JPH03240729A - Solid pharmaceutical with promoted absorption for internal use - Google Patents
Solid pharmaceutical with promoted absorption for internal useInfo
- Publication number
- JPH03240729A JPH03240729A JP2033491A JP3349190A JPH03240729A JP H03240729 A JPH03240729 A JP H03240729A JP 2033491 A JP2033491 A JP 2033491A JP 3349190 A JP3349190 A JP 3349190A JP H03240729 A JPH03240729 A JP H03240729A
- Authority
- JP
- Japan
- Prior art keywords
- weight
- absorption
- oxicam
- chlortenoxicam
- internal use
- 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
- 238000010521 absorption reaction Methods 0.000 title claims abstract description 10
- 239000007787 solid Substances 0.000 title claims abstract description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims abstract description 26
- 239000002260 anti-inflammatory agent Substances 0.000 claims abstract description 14
- 229960002202 lornoxicam Drugs 0.000 claims abstract description 13
- OXROWJKCGCOJDO-JLHYYAGUSA-N lornoxicam Chemical compound O=C1C=2SC(Cl)=CC=2S(=O)(=O)N(C)\C1=C(\O)NC1=CC=CC=N1 OXROWJKCGCOJDO-JLHYYAGUSA-N 0.000 claims abstract description 13
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims abstract description 13
- 235000017557 sodium bicarbonate Nutrition 0.000 claims abstract description 13
- 229940069428 antacid Drugs 0.000 claims abstract description 12
- 239000003159 antacid agent Substances 0.000 claims abstract description 12
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims abstract description 7
- 230000001458 anti-acid effect Effects 0.000 claims abstract description 7
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims abstract description 6
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 claims abstract description 6
- 229960001545 hydrotalcite Drugs 0.000 claims abstract description 6
- 229910001701 hydrotalcite Inorganic materials 0.000 claims abstract description 6
- 235000019700 dicalcium phosphate Nutrition 0.000 claims abstract description 5
- 229960002871 tenoxicam Drugs 0.000 claims abstract description 4
- WZWYJBNHTWCXIM-UHFFFAOYSA-N tenoxicam Chemical compound O=C1C=2SC=CC=2S(=O)(=O)N(C)C1=C(O)NC1=CC=CC=N1 WZWYJBNHTWCXIM-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229960002702 piroxicam Drugs 0.000 claims abstract description 3
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229940124599 anti-inflammatory drug Drugs 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- WMGSQTMJHBYJMQ-UHFFFAOYSA-N aluminum;magnesium;silicate Chemical compound [Mg+2].[Al+3].[O-][Si]([O-])([O-])[O-] WMGSQTMJHBYJMQ-UHFFFAOYSA-N 0.000 claims description 4
- 239000000395 magnesium oxide Substances 0.000 claims description 3
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 3
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 abstract description 8
- 238000002156 mixing Methods 0.000 abstract description 4
- 238000010828 elution Methods 0.000 abstract description 3
- 208000004371 toothache Diseases 0.000 abstract description 3
- 208000002193 Pain Diseases 0.000 abstract description 2
- -1 magnesium metasilicate aluminate Chemical class 0.000 abstract description 2
- 230000036407 pain Effects 0.000 abstract description 2
- 208000024891 symptom Diseases 0.000 abstract description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 abstract 1
- 239000006185 dispersion Substances 0.000 abstract 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 abstract 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 abstract 1
- 239000000347 magnesium hydroxide Substances 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 18
- 239000008187 granular material Substances 0.000 description 17
- 238000009472 formulation Methods 0.000 description 13
- 238000004090 dissolution Methods 0.000 description 12
- 239000002775 capsule Substances 0.000 description 9
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 239000000523 sample Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 6
- 238000007922 dissolution test Methods 0.000 description 6
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 6
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 6
- 229910002012 Aerosil® Inorganic materials 0.000 description 5
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 238000005469 granulation Methods 0.000 description 5
- 230000003179 granulation Effects 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 5
- 239000008108 microcrystalline cellulose Substances 0.000 description 5
- 229940016286 microcrystalline cellulose Drugs 0.000 description 5
- 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 4
- 239000012530 fluid Substances 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 239000007902 hard capsule Substances 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 235000010724 Wisteria floribunda Nutrition 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000013068 control sample Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 210000004051 gastric juice Anatomy 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- PGFBRHFANBMLLX-UHFFFAOYSA-K calcium sodium dihydrogen phosphate carbonate Chemical compound [Na+].[Ca+2].OC([O-])=O.OP([O-])([O-])=O PGFBRHFANBMLLX-UHFFFAOYSA-K 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 239000001761 ethyl methyl cellulose Substances 0.000 description 1
- 235000010944 ethyl methyl cellulose Nutrition 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 238000012812 general test Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 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 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野コ
本発明は、速効性を期待するオキシカム系抗炎症剤に関
する。DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to an oxicam anti-inflammatory agent expected to be rapidly effective.
［従来の技術］
従来、オキシカム系抗炎症剤の速効性を検討した技術は
知られていない。[Prior Art] Conventionally, there has been no known technique for examining the rapid effectiveness of oxicam anti-inflammatory agents.
［発明が解決しようとする課題］
従って、オキシカム系抗炎症剤は、鎮痛、歯痛などの速
い吸収を要求される症状には満足できる製剤はなかった
。[Problems to be Solved by the Invention] Therefore, there have been no formulations of oxicam-based anti-inflammatory agents that can satisfy symptoms that require rapid absorption, such as analgesia and toothache.
３）制酸剤が、炭酸水素ナトリウム、リン酸水素カルシ
ウム、メタケイ酸アルミン酸マグネシウム、本酸化マグ
ネシウム、合成ヒドロタルサイトである請求項１または
請求項２記載の内服用固形剤。3) The solid preparation for internal use according to claim 1 or 2, wherein the antacid is sodium hydrogen carbonate, calcium hydrogen phosphate, magnesium aluminate metasilicate, present magnesium oxide, or synthetic hydrotalcite.
［課題を解決するための手段］
本発明者らは、ある種の制酸剤を配合させることにより
、溶出性が良く、人における吸収の立ち上がりが極めて
速く且つバラツキの少ない製剤を見出し、この知見に基
づき本発明を完成した。[Means for Solving the Problems] The present inventors have discovered a formulation that has good dissolution properties, has extremely rapid onset of absorption in humans, and has little variation by incorporating a certain type of antacid, and has based this knowledge on The present invention was completed based on this.
本発明は、制酸剤一種または二種以上を配合し、オキシ
カム系抗炎症薬の吸収性を促進することを特徴とする内
服用固形剤である。The present invention is a solid preparation for internal use, which is characterized by containing one or more antacids to promote absorption of an oxicam anti-inflammatory drug.
本発明で用いられる抗炎症剤とは、クロルテノキシカム
、テノキシカム、ピロキシカムなどのオキシカム系抗炎
症薬が挙げられる。The anti-inflammatory agents used in the present invention include oxicam anti-inflammatory agents such as chlortenoxicam, tenoxicam, and piroxicam.
本発明で用いられる制酸剤は、炭酸水素ナトリウム、リ
ン酸水素カルシウム、メタケイ酸アルミン酸マグネシウ
ム、本酸化マグネシウム、合成ヒドロタルサイトなどで
ある。The antacids used in the present invention include sodium hydrogen carbonate, calcium hydrogen phosphate, magnesium aluminate metasilicate, present magnesium oxide, and synthetic hydrotalcite.
本発明で用いられる制酸剤の配合量は、オキシカム系抗
炎症薬の種類、制酸剤の種類や剤形によって異なるが、
オキシカム系抗炎症薬１重量部に対して１０重量部〜５
０重量部が好ましく、１０重量部〜４０重量部が更に好
ましい。The amount of the antacid used in the present invention varies depending on the type of oxicam anti-inflammatory drug, the type and dosage form of the antacid, but
10 parts by weight to 5 parts by weight per 1 part by weight of oxicam anti-inflammatory drug
0 parts by weight is preferable, and 10 parts by weight to 40 parts by weight are more preferable.
例えば、錠剤の場合は、クロルテノキシカム１重量部に
対して炭酸水素ナトリウムを１重量部以上配合すれば溶
出性が向上し、１０重量部以上配合すれば極めて溶出性
が向上する。しかし、２０重量部より多く配合すると硬
度が低下し適切な錠剤が得られないし、１５重量部より
多く配合するとコーティングの際に割れや欠けができる
など成形性の面での問題が生じる。For example, in the case of tablets, if 1 part by weight or more of sodium bicarbonate is blended with 1 part by weight of chlortenoxicam, the dissolution property will be improved, and if 10 parts by weight or more is blended, the dissolution property will be significantly improved. However, if more than 20 parts by weight is added, the hardness decreases and suitable tablets cannot be obtained, and if more than 15 parts by weight is added, problems with moldability such as cracking or chipping occur during coating.
この炭酸水素ナトリウム成形性の問題には、リン酸水素
カルシウムなど２種以上の制酸剤を配合することによっ
である程度解決することができる。This problem of sodium bicarbonate moldability can be solved to some extent by incorporating two or more types of antacids such as calcium hydrogen phosphate.
また合成ヒドロタルサイトであれば、クロルテノキシカ
ム１重量部に対して合成ヒドロタルサイ１１５重量部以
上配合すれば溶出性が向上するが、４０重量部より多く
配合するとクロルテノキシカムの吸着が激しくなり、溶
出並びに吸収の低下が認められる。In addition, in the case of synthetic hydrotalcite, if 115 parts by weight or more of synthetic hydrotalcite is added to 1 part by weight of chlortenoxicam, the dissolution properties will be improved, but if more than 40 parts by weight is added, the adsorption of chlortenoxicam will become intense, resulting in poor elution and Decreased absorption is observed.
一方、顆粒剤の場合は、クロルテノキシカム１重量部に
対してメタケイ酸アルミン酸マグネシウム２０重量部〜
４０重量部を配合すると好ましく、１５重量部〜３０重
量部を配合すると更に好ましい。４０重量部以上になる
と造粒が困難となり流動性の良い顆粒が製造できない。On the other hand, in the case of granules, 20 parts by weight of magnesium aluminate metasilicate per 1 part by weight of chlortenoxicam.
It is preferable to mix 40 parts by weight, and more preferably to mix 15 parts by weight to 30 parts by weight. If it exceeds 40 parts by weight, granulation becomes difficult and granules with good fluidity cannot be produced.
また、炭酸水素ナトリウムの場合はクロルテノキシカム
１重量部に対して炭酸水素ナトリウム１重量部以上であ
れば溶出性が向上するが、２０重量部以上多く配合する
と顆粒の成形性が悪くなり、コーティングを施す場合に
は、顆粒表面が欠けてしまう。In addition, in the case of sodium bicarbonate, if 1 part by weight or more of sodium bicarbonate is added to 1 part by weight of chlortenoxicam, the dissolution properties will be improved, but if more than 20 parts by weight is added, the formability of the granules will deteriorate and the coating will be difficult. If this is done, the surface of the granules will be chipped.
次に本発明の製剤の製造方法は、錠剤、！１粒とも一般
的な製造方法で製造できる６例えば、オキシカム系抗炎
症薬に制酸剤を加えて、粉砕し、次に賦形剤（例えば、
乳糖、葡萄糖などの糖類、Ｄ−ソルビトール、マンニト
ールなどの糖アルコール類、微結晶セルロースなどのセ
ルロース類、コーンスターチなどの澱粉類、アエロジル
）及ヒ崩壊剤（カルボキシメチルセルロースカルシウム
、低置換ヒドロキシプロピルセルロースなどのセルロー
ス類、ポリビニルポリピロリドン、クロス力ロメロース
ナトリウム）更に、結合剤（ヒドロキシプロピルセルロ
ース、ヒドロキシプロピルメチルセルロース、エチルセ
ルロース、メチルセルロースなどのセルロース類、ポリ
ビニルピロリドン）を加えて、混合若しくは粉砕し、ア
ルコールと精製水の混液で造粒する。造粒は攪拌造粒機
、流動層造粒機、ニーダ、転勤造粒機、遠心流動造粒機
、押し出し造粒機、真空造粒機などが使用可能である。Next, the method for manufacturing the formulation of the present invention includes tablets,! Each tablet can be manufactured using a standard manufacturing method.6 For example, an antacid is added to an oxicam anti-inflammatory drug, crushed, and then an excipient (e.g.
Sugars such as lactose and glucose, sugar alcohols such as D-sorbitol and mannitol, celluloses such as microcrystalline cellulose, starches such as cornstarch, Aerosil), and disintegrants (carboxymethyl cellulose calcium, low substituted hydroxypropyl cellulose, etc.) Furthermore, a binder (celluloses such as hydroxypropyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, methyl cellulose, and polyvinyl pyrrolidone) is added, mixed or crushed, and alcohol and purified water are added. Granulate with a mixture of. For granulation, a stirring granulator, a fluidized bed granulator, a kneader, a transfer granulator, a centrifugal fluid granulator, an extrusion granulator, a vacuum granulator, etc. can be used.
次いで、製した造粒物を乾燥し、散剤、細粒剤、顆粒
剤を調製する。Next, the produced granules are dried to prepare powders, fine granules, and granules.
カプセル剤及び錠剤に関しては、造粒物に滑沢剤（例え
ば、ステアリン酸マグネシウム、ステアノン酸カルシウ
ム、タルク、硬化油など）を加える。For capsules and tablets, lubricants (eg, magnesium stearate, calcium stearonate, talc, hydrogenated oils, etc.) are added to the granulation.
なお、細粒剤、顆粒剤及び錠剤には、コーティングを施
すことにより、−層服用しやすいものとなる。In addition, fine granules, granules, and tablets can be coated to make them easier to take.
［発明の効果］
本発明により、抗炎症薬の速効性が著しく改善され、鎮
痛、歯痛などの速い吸収を要求される症状に有用である
。[Effects of the Invention] The present invention significantly improves the rapid effectiveness of anti-inflammatory drugs, and is useful for pain relief, toothache, and other conditions that require rapid absorption.
［実施例］
以下、実施例及び試験例を挙げて本発明を具体的に説明
する。[Example] Hereinafter, the present invention will be specifically explained with reference to Examples and Test Examples.
実施例１〜Ｂ
表 １ 実施例１−８の処方例
表１に示した処方１〜Ｂに基づいてクロルテノキシカム
と炭酸水素ナトリウムの配合比を変化させ錠剤を調製し
た。Examples 1 to B Table 1 Prescription Examples of Examples 1 to 8 Based on Prescriptions 1 to B shown in Table 1, tablets were prepared by varying the blending ratio of chlortenoxicam and sodium hydrogen carbonate.
調製方法は、次の通りである。即ち、まずクロルテノキ
シカムと炭酸水素ナトリウムを混合粉砕し、次いで乳糖
、微結晶セルロース、アエロジル、低置換ヒドロキシプ
ロピルセルロース、及びヒドロキシプロピルセルロース
を混合した。次に攪拌造粒機（バーチカルグラニユレー
タ−；富士産業社製）にこの混合物を投与し、アルコー
ルと精製水の混液を加え、ブレードの回転を３０Ｏｒｐ
ｍ、クロススクリューの回転を１０００ｒｐｍで造粒し
た。The preparation method is as follows. That is, first, chlortenoxicam and sodium hydrogen carbonate were mixed and ground, and then lactose, microcrystalline cellulose, Aerosil, low substituted hydroxypropyl cellulose, and hydroxypropyl cellulose were mixed. Next, this mixture was administered to a stirring granulator (vertical granulator; manufactured by Fuji Sangyo Co., Ltd.), a mixture of alcohol and purified water was added, and the blade rotation was adjusted to 30 rpm.
m, granulation was carried out with a cross screw rotation of 1000 rpm.
流動層乾燥機で乾燥後、スピードミルを用い、ＺＯメツ
シュ以下に整粒した。この整粒した顆粒にステアリン酸
マグネシウムを加え、十分に混合した後、打錠機により
７ｍｍ径の錠剤を製造した。After drying in a fluidized bed dryer, the particles were sized to ZO mesh or less using a speed mill. Magnesium stearate was added to the sized granules, mixed thoroughly, and then tablets with a diameter of 7 mm were manufactured using a tablet machine.
（単位；■ン
実施例９
（処方９）
クロルテノキシカム
炭酸水素ナトリウム
燐酸水素カルシウム無水ＧＳ
微結晶セルロース
アエロジル
低置換ヒドロキシ
プロピルセルロース
ヒドロキシプロピルセルロース
ステアリン酸カルシウム
２■
２０■
０ｎｇ
０ｎｘ
２．５■
５ｒｎｇ
１０１１ｇ
０．５■
実施例１０．１１
表 ２ 実施例１０．１１のあ吉例
上記の処方に基づいて実施例１〜８に記載の製造法と同
様にして錠剤を製造した。(Units: ■ Example 9 (Formulation 9) Chlortenoxicam Sodium Bicarbonate Calcium Hydrogen Phosphate Anhydrous GS Microcrystalline Cellulose Aerosil Low Substituted Hydroxypropyl Cellulose Hydroxypropyl Cellulose Calcium Stearate 2■ 20■ 0ng 0nx 2.5■ 5rng 1011g 0. 5■ Example 10.11 Table 2 Akishi example of Example 10.11 Based on the above formulation, tablets were manufactured in the same manner as in the manufacturing method described in Examples 1 to 8.
（単位；■）
表２に示した処方１０と処方１１に基づいてテノキシカ
ム及びピ乙キシカムと炭酸水素ナトリウムの配合比を変
化させ錠剤を調製した。(Unit: ■) Based on Formulation 10 and Formulation 11 shown in Table 2, tablets were prepared by varying the blending ratio of tenoxicam, piotoxicam, and sodium hydrogen carbonate.
調製方法は、次の通りである。即ち、まずテノキシカ１
またはビ各キ′力４と炭酸水素ナトリウムを混合粉砕し
、次いで燐酸水素カルシウム無水ｃｓ、低を換ヒドロキ
シプロピルセルロース、アエロジル及びヒドロキシプロ
ピルセルロースを混和した。次に攪拌造粒機（バーチカ
ルグラニユレータ−；富士産業社製）にこの混合物を投
与し、アルコールと精製水の混液を加え、ブレードの回
転を３０Ｏｒｐｍ、クロススクリューの回転を１１００
０ｒｐで造粒した。流動層乾燥機で乾燥後、スピードミ
ルを用い、２０メツシユ以下に整粒した。この整粒した
顆粒にステアリン酸マグネシウムを加え、十分に混合し
た後、打錠機により７ｍ径の錠剤を製造した。The preparation method is as follows. That is, first, Tenoxica 1
Alternatively, each force 4 and sodium hydrogen carbonate were mixed and pulverized, and then calcium hydrogen phosphate anhydrous CS, hydrogenated hydroxypropyl cellulose, Aerosil and hydroxypropyl cellulose were mixed. Next, this mixture was administered to a stirring granulator (vertical granulator; manufactured by Fuji Sangyo Co., Ltd.), a mixture of alcohol and purified water was added, the rotation of the blade was 30 Orpm, and the rotation of the cross screw was 1100 rpm.
Granulation was carried out at 0 rpm. After drying in a fluidized bed dryer, the particles were sized to 20 meshes or less using a speed mill. Magnesium stearate was added to the sized granules, mixed thoroughly, and then tablets with a diameter of 7 m were manufactured using a tablet machine.
実施例１３
処方１０に基づいて一般的な顆粒の製法により製造した
顆粒を３号硬カプセルに充填し、カプセル剤を得た。Example 13 Granules manufactured by a general granule manufacturing method based on Formulation 10 were filled into No. 3 hard capsules to obtain capsules.
実施例１４
処方１１に基づいて製造した顆粒を３号硬カプセルに充
填し、カプセル剤を得た。Example 14 Granules produced based on Formulation 11 were filled into No. 3 hard capsules to obtain capsules.
試験例１（錠剤の溶出試験） （検体） 検体１〜９；実施例１〜９の錠剤各１個を用いた。Test example 1 (tablet dissolution test) (sample) Samples 1 to 9: One tablet each of Examples 1 to 9 was used.
対照検体；下記の錠剤各１個。Control specimen: 1 each of the following tablets.
実施例１２
処方９に基ついて一般的な顆粒の製法により製造した顆
粒を３号硬カプセルに充填しカプセル剤を得た。Example 12 Granules produced based on Formulation 9 by a general granule production method were filled into No. 3 hard capsules to obtain capsules.
（処方）
クロルテノキシカム ２■乳糖
４０ｍｇ微結晶セルロース
４１．５■アエロジル １■低
置換ヒドロキシ
プロピルセルロース １０■
ヒドロキシプロピルセルロース ５■ステアリン酸マ
グネシウム ０．５ｒｎｇ（結果）
表３に示す。(Prescription) Chlortenoxicam 2 ■ Lactose
40mg microcrystalline cellulose
41.5 ■ Aerosil 1 ■ Low substituted hydroxypropyl cellulose 10 ■ Hydroxypropyl cellulose 5 ■ Magnesium stearate 0.5 rng (results) Table 3 shows.
表 ３ 人工胃液における溶出性
上記の処方に基づいて実施例２と同様にして錠剤を製造
した。Table 3 Dissolution properties in artificial gastric juice Tablets were manufactured in the same manner as in Example 2 based on the above formulation.
（試験方法）
人口胃液における溶出試験はパドル法（１０１００ｒｐ
で行い、人工胃液として日本薬局方・一般試験法崩壊試
験の第１液（ｐ Ｈ−１，２） ９００ｍ１ｌ （３７
°Ｃ）を用いた。また、溶出した主薬の定量は吸光度法
により行なった。(Test method) The dissolution test in artificial gastric fluid was performed using the paddle method (10100rp
900 ml (37
°C) was used. In addition, the eluted main drug was quantified by absorbance method.
表３に示したように検体６，７は炭酸水素ナトノウムが
全くないあ方に比べ、顕著な溶出性の改善が認められた
。また、炭酸水素ナト１ノウムのクロルテノキシカムに
対する比率が高くなると生薬の溶出性が良くなっている
が、処方８になると、あ方６，７に比べ、初期の溶出が
低くなっていた。これは溶出試験中に錠剤が浮上し、錠
剤の崩壊が延長したためである。また錠剤の浮上は乳糖
より比重の軽い、微結晶セルロースを使用したためと思
われる。As shown in Table 3, in Samples 6 and 7, a remarkable improvement in dissolution was observed compared to the sample containing no sodium bicarbonate. Furthermore, as the ratio of sodium bicarbonate to chlortenoxicam increases, the dissolution of the herbal medicine improves, but for formulation 8, the initial dissolution was lower than for formulations 6 and 7. This is because the tablet floated during the dissolution test, prolonging the disintegration of the tablet. The floating of the tablets is also thought to be due to the use of microcrystalline cellulose, which has a lower specific gravity than lactose.
検体９の人工胃液中における溶出性は、５分で１００２
溶出することが認められた。The dissolution rate of sample 9 in artificial gastric juice is 1002 in 5 minutes.
Elution was observed.
（結果） 表４に示す。(result) It is shown in Table 4.
表 ４ カプセル剤の溶出性 試験例２（カプセル剤の溶出試験） （検体） 検体１；実施例１２のカプセル剤１個。Table 4 Dissolution properties of capsules Test example 2 (dissolution test of capsules) (sample) Specimen 1: 1 capsule of Example 12.
検体２；実施例１３のカプセル剤１個。Specimen 2: 1 capsule of Example 13.
検体３；実施例１４のカプセル剤１個。Specimen 3: 1 capsule of Example 14.
（試験方法）
人口胃液における溶出試験を実施した。尚、溶出試験は
パドル法（１１００ｒｐ ）で行い、人工胃液として日
本薬局方・一般試験法崩壊試験の第１液（ｐ Ｈ＝ １
．２） ９００ｍＱ （３７”Ｃ）を用いた。また、
溶出した上薬の定量は吸光度法により行なった。(Test method) A dissolution test using artificial gastric fluid was conducted. The dissolution test was performed using the paddle method (1100 rpm), and the first solution (pH = 1) of the Japanese Pharmacopoeia/General Test Method disintegration test was used as the artificial gastric fluid.
．． 2) 900mQ (37”C) was used. Also,
The amount of eluted drug was determined by absorbance method.
（単位；％） 錠剤と同様の溶出性であった。(unit;%) The dissolution properties were similar to those of tablets.
試験例３
（検体）
検体１；実施例９の錠剤１個
対照検体；試験例１で用いた対照検体の錠剤１個
（試験方法）
健康志願者６名による吸収実験をクロスオーバー法によ
り実施した。Test Example 3 (Sample) Sample 1: 1 tablet of Example 9 Control sample: 1 tablet of the control sample used in Test Example 1 (Test method) An absorption experiment with 6 healthy volunteers was conducted using a crossover method. .
（結果） 結果は２表５に示す。(result) The results are shown in Table 2.
表 ５ 薬動力学的パラメーター
試験例４
実施例６，７，８．９の錠剤各１個を検体１〜４として
用い硬度計（Ｓｃｈｌｅｕｎｉｇｅｒ−４Ｍ ）により
、錠剤の硬度を測定した。Table 5 Pharmacodynamic Parameter Test Example 4 Using one tablet each of Examples 6, 7, and 8.9 as specimens 1 to 4, the hardness of the tablets was measured using a hardness meter (Schleuniger-4M).
（結果） 結果を表６に示す。(result) The results are shown in Table 6.
表６
表５から明らかなように、検体ｉｔ対対照トイ本番比べ
１．、、、（最高血中濃度到達時間）力（早くなり、Ｃ
，、、、（最高血中濃度）が高くなってし〜る。Table 6 As is clear from Table 5, the actual comparison between the sample IT and the control toy is 1. ,,, (time to reach maximum blood concentration) force (faster, C
,,,, (maximum blood concentration) has become high.
錠剤として適切な硬度硬度は、６．０以上の値である。Hardness suitable for tablets is a value of 6.0 or more.
Claims (1)
系抗炎症薬の吸収性を促進することを特徴とする内服用
固形剤。 ２）オキシカム系抗炎症薬が、クロルテノキシカム、テ
ノキシカム、ピロキシカムである請求項１項記載の内服
用固形剤。 ３）制酸剤が、炭酸水素ナトリウム、リン酸水素カルシ
ウム、メタケイ酸アルミン酸マグネシウム、酸化マグネ
シウム、合成ヒドロタルサイトである請求項１または請
求項２記載の内服用固形剤。[Scope of Claims] 1) A solid preparation for internal use, characterized in that it contains one or more antacids to promote absorption of an oxicam anti-inflammatory drug. 2) The solid preparation for internal use according to claim 1, wherein the oxicam anti-inflammatory drug is chlortenoxicam, tenoxicam, or piroxicam. 3) The solid preparation for internal use according to claim 1 or 2, wherein the antacid is sodium hydrogen carbonate, calcium hydrogen phosphate, magnesium aluminate metasilicate, magnesium oxide, or synthetic hydrotalcite.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2033491A JP2906528B2 (en) | 1990-02-14 | 1990-02-14 | Solid preparation for internal use with enhanced absorption |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2033491A JP2906528B2 (en) | 1990-02-14 | 1990-02-14 | Solid preparation for internal use with enhanced absorption |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH03240729A true JPH03240729A (en) | 1991-10-28 |
| JP2906528B2 JP2906528B2 (en) | 1999-06-21 |
Family
ID=12388029
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2033491A Expired - Lifetime JP2906528B2 (en) | 1990-02-14 | 1990-02-14 | Solid preparation for internal use with enhanced absorption |
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| Country | Link |
|---|---|
| JP (1) | JP2906528B2 (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998029137A1 (en) * | 1996-12-25 | 1998-07-09 | Yamanouchi Pharmaceutical Co., Ltd. | Immediately disintegrable medicinal compositions |
| WO2000015195A1 (en) * | 1998-09-10 | 2000-03-23 | Nycomed Danmark A/S | Quick release pharmaceutical compositions of drug substances |
| JP2005047908A (en) * | 2003-07-16 | 2005-02-24 | Taisho Pharmaceut Co Ltd | Antiinflammatory/analgesic composition for external use |
| WO2005105102A1 (en) * | 2004-05-04 | 2005-11-10 | Equitech Corporation | Improved nsaid composition |
| WO2006056042A1 (en) * | 2004-11-03 | 2006-06-01 | Equitech Corporation | Nsaid compositions exhibiting clinical superiority |
| JP2008504307A (en) * | 2004-06-29 | 2008-02-14 | ニコメド ダンマルク アンパーツゼルスカブ | Production of immediate release pharmaceutical composition of water-insoluble drug and pharmaceutical composition obtained by the method of the present invention |
| WO2009055925A1 (en) * | 2007-10-31 | 2009-05-07 | Equitech Corporation | Enhanced nsaid formulations |
| WO2012043709A1 (en) | 2010-09-30 | 2012-04-05 | 塩野義製薬株式会社 | Preparation for improving solubility of poorly soluble drug |
| US8231899B2 (en) | 1998-09-10 | 2012-07-31 | Nycomed Danmark Aps | Quick release pharmaceutical compositions of drug substances |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009513512A (en) * | 2003-07-09 | 2009-04-02 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Composition comprising meloxicam |
-
1990
- 1990-02-14 JP JP2033491A patent/JP2906528B2/en not_active Expired - Lifetime
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998029137A1 (en) * | 1996-12-25 | 1998-07-09 | Yamanouchi Pharmaceutical Co., Ltd. | Immediately disintegrable medicinal compositions |
| US6899899B2 (en) | 1996-12-25 | 2005-05-31 | Yamanouchi Pharmaceutical Co., Ltd. | Rapidly disintegrable pharmaceutical composition |
| WO2000015195A1 (en) * | 1998-09-10 | 2000-03-23 | Nycomed Danmark A/S | Quick release pharmaceutical compositions of drug substances |
| JP2002524492A (en) * | 1998-09-10 | 2002-08-06 | ニュコメデ ダンマルク アクティーゼルスカブ | Pharmaceutical compositions for rapid release of pharmaceutical substances |
| US8231899B2 (en) | 1998-09-10 | 2012-07-31 | Nycomed Danmark Aps | Quick release pharmaceutical compositions of drug substances |
| JP2012082197A (en) * | 1998-09-10 | 2012-04-26 | Nycomed Danmark Aps | Quick release pharmaceutical composition of drug substance |
| JP2005047908A (en) * | 2003-07-16 | 2005-02-24 | Taisho Pharmaceut Co Ltd | Antiinflammatory/analgesic composition for external use |
| WO2005105102A1 (en) * | 2004-05-04 | 2005-11-10 | Equitech Corporation | Improved nsaid composition |
| JP2011213730A (en) * | 2004-06-29 | 2011-10-27 | Nycomed Danmark Aps | Production of quick release pharmaceutical composition of water-insoluble drug and pharmaceutical composition obtained by the method |
| JP2008504307A (en) * | 2004-06-29 | 2008-02-14 | ニコメド ダンマルク アンパーツゼルスカブ | Production of immediate release pharmaceutical composition of water-insoluble drug and pharmaceutical composition obtained by the method of the present invention |
| US20130059842A1 (en) * | 2004-06-29 | 2013-03-07 | Nycomed Danmark Aps | Manufacturing of quick release pharmaceutical compositons of water insoluble drugs and pharmaceutical compositions obtained by the process of the invention |
| WO2006056042A1 (en) * | 2004-11-03 | 2006-06-01 | Equitech Corporation | Nsaid compositions exhibiting clinical superiority |
| WO2009055925A1 (en) * | 2007-10-31 | 2009-05-07 | Equitech Corporation | Enhanced nsaid formulations |
| WO2012043709A1 (en) | 2010-09-30 | 2012-04-05 | 塩野義製薬株式会社 | Preparation for improving solubility of poorly soluble drug |
| US9427402B2 (en) | 2010-09-30 | 2016-08-30 | Shionogi & Co. Ltd. | Preparation for improving solubility of poorly soluble drug |
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