JP2007302688A5

JP2007302688A5 -

Info

Publication number: JP2007302688A5
Application number: JP2007184031A
Authority: JP
Filing date: 2007-07-13
Publication date: 2008-02-28

Description

増量剤または結合剤の例には、アラビアゴム、アルギン酸、リン酸水素カルシウム（二塩基性）、カルボキシメチルセルロース、カルボキシメチルセルロースナトリウム、ヒドロキシエチルセルロース、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、デキストリン、デキストレート類（dextrates）、ショ糖、タイロース（tylose）、予備ゼラチン化デンプン（pregelatinized starch）、硫酸カルシウム、アミロース、グリシン、ベントナイト、マルトース、ソルビトール、エチルセルロース、リン酸水素二ナトリウム、ピロ亜硫酸二ナトリウム、ポリビニルアルコール、ゼラチン、ブドウ糖、グアーガム（guar gum）、液体ブドウ糖（liquid glucose）、コンプレッシブル糖（compressible sugar）、ケイ酸アルミニウムマグネシウム（magnesium aluminum silicate）、マルトデキストリン、ポリエチレンオキシド、ポリメタクリレート類、ポビドン、アルギン酸ナトリウム、トラガカント(tragacanth)、微晶質セルロース(microcrystalline cellulose)、デンプンおよびゼインが含まれる。最も好ましい増量剤または結合剤は、微晶質セルロースである。 Examples of extenders or binders include gum arabic, alginic acid, calcium hydrogen phosphate (dibasic), carboxymethylcellulose, sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, dextrin, dextrates ), sucrose, Tylose (Tylose), preliminary gelatinized starch (pregelatinized starch), calcium sulfate, amylose, glycine, bentonite, maltose, sorbitol, ethylcellulose, disodium hydrogen phosphate, sodium metabisulfite two, polyvinyl alcohol, gelatin , Glucose, guar gum, liquid glucose, compressible sugar, magnesium aluminum silicate (magnes) ium aluminum silicate), maltodextrin, polyethylene oxide, polymethacrylates, povidone, sodium alginate, tragacanth, microcrystalline cellulose , starch and zein. The most preferred bulking agent or binder is microcrystalline cellulose.

崩壊剤の例には、アルギン酸、カルボキシメチルセルロース、カルボキシメチルセルロースナトリウム、ヒドロキシプロピルセルロース（低置換度）、微晶質セルロース、セルロース粉末、コロイド状二酸化ケイ素、クロスカルメロースナトリウム（sodium croscarmellose）、クロスポビドン（crospovidone）、メチルセルロ−ス、ポラクリリンカリウム（polacrilin potassium）、ポビドン、アルギン酸ナトリウム、スターチグリコール酸ナトリウム（sodium starch glycolate）、デンプン、ピロ亜硫酸二ナトリウム、エダタミル二ナトリウム（disodium edathamil）、エデト酸ナトリウム、エチレンジアミン四酢酸二ナトリウム（ＥＤＴＡ）、架橋ポリビニルピロリジン類（crosslinked polyvinylpyrollidines）、予備ゼラチン化デンプン、カルボキシメチルデンプン、カルボキシメチルデンプンナトリウム（sodium carboxymethyl starch）および微晶質セルロースが含まれる。最も好ましい崩壊剤は、クロスカルメロースナトリウム（sodium crosscarmelose）である。 Examples of disintegrants include alginic acid, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose (low substitution), microcrystalline cellulose, cellulose powder, colloidal silicon dioxide, sodium croscarmellose, crospovidone ( crospovidone), methylcellulose, polacrilin potassium, povidone, sodium alginate, sodium starch glycolate, starch, disodium pyrosulfite, disodium edathamil, sodium edetate, ethylenediamine disodium (EDTA), cross-linked polyvinyl pyrrolidines (crosslinked polyvinylpyrollidines), preliminary gelatinized starch, carboxymethyl starch, carboxy Sodium carboxymethyl starch and microcrystalline cellulose are included. The most preferred disintegrant is sodium crosscarmelose.

シリカフローコンディショナーの例には、コロイド状二酸化ケイ素およびケイ酸アルミニウムマグネシウムが含まれる。最も好ましいシリカフローコンディショナーは、コロイド状二酸化ケイ素である。 Examples of silica flow conditioners include colloidal silicon dioxide and magnesium aluminum silicate. The most preferred silica flow conditioner is colloidal silicon dioxide.

Claims

A fast-acting drug for oral administration having a core having an enteric coating consisting of at least one layer, wherein the core contains an excipient containing pyridoxine hydrochloride and doxylamine succinate as active ingredients, and a disintegrant, Disintegrants are croscarmellose sodium, alginic acid, carboxymethylcellulose, sodium carboxymethylcellulose, low-substituted hydroxypropylcellulose, microcrystalline cellulose, cellulose powder, colloidal silicon dioxide, crospovidone, methylcellulose, polacrilin potassium, povidone , Sodium alginate, Sodium starch glycolate, Starch, Disodium pyrosulfite, Disodium edatamil, Sodium edetate, Disodium ethylenediaminetetraacetate, Cross-linked polyvinylpyrrolidine, Preliminary gelatin Starch, is at least one selected from carboxymethyl starch and carboxymethyl group consisting of starch sodium, the velocity efficacy for oral administration drug in phosphate buffer 1000ml of pH 6.8, at 37 ° C., 2-inch elution A rapid-acting formulation characterized by satisfying the following elution characteristics (a) to (d) when measured under conditions of 100 revolutions per minute using a test apparatus.
(A) At 30 minutes after the start of the test, at least 40% of the total amount of pyridoxine hydrochloride and doxylamine succinate elutes;
(B) At 60 minutes after the start of the test, at least 70% of the total amount of each of pyridoxine hydrochloride and doxylamine succinate elutes;
(C) At 90 minutes after the start of the test, at least 80% of the total amount of each of pyridoxine hydrochloride and doxylamine succinate elutes;
(D) At 120 minutes after the start of the test, at least 90% of the total amounts of pyridoxine hydrochloride and doxylamine succinate are eluted.

The following elution characteristics (a) to (c) are satisfied when measured under conditions of 100 revolutions per minute using a type 2 elution test apparatus at 37 ° C. in 1000 ml of pH 6.8 phosphate buffer. The fast-acting drug for oral administration according to claim 1.
(A) At 15 minutes after the start of the test, at least 20% of the total amount of each of pyridoxine hydrochloride and doxylamine succinate elutes;
(B) at least 60% of the total amount of each of pyridoxine hydrochloride and doxylamine succinate at 45 minutes after the start of the test;
(C) At 75 minutes after the start of the test, at least 80% of the total amount of each of pyridoxine hydrochloride and doxylamine succinate elutes.

The excipient further comprises a bulking agent or binder, the bulking agent or binder comprising microcrystalline cellulose, gum arabic, alginic acid, calcium hydrogen phosphate (dibasic), carboxymethylcellulose, sodium carboxymethylcellulose, hydroxy Ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, dextrin, dextrates, sucrose, tyrose, pregelatinized starch, calcium sulfate, amylose, glycine, bentonite, maltose, sorbitol, ethylcellulose, disodium hydrogen phosphate, disulfur pyrosulfite Sodium, polyvinyl alcohol, gelatin, glucose, guar gum, liquid glucose, compressible sugar, magnesium aluminum silicate, maltodextrin, poly Chiren'okishido, polymethacrylates, povidone, sodium alginate, tragacanth, fast-acting oral agent according to claim 1 or 2, characterized in that at least one selected from the group consisting of starch and zein.

Pyridoxine hydrochloride and doxylamine succinate within 5 minutes from the start of the test when measured under conditions of 100 rpm per minute using a type 2 dissolution test apparatus at 37 ° C. in 1000 ml of pH 6.8 phosphate buffer The fast-acting drug for oral administration according to any one of claims 1 to 3 , wherein at least 40% of the total amount of each drug is eluted.

The excipient further comprises a lubricant, the lubricant comprising magnesium stearate, calcium stearate, canola oil, glyceryl palmitate stearate, type I hydrogenated vegetable oil, magnesium oxide, mineral oil, poloxamer, polyethylene glycol, From sodium lauryl sulfate, sodium stearate fumarate, stearic acid, talc, zinc stearate, glyceryl behenate, magnesium lauryl sulfate, boric acid, sodium benzoate, sodium acetate, sodium benzoate / sodium acetate (mixture) and DL leucine The fast-acting drug for oral administration according to any one of claims 1 to 4, wherein the drug is at least one selected from the group consisting of:

The excipient according to any one of claims 1 to 5 , wherein the excipient further comprises a silica flow conditioner, and the silica flow conditioner is at least one selected from the group consisting of colloidal silicon dioxide and aluminum magnesium silicate. Fast-acting oral agent according to any.

The excipient further comprises a stabilizer, the stabilizer comprising magnesium trisilicate, gum arabic, albumin, polyvinyl alcohol, alginic acid, bentonite, calcium hydrogen phosphate, carboxymethyl cellulose, hydroxypropyl cellulose, colloidal silicon dioxide, Cyclodextrins, glyceryl monostearate, hydroxypropylmethylcellulose, magnesium magnesium silicate, propylene glycol, propylene glycol alginate, sodium alginate, carnauba wax, xanthan gum, starch, stearate (s), stearic acid, monoglyceride stearate and stearyl The fast-acting oral medicine according to any one of claims 1 to 6, which is at least one selected from the group consisting of alcohols. Given for the drug.

The fast-acting drug for oral administration according to any one of claims 3 to 7, wherein the bulking agent or binder is composed of microcrystalline cellulose.

The rapid-acting drug for oral administration according to any one of claims 1 to 8, wherein the disintegrant is composed of croscarmellose sodium.

The fast-acting drug for oral administration according to any one of claims 1 to 9, wherein the core includes the following (a) to (c).
(A) 4-10% by weight of pyridoxine hydrochloride;
(B) 4-10% by weight of doxylamine succinate; and
(C) 0.5-5% by weight croscarmellose sodium.

The fast-acting drug for oral administration according to any one of claims 5 to 10, wherein the lubricant is composed of magnesium stearate.

The rapid-acting drug for oral administration according to any one of claims 6 to 11, wherein the silica flow conditioner is composed of colloidal silicon dioxide.

13. The fast-acting drug for oral administration according to any one of claims 7 to 12, wherein the stabilizer is composed of magnesium trisilicate.

The fast-acting drug for oral administration according to any one of claims 1 to 13, wherein the core includes the following (a) to (g).
(A) 4-10% by weight of pyridoxine hydrochloride;
(B) 4-10% by weight of doxylamine succinate;
(C) 40-80% by weight of microcrystalline cellulose;
(D) 10-30% by weight of magnesium trisilicate;
(E) 0.5-5% by weight silicon dioxide;
(F) 0.5-5% by weight croscarmellose sodium; and (g) 0.5-5% by weight magnesium stearate.

The fast-acting drug for oral administration according to claim 14 , wherein the core includes the following (a) to (g).
(A) 7% by weight of pyridoxine hydrochloride;
(B) 7% by weight of doxylamine succinate;
(C) 62% by weight of microcrystalline cellulose;
(D) 18 wt% magnesium silicate;
(E) 0.7% by weight silicon dioxide;
(F) 2.5% by weight croscarmellose sodium; and (g) 2.8% by weight magnesium stearate.

The fast-acting drug for oral administration according to any one of claims 1 to 15, wherein the enteric coating comprising at least one layer is formed from an aqueous raw material.

The enteric coating comprising at least one layer is composed of a seal coating that covers the core, an authentic enteric coating that covers the seal coating, and a cosmetic coating that covers the true enteric coating. The fast-acting drug for oral administration according to claim 16 .

The fast-acting drug for oral administration according to any one of claims 1 to 17, which is a prescription for alleviating symptoms of mammalian nausea and vomiting.

The fast-acting oral drug according to any one of claims 1 to 17, which is a prescription for alleviating symptoms of nausea and vomiting during human pregnancy.

A drug for alleviating symptoms associated with nausea and vomiting, including the rapid-acting drug for oral administration according to any one of claims 1 to 17 .

A method for producing the rapid-acting drug for oral administration according to any one of claims 6 to 17, comprising the following steps.
-Mixing doxylamine succinate and silica flow conditioner to obtain a pre-blend;
Mixing the preblend with pyridoxine hydrochloride to obtain an active ingredient blend;
Mix the active ingredient blend with inactive excipients bulking agent or binder, disintegrant, lubricant and stabilizer to obtain the final blend; and • Tablet and coat the final blend.

The final tableting and coating step includes compressing the final blend into a tablet shape, applying a seal coating to the resulting tablet shape, then applying an enteric coating, and then applying a colored coating. The method of claim 21 .