JP2000086503A - Tablet medicine composition - Google Patents
Tablet medicine compositionInfo
- Publication number
- JP2000086503A JP2000086503A JP10268937A JP26893798A JP2000086503A JP 2000086503 A JP2000086503 A JP 2000086503A JP 10268937 A JP10268937 A JP 10268937A JP 26893798 A JP26893798 A JP 26893798A JP 2000086503 A JP2000086503 A JP 2000086503A
- Authority
- JP
- Japan
- Prior art keywords
- hydroxypropylcellulose
- tablet
- weight
- pharmaceutical composition
- present
- 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
- 239000003814 drug Substances 0.000 title claims abstract description 28
- 239000000203 mixture Substances 0.000 title claims abstract description 13
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims abstract description 33
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims abstract description 33
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims abstract description 33
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims abstract description 19
- 229920002261 Corn starch Polymers 0.000 claims abstract description 15
- 239000008120 corn starch Substances 0.000 claims abstract description 15
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 33
- 229940079593 drug Drugs 0.000 claims description 20
- 239000008101 lactose Substances 0.000 claims description 15
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 12
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 9
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 9
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 9
- PYTMYKVIJXPNBD-OQKDUQJOSA-N 2-[4-[(z)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethylethanamine;hydron;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(/Cl)C1=CC=CC=C1 PYTMYKVIJXPNBD-OQKDUQJOSA-N 0.000 claims description 6
- 229940046989 clomiphene citrate Drugs 0.000 claims description 6
- 229940099112 cornstarch Drugs 0.000 claims description 3
- 229940071676 hydroxypropylcellulose Drugs 0.000 claims description 3
- 229960001375 lactose Drugs 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 8
- 238000010828 elution Methods 0.000 abstract description 3
- 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 abstract 1
- 229910052708 sodium Inorganic materials 0.000 abstract 1
- 239000011734 sodium Substances 0.000 abstract 1
- 238000004090 dissolution Methods 0.000 description 14
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- 230000014759 maintenance of location Effects 0.000 description 8
- 238000006467 substitution reaction Methods 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 239000000454 talc Substances 0.000 description 5
- 229910052623 talc Inorganic materials 0.000 description 5
- 238000009472 formulation Methods 0.000 description 4
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 3
- 238000005336 cracking Methods 0.000 description 3
- 229960005168 croscarmellose Drugs 0.000 description 3
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 3
- 239000007884 disintegrant Substances 0.000 description 3
- 238000007922 dissolution test Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- -1 for example Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 2
- 229960004884 fluconazole Drugs 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- DOMXUEMWDBAQBQ-WEVVVXLNSA-N terbinafine Chemical compound C1=CC=C2C(CN(C\C=C\C#CC(C)(C)C)C)=CC=CC2=C1 DOMXUEMWDBAQBQ-WEVVVXLNSA-N 0.000 description 2
- 229960002722 terbinafine Drugs 0.000 description 2
- 229960001722 verapamil Drugs 0.000 description 2
- TURGQPDWYFJEDY-UHFFFAOYSA-N 1-hydroperoxypropane Chemical compound CCCOO TURGQPDWYFJEDY-UHFFFAOYSA-N 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 description 1
- 229940092705 beclomethasone Drugs 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- ABJKWBDEJIDSJZ-UHFFFAOYSA-N butenafine Chemical compound C=1C=CC2=CC=CC=C2C=1CN(C)CC1=CC=C(C(C)(C)C)C=C1 ABJKWBDEJIDSJZ-UHFFFAOYSA-N 0.000 description 1
- 229960002962 butenafine Drugs 0.000 description 1
- 239000002327 cardiovascular agent Substances 0.000 description 1
- 229940125692 cardiovascular agent Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- LBHIOVVIQHSOQN-UHFFFAOYSA-N nicorandil Chemical compound [O-][N+](=O)OCCNC(=O)C1=CC=CN=C1 LBHIOVVIQHSOQN-UHFFFAOYSA-N 0.000 description 1
- 229960002497 nicorandil Drugs 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- 229960005294 triamcinolone Drugs 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、クエン酸クロミフ
ェンなどの水難溶性又は不溶性薬物の投与に好適な、錠
剤医薬組成物に関する。TECHNICAL FIELD The present invention relates to a tablet pharmaceutical composition suitable for administration of a poorly water-soluble or insoluble drug such as clomiphene citrate.
【０００２】[0002]
【従来の技術】クエン酸クロミフェンなどの水難溶性又
は不溶性薬物の経口投与製剤に於いて、重要なことは、
素早く該薬物を溶出させて吸収させることであり、この
為の崩壊剤や賦形剤の組み合わせが種々考え出されてい
る。この様な崩壊・溶出特性に優れた賦形剤としては、
近年、クロスカルメロースナトリウムが開発されてい
る。しかしながら、この様な溶出特性を向上させると、
今度は錠剤などの輸送・運搬時に於ける安定性が問題と
なる。これは、この様な放出特性に優れる製剤に於いて
は、往々にして錠剤の強度が低いためである。即ち、充
分な強度を保ちながら、水難溶性又は不溶性薬物の溶出
特性に優れる錠剤医薬組成物の開発が望まれていた。更
に、嚥下する事を考慮して、錠剤そのものの軽量小型化
も望まれていた。その為、加圧成形時に締まりよく、高
密度の錠剤になることも望まれていた。2. Description of the Related Art In oral administration of poorly water-soluble or insoluble drugs such as clomiphene citrate, it is important that:
The drug is quickly eluted and absorbed, and various combinations of disintegrants and excipients for this purpose have been devised. As excipients with excellent disintegration and dissolution characteristics,
In recent years, croscarmellose sodium has been developed. However, when such elution characteristics are improved,
This time, the stability of tablets during transportation is a problem. This is because tablets with such excellent release characteristics often have low tablet strength. That is, it has been desired to develop a tablet pharmaceutical composition which is excellent in dissolution characteristics of a poorly water-soluble or insoluble drug while maintaining sufficient strength. Further, in consideration of swallowing, it has been desired to reduce the weight and size of the tablet itself. For this reason, it has been desired that the tablet be tight and compact at the time of pressure molding.
【０００３】一方、乳糖、とうもろこしでんぷん、クロ
スカルメロースナトリウム、通常と低置換度の２種のヒ
ドロキシプロピルセルロースは何れも、医薬製剤の成分
としては公知のものであり、広く製剤成分として使用さ
れているが、これらの成分全てと水難溶性或いは不溶性
の薬物と組み合わせて、溶出特性に優れる錠剤を作成す
る技術については、全く知られていなかった。On the other hand, lactose, corn starch, croscarmellose sodium, and two types of hydroxypropylcellulose having a normal or low degree of substitution are all known as components of pharmaceutical preparations and widely used as preparation components. However, no technique has been known for preparing tablets having excellent dissolution characteristics by combining all of these components with a poorly water-soluble or insoluble drug.
【０００４】[0004]
【発明が解決しようとする課題】本発明は、この様な状
況下為されたものであり、水難溶性或いは不溶性の薬物
を含有する、溶出特性に優れる錠剤を提供することを課
題とする。SUMMARY OF THE INVENTION The present invention has been made under such circumstances, and it is an object of the present invention to provide a tablet containing a poorly water-soluble or insoluble drug and having excellent dissolution characteristics.
【０００５】[0005]
【課題の解決手段】この様な状況に鑑みて、本発明者等
は、水難溶性或いは不溶性の薬物を含有する、溶出特性
に優れる錠剤を求めて、鋭意研究努力を重ねた結果、水
難溶性又は不溶性薬物と乳糖ととうもろこしでんぷんと
クロスカルメロースナトリウムとヒドロキシプロピルセ
ルロースとを含有する錠剤医薬組成物に於いて、該ヒド
ロキシプロピルセルロースとして、通常のヒドロキシプ
ロピルセルロースと低置換度のヒドロキシプロピルセル
ロースとの２種類のヒドロキシプロピルセルロースを含
有することを特徴とする、錠剤医薬組成物がその様な特
性を備えていることを見いだし、発明を完成させるに至
った。以下、本発明について、実施の形態を中心に更に
詳細に説明を加える。In view of such circumstances, the present inventors have intensively studied for a tablet containing a poorly water-soluble or insoluble drug and having excellent dissolution characteristics. In a tablet pharmaceutical composition containing an insoluble drug, lactose, corn starch, croscarmellose sodium and hydroxypropylcellulose, the hydroxypropylcellulose may be a mixture of ordinary hydroxypropylcellulose and low-substituted hydroxypropylcellulose. It has been found that a tablet pharmaceutical composition characterized by containing various kinds of hydroxypropylcellulose has such properties, and has completed the invention. Hereinafter, the present invention will be described in more detail focusing on embodiments.
【０００６】[0006]
【発明の実施の形態】（１）本発明の錠剤医薬組成物が
含有する水難溶性或いは不溶性の薬物 本発明の錠剤医薬組成物が含有する水難溶性或いは不溶
性の薬物は、水に対する溶解度が５％以下の薬物のもの
を言い、例えば、ニフェジピン、ニコランジル、ベラパ
ミル、トラパジル等の循環器用薬、エストラジオール、
トリアムシノロン、ベクロメタゾン、クエン酸クロミフ
ェン等のホルモン剤、ブテナフィン、テルビナフィン、
フルコナゾール等の抗真菌剤等が例示できる。これらの
中では、クエン酸クロミフェンが本発明の錠剤医薬組成
物で使用する薬物としては、特に好ましい。これは、前
記製剤成分とこの薬物の相性が良いからである。本発明
の錠剤医薬組成物に於ける、前記薬物の好ましい含有量
は、１０〜５０重量％であり、更に好ましくは、２０〜
４０重量％である。DESCRIPTION OF THE PREFERRED EMBODIMENTS (1) Poorly water-soluble or insoluble drug contained in the tablet pharmaceutical composition of the present invention The poorly water-soluble or insoluble drug contained in the tablet pharmaceutical composition of the present invention has a water solubility of 5%. Refers to the following drugs, for example, cardiovascular drugs such as nifedipine, nicorandil, verapamil, trapadil, estradiol,
Hormones such as triamcinolone, beclomethasone, clomiphene citrate, butenafine, terbinafine,
Examples include antifungal agents such as fluconazole. Among these, clomiphene citrate is particularly preferred as a drug used in the tablet pharmaceutical composition of the present invention. This is because the drug is well compatible with the drug component. The preferred content of the drug in the tablet pharmaceutical composition of the present invention is 10 to 50% by weight, more preferably 20 to 50% by weight.
40% by weight.
【０００７】（２）本発明の錠剤医薬組成物が含有する
乳糖 本発明の錠剤医薬組成物が含有する乳糖は、中性で薬効
成分との反応性が少なく、古来より医薬組成物の賦形剤
として広く使用されているもので、錠剤などに成形する
際に、該成形物の締まりを良くする特性を有しているこ
とが知られている。しかし、反面、乳糖は崩壊性を遅ら
せる傾向にあるため、溶出性を高める為には、崩壊剤な
どと共に使用することが多い成分である。本発明に於い
ても、この様な傾向のため、錠剤の形態維持に必要で充
分な量を含有させることが望ましく、具体的には、３０
〜６０重量％が好ましく、更に好ましくは４０〜５０重
量％含有させるのが良い。又、粒径に関しては、細かす
ぎると崩壊性が損なわれることがあり、粗すぎると錠剤
の形態維持性が損なわれるので、５０パス３００オン程
度の粒度のものが好ましく、１００パス２００オンが更
に好ましい。(2) Lactose Contained in the Tablet Pharmaceutical Composition of the Present Invention Lactose contained in the tablet pharmaceutical composition of the present invention is neutral, has little reactivity with medicinal ingredients, and has been used to shape pharmaceutical compositions since ancient times. It is widely used as an agent and is known to have the property of improving the tightness of the molded product when it is molded into tablets or the like. However, on the other hand, lactose is a component often used together with a disintegrant or the like in order to enhance dissolution because lactose tends to delay disintegration. Also in the present invention, due to such a tendency, it is desirable to contain a sufficient amount necessary for maintaining the form of the tablet.
The content is preferably from 60 to 60% by weight, more preferably from 40 to 50% by weight. Regarding the particle size, if it is too fine, disintegration may be impaired, and if it is too coarse, the shape retention of the tablet may be impaired. preferable.
【０００８】（３）本発明の錠剤医薬組成物が含有する
とうもろこしでんぷん 本発明の錠剤医薬組成物が含有するとうもろこしでんぷ
んは、医薬製剤に於いて、崩壊剤として使用するもので
あり、このものは崩壊性は促進し薬物溶出を促す作用を
有するが、多すぎると形態維持性を大きく損なう欠点も
有する。この為、本発明の錠剤医薬組成物に於いては、
その含有量は、１０〜３０重量％が好ましく、１５〜２
５重量％が更に好ましい。(3) Corn starch containing the tablet pharmaceutical composition of the present invention Corn starch containing the tablet pharmaceutical composition of the present invention is used as a disintegrant in a pharmaceutical preparation. Although it has the effect of accelerating the disintegration and promoting the dissolution of a drug, it has the disadvantage that too much of it will greatly impair the shape retention. Therefore, in the tablet pharmaceutical composition of the present invention,
The content is preferably 10 to 30% by weight, and 15 to 2% by weight.
5% by weight is more preferred.
【０００９】（４）本発明の錠剤医薬組成物が含有する
クロスカルメロース 本発明の錠剤医薬組成物が含有するクロスカルメロース
は、医薬組成物の賦形剤として近年開発され、使用され
ているもので、このものについては、崩壊性を良くし、
崩壊液のｐＨに左右されない特性を有していることが知
られている。しかし、反面、このものは硬度を高める傾
向にあるため、溶出性を高める為には、崩壊剤などと共
に使用することが多い成分である。本発明に於いても、
この様な傾向のため、錠剤の形態維持に必要で充分な量
を含有させることが望ましく、具体的には、０．５〜１
０重量％が好ましく、１〜５重量％が更に好ましい。(4) Croscarmellose contained in the tablet pharmaceutical composition of the present invention Croscarmellose contained in the tablet pharmaceutical composition of the present invention has recently been developed and used as an excipient of the pharmaceutical composition. The thing about this thing is to improve the disintegration,
It is known that it has characteristics that are not affected by the pH of the disintegration liquid. However, on the other hand, this is a component that is often used together with a disintegrating agent or the like in order to increase dissolution since it tends to increase hardness. In the present invention,
Due to such a tendency, it is desirable to include a necessary and sufficient amount for maintaining the form of the tablet.
It is preferably 0% by weight, more preferably 1 to 5% by weight.
【００１０】（５）本発明の錠剤医薬組成物が含有する
ヒドロキシプロピルセルロース 本発明の錠剤医薬組成物が含有するヒドロキシプロピル
セルロースは、医薬で結合剤として使用されているもの
であって、化学的にはセルロースのヒドロキシプロピル
エーテルである。ここで通常のヒドロキシプロピルセル
ロースはヒドロキシプロピル基がセルロースの水酸基の
５０〜８０％に結合しているのに対し、低置換度のヒド
ロキシプロピルセルロースの場合には５〜２０％に結合
している。又、水に対する溶状も、通常のものが水に溶
けて粘性のある液になるのに対して、低置換度のものは
膨潤するが水には溶けないと言う性質を有する。本発明
の錠剤医薬組成物に於いては、この２者の違いを利用し
て組み合わせることにより、形態維持作用と崩壊作用の
両者を具現する結合剤組成を見いだし、応用した。本発
明の錠剤医薬組成物に於けるヒドロキシプロピルセルロ
ースの好ましい含有量は、通常のものと低置換度のもの
を合わせて、０．５〜５重量％が好ましく、１〜３重量
％が更に好ましい。又、この中に於ける通常のものと低
置換度のものの割合は、通常のヒドロキシプロピルセル
ロースと低置換度のヒドロキシプロピルセルロースの組
成が１：２〜１：４であることが、形態維持性と崩壊性
の兼ね合いで好ましい。(5) Hydroxypropylcellulose contained in the tablet pharmaceutical composition of the present invention Hydroxypropylcellulose contained in the tablet pharmaceutical composition of the present invention is used as a binder in medicine, and Is hydroxypropyl ether of cellulose. Here, ordinary hydroxypropyl cellulose has hydroxypropyl groups bound to 50 to 80% of the hydroxyl groups of cellulose, whereas low-substituted hydroxypropylcellulose binds to 5 to 20%. In addition, as for the solubility in water, a normal one dissolves in water and becomes a viscous liquid, whereas a low substitution degree swells but does not dissolve in water. In the tablet pharmaceutical composition of the present invention, a binder composition realizing both a shape maintaining action and a disintegrating action was found by applying the difference between the two, and applied. The preferred content of hydroxypropylcellulose in the tablet pharmaceutical composition of the present invention is preferably 0.5 to 5% by weight, more preferably 1 to 3% by weight, including the ordinary and low-substituted ones. . The ratio between the normal and low-substituted hydroxypropylcellulose in the above composition is such that the composition of ordinary hydroxypropylcellulose and low-substituted hydroxypropylcellulose is 1: 2 to 1: 4. And disintegration is preferred.
【００１１】（６）本発明の錠剤医薬組成物 本発明の錠剤医薬組成物は、上記水難溶性又は不溶性薬
物と乳糖ととうもろこしでんぷんとクロスカルメロース
ナトリウムとヒドロキシプロピルセルロースとを含有す
る錠剤医薬組成物に於いて、該ヒドロキシプロピルセル
ロースとして、通常のヒドロキシプロピルセルロースと
低置換度のヒドロキシプロピルセルロースとの２種類の
ヒドロキシプロピルセルロースを含有することを特徴と
する。本発明の錠剤医薬組成物に於いては、これらの必
須成分以外に、本発明の効果を損なわない範囲に於い
て、通常医薬組成物で使用される任意成分を含有するこ
とが出来る。かかる任意成分としては、例えば、ステア
リン酸マグネシウムやステアリン酸亜鉛等の滑沢剤、タ
ルクや二酸化チタン等の粉体成分、塩化ナトリウムや塩
化カリウムなどの無機塩類、緩衝塩類、着色剤、コーテ
ィング剤等が例示できる。これらの原料を常法に従って
処理することにより、本発明の錠剤医薬組成物を製造す
ることが出来る。かくして得られた錠剤医薬組成物は、
形状維持性と溶出性に優れる上、締まりが良いので、高
密度でコンパクトな錠剤である。(6) Tablet pharmaceutical composition of the present invention The tablet pharmaceutical composition of the present invention comprises the above-mentioned poorly water-soluble or insoluble drug, lactose, corn starch, croscarmellose sodium and hydroxypropylcellulose. Wherein said hydroxypropylcellulose contains two types of hydroxypropylcellulose, namely, normal hydroxypropylcellulose and low-substituted hydroxypropylcellulose. The tablet pharmaceutical composition of the present invention may contain, in addition to these essential components, optional components usually used in pharmaceutical compositions within a range that does not impair the effects of the present invention. Such optional components include, for example, lubricants such as magnesium stearate and zinc stearate, powder components such as talc and titanium dioxide, inorganic salts such as sodium chloride and potassium chloride, buffer salts, coloring agents, coating agents and the like. Can be exemplified. By processing these raw materials according to a conventional method, the tablet pharmaceutical composition of the present invention can be produced. The tablet pharmaceutical composition thus obtained is
It is a high-density and compact tablet because it has excellent shape retention and dissolution properties, and has good tightness.
【００１２】[0012]
【実施例】以下に、実施例を挙げて、本発明について更
に詳細に説明を加えるが、本発明がかかる実施例のみに
限定されないことは言うまでもない。EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, but it goes without saying that the present invention is not limited to only these Examples.
【００１３】＜実施例１＞以下に示す処方に従って錠剤
を作成した。即ち、処方成分を混合し、少量の水を加え
て練合造粒した。このものを４５℃、１０時間真空乾燥
し、篩過して（１４メッシュパス）打錠して錠剤を得
た。このものを局方に従って溶出試験を実施した。又、
瓶に詰めて３０回振盪した場合の破損状況も合わせて調
べた。これらの検討は、乳糖をとうもろこしでんぷんに
置換した比較例１、とうもろこしでんぷんを乳糖に置換
した比較例２、クロスカルメロースをとうもろこしでん
ぷんに置換した比較例３、ヒドロキシプロピルセルロー
スを通常のもののみにした比較例４及び低置換度のもの
のみにした比較例５についても行った。結果を表１に示
す。又、錠剤の形状も測定し、密度を求めた。これらの
結果より、本発明の錠剤医薬組成物は崩壊性と形状維持
性に優れる上、形態がコンパクトであることが判る。更
にこれは製剤成分の組み合わせ効果であることも判る。 クエン酸クロミフェン ２８ 重量部 乳糖（１００パス２００オン） ４４ 重量部 とうもろこしでんぷん １９ 重量部 クロスカルメロースナトリウム ４ 重量部 ヒドロキシプロピルセルロース（通常） ０．５重量部 ヒドロキシプロピルセルロース（低置換度） １．５重量部 タルク ２ 重量部 ステアリン酸マグネシウム １ 重量部 （溶出試験の判定基準） ○：９５％以上 △：９０％以上９５％未満 ×：９０％未満 （形状維持性試験の判定基準） ○：錠剤割れ無し △：１０％未満の錠剤割れの発生 ×：１０％以上の錠剤割れの発生Example 1 A tablet was prepared according to the following formulation. That is, the prescription components were mixed, and a small amount of water was added and kneaded and granulated. This was vacuum dried at 45 ° C. for 10 hours, sieved (14 mesh pass) and tableted to obtain a tablet. This was subjected to a dissolution test according to the Pharmacopoeia. or,
The state of damage when the bottle was filled and shaken 30 times was also examined. In these studies, Comparative Example 1 in which lactose was replaced with corn starch, Comparative Example 2 in which corn starch was replaced with lactose, Comparative Example 3 in which croscarmellose was replaced with corn starch, and only hydroxypropyl cellulose were used as ordinary ones Comparative Example 4 and Comparative Example 5 having only a low substitution degree were also performed. Table 1 shows the results. In addition, the shape of the tablet was also measured to determine the density. From these results, it can be seen that the tablet pharmaceutical composition of the present invention is excellent in disintegratability and shape retention, and is compact in form. Further, it can be understood that this is a combination effect of the preparation components. Clomiphene citrate 28 parts by weight Lactose (100 passes, 200 ounces) 44 parts by weight Corn starch 19 parts by weight Croscarmellose sodium 4 parts by weight Hydroxypropylcellulose (normal) 0.5 parts by weight Hydroxypropylcellulose (low substitution degree) 1.5 Parts by weight talc 2 parts by weight magnesium stearate 1 part by weight (criterion for dissolution test) ○: 95% or more △: 90% or more and less than 95% ×: less than 90% (criterion for shape retention test) ○: tablet cracking None Δ: Tablet cracking of less than 10% ×: Tablet cracking of 10% or more
【００１４】[0014]
【表１】 [Table 1]
【００１５】＜実施例２＞上記実施例１の錠剤につい
て、日局に従って溶出試験を３０分まで行った。結果を
表２に示す。これより、本発明の錠剤医薬組成物は、優
れた、溶出性を有することが判る。<Example 2> The tablets of Example 1 were subjected to a dissolution test for up to 30 minutes according to the Japanese Pharmacopoeia. Table 2 shows the results. This indicates that the tablet pharmaceutical composition of the present invention has excellent dissolution properties.
【００１６】[0016]
【表２】 [Table 2]
【００１７】＜実施例３＞実施例１と同様に下記の処方
に従って、錠剤を得た。このものは優れた、形態維持性
と溶出性を兼ね備えていた。 ベラパミル ２８ 重量部 乳糖（１００パス２００オン） ４４ 重量部 とうもろこしでんぷん １９ 重量部 クロスカルメロースナトリウム ４ 重量部 ヒドロキシプロピルセルロース（通常） ０．５重量部 ヒドロキシプロピルセルロース（低置換度） １．５重量部 タルク ２ 重量部 ステアリン酸マグネシウム １ 重量部Example 3 A tablet was obtained in the same manner as in Example 1 according to the following formulation. This product had excellent shape retention and dissolution properties. Verapamil 28 parts by weight Lactose (100 passes, 200 ounces) 44 parts by weight Corn starch 19 parts by weight Croscarmellose sodium 4 parts by weight Hydroxypropyl cellulose (normal) 0.5 parts by weight Hydroxypropyl cellulose (low substitution degree) 1.5 parts by weight Talc 2 parts by weight Magnesium stearate 1 part by weight
【００１８】＜実施例４＞実施例１と同様に下記の処方
に従って、錠剤を得た。このものは優れた、形態維持性
と溶出性を兼ね備えていた。 フルコナゾール ２８ 重量部 乳糖（１００パス２００オン） ４４ 重量部 とうもろこしでんぷん １９ 重量部 クロスカルメロースナトリウム ４ 重量部 ヒドロキシプロピルセルロース（通常） ０．５重量部 ヒドロキシプロピルセルロース（低置換度） １．５重量部 タルク ２ 重量部 ステアリン酸マグネシウム １ 重量部Example 4 A tablet was obtained in the same manner as in Example 1 according to the following formulation. This product had excellent shape retention and dissolution properties. Fluconazole 28 parts by weight Lactose (100 passes, 200 ounces) 44 parts by weight Corn starch 19 parts by weight Croscarmellose sodium 4 parts by weight Hydroxypropylcellulose (normal) 0.5 parts by weight Hydroxypropylcellulose (low substitution degree) 1.5 parts by weight Talc 2 parts by weight Magnesium stearate 1 part by weight
【００１９】＜実施例５＞実施例１と同様に下記の処方
に従って、錠剤を得た。このものは優れた、形態維持性
と溶出性を兼ね備えていた。 テルビナフィン ２８ 重量部 乳糖（１００パス２００オン） ４４ 重量部 とうもろこしでんぷん １９ 重量部 クロスカルメロースナトリウム ４ 重量部 ヒドロキシプロピルセルロース（通常） ０．５重量部 ヒドロキシプロピルセルロース（低置換度） １．５重量部 タルク ２ 重量部 ステアリン酸マグネシウム １ 重量部Example 5 A tablet was obtained in the same manner as in Example 1 according to the following formulation. This product had excellent shape retention and dissolution properties. Terbinafine 28 parts by weight Lactose (100 passes, 200 ounces) 44 parts by weight Corn starch 19 parts by weight Croscarmellose sodium 4 parts by weight Hydroxypropylcellulose (normal) 0.5 parts by weight Hydroxypropylcellulose (low substitution degree) 1.5 parts by weight Talc 2 parts by weight Magnesium stearate 1 part by weight
【００２０】[0020]
【発明の効果】本発明によれば、水難溶性或いは不溶性
の薬物を含有する、溶出特性に優れる錠剤を提供するこ
とができる。According to the present invention, it is possible to provide a tablet containing a poorly water-soluble or insoluble drug and having excellent dissolution characteristics.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 高橋 勇 埼玉県入間郡大井町亀久保1130−４ 株式 会社科薬内 (72)発明者 矢崎 尚 神奈川県横浜市戸塚区柏尾町560 ポーラ 化成工業株式会社戸塚研究所内 Ｆターム(参考） 4C076 AA37 BB01 CC30 DD28 DD41 DD67 EE32 EE38B FF06 4C206 AA01 AA02 FA23 KA15 MA03 MA05 MA55 MA72 NA11 ZA81 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Isamu Takahashi 1130-4 Kamekubo, Oi-machi, Iruma-gun, Saitama Pref. F-term in the Totsuka Laboratory (reference) 4C076 AA37 BB01 CC30 DD28 DD41 DD67 EE32 EE38B FF06 4C206 AA01 AA02 FA23 KA15 MA03 MA05 MA55 MA72 NA11 ZA81
Claims (4)
ろこしでんぷんとクロスカルメロースナトリウムとヒド
ロキシプロピルセルロースとを含有する錠剤医薬組成物
に於いて、該ヒドロキシプロピルセルロースとして、通
常のヒドロキシプロピルセルロースと低置換度のヒドロ
キシプロピルセルロースとの２種類のヒドロキシプロピ
ルセルロースを含有することを特徴とする、錠剤医薬組
成物。1. A tablet pharmaceutical composition comprising a poorly water-soluble or insoluble drug, lactose, corn starch, croscarmellose sodium and hydroxypropylcellulose, wherein said hydroxypropylcellulose is low-substituted with ordinary hydroxypropylcellulose. A tablet pharmaceutical composition comprising two types of hydroxypropylcellulose, each having a different hydroxypropylcellulose content.
常のヒドロキシプロピルセルロースと低置換度のヒドロ
キシプロピルセルロースの組成が１：２〜１：４である
ことを特徴とする、請求項１に記載の錠剤医薬組成物。2. The tablet medicine according to claim 1, wherein the composition of normal hydroxypropylcellulose and low-substituted hydroxypropylcellulose in hydroxypropylcellulose is 1: 2 to 1: 4. Composition.
３：１〜３：２であることを特徴とする、請求項１又は
２に記載の錠剤医薬組成物。3. The tablet pharmaceutical composition according to claim 1, wherein the mixing ratio of lactose and corn starch is 3: 1 to 3: 2.
ミフェンである、請求項１に記載の錠剤医薬組成物。4. The tablet pharmaceutical composition according to claim 1, wherein the poorly water-soluble or insoluble drug is clomiphene citrate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10268937A JP2000086503A (en) | 1998-09-07 | 1998-09-07 | Tablet medicine composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10268937A JP2000086503A (en) | 1998-09-07 | 1998-09-07 | Tablet medicine composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2000086503A true JP2000086503A (en) | 2000-03-28 |
Family
ID=17465362
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10268937A Pending JP2000086503A (en) | 1998-09-07 | 1998-09-07 | Tablet medicine composition |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2000086503A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002024166A1 (en) * | 2000-09-22 | 2002-03-28 | Sumitomo Pharmaceuticals Company, Limited | Oral preparations with favorable disintegration characteristics |
| JP2003520252A (en) * | 2000-01-20 | 2003-07-02 | ノバルティス アクチエンゲゼルシャフト | Terbinafine-containing pharmaceutical composition |
| JP2006257068A (en) * | 2005-08-10 | 2006-09-28 | Takada Seiyaku Kk | High content terbinafine hydrochloride tablet and method for producing the same |
| JP2007161706A (en) * | 2005-11-15 | 2007-06-28 | Taisho Pharmaceut Co Ltd | Antyusan-containing tablet |
| JP2010031022A (en) * | 2002-10-15 | 2010-02-12 | Novartis Ag | Deferasirox dispersible tablet |
-
1998
- 1998-09-07 JP JP10268937A patent/JP2000086503A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003520252A (en) * | 2000-01-20 | 2003-07-02 | ノバルティス アクチエンゲゼルシャフト | Terbinafine-containing pharmaceutical composition |
| WO2002024166A1 (en) * | 2000-09-22 | 2002-03-28 | Sumitomo Pharmaceuticals Company, Limited | Oral preparations with favorable disintegration characteristics |
| US7727553B2 (en) | 2000-09-22 | 2010-06-01 | Dainippon Sumitomo Pharma Co., Ltd. | Oral preparations with favorable disintegration characteristics |
| JP2010031022A (en) * | 2002-10-15 | 2010-02-12 | Novartis Ag | Deferasirox dispersible tablet |
| JP2016094435A (en) * | 2002-10-15 | 2016-05-26 | ノバルティス アーゲー | Dispersible tablets of deferasirox |
| JP2006257068A (en) * | 2005-08-10 | 2006-09-28 | Takada Seiyaku Kk | High content terbinafine hydrochloride tablet and method for producing the same |
| JP2007161706A (en) * | 2005-11-15 | 2007-06-28 | Taisho Pharmaceut Co Ltd | Antyusan-containing tablet |
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