JP2007145758A - Stabilized pharmaceutical formulation - Google Patents
Stabilized pharmaceutical formulation Download PDFInfo
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- JP2007145758A JP2007145758A JP2005342211A JP2005342211A JP2007145758A JP 2007145758 A JP2007145758 A JP 2007145758A JP 2005342211 A JP2005342211 A JP 2005342211A JP 2005342211 A JP2005342211 A JP 2005342211A JP 2007145758 A JP2007145758 A JP 2007145758A
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- ibuprofen
- tranexamic acid
- desiccant
- pharmaceutical formulation
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- 239000008194 pharmaceutical composition Substances 0.000 title abstract description 5
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims abstract description 31
- 229960001680 ibuprofen Drugs 0.000 claims abstract description 31
- 229960000401 tranexamic acid Drugs 0.000 claims abstract description 25
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 claims abstract description 25
- 239000002274 desiccant Substances 0.000 claims abstract description 22
- NTCYWJCEOILKNG-ROLPUNSJSA-N [(1r,2s)-1-hydroxy-1-phenylpropan-2-yl]-dimethylazanium;chloride Chemical compound Cl.CN(C)[C@@H](C)[C@H](O)C1=CC=CC=C1 NTCYWJCEOILKNG-ROLPUNSJSA-N 0.000 claims abstract description 9
- 229960000920 dihydrocodeine Drugs 0.000 claims abstract description 9
- RBOXVHNMENFORY-DNJOTXNNSA-N dihydrocodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC RBOXVHNMENFORY-DNJOTXNNSA-N 0.000 claims abstract description 9
- 229940073563 dl- methylephedrine hydrochloride Drugs 0.000 claims abstract description 9
- QFRKWSPTCBGLSU-UHFFFAOYSA-M potassium 4-hydroxy-3-methoxybenzene-1-sulfonate Chemical compound [K+].COC1=CC(S([O-])(=O)=O)=CC=C1O QFRKWSPTCBGLSU-UHFFFAOYSA-M 0.000 claims abstract description 9
- 229940069505 potassium guaiacolsulfonate Drugs 0.000 claims abstract description 9
- DBAKFASWICGISY-DASCVMRKSA-N Dexchlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C1([C@H](CCN(C)C)C=2N=CC=CC=2)=CC=C(Cl)C=C1 DBAKFASWICGISY-DASCVMRKSA-N 0.000 claims abstract description 8
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 18
- 238000010521 absorption reaction Methods 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 229940079593 drug Drugs 0.000 abstract description 10
- 239000003814 drug Substances 0.000 abstract description 10
- 230000003993 interaction Effects 0.000 abstract description 10
- 239000000203 mixture Substances 0.000 abstract description 6
- 238000002156 mixing Methods 0.000 abstract description 5
- 238000009472 formulation Methods 0.000 abstract description 4
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 239000003826 tablet Substances 0.000 description 25
- 238000002360 preparation method Methods 0.000 description 13
- 238000004806 packaging method and process Methods 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 239000000654 additive Substances 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 5
- 239000007941 film coated tablet Substances 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 4
- 239000011521 glass Substances 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
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 3
- 239000007894 caplet Substances 0.000 description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 3
- 239000002075 main ingredient Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000008961 swelling Effects 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 description 2
- 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 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 229960001681 croscarmellose sodium Drugs 0.000 description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 238000004513 sizing Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 101100087414 Arabidopsis thaliana RH20 gene Proteins 0.000 description 1
- 101100033939 Arabidopsis thaliana RH55 gene Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 229910021536 Zeolite Inorganic materials 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 229960003291 chlorphenamine Drugs 0.000 description 1
- SOYKEARSMXGVTM-UHFFFAOYSA-N chlorphenamine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 SOYKEARSMXGVTM-UHFFFAOYSA-N 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 229940031705 hydroxypropyl methylcellulose 2910 Drugs 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000012858 packaging process Methods 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 239000010457 zeolite Substances 0.000 description 1
Abstract
Description
本発明は、安定化された医薬製剤、さらに詳しくは、イブプロフェンおよびトラネキサム酸、またはイブプロフェンおよびトラネキサム酸と、ｄ−マレイン酸クロルフェニラミン、リン酸ジヒドロコデイン、ｄｌ−塩酸メチルエフェドリンおよびグアヤコールスルホン酸カリウムから選ばれる少なくとも１種の主薬を配合した医薬製剤における、主にイブプロフェンおよびトラネキサム酸の相互作用による製剤外観の不安定化、特に製剤の膨張を乾燥剤により改善した医薬製剤に関する。 The present invention relates to stabilized pharmaceutical formulations, more particularly ibuprofen and tranexamic acid, or ibuprofen and tranexamic acid and d-chlorpheniramine maleate, dihydrocodeine phosphate, dl-methylephedrine hydrochloride and potassium guaiacol sulfonate. The present invention relates to a pharmaceutical preparation in which at least one selected main drug is blended, and the appearance of the preparation is destabilized mainly by the interaction of ibuprofen and tranexamic acid, and in particular, the swelling of the preparation is improved by a desiccant.
医薬製剤品、特に一般用医薬製剤では配合される主薬や添加物が多いため、相互作用を起こし、物理化学的変化（外観変化、融点降下、膨張等）を起こしやすい。とりわけ、低融点物質などを多く配合する製剤においては、薬物や添加物間の相互作用によって、安定性評価の保存中に物理化学的変化によって、錠剤が膨張する現象が見られる。この現象により、素錠であれば素錠表面や側面にヒビが出る場合があり、またフィルムコーティング錠であれば、フィルムの亀裂及びフィルム剥離のような外観不良が発生する。
一般に、薬物や添加物間の相互作用を改善するには、例えば、要因となる薬物同士を分離させて配合したり、薬物同士が接触しないように各々コーティングしたり、さらには有核錠や積層錠、糖衣錠等にするという手段が用いられる。しかし、これらの方法は、それぞれの薬物の配合量が多い場合など分離させるために多量の賦形剤や添加剤が必要となり、錠剤が大きくなりすぎて服用性が悪くなるという問題がでてくる。また、特殊な錠剤にするには製造法が煩雑になりコストアップにつながるという欠点もある。
イブプロフェンおよびトラネキサム酸を配合した医薬製剤もこのような相互作用を起こす製剤であるが、その相互作用を改善する上記のような問題のない技術はこれまで見当たらない。
特許文献１には、イブプロフェンの昇華を乾燥剤の配合で防止することが開示されているが、イブプロフェンとトラネキサム酸の相互作用の改善について示唆するものではない。また、例えば、特許文献２および３には、イブプロフェンとトラネキサム酸を配合してなる医薬製剤が開示されているが、これらの文献も両成分の相互作用の改善を示唆するものではない。
In general, in order to improve the interaction between drugs and additives, for example, the factor drugs are separated from each other, coated so that the drugs do not come into contact with each other, or a dry-coated tablet or laminate Means such as tablets, dragees and the like are used. However, these methods require a large amount of excipients and additives to separate them, for example, when the amount of each drug is large, and there is a problem that the tablet becomes too large and the doseability becomes poor. . In addition, there is a drawback in that the manufacturing method becomes complicated for a special tablet, leading to an increase in cost.
A pharmaceutical preparation containing ibuprofen and tranexamic acid is also a preparation that causes such an interaction. However, there has not been found a technique that does not have the above-mentioned problems to improve the interaction.
Patent Document 1 discloses that the sublimation of ibuprofen is prevented by adding a desiccant, but does not suggest improvement of the interaction between ibuprofen and tranexamic acid. Further, for example, Patent Documents 2 and 3 disclose pharmaceutical preparations comprising ibuprofen and tranexamic acid, but these documents do not suggest improvement of the interaction between the two components.
本発明は、イブプロフェンおよびトラネキサム酸を含む製剤、またはイブプロフェンおよびトラネキサム酸に加えて、ｄ−マレイン酸クロルフェニラミン、リン酸ジヒドロコデイン、ｄｌ−塩酸メチルエフェドリンおよびグアヤコールスルホン酸カリウムから選ばれる少なくとも１種の主薬を配合してなる医薬製剤において、特殊な製剤にすることで製造法を煩雑にすることなく、通常用いられる簡便な手法で、製剤の膨張を改善することを課題とするものである。 The present invention relates to a preparation comprising ibuprofen and tranexamic acid, or at least one selected from ibuprofen and tranexamic acid, d-chlorpheniramine maleate, dihydrocodeine phosphate, dl-methylephedrine hydrochloride and potassium guaiacol sulfonate. An object of the present invention is to improve the swelling of a preparation by a commonly used simple method without complicating the production method by making a special preparation in a pharmaceutical preparation containing a main ingredient.
上記課題に鑑み、本発明者らは鋭意検討の結果、イブプロフェンおよびトラネキサム酸、またはイブプロフェンおよびトラネキサム酸と、ｄ−マレイン酸クロルフェニラミン、リン酸ジヒドロコデイン、ｄｌ−塩酸メチルエフェドリンおよびグアヤコールスルホン酸カリウムから選ばれる少なくとも１種の主薬を配合した医薬製剤、特に、錠剤に通常用いられる乾燥剤を包装工程で同封することで、製剤の膨張が抑えられ、外観の安定化が図れることを見出し、本発明を完成するに至った。 In view of the above problems, as a result of intensive studies, the present inventors have determined from ibuprofen and tranexamic acid, or ibuprofen and tranexamic acid, chlorpheniramine d-maleate, dihydrocodeine phosphate, dl-methylephedrine hydrochloride and potassium guaiacol sulfonate. The present invention has found that pharmaceutical preparations containing at least one selected active ingredient, in particular, the desiccant usually used for tablets can be enclosed in the packaging process, so that the expansion of the preparation can be suppressed and the appearance can be stabilized. It came to complete.
すなわち、本発明は、（ａ）イブプロフェンおよびトラネキサム酸を重量比で１：１〜２の割合で配合してなる医薬製剤、または（ｂ）イブプロフェンおよびトラネキサム酸を重量比で１：０．１〜５の割合で含有し、さらに、ｄ−マレイン酸クロルフェニラミン、リン酸ジヒドロコデイン、ｄｌ−塩酸メチルエフェドリンおよびグアヤコールスルホン酸カリウムから選ばれる少なくとも１種の主薬を配合してなる医薬製剤であって、配合したイブプロフェン１重量部に対して（ａ）の場合は、０．１〜５重量部の割合で、（ｂ）の場合は、０．０１〜１０重量部の割合で乾燥剤を同封した包装とすることを特徴とする医薬製剤を提供するものである。本発明においては、乾燥剤の吸水能力が関係湿度ＲＨ２０％で６％以上であり、関係湿度ＲＨ５５％で１６．５％以上（各２５℃７２時間）であることが好ましい。 That is, the present invention relates to (a) a pharmaceutical preparation comprising ibuprofen and tranexamic acid in a weight ratio of 1: 1 to 2, or (b) ibuprofen and tranexamic acid in a weight ratio of 1: 0.1 to 0.1. A pharmaceutical preparation comprising at least one active ingredient selected from d-chlorpheniramine maleate, dihydrocodeine phosphate, dl-methylephedrine hydrochloride and potassium guaiacol sulfonate, In the case of (a) with respect to 1 part by weight of ibuprofen blended, 0.1 to 5 parts by weight in the case of (a), and in the case of (b), a packaging in which a desiccant is enclosed at a ratio of 0.01 to 10 parts by weight The present invention provides a pharmaceutical preparation characterized by the following. In the present invention, it is preferable that the water absorption capacity of the desiccant is 6% or more at a relative humidity RH of 20% and 16.5% or more (each at 25 ° C. for 72 hours) at a relative humidity RH of 55%.
本発明においては、イブプロフェンとトラネキサム酸の相互作用が製剤を膨張させる主要因であり、それ以外の薬物が配合されるとさらに膨張が助長されると考えられ、その膨張に対して乾燥剤を同封することで、乾燥剤の乾燥能力（吸着性能）により膨張が改善されると考えられる。 In the present invention, the interaction between ibuprofen and tranexamic acid is the main factor that causes the formulation to swell, and it is thought that when other drugs are added, the expansion is further promoted. By doing so, it is considered that the expansion is improved by the drying ability (adsorption performance) of the desiccant.
本発明の医薬製剤は、（ａ）イブプロフェンおよびトラネキサム酸、または（ｂ）イブプロフェンおよびトラネキサム酸と、ｄ−マレイン酸クロルフェニラミン、リン酸ジヒドロコデイン、ｄｌ−塩酸メチルエフェドリンおよびグアヤコールスルホン酸カリウムから選ばれる少なくとも１種の主薬を薬効成分として配合したものである。（ｂ）の製剤の場合、ｄ−マレイン酸クロルフェニラミン、リン酸ジヒドロコデイン、ｄｌ−塩酸メチルエフェドリンおよびグアヤコールスルホン酸カリウムから選ばれる少なくとも１種の主薬については、その配合の組み合わせは特に限定するものではない。 The pharmaceutical preparation of the present invention is selected from (a) ibuprofen and tranexamic acid or (b) ibuprofen and tranexamic acid and d-chlorpheniramine maleate, dihydrocodeine phosphate, dl-methylephedrine hydrochloride and potassium guaiacol sulfonate At least one main drug is blended as a medicinal ingredient. In the case of the preparation of (b), the combination of the at least one active ingredient selected from d-chlorpheniramine maleate, dihydrocodeine phosphate, dl-methylephedrine hydrochloride and potassium guaiacol sulfonate is particularly limited. is not.
（ａ）の製剤の場合、イブプロフェンおよびトラネキサム酸を重量比で１：１〜２、好ましくは１：１〜１．７の割合で配合し、乾燥剤は、配合したイブプロフェン１重量部に対して０．１〜５重量部の割合で同封する。
（ｂ）の製剤の場合、イブプロフェンとトラネキサム酸の配合割合についてはより広い配合割合の範囲で錠剤の膨張が発生する傾向があり、イブプロフェンおよびトラネキサム酸を重量比で１：０．１〜５、好ましくは１：０．５〜３の割合とする。イブプロフェンおよびトラネキサム酸以外の主薬の配合割合は特に限定するものではない。乾燥剤は、イブプロフェン１重量部に対して、０．０１〜１０重量部、好ましくは０．０５〜８重量部、さらに好ましくは０．１〜５重量部で同封する。
In the case of the preparation of (a), ibuprofen and tranexamic acid are mixed at a weight ratio of 1: 1 to 2, preferably 1: 1 to 1.7, and the desiccant is based on 1 part by weight of the mixed ibuprofen. Enclose at 0.1 to 5 parts by weight.
In the case of the preparation of (b), there is a tendency that tablet expansion occurs in a wider range of the mixing ratio of ibuprofen and tranexamic acid, and ibuprofen and tranexamic acid are in a weight ratio of 1: 0.1 to 5, The ratio is preferably 1: 0.5 to 3. The mixing ratio of the main drug other than ibuprofen and tranexamic acid is not particularly limited. A desiccant is enclosed by 0.01-10 weight part with respect to 1 weight part of ibuprofen, Preferably it is 0.05-8 weight part, More preferably, it is 0.1-5 weight part.
本発明の医薬製剤は、通常配合される賦形剤や添加剤等を用いて、常法により、錠剤等とすることができ、その大きさ、形状、質量は特に限定するものではなく、例えば、素錠、フィルムコーティング錠、糖衣錠等の標準的な、例えば、円形錠、オブロング錠、オーバル錠、カプレット等とすることができる。用いる賦形剤や添加剤の種類および配合量について特に限定されるものではない。 The pharmaceutical preparation of the present invention can be made into tablets and the like by conventional methods using excipients and additives that are usually blended, and the size, shape, and mass are not particularly limited. Standard tablets such as uncoated tablets, film-coated tablets, sugar-coated tablets, for example, round tablets, oblong tablets, oval tablets, caplets and the like. It does not specifically limit about the kind and compounding quantity of the excipient | filler and additive to be used.
用いる乾燥剤は、特に種類、性能および量を限定するものではないが、吸水能力が高いものほど効果が大きく、好ましくは、吸水能力が関係湿度ＲＨ２０％で６％以上であり、関係湿度ＲＨ５５％で１６．５％以上（各２５℃７２時間）である。乾燥剤の種類としては、例えば、シリカゲル系乾燥剤、ゼオライト系乾燥剤、活性炭系乾燥剤などが挙げられる。また、乾燥剤の形状も特に限定するものではなく、例えば、瓶包装の場合は蓋の裏に付くタイプや瓶内への投げ込みタイプなどが挙げられ、ＰＴＰ包装の場合はシート状のタイプなどが挙げられる。
以下、実施例、比較例、実験例を挙げて本発明をさらに詳しく説明するが、本発明はこれらに限定されるものではない。
The type, performance, and amount of the desiccant used are not particularly limited, but the higher the water absorption capacity, the greater the effect. Preferably, the water absorption capacity is 6% or more when the relative humidity is RH20%, and the relative humidity is RH55%. 16.5% or more (each 25 ° C. for 72 hours). Examples of the desiccant include a silica gel desiccant, a zeolite desiccant, and an activated carbon desiccant. In addition, the shape of the desiccant is not particularly limited. For example, in the case of bottle packaging, there are a type attached to the back of the lid, a throwing type into the bottle, etc., and in the case of PTP packaging, a sheet type etc. Can be mentioned.
EXAMPLES Hereinafter, although an Example, a comparative example, and an experiment example are given and this invention is demonstrated in more detail, this invention is not limited to these.
表１に示す処方により、流動層造粒機（ＭＰ−１０：パウレック社製）を用いてヒドロキシプロピルセルロース溶液を噴霧し、常法により造粒した。そしてこの造粒末（２９７０ｇ）を整粒（パワーミル・Ｐ−３型：昭和化学機械製）し、その整粒末に対して、結晶セルロース、クロスカルメロースナトリウム、軽質無水ケイ酸、ステアリン酸マグネシウムを添加して混合（タンブラー混合機：昭和化学機械製）を行い打錠末とし、その後ロータリー式打錠機（コレクト１９Ｋ：菊水製作所製）にて４５０ｍｇ／錠の素錠（カプレットタイプ）を製した。その素錠にフィルム液（ヒドロキシプロピルメチルセルロース２９１０：コポリビドン：タルク：酸化チタン＝６５．２５：６．７５：９：９）固形分濃度１０％を噴霧してコーティング（増加重量１５ｍｇ／錠）を行い（ハイコーター２０：フロイント産業製）、フィルムコーティング錠を得た。そのフィルムコーティング錠３０錠と乾燥剤（セラム２ｇ）を６Ｋガラス瓶に入れ、瓶包装形体とした。 According to the formulation shown in Table 1, the hydroxypropylcellulose solution was sprayed using a fluidized bed granulator (MP-10: manufactured by Paulek) and granulated by a conventional method. And this granulated powder (2970 g) is sized (power mill type P-3: manufactured by Showa Kagaku Kikai Co., Ltd.), and with respect to the sized powder, crystalline cellulose, croscarmellose sodium, light anhydrous silicic acid, magnesium stearate And then mixing (tumbler mixer: Showa Kagaku Kikai Co., Ltd.) to obtain a tableting powder, and then using a rotary tableting machine (Collect 19K: manufactured by Kikusui Seisakusho) to produce 450 mg / tablet uncoated tablet (caplet type) did. The uncoated tablets were sprayed with a film solution (hydroxypropylmethylcellulose 2910: copolyvidone: talc: titanium oxide = 65.25: 6.75: 9: 9) with a solid content concentration of 10% and coated (increased weight 15 mg / tablet). (High coater 20: manufactured by Freund Corporation), a film-coated tablet was obtained. Thirty film-coated tablets and a desiccant (serum 2 g) were placed in a 6K glass bottle to form a bottle packaging shape.
表２に示す処方により、I群はバーチカルグラニュレーター（パウレック社製）を用いて、ヒドロキシプロピルセルロース溶液を添加し、常法により造粒（８７６ｇ）した。その後、湿式整粒（パワーミル・Ｐ−３型：昭和化学機械製）し、流動層乾燥機（ＭＰ−１０：パウレック社製）にて乾燥を行い、再度整粒（パワーミル・Ｐ−３型：昭和化学機械製）を行い、I群整粒末とした。M群は流動層造粒機（ＭＰ−１０：パウレック社製）を用いてヒドロキシプロピルセルロース溶液を噴霧し、常法により造粒した。そしてこの造粒末（２０３４ｇ）を整粒（パワーミル・Ｐ−３型：昭和化学機械製）した。これらの整粒末に対して、結晶セルロース、クロスカルメロースナトリウム、軽質無水ケイ酸、ステアリン酸マグネシウムを添加して混合（タンブラー混合機：昭和化学機械製）を行い打錠末とし、その後ロータリー式打錠機（コレクト１９Ｋ：菊水製作所製）にて４５０ｍｇ／錠の素錠（カプレットタイプ）を製した。その素錠３０錠と乾燥剤（セラム２ｇ）を６Ｋガラス瓶に入れ、瓶包装形体とした。 According to the formulation shown in Table 2, Group I was granulated by a conventional method (876 g) by adding a hydroxypropylcellulose solution using a vertical granulator (manufactured by POWREC). Thereafter, wet sizing (power mill, P-3 type: Showa Kagaku Kikai Co., Ltd.), drying with a fluidized bed dryer (MP-10: manufactured by Paulek), and sizing again (power mill, P-3 type: Showa Kagaku Kikai Co., Ltd.) to obtain Group I sized powder. Group M was sprayed with a hydroxypropylcellulose solution using a fluidized bed granulator (MP-10: manufactured by Paulek) and granulated by a conventional method. The granulated powder (2034 g) was sized (Power Mill / P-3 type: Showa Chemical Machinery). To these sized powders, crystalline cellulose, croscarmellose sodium, light anhydrous silicic acid, magnesium stearate are added and mixed (tumbler mixer: manufactured by Showa Chemical Machinery Co., Ltd.) to form a tableting powder, and then a rotary type An uncoated tablet (caplet type) of 450 mg / tablet was manufactured with a tableting machine (collect 19K: manufactured by Kikusui Seisakusho). Thirty uncoated tablets and a desiccant (serum 2 g) were placed in a 6K glass bottle to form a bottle packaging shape.
実施例１で製したフィルムコーティング錠３０錠を６Ｋガラス瓶に入れ、瓶包装形体とした（乾燥剤無し）。 Thirty film-coated tablets produced in Example 1 were placed in a 6K glass bottle to form a bottle packaging (no desiccant).
実施例２で製した素錠３０錠を６Ｋガラス瓶に入れ、瓶包装形体とした（乾燥剤無し）。 Thirty uncoated tablets produced in Example 2 were placed in a 6K glass bottle to form a bottle packaging (no desiccant).
実施例１、実施例２および比較例１、比較例２の瓶包装形体品を６０℃に４日間保存した。その後、錠剤の厚みをダイヤルゲージで測定した。
以下の式（１）に従って膨張割合を出し、その結果を表３に示す。
［数１］
膨張割合（％）＝保存後の検体の厚み／Initialの検体の厚み×１００ （１）
この結果から、本発明により錠剤の膨張は抑制でき、外観品質の安定した医薬品が提供できることが分かる。
The bottle packaged products of Example 1, Example 2, Comparative Example 1, and Comparative Example 2 were stored at 60 ° C. for 4 days. Thereafter, the tablet thickness was measured with a dial gauge.
The expansion ratio was calculated according to the following formula (1), and the result is shown in Table 3.
[Equation 1]
Expansion ratio (%) = Thickness of specimen after storage / Initial specimen thickness × 100 (1)
From this result, it can be seen that the present invention can suppress the expansion of the tablet and provide a pharmaceutical product with stable appearance quality.
本発明に従って、イブプロフェンおよびトラネキサム酸、またはイブプロフェンおよびトラネキサム酸と、ｄ−マレイン酸クロルフェニラミン、リン酸ジヒドロコデイン、ｄｌ−塩酸メチルエフェドリンおよびグアヤコールスルホン酸カリウムから選ばれる少なくとも１種の主薬を配合した医薬製剤に乾燥剤を同封することで、製剤の膨張を改善し、外観品質を安定化した医薬製剤を提供することができる。
According to the present invention, a pharmaceutical comprising ibuprofen and tranexamic acid, or ibuprofen and tranexamic acid, and at least one main ingredient selected from d-chlorpheniramine maleate, dihydrocodeine phosphate, dl-methylephedrine hydrochloride and potassium guaiacol sulfonate By enclosing a desiccant in the preparation, it is possible to provide a pharmaceutical preparation that improves the expansion of the preparation and stabilizes the appearance quality.
Claims (2)
The pharmaceutical preparation according to claim 1, wherein the desiccant has a water absorption capacity of 6% or more at a relative humidity RH of 20% and 16.5% or more (at 25 ° C for 72 hours each) at a relative humidity of RH 55%.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007284423A (en) * | 2006-03-24 | 2007-11-01 | Daiichi Sankyo Healthcare Co Ltd | Pharmaceutical preparation and method for producing the same |
| JP2008266270A (en) * | 2007-04-25 | 2008-11-06 | Kowa Co | Solid preparation containing ibuprofen, tranexamic acid and sugar alcohol |
| JP2011246441A (en) * | 2010-03-31 | 2011-12-08 | Kowa Co | Pharmaceutical composition containing loxoprofen or salt of the same |
| JP2011246437A (en) * | 2010-01-29 | 2011-12-08 | Kowa Co | Pharmaceutical composition containing loxoprofen or salt of the same |
| JP2013163698A (en) * | 2006-03-24 | 2013-08-22 | Daiichi Sankyo Healthcare Co Ltd | Pharmaceutical preparation and method for producing the same |
| JP2014218522A (en) * | 2008-09-04 | 2014-11-20 | 興和株式会社 | Loxoprofen-containing pharmaceutical composition |
| JP2019019128A (en) * | 2017-07-18 | 2019-02-07 | 武田コンシューマーヘルスケア株式会社 | Film coating tablet |
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|---|---|---|---|---|
| JPH0948728A (en) * | 1995-03-27 | 1997-02-18 | Shiseido Co Ltd | Antipyretic and analgesic agent |
| JP2005187328A (en) * | 2003-12-24 | 2005-07-14 | Lion Corp | Antipyretic and analgesic composition comprising ibuprofen and drug for common cold |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0948728A (en) * | 1995-03-27 | 1997-02-18 | Shiseido Co Ltd | Antipyretic and analgesic agent |
| JP2005187328A (en) * | 2003-12-24 | 2005-07-14 | Lion Corp | Antipyretic and analgesic composition comprising ibuprofen and drug for common cold |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007284423A (en) * | 2006-03-24 | 2007-11-01 | Daiichi Sankyo Healthcare Co Ltd | Pharmaceutical preparation and method for producing the same |
| JP2013163698A (en) * | 2006-03-24 | 2013-08-22 | Daiichi Sankyo Healthcare Co Ltd | Pharmaceutical preparation and method for producing the same |
| JP2008266270A (en) * | 2007-04-25 | 2008-11-06 | Kowa Co | Solid preparation containing ibuprofen, tranexamic acid and sugar alcohol |
| JP2014218522A (en) * | 2008-09-04 | 2014-11-20 | 興和株式会社 | Loxoprofen-containing pharmaceutical composition |
| JP2011246437A (en) * | 2010-01-29 | 2011-12-08 | Kowa Co | Pharmaceutical composition containing loxoprofen or salt of the same |
| JP2011246441A (en) * | 2010-03-31 | 2011-12-08 | Kowa Co | Pharmaceutical composition containing loxoprofen or salt of the same |
| JP2019019128A (en) * | 2017-07-18 | 2019-02-07 | 武田コンシューマーヘルスケア株式会社 | Film coating tablet |
| JP7130481B2 (en) | 2017-07-18 | 2022-09-05 | アリナミン製薬株式会社 | film coated tablets |
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