JP2008150298A - Diphenhydramine-containing medicine composition having improved solubility - Google Patents
Diphenhydramine-containing medicine composition having improved solubility Download PDFInfo
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- JP2008150298A JP2008150298A JP2006337929A JP2006337929A JP2008150298A JP 2008150298 A JP2008150298 A JP 2008150298A JP 2006337929 A JP2006337929 A JP 2006337929A JP 2006337929 A JP2006337929 A JP 2006337929A JP 2008150298 A JP2008150298 A JP 2008150298A
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- diphenhydramine
- pharmaceutical composition
- medicine composition
- macrogol
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- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 title claims abstract description 21
- 229960000520 diphenhydramine Drugs 0.000 title claims abstract description 21
- 239000003814 drug Substances 0.000 title abstract description 7
- 239000000203 mixture Substances 0.000 title abstract description 7
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229960003511 macrogol Drugs 0.000 claims abstract description 16
- 239000002253 acid Substances 0.000 claims abstract description 14
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 239000002775 capsule Substances 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 24
- 239000002904 solvent Substances 0.000 claims description 6
- 239000004014 plasticizer Substances 0.000 claims description 4
- 239000004094 surface-active agent Substances 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 abstract description 7
- 238000004090 dissolution Methods 0.000 abstract description 5
- 206010041349 Somnolence Diseases 0.000 abstract description 4
- 238000010521 absorption reaction Methods 0.000 abstract description 4
- 208000032140 Sleepiness Diseases 0.000 abstract description 3
- 230000037321 sleepiness Effects 0.000 abstract description 3
- -1 glycerin fatty acid ester Chemical class 0.000 description 10
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- 239000000194 fatty acid Substances 0.000 description 7
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- 230000000694 effects Effects 0.000 description 6
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- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
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- 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
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
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- 229920002134 Carboxymethyl cellulose 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-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
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- MQIUGAXCHLFZKX-UHFFFAOYSA-N Di-n-octyl phthalate Natural products CCCCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCCCCCC MQIUGAXCHLFZKX-UHFFFAOYSA-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
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
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- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229940023476 agar Drugs 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- BJQHLKABXJIVAM-UHFFFAOYSA-N bis(2-ethylhexyl) phthalate Chemical compound CCCCC(CC)COC(=O)C1=CC=CC=C1C(=O)OCC(CC)CCCC BJQHLKABXJIVAM-UHFFFAOYSA-N 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 229950008138 carmellose Drugs 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940124579 cold medicine Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 239000003172 expectorant agent Substances 0.000 description 1
- 230000003419 expectorant effect Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 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
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 239000001069 triethyl citrate Substances 0.000 description 1
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 1
- 235000013769 triethyl citrate Nutrition 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
本発明は、溶解性を改善したジフェンヒドラミンの経口投与用組成物、及びこれを含有するカプセル剤に関する。 The present invention relates to a composition for oral administration of diphenhydramine with improved solubility, and a capsule containing the same.
ジフェンヒドラミン及びその酸付加塩は抗ヒスタミン作用と中枢作用を有し、鼻炎、感冒薬及び鎮咳去痰薬の有効成分として用いられているが、副作用として眠気を生じることが判明している。現在、この副作用である眠気をいわば効能とした睡眠改善薬として、ジフェンヒドラミン及びその酸付加塩は使用されている。 Diphenhydramine and its acid addition salts have antihistamine and central effects and are used as active ingredients in rhinitis, cold medicine and antitussive expectorant, but have been found to cause drowsiness as a side effect. Currently, diphenhydramine and acid addition salts thereof are used as sleep-improving drugs that are effective in terms of the side effect of sleepiness.
ところが、現在用いられているジフェンヒドラミンまたはその酸付加塩含有製剤の剤形は錠剤型であり、その錠剤は服用後体内で崩壊した後、溶解吸収されるため、崩壊及び溶解に時間を要した。睡眠改善薬としてジフェンヒドラミン含有製剤を服用する際は、速やかな眠気の発現が求められるため、迅速な溶解吸収は製剤の性能を著しく向上させるものである。上記特開２００３−３００８７２号の特許出願を初めとして、溶解性を向上するための製剤も提案されているが、必ずしも十分な効果が得られていない。 However, the currently used dosage form of diphenhydramine or its acid addition salt-containing preparation is a tablet type, and since the tablet disintegrates in the body after taking it, it takes time to disintegrate and dissolve. When taking a diphenhydramine-containing preparation as a sleep-improving drug, rapid onset of sleepiness is required, and thus rapid dissolution and absorption significantly improve the performance of the preparation. Preparations for improving the solubility have been proposed including the patent application of the above-mentioned JP-A No. 2003-300872, but sufficient effects are not necessarily obtained.
本発明者らは上記課題を解決するために鋭意検討した結果、ジフェンヒドラミンまたはその酸付加塩をマクロゴールに溶解せしめることによって、速やかな溶解吸収特性を有する医薬組成物を確立した。 As a result of intensive studies to solve the above-mentioned problems, the present inventors have established a pharmaceutical composition having a rapid dissolution / absorption characteristic by dissolving diphenhydramine or an acid addition salt thereof in macrogol.
従って、本発明は下記の医薬品組成物に関する。
（１）ジフェンヒドラミンまたはその酸付加塩１重量部に対しマクロゴール１〜２０重量部を含有してなる医薬組成物。
Accordingly, the present invention relates to the following pharmaceutical composition.
(1) A pharmaceutical composition comprising 1 to 20 parts by weight of macrogol per 1 part by weight of diphenhydramine or an acid addition salt thereof.
（２）さらに、界面活性剤及び／または可塑剤を含有する（１）記載の医薬組成物。 (2) The pharmaceutical composition according to (1), further comprising a surfactant and / or a plasticizer.
（３）さらに、溶解補助剤を含有する（１）または（２）に記載の医薬組成物。 (3) The pharmaceutical composition according to (1) or (2), further comprising a solubilizing agent.
上記（１）〜（３）のいずれか１項に記載の医薬組成物を充填してなるカプセル剤。 Capsules formed by filling the pharmaceutical composition according to any one of (1) to (3) above.
本発明のジフェンヒドラミンまたはその酸付加塩含有医薬組成物は、水分散性に優れ、経口投与時に速やかな溶解吸収が期待できるため、製剤の有効性を著しく高めることが可能となった。 The diphenhydramine or acid addition salt-containing pharmaceutical composition of the present invention is excellent in water dispersibility and can be expected to rapidly dissolve and absorb upon oral administration, so that the effectiveness of the preparation can be remarkably increased.
本発明の医薬組成物はジフェンヒドラミンまたはその酸付加塩をマクロゴールに溶解することを特徴とした経口製剤である。 The pharmaceutical composition of the present invention is an oral preparation characterized by dissolving diphenhydramine or an acid addition salt thereof in macrogol.
本発明に使用するマクロゴールは、酸化エチレンと水との付加重合体であり、例えば、マクロゴール２００，マクロゴール３００，マクロゴール４００，マクロゴール６００，マクロゴール１０００，マクロゴール１５００，マクロゴール１５４０，マクロゴール４０００，マクロゴール６０００，マクロゴール２００００及びマクロゴール３５０００またはそれらの合成品から選択される１種またはそれ以上の物質である。 The macrogol used in the present invention is an addition polymer of ethylene oxide and water. For example, macrogol 200, macrogol 300, macrogol 400, macrogol 600, macrogol 1000, macrogol 1500, macrogol 1540 , Macrogol 4000, Macrogol 6000, Macrogol 20000 and Macrogol 35000, or one or more substances selected from these synthetic products.
マクロゴールは、ジフェンヒドラミンまたはその酸付加塩１重量部に対し、１〜２０重量部、好ましくは２〜１５重量部、より好ましくは５〜１０重量部の量で含まれる。 Macrogol is contained in an amount of 1 to 20 parts by weight, preferably 2 to 15 parts by weight, more preferably 5 to 10 parts by weight, based on 1 part by weight of diphenhydramine or an acid addition salt thereof.
本発明に使用する界面活性剤は、例えばグリセリン脂肪酸エステル、多価アルコール脂肪酸エステル、ポリオキシエチレンソルビタン脂肪酸エステル、ソルビタン脂肪酸エステル、ショ糖脂肪酸エステル、飽和ポリグリコール化グリセリド、ポリオキシエチレンポリオキシプロピレングリコール、アセチルグリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステル、レシチン及びポリオキシエチレン硬化ヒマシ油等から選択される、１種またはそれ以上の物質であるが、本発明は前記物質に限定されるものではない。 The surfactant used in the present invention is, for example, glycerin fatty acid ester, polyhydric alcohol fatty acid ester, polyoxyethylene sorbitan fatty acid ester, sorbitan fatty acid ester, sucrose fatty acid ester, saturated polyglycolized glyceride, polyoxyethylene polyoxypropylene glycol , Acetylglycerin fatty acid ester, polyglycerin fatty acid ester, lecithin, polyoxyethylene hydrogenated castor oil and the like, but the present invention is not limited to the above-mentioned substances.
界面活性剤は、ジフェンヒドラミンまたはその酸付加塩１重量部に対し、好ましくは０．００１〜１重量部、より好ましくは０．０１〜０．１重量部の量で含まれる。 The surfactant is contained in an amount of preferably 0.001 to 1 part by weight, more preferably 0.01 to 0.1 part by weight with respect to 1 part by weight of diphenhydramine or an acid addition salt thereof.
本発明の医薬組成物またはこれを含有するカプセル剤において、可塑剤及びその他慣用の添加剤を含有させることにより、更に流動性が改善され、溶液の安定性を高める効果を奏することが確認された。 In the pharmaceutical composition of the present invention or the capsule containing the same, it has been confirmed that by including a plasticizer and other conventional additives, the fluidity is further improved and the effect of increasing the stability of the solution is exhibited. .
可塑剤の例としては、プロピレングリコール、トリアセチン、フタル酸ジエチル、フタル酸ジオクチル、フタル酸ジブチル、ミリスチン酸イソプロピル、グリセリン、ソルビトール、不飽和脂肪酸、中鎖脂肪酸トリグリセリド及びクエン酸トリエチルから選択される１種またはそれ以上の物質が挙げられる。 Examples of plasticizers include propylene glycol, triacetin, diethyl phthalate, dioctyl phthalate, dibutyl phthalate, isopropyl myristate, glycerin, sorbitol, unsaturated fatty acids, medium chain fatty acid triglycerides and triethyl citrate. Or more than that.
本発明の医薬組成物は更に溶解補助剤を含有してもよい。溶解補助剤の例としては、クロスポビドン、ポビドン、コポリビドン、エチルセルロース、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、ポリビニルアルコール、メチルセルロース、カルメロース等の合成高分子、ならびにゼラチン、デキストリン、アルギン酸ナトリウム、カラギーナン、寒天及び加工デンプン等の天然由来高分子から選択される１種またはそれ以上の物質が挙げられる。 The pharmaceutical composition of the present invention may further contain a solubilizing agent. Examples of solubilizers include crospovidone, povidone, copolyvidone, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, methylcellulose, carmellose, and the like, as well as gelatin, dextrin, sodium alginate, carrageenan, agar and processed One or more substances selected from naturally-derived polymers such as starch may be mentioned.
本発明の医薬組成物またはこれを含有するカプセル剤において、溶解補助剤を含有させることにより、ジフェンヒドラミンの溶解安定性を更に高める効果を奏することが確認された。 It was confirmed that the pharmaceutical composition of the present invention or the capsule containing the same has the effect of further enhancing the dissolution stability of diphenhydramine by containing a solubilizing agent.
溶解補助剤は、ジフェンヒドラミンまたはその酸付加塩１重量部に対し、好ましくは０．０１〜１０重量部、より好ましくは０．１〜５重量部の量で含まれる。 The solubilizing agent is preferably contained in an amount of 0.01 to 10 parts by weight, more preferably 0.1 to 5 parts by weight with respect to 1 part by weight of diphenhydramine or an acid addition salt thereof.
本発明のカプセル剤は、軟カプセル剤であっても硬カプセル剤であってもよい。軟カプセル剤は、平板法、ロータリーダイ法、シームレスカプセル法等、常法により、本発明の医薬組成物をゼラチン等の軟カプセル用の皮膜に充填することにより製造することができ、また硬カプセル剤は、常法により、本発明の医薬組成物をゼラチン等の硬カプセルに封入することにより製造することができる。 The capsule of the present invention may be a soft capsule or a hard capsule. Soft capsules can be produced by filling the pharmaceutical composition of the present invention into a film for soft capsules such as gelatin by a conventional method such as a flat plate method, a rotary die method, a seamless capsule method, etc. The agent can be produced by encapsulating the pharmaceutical composition of the present invention in a hard capsule such as gelatin by a conventional method.
以下に実施例により本発明を更に具体的に説明するが、本発明はこれらに限定されるものではない。 The present invention will be described more specifically with reference to the following examples. However, the present invention is not limited to these examples.
下記の表１に示す成分を混合し医薬組成物を調製した。該医薬組成物を常法により充填して、軟カプセル剤を製造した。
The components shown in Table 1 below were mixed to prepare a pharmaceutical composition. The pharmaceutical composition was filled by a conventional method to produce a soft capsule.
下記の表２に示す成分を混合し医薬組成物を調製した。該医薬組成物を常法により充填して、軟カプセル剤を製造した。 The components shown in Table 2 below were mixed to prepare a pharmaceutical composition. The pharmaceutical composition was filled by a conventional method to produce a soft capsule.
下記の表３に示す成分を混合し医薬組成物を調製した。該医薬組成物を常法により充填して、軟カプセル剤を製造した。 The components shown in Table 3 below were mixed to prepare a pharmaceutical composition. The pharmaceutical composition was filled by a conventional method to produce a soft capsule.
〔溶出試験〕
各実施例で製造された軟カプセル剤について、日本薬局方溶出試験法により、ジフェンヒドラミンの溶出試験を実施した。
結果を図１に示す。
[Dissolution test]
About the soft capsule manufactured by each Example, the elution test of the diphenhydramine was implemented by the Japanese Pharmacopoeia elution test method.
The results are shown in FIG.
本発明により、速やかな溶解吸収特性を有するジフェンヒドラミンまたはその酸付加塩含有医薬組成物を提供することが可能となった。 According to the present invention, it has become possible to provide a pharmaceutical composition containing diphenhydramine or an acid addition salt thereof having rapid dissolution and absorption characteristics.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008184430A (en) * | 2007-01-30 | 2008-08-14 | Ss Pharmaceut Co Ltd | Soft capsule |
| JP2012046505A (en) * | 2010-07-29 | 2012-03-08 | Fuji Capsule Kk | Composition for seamless capsule filling |
| WO2014010008A1 (en) * | 2012-07-09 | 2014-01-16 | 東洋カプセル株式会社 | Capsule-filling composition of candesartan cilexetil |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004099510A (en) * | 2002-09-09 | 2004-04-02 | Ss Pharmaceut Co Ltd | Hypnotic solid preparation |
| WO2007072923A1 (en) * | 2005-12-22 | 2007-06-28 | Kowa Company, Ltd. | Preparation for external use having improved temporal stability of steroid |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004099510A (en) * | 2002-09-09 | 2004-04-02 | Ss Pharmaceut Co Ltd | Hypnotic solid preparation |
| WO2007072923A1 (en) * | 2005-12-22 | 2007-06-28 | Kowa Company, Ltd. | Preparation for external use having improved temporal stability of steroid |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008184430A (en) * | 2007-01-30 | 2008-08-14 | Ss Pharmaceut Co Ltd | Soft capsule |
| JP2012046505A (en) * | 2010-07-29 | 2012-03-08 | Fuji Capsule Kk | Composition for seamless capsule filling |
| WO2014010008A1 (en) * | 2012-07-09 | 2014-01-16 | 東洋カプセル株式会社 | Capsule-filling composition of candesartan cilexetil |
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