
ａと、（ｂ）エーテル化度０．８〜２．０のＣＭＣ−Ｎ
ａを、（ａ）：（ｂ）＝１０：９０〜５０：５０（重量
比）の割合で混合してなる粉末粒度が１７７μｍ以下で
ある錠剤用崩壊剤である。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to (a) CMC-N having a degree of etherification of 0.2 to 0.5 and a degree of oxidation of 0.01 to 0.2.
a, and (b) CMC-N having a degree of etherification of 0.8 to 2.0.
a): (b) = 10: 90 to 50:50 (weight ratio) is mixed to obtain a tablet disintegrant having a powder particle size of 177 μm or less.
【０００９】本発明に使用するＣＭＣ−Ｎａは、崩壊性
の強いエーテル化度０．２〜０．５、酸化度０．０１〜
０．２のＣＭＣ−Ｎａ、および粘結性の強いエーテル化
度０．８〜２．０のＣＭＣ−Ｎａを最適な比率で混合す
ることによって、従来にない両方の機能を得ることがで
きる。The CMC-Na used in the present invention has a highly degradable etherification degree of 0.2 to 0.5 and an oxidation degree of 0.01 to 0.5.
By mixing the CMC-Na of 0.2 and the CMC-Na having a strong cohesive degree of etherification of 0.8 to 2.0 in an optimum ratio, both functions which have not existed before can be obtained.
【００１０】ＣＭＣ−Ｎａは水に溶解し粘結剤として用
いるが、エーテル化度を低下(０．５以下）させること
で不溶傾向を示すようになる。さらに、酸化度を特定す
ることで、一定範囲のカルボキシメチルセルロース酸が
得られ、不溶化がより助長される。[0010] CMC-Na is dissolved in water and used as a binder. However, when the degree of etherification is reduced (0.5 or less), it tends to be insoluble. Further, by specifying the degree of oxidation, a certain range of carboxymethylcellulose acid is obtained, and insolubilization is further promoted.
【００１１】このＣＭＣ−Ｎａに粘結力の強いエーテル
化度の高い（０．８以上）ＣＭＣ−Ｎａを配合すること
が重要な要素になる。It is an important factor to mix CMC-Na with strong caking force and high etherification degree (0.8 or more) to this CMC-Na.
【００１２】低エーテル化度のＣＭＣ−Ｎａは、崩壊剤
としての機能が発揮される。エーテル化度は０．２〜
０．５であることが必要であるが、０．２〜０．４であ
ることが好ましい。エーテル化度は低いほど、酸化度は
高いほど水溶性が低下し、胃や腸での錠剤崩壊が促進さ
れるからである。CMC-Na having a low degree of etherification exhibits a function as a disintegrant. The degree of etherification is 0.2 ~
It is necessary to be 0.5, but preferably 0.2 to 0.4. This is because the lower the degree of etherification and the higher the degree of oxidation, the lower the water solubility, and the faster the disintegration of the tablet in the stomach and intestines.
【００１３】この低エーテル化度のＣＭＣ−Ｎａの酸化
度は、０．０１〜０．２であることが必要であるが、
０．１〜０．２であることが好ましい。The degree of oxidation of CMC-Na having a low degree of etherification needs to be 0.01 to 0.2.
It is preferably 0.1 to 0.2.
【００１４】高エーテル化度ＣＭＣ−Ｎａは、粘結剤と
しての機能が発揮される。そして、錠剤用の成形時にお
けるカケなどの発生抑制による歩留向上、取り扱い時の
形状安定化の効果がある。エーテル化度は０．８〜２．
０であることが必要であるが、１．０〜１．５であるこ
とが好ましい。エーテル化度は高いほど好ましいが、
２．０以上ではＣＭＣ−Ｎａ製造時の薬剤量増に伴なっ
てコストが高くなるため好ましくなく、０．８以下では
粘結力が不足する。CMC-Na with a high degree of etherification exhibits a function as a binder. In addition, there is an effect of improving the yield by suppressing the occurrence of chips and the like at the time of molding for tablets and stabilizing the shape at the time of handling. The degree of etherification is 0.8-2.
It is necessary to be 0, but it is preferably 1.0 to 1.5. The higher the degree of etherification, the better, but
If it is 2.0 or more, the cost increases with an increase in the amount of the drug during the production of CMC-Na, which is not preferable.
【００１５】この２種類のＣＭＣ−Ｎａを配合し、
（ａ）：（ｂ）＝１０：９０〜５０：５０の重量割合で
混合することが必要であるが、２０：８０〜４０：６０
であることが好ましい。低エーテル化度ＣＭＣ−Ｎａが
１割以下になると錠剤の崩壊性が低下し、５割以上にな
ると胃や腸での崩壊が遅れ薬効成分の吸収遅れ、歩留ま
りの低下が生ずる。[0015] The two kinds of CMC-Na are blended,
(A) :( b) = It is necessary to mix at a weight ratio of 10:90 to 50:50, but 20:80 to 40:60.
It is preferred that When the degree of low etherification CMC-Na is less than 10%, the disintegration of the tablet is reduced, and when it is more than 50%, disintegration in the stomach and intestine is delayed, resulting in a delay in absorption of the medicinal component and a decrease in yield.
【００１６】粉末粒度１７７μｍ以下、すなわち１７７
μｍのメッシュを全通することを条件としたのは、粗い
場合、錠剤の表面状態の平滑性に欠けること、均一混合
性に欠けることより範囲を限定したものである。一方、
粉末粒度は細かくしてもよいが、製造コストを考慮した
場合、２７μｍ以上であることが好ましい。The powder particle size is 177 μm or less, ie, 177
The condition that all the particles pass through the mesh of μm is that the range is limited due to lack of smoothness of the surface state of the tablet and lack of uniform mixing in a rough case. on the other hand,
The particle size of the powder may be fine, but is preferably 27 μm or more in consideration of the production cost.
【００１７】以下に実施例を用いて本発明をより詳細に
説明するが、本発明はこれらのみに限定されるものでは
ない。Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto.
【００１８】[0018]
【実施例】（評価方法） １．錠剤の分析方法 （１）表面状態 打錠後の錠剤を目視で比較し、以下の基準で評価した。 ◎：キメが細かく艶がありカケがない。 ○：カケはないがキメ、艶にやや劣る。 △：カケはないが、表面が粗くキメ、艶に劣る。 ×：カケがあり、表面が粗い。[Embodiment] (Evaluation method) Tablet Analysis Method (1) Surface Condition Tablets after tableting were visually compared and evaluated according to the following criteria. A: The texture is fine and glossy, and there is no chipping. ：: No chipping, but slightly inferior in texture and luster. Δ: There is no chip, but the surface is rough and texture is poor. ×: There is chipping and the surface is rough.
【００１９】（２）錠剤の成形強度 ストロープの粉化率試験機を用い、錠剤２０ｇを秤量し
て、ストロープの粉化率試験機にて１０分間回転させ
た。回転終了後、錠剤を取り出して１０メッシュ篩で粉
化したものを除いた重量を測定し、次式により成形強度
を計算した。(2) Tablet Strength The tablet was weighed in an amount of 20 g using a stroop powdering rate tester, and was rotated for 10 minutes using a stroop powdering rate tester. After the rotation was completed, the tablet was taken out, the weight excluding the powder that had been powdered with a 10-mesh sieve was measured, and the molding strength was calculated by the following equation.
【００２０】[0020]
【数１】 (Equation 1)
【００２１】（３）錠剤の硬度 キヤ式硬度計にて試料を５個測定し、その平均値を硬度
（ｋｇ）とした。(3) Tablet Hardness Five samples were measured with a key hardness meter, and the average value was defined as hardness (kg).
【００２２】（４）崩壊性 ５００ｍｌのビーカーに局方第一液(人工胃液)５００ｍ
ｌを取り、錠剤２個を投入した。攪拌翼で錠剤に羽根が
あたらない様に５０ｒｐｍで回転を与え、完全に分散す
るのに要する時間（秒）を測定した。(4) Disintegration 500m of first solution (artificial gastric juice) in a 500ml beaker
1 and two tablets were charged. The tablet was rotated at 50 rpm with a stirring blade so that the blade did not hit the blade, and the time (second) required for complete dispersion was measured.
【００２３】２．ＣＭＣ−Ｎａの分析方法 （１）エーテル化度（ＤＳ） 試料０．５〜０．８ｇを精秤し、ろ紙に包んで磁性ルツ
ボ中で灰化した。冷却後、これを５００ｍｌビーカーに
移し、水約２５０ｍｌ、ピペットでＮ／１０硫酸３５ｍ
ｌを加えて、３０分間煮沸した。これを冷却し、フェノ
ールフタレイン指示薬を加えて、過剰の酸をＮ／１０水
酸化カリウムで逆滴定し、次式によりエーテル化度を求
めた。2. Analysis method of CMC-Na (1) Degree of etherification (DS) A 0.5 to 0.8 g sample was precisely weighed, wrapped in filter paper, and incinerated in a magnetic crucible. After cooling, this was transferred to a 500 ml beaker, about 250 ml of water, and 35 ml of N / 10 sulfuric acid with a pipette.
1 and boiled for 30 minutes. This was cooled, a phenolphthalein indicator was added, and excess acid was back titrated with N / 10 potassium hydroxide, and the degree of etherification was determined by the following equation.
【００２４】[0024]
【数２】 (Equation 2)
【００２５】（式中、ｆ1はＮ／１０硫酸の力価、Ｓ1は
Ｎ／１０水酸化カリウムの滴定量（ｍｌ）、ｆ2はＮ／
１０水酸化カリウムの力価を示す。）(Where f 1 is the titer of N / 10 sulfuric acid, S 1 is the titer (ml) of N / 10 potassium hydroxide, and f 2 is the N /
The titer of potassium hydroxide 10 is shown. )
【００２６】[0026]
【数３】 (Equation 3)
【００２７】（２）酸化度 試料０．８〜１．２ｇを３００ｍｌ三角フラスコに精秤
し、水約２０ｍｌを加えて溶かした。これにＮ／１０水
酸化カリウム２０ｍｌをピペットで加え、１０分間煮沸
した後、冷却してフェノールフタレイン指示薬を加えて
Ｎ／１０硫酸で滴定した。同時に空試験を行って、次式
により酸化度を求めた。(2) Degree of oxidation 0.8 to 1.2 g of a sample was precisely weighed in a 300 ml Erlenmeyer flask, and dissolved by adding about 20 ml of water. To this, 20 ml of N / 10 potassium hydroxide was added by a pipette, and after boiling for 10 minutes, the mixture was cooled, a phenolphthalein indicator was added, and the mixture was titrated with N / 10 sulfuric acid. At the same time, a blank test was performed, and the degree of oxidation was determined by the following equation.
【００２８】[0028]
【数４】 (Equation 4)
【００２９】[0029]
【数５】 (Equation 5)
【００３０】（式中、ｆ1はＮ／１０硫酸の力価、Ｓ2は
Ｎ／１０硫酸の滴定量（ｍｌ）、ｆ2はＮ／１０水酸化
カリウムの力価を示す。） （３）水分 試料１〜２ｇを秤量瓶に精秤し、１０５±０．２℃の低
温乾燥機中で２時間乾燥し、その減量から次式により水
分（％）を算出した。(Where f 1 is the titer of N / 10 sulfuric acid, S 2 is the titer of N / 10 sulfuric acid (ml), and f 2 is the titer of N / 10 potassium hydroxide.) ) Moisture A sample (1 to 2 g) was precisely weighed in a weighing bottle, dried in a low-temperature dryer at 105 ± 0.2 ° C for 2 hours, and the water content (%) was calculated from the weight loss by the following formula.
【００３１】[0031]
【数６】 (Equation 6)
【００３２】（４）１％水溶液粘度 ３００ｍｌトールビーカーに２．５ｇの試料を精秤し、
次式によって求めた溶解水量を加えて試料をガラス棒に
て分散させた。(4) Viscosity of 1% aqueous solution 2.5 g of a sample was precisely weighed in a 300 ml tall beaker.
The sample was dispersed with a glass rod by adding the amount of dissolved water determined by the following equation.
【００３３】１％水溶液の水量（ｇ）＝試料（ｇ）×
（９９−水分（％）） 水分は上記の水分値を利用する。上記水溶液を一夜放置
後、メグネチックスターラーで約５分間攪拌させ、完全
な溶液とした後、３０分間２５℃恒温槽中で溶液を２５
℃にする。その後ガラス棒で緩やかにかき混ぜた後、Ｂ
Ｍ型粘度計の適当なローターおよびガードを取り付け、
６０ｒｐｍの回転数で回転３分後の目盛りを読み取っ
た。Water amount (g) of 1% aqueous solution = sample (g) ×
(99-moisture (%)) The above moisture value is used for moisture. After leaving the aqueous solution to stand overnight, it was stirred for about 5 minutes with a magnetic stirrer to obtain a complete solution.
Temperature. After gently stirring with a glass rod,
Attach appropriate rotor and guard of M type viscometer,
The scale was read 3 minutes after the rotation at a rotation speed of 60 rpm.
【００３４】粘度（ｍＰａ・ｓ）＝読み取り目盛り ×
係数 実施例１〜５および比較例１〜７ （ＣＭＣ−Ｎａの合成方法）５Ｌ二軸ニーダー型反応機
に、表１に示す量の苛性ソーダを水４００ｇとイソプロ
ピルアルコール１６００ｇの混合溶媒に溶解したものを
仕込んだ。その後、ニーダーを攪拌させながらチップ状
の無水セルロース（パルプ材種の異なるものを真空乾燥
させて無水物とした）２００ｇを５分間かけて投入し
た。２５℃で３０分間攪拌後、表１に示す量のモノクロ
ール酢酸を水２０ｇとイソプロピルアルコール８０ｇに
溶解したものを１０分間かけて添加した。添加後２０分
間攪拌した後、７７℃まで昇温し９０分間反応させた。
反応終了後、５０℃まで冷却し過剰の苛性ソーダを２５
％酢酸でｐＨ７．０〜７．２に中和した。この反応ＣＭ
Ｃ−Ｎａ全量を、８０％メチルアルコール１０Ｌ（室温
（約２５℃））３０分で３回精製した。精製後、減圧濾
過機でＣＭＣ−Ｎａを絞り、湿潤状のＣＭＣ−Ｎａを加
熱乾燥機で乾燥し揮発分１０％以下にした。Viscosity (mPa · s) = read scale ×
Coefficients Examples 1 to 5 and Comparative Examples 1 to 7 (Synthesis method of CMC-Na) Caustic soda in an amount shown in Table 1 was dissolved in a mixed solvent of 400 g of water and 1600 g of isopropyl alcohol in a 5 L twin-screw kneader type reactor. Was charged. Thereafter, while stirring the kneader, 200 g of anhydrous cellulose in the form of chips (a pulp material of a different type was dried under vacuum to obtain an anhydrous material) was charged over 5 minutes. After stirring at 25 ° C. for 30 minutes, a solution prepared by dissolving the amount of monochloroacetic acid shown in Table 1 in 20 g of water and 80 g of isopropyl alcohol was added over 10 minutes. After stirring for 20 minutes after the addition, the temperature was raised to 77 ° C. and reacted for 90 minutes.
After completion of the reaction, the reaction mixture was cooled to 50 ° C. to remove excess caustic soda.
% Acetic acid to pH 7.0-7.2. This reaction CM
The total amount of C-Na was purified three times in 10 L of 80% methyl alcohol (room temperature (about 25 ° C.)) for 30 minutes. After the purification, the CMC-Na was squeezed with a reduced pressure filter, and the wet CMC-Na was dried with a heating drier to reduce the volatile content to 10% or less.
【００３５】一方、酸化度についてはつぎのような処理
をした。ＣＭＣ−Ｎａを精製する時、３回目に酢酸を所
定量添加して、ＣＭＣ−Ｎａの１％水溶液ｐＨを５．５
〜６．５とし、その後、減圧濾過機でＣＭＣ−Ｎａを絞
り加熱乾燥を前述のように実施した。さらに、１２０〜
１３０℃で６０分加熱をした。表１に、ＣＭＣ−Ｎａの
製造条件を示す。On the other hand, the following treatment was performed for the degree of oxidation. When purifying CMC-Na, a predetermined amount of acetic acid is added for the third time to adjust the pH of a 1% aqueous solution of CMC-Na to 5.5.
After that, CMC-Na was squeezed out by a reduced pressure filter and heated and dried as described above. In addition, 120-
Heated at 130 ° C. for 60 minutes. Table 1 shows the production conditions for CMC-Na.
【００３６】得られたＣＭＣ−Ｎａを粉砕機で粉砕し１
７７ミクロンの篩にかけたＰａｓｓ品をサンプルとし
た。The obtained CMC-Na was pulverized with a pulverizer and
A Pass product passed through a 77-micron sieve was used as a sample.
【００３７】[0037]
【表１】 [Table 1]
【００３８】（錠剤の作製）アスコルビン酸（試薬１
級）、微結晶セルロース（アビセルＰＨ１０１、旭化成
工業(株)製）、乳糖（試薬）、タルク（試薬）、ステア
リン酸マグネシウム（試薬）を以下の量使用して、錠剤
を打錠法により作製し評価した。(Preparation of tablet) Ascorbic acid (reagent 1)
Grade), microcrystalline cellulose (Avicel PH101, manufactured by Asahi Kasei Kogyo Co., Ltd.), lactose (reagent), talc (reagent), and magnesium stearate (reagent) in the following amounts to prepare tablets by the tableting method. evaluated.
【００３９】なお、打錠条件は、錠剤径１２ｍｍφ、厚
さ５ｍｍ、重量約９００ｍｇで、打錠圧４ｔｏｎとし
た。The tableting conditions were a tablet diameter of 12 mmφ, a thickness of 5 mm, a weight of about 900 mg, and a tableting pressure of 4 tons.
【００４０】 錠剤組成 アスコルビン酸 ４０．０ アビセルＰＨ１０１ ３５．０ 乳糖 １７．０ ＣＭＣ−Ｎａ ３．０ タルク ４．５ ステアリン酸マグネシウム ０．５ 計 １００．０（重量 ％） 合成したＣＭＣ−Ｎａのエーテル化度、酸化度、および
１％水溶液粘度を前記評価方法にしたがって評価した。
結果を表２に示す。Tablet composition Ascorbic acid 40.0 Avicel PH101 35.0 Lactose 17.0 CMC-Na 3.0 Talc 4.5 Magnesium stearate 0.5 Total 100.0 (% by weight) Synthetic ether of CMC-Na The degree of oxidation, the degree of oxidation, and the viscosity of a 1% aqueous solution were evaluated according to the above-mentioned evaluation methods.
Table 2 shows the results.
【００４１】また、実施例１〜５および比較例５〜７で
は高エーテル化度ＣＭＣ−Ｎａおよび低エーテル化度Ｃ
ＭＣ−Ｎａを、７０：３０の重量比で混合し、前記方法
で錠剤を作製した。なお、比較例４ではカルボキシメチ
ルセルロースカルシウム（ＣＭＣ−Ｃａ、ＥＣＧ−５０
５、ニチリン化学工業（株）製）を用いて、前記方法で
錠剤を作製した。In Examples 1 to 5 and Comparative Examples 5 to 7, the degree of high etherification CMC-Na and the degree of low etherification C
MC-Na was mixed at a weight ratio of 70:30, and tablets were prepared by the method described above. In Comparative Example 4, carboxymethylcellulose calcium (CMC-Ca, ECG-50) was used.
5, Nichirin Chemical Industry Co., Ltd.) to produce tablets by the above method.
【００４２】えられた錠剤を、前記評価方法にしたがっ
て評価した。結果を表２に示す。The obtained tablets were evaluated according to the above evaluation method. Table 2 shows the results.
【００４３】[0043]
【表２】 [Table 2]
【００４４】[0044]
【発明の効果】本発明によれば、加圧成型して得る錠剤
において、錠剤の成型強度を保持しつつ、崩壊性に優れ
た錠剤が得られる。According to the present invention, a tablet obtained by press molding can be obtained with excellent disintegration properties while maintaining the molding strength of the tablet.
【００４５】錠剤用の表面状態、強度と崩壊性の関係
は、裏腹の関係にあり、使用する添加剤によりこの効果
が決まる。一方を満足すれば一方が満足されないが、本
願のＣＭＣ−Ｎａを使用することで両方の効果を高める
ことができる。The relationship between the surface condition, strength and disintegration of tablets is contrary, and the effect is determined by the additives used. If one is satisfied, the other is not satisfied, but both effects can be enhanced by using the CMC-Na of the present invention.
Claims (1)
化度０．０１〜０．２のカルボキシメチルセルロースナ
トリウムと、（ｂ）エーテル化度０．８〜２．０のカル
ボキシメチルセルロースナトリウムを、（ａ）：（ｂ）
＝１０：９０〜５０：５０（重量比）の割合で混合して
なる粉末粒度が１７７μｍ以下である錠剤用崩壊剤。1. A sodium carboxymethyl cellulose having a degree of etherification of 0.2 to 0.5 and a degree of oxidation of 0.01 to 0.2, and (b) carboxymethyl cellulose having a degree of etherification of 0.8 to 2.0. Sodium is (a): (b)
= 10: 90 to 50:50 (weight ratio): a disintegrant for tablets having a powder particle size of 177 μm or less mixed.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP03872899A JP3310233B2 (en) | 1999-02-17 | 1999-02-17 | Disintegrant for tablets |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP03872899A JP3310233B2 (en) | 1999-02-17 | 1999-02-17 | Disintegrant for tablets |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2000239186A true JP2000239186A (en) | 2000-09-05 |
| JP3310233B2 JP3310233B2 (en) | 2002-08-05 |
Family
ID=12533401
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP03872899A Expired - Fee Related JP3310233B2 (en) | 1999-02-17 | 1999-02-17 | Disintegrant for tablets |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3310233B2 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002293987A (en) * | 2001-03-30 | 2002-10-09 | Kobayashi Pharmaceut Co Ltd | Water gel composition |
| EP1329217A1 (en) * | 2000-10-06 | 2003-07-23 | Takeda Chemical Industries, Ltd. | Solid preparations |
| JP2013136541A (en) * | 2011-12-28 | 2013-07-11 | Kao Corp | Solid bathing agent |
| JP2013139396A (en) * | 2011-12-28 | 2013-07-18 | Kao Corp | Solid bathing agent |
-
1999
- 1999-02-17 JP JP03872899A patent/JP3310233B2/en not_active Expired - Fee Related
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1329217A1 (en) * | 2000-10-06 | 2003-07-23 | Takeda Chemical Industries, Ltd. | Solid preparations |
| EP1329217A4 (en) * | 2000-10-06 | 2007-04-04 | Takeda Pharmaceutical | Solid preparations |
| US7510728B2 (en) | 2000-10-06 | 2009-03-31 | Takeda Pharmaceutical Company Limited | Solid preparations |
| JP2002293987A (en) * | 2001-03-30 | 2002-10-09 | Kobayashi Pharmaceut Co Ltd | Water gel composition |
| JP4717241B2 (en) * | 2001-03-30 | 2011-07-06 | 小林製薬株式会社 | Aqueous gel composition |
| JP2013136541A (en) * | 2011-12-28 | 2013-07-11 | Kao Corp | Solid bathing agent |
| JP2013139396A (en) * | 2011-12-28 | 2013-07-18 | Kao Corp | Solid bathing agent |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3310233B2 (en) | 2002-08-05 |
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