JP2017078053A

JP2017078053A - Tablet of fexofenadine hydrochloride

Info

Publication number: JP2017078053A
Application number: JP2015219885A
Authority: JP
Inventors: 克史石田; Katsushi Ishida; 一訓大倉; Kazukuni Okura
Original assignee: SHIGAKEN PHARM IND CO Ltd
Current assignee: SHIGAKEN PHARM IND CO Ltd
Priority date: 2015-10-21
Filing date: 2015-10-21
Publication date: 2017-04-27

Abstract

PROBLEM TO BE SOLVED: To provide a solid preparation with suppressed bitter taste, the preparation comprising fexofenadine or a pharmaceutically acceptable salt thereof, an aminoalkyl methacrylate copolymer E, and citric acid.SOLUTION: The present invention provides a solid preparation excellent in suppressing its bitter taste, the preparation comprising fexofenadine or a pharmaceutically acceptable salt thereof blended with an aminoalkyl methacrylate copolymer E, and citric acid.SELECTED DRAWING: None

Description

本発明は、フェキソフェナジン塩酸塩、アミノアルキルメタクリレートコポリマーＥ及びクエン酸を配合した苦味マスキングに関するものである。 The present invention relates to bitterness masking comprising fexofenadine hydrochloride, aminoalkyl methacrylate copolymer E and citric acid.

フェキソフェナジン塩酸塩は、アレルギー性疾患治療剤として医療用または一般用医薬品として使用されている。なお、本成分は味が苦いため、服用し易くするには、苦味をマスキングする必要がある。経口投与ではハンドリングや服用のし易さから錠剤タイプが好まれる傾向がある。この錠剤タイプで味のマスキングを考えた場合、錠剤を制した後コーティングを施す方法や、薬物自体にコーティングを施す方法が一般的であるが、共に調製時間を有するため、コーティングを必要としない一般的な製剤に比べコストは高くなる。 Fexofenadine hydrochloride is used as a medical or general drug as a therapeutic agent for allergic diseases. In addition, since this component is bitter in taste, it is necessary to mask the bitterness in order to make it easy to take. For oral administration, tablet type tends to be preferred for ease of handling and administration. When considering masking of taste in this tablet type, the method of applying the coating after controlling the tablet and the method of applying the coating to the drug itself are common, but since both have the preparation time, the coating is not required. Costs are higher than typical formulations.

また、医薬品の市場ニーズからは、剤型として錠剤を好まれる傾向であるが、近年、更に服用のし易い口腔内崩壊錠を選択肢として求める要求もあった。 In addition, although there is a tendency to prefer tablets as a dosage form from the market needs of pharmaceuticals, there has recently been a demand for an orally disintegrating tablet that is easier to take as an option.

このようなことから、フェキソフェナジン塩酸塩のアレルギー性疾患治療薬として、口腔内崩壊錠であつ、かつ、簡易な苦味マスキングで調製可能な技術が望まれていた。 For these reasons, there has been a demand for a technique that is an orally disintegrating tablet and can be prepared with simple bitterness masking as a therapeutic agent for allergic diseases of fexofenadine hydrochloride.

従って本発明の目的は、フェキソフェナジン塩酸塩を含有する口腔内崩壊錠であって、かつ、簡易な工程で苦味のマスキングが可能な方法にある。 Accordingly, an object of the present invention is an orally disintegrating tablet containing fexofenadine hydrochloride and a method capable of masking bitterness by a simple process.

本発明者は、フェキソフェナジン塩酸塩を含有する口腔内崩壊錠であって、かつ、簡易な工程で苦味のマスキングが可能な方法を目的として検討を行った。その結果、フェキソフェナジン塩酸塩にアミノアルキルメタクリレートコポリマーＥを添加し、クエン酸を溶解させた水溶液を用いて造粒することで、課題を解決するに至った。 The inventor of the present invention has studied for an orally disintegrating tablet containing fexofenadine hydrochloride and capable of masking bitterness by a simple process. As a result, the aminoalkyl methacrylate copolymer E was added to fexofenadine hydrochloride, and granulation was performed using an aqueous solution in which citric acid was dissolved, thereby solving the problem.

本発明は、簡易な造粒方法で、苦味のマスキングされた口腔内崩壊錠を製することができる。 The present invention can produce a bitter-masked orally disintegrating tablet by a simple granulation method.

本発明に使用するフェキソフェナジン塩酸塩は、第１６改正日本薬局方に準じるものである。 The fexofenadine hydrochloride used in the present invention conforms to the 16th revised Japanese Pharmacopoeia.

以下、実施例と比較例を挙げて本発明を説明するが、本発明はこれらに限定されるものではない。 EXAMPLES Hereinafter, although an Example and a comparative example are given and this invention is demonstrated, this invention is not limited to these.

（実施例１）
表１の記載処方のフェキソフェナジン塩酸塩及びアミノアルキルメタクリレートコポリマーＥを高速撹拌造粒機（ハイスピードミキサーＦＳ‐ＧＳ‐１０深江パウテック（株）製）で混合後、予め溶解させたクエン酸水溶液を添加し造粒を行う。この造粒品を流動層乾燥機（フローコーターＦＬＯ‐５、フロイント産業（株）製）にて乾燥する。得られた乾燥品を整粒機（フラッシュミルＦＬ‐２００、不二パウダル（株）製）の直径１ｍｍ丸穴のスクリーンを用いて整粒する。得られた整粒品に適当な賦形剤、矯味剤、流動化剤、崩壊剤、滑沢剤を添加しポリ袋にて混合し、打錠用混合品とする。この打錠用混合品を、ロータリー式打錠機（ＨＴ‐Ｐ２２、（株）畑鐵工所製）を用いて、直径９ｍｍ、２２０ｍｇ／錠の錠剤を製した。Example 1
Citric acid aqueous solution in which fexofenadine hydrochloride and aminoalkyl methacrylate copolymer E having the formulation shown in Table 1 were mixed with a high-speed agitation granulator (High Speed Mixer FS-GS-10, manufactured by Fukae Powtech Co., Ltd.) and dissolved in advance. And granulate. This granulated product is dried with a fluidized bed dryer (Flow coater FLO-5, manufactured by Freund Corporation). The obtained dried product is sized using a 1 mm diameter round hole screen of a sizing machine (Flash Mill FL-200, manufactured by Fuji Powder Co., Ltd.). Appropriate excipients, flavoring agents, fluidizing agents, disintegrants, and lubricants are added to the resulting granulated product and mixed in a plastic bag to obtain a mixed product for tableting. This tablet mixture was tableted with a diameter of 9 mm and 220 mg / tablet using a rotary tableting machine (HT-P22, manufactured by Hata Seiko Co., Ltd.).

（比較例１）
表１の記載処方のフェキソフェナジン塩酸塩、適当な賦形剤、矯味剤及び流動化剤を万能混合撹拌機（５ＤＭ、（株）品川工業所製）で混合後、予め適当な結合剤を溶解させた水溶液を添加し造粒を行う。この造粒品を棚式乾燥機（ＤＫ６００、ＹＡＭＡＴＯ製）にて乾燥する。得られた乾燥品を目開き１ｍｍの篩を用いて整粒する。得られた整粒品に適当な矯味剤、流動化剤、崩壊剤及び滑沢剤を添加しポリ袋にて混合し、打錠用混合品とする。この打錠用混合品を、ロータリー式打錠機（ＨＴ‐Ｐ２２、（株）畑鐵工所製）を用いて、直径９ｍｍ、２２０ｍｇ／錠の錠剤を製した。(Comparative Example 1)
After mixing fexofenadine hydrochloride of the formulation shown in Table 1, appropriate excipients, flavoring agents and fluidizing agents with a universal mixing stirrer (5DM, manufactured by Shinagawa Kogyo Co., Ltd.), an appropriate binder is added in advance. The dissolved aqueous solution is added and granulated. This granulated product is dried with a shelf dryer (DK600, manufactured by YAMATO). The obtained dried product is sized using a sieve having an opening of 1 mm. Appropriate flavoring agents, fluidizing agents, disintegrants and lubricants are added to the resulting granulated product and mixed in a plastic bag to obtain a mixed product for tableting. This tablet mixture was tableted with a diameter of 9 mm and 220 mg / tablet using a rotary tableting machine (HT-P22, manufactured by Hata Seiko Co., Ltd.).

（比較例２）
表１の記載処方のフェキソフェナジン塩酸塩、アミノアクリルメタクリレートコポリマーＥ、適当な賦形剤、矯味剤及び流動化剤を万能混合撹拌機（５ＤＭ、（株）品川工業所製）で混合後、予め適当な結合剤を溶解させた水溶液を添加し造粒を行う。この造粒品を棚式乾燥機（ＤＫ６００、ＹＡＭＡＴＯ製）にて乾燥する。得られた乾燥品を目開き１ｍｍの篩を用いて整粒する。得られた整粒品に適当な矯味剤、流動化剤、崩壊剤及び滑沢剤を添加しポリ袋にて混合し、打錠用混合品とする。この打錠用混合品を、ロータリー式打錠機（ＨＴ−Ｐ２２、（株）畑鐵工所製）を用いて、直径９ｍｍ、２２０ｍｇ／錠の錠剤を製した。(Comparative Example 2)
After mixing fexofenadine hydrochloride, aminoacryl methacrylate copolymer E, suitable excipients, corrigents and fluidizing agents with the formulation shown in Table 1 with a universal mixing stirrer (5DM, manufactured by Shinagawa Kogyo Co., Ltd.) Granulation is performed by adding an aqueous solution in which an appropriate binder is dissolved in advance. This granulated product is dried with a shelf dryer (DK600, manufactured by YAMATO). The obtained dried product is sized using a sieve having an opening of 1 mm. Appropriate flavoring agents, fluidizing agents, disintegrants and lubricants are added to the resulting granulated product and mixed in a plastic bag to obtain a mixed product for tableting. This tableting mixture was manufactured using a rotary tableting machine (HT-P22, manufactured by Hata Seiko Co., Ltd.) to produce tablets with a diameter of 9 mm and 220 mg / tablet.

（比較例３）
表１の記載処方のフェキソフェナジン塩酸塩、クエン酸、適当な賦形剤、矯味剤及び流動化剤を万能混合撹拌機（５ＤＭ、（株）品川工業所製）で混合後、予め適当な結合剤を溶解させた水溶液を添加し造粒を行う。この造粒品を棚式乾燥機（ＤＫ６００、ＹＡＭＡＴＯ製）にて乾燥する。得られた乾燥品を目開き１ｍｍの篩を用いて整粒する。得られた整粒品に適当な矯味剤、流動化剤、崩壊剤及び滑沢剤を添加しポリ袋にて混合し、打錠用混合品とする。この打錠用混合品を、ロータリー式打錠機（ＨＴ‐Ｐ２２、（株）畑鐵工所製）を用いて、直径９ｍｍ、２２０ｍｇ／錠の錠剤を製した。(Comparative Example 3)
After mixing fexofenadine hydrochloride, citric acid, appropriate excipients, taste-masking agents and fluidizing agents with the formulation shown in Table 1 with a universal mixing stirrer (5DM, manufactured by Shinagawa Kogyo Co., Ltd.) Granulation is performed by adding an aqueous solution in which a binder is dissolved. This granulated product is dried with a shelf dryer (DK600, manufactured by YAMATO). The obtained dried product is sized using a sieve having an opening of 1 mm. Appropriate flavoring agents, fluidizing agents, disintegrants and lubricants are added to the resulting granulated product and mixed in a plastic bag to obtain a mixed product for tableting. This tablet mixture was tableted with a diameter of 9 mm and 220 mg / tablet using a rotary tableting machine (HT-P22, manufactured by Hata Seiko Co., Ltd.).

（試験例）
前記の実施例１、比較例１〜３で得た口腔内崩壊錠を用いて、３名のパネラーにて官能試験を行った。試験は、錠剤１錠を口腔内で溶かして服用し、苦味を表２の基準で評価した。(Test example)
Using the orally disintegrating tablets obtained in Example 1 and Comparative Examples 1 to 3, a sensory test was performed with three panelists. In the test, one tablet was dissolved in the oral cavity, and the bitterness was evaluated according to the criteria shown in Table 2.

表３、表４の通りの結果を得る、 The results shown in Table 3 and Table 4 are obtained.

Claims

A solid preparation comprising fexofenadine or a pharmaceutically acceptable salt thereof, aminoalkyl methacrylate copolymer E and citric acid.

The aminoalkyl methacrylate copolymer E is 0.01 to 950 parts by weight and citric acid is 0.01 to 25 parts by weight with respect to both parts of fexofenadine or a pharmaceutically acceptable salt thereof. Solid formulation.

The solid formulation of Claims 1-2 whose dosage form is an orally disintegrating tablet, a tablet, a chewable tablet, and a granule.