JP6589979B2 - 錠剤組成物、及び錠剤組成物の崩壊性・溶出性改善方法 - Google Patents
錠剤組成物、及び錠剤組成物の崩壊性・溶出性改善方法 Download PDFInfo
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- JP6589979B2 JP6589979B2 JP2017511050A JP2017511050A JP6589979B2 JP 6589979 B2 JP6589979 B2 JP 6589979B2 JP 2017511050 A JP2017511050 A JP 2017511050A JP 2017511050 A JP2017511050 A JP 2017511050A JP 6589979 B2 JP6589979 B2 JP 6589979B2
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Description
[1].(A)30〜70質量%のラクトフェリン、(B)0.12〜1.0質量%のステアリン酸塩、及び(C)マルチトール、イソマルト及びエリスリトールから選ばれる糖アルコールを含み、(B)/(A)×100で表される(A)成分と(B)成分との配合質量比が0.4〜1.6、かつ(C)/(A)で表される(C)成分と(A)成分との配合質量比が0.3〜0.8である錠剤組成物。
[2].前記(B)ステアリン酸塩が、ステアリン酸カルシウム又はステアリン酸マグネシウムである[1]記載の錠剤組成物。
[3].(C)成分の配合量が、15〜50質量%である[1]又は[2]記載の錠剤組成物。
[4].(A)30〜70質量%のラクトフェリンを含む錠剤組成物の崩壊性及び前記ラクトフェリンの溶出性を改善する方法であって、前記錠剤組成物に(B)0.12〜1.0質量%のステアリン酸塩、及び(C)マルチトール、イソマルト及びエリスリトールから選ばれる糖アルコールを、(B)/(A)×100で表される(A)成分と(B)成分との配合質量比が0.4〜1.6、かつ(C)/(A)で表される(C)成分と(A)成分との配合質量比が0.3〜0.8となる範囲で配合することを特徴とする、錠剤組成物の崩壊性及び溶出性改善方法。
[5].(A)30質量%以上のラクトフェリン、及び(B1)0.12〜1.0質量%のステアリン酸カルシウムを含む錠剤組成物。
[6].(B1)/(A)×100で表される(A)成分と(B1)成分との配合質量比が、0.25〜3である[5]記載の錠剤組成物。
[7].更に、(C)糖又は糖アルコールを5質量%以上含む[5]又は[6]記載の錠剤組成物。
[8].(A)30質量%以上のラクトフェリンを含む錠剤組成物の崩壊性及び前記ラクトフェリンの溶出性を改善する方法であって、前記錠剤組成物に(B1)0.12〜1.0質量%のステアリン酸カルシウムを配合することを特徴とする、錠剤組成物の崩壊性及び溶出性改善方法。
本発明の錠剤組成物は、(A)ラクトフェリンを30質量%以上含む。ラクトフェリンは、高い脂肪減少効果を有する機能性成分である。(A)ラクトフェリンの配合量の下限は、組成物中32質量%が好ましく、35質量%がより好ましい。一方、その上限は、特に限定されず、99.88質量%が好ましいが、打錠する際の成形性の観点から、80質量%が好ましく、70質量%がより好ましく、50質量%が更に好ましい。
本発明の錠剤組成物において、(B)ステアリン酸塩は、滑沢剤として機能する。本発明の錠剤組成物は、(B)ステアリン酸塩を含むことで経時的な溶出性低下が抑制され、長期保存後であっても溶出性が良好なものとなる。
本発明の錠剤組成物は、(C)成分として糖又は糖アルコールを含んでもよい。(C)糖又は糖アルコールは賦形剤として機能する。(C)糖又は糖アルコールを含むことで、ラクトフェリンの溶出性を更に向上させることができる。
本発明の錠剤組成物は、本発明の効果を損なわない範囲で、その他の成分を1種単独で又は2種以上を適宜組み合わせて、適量用いることができる。その他の成分としては、例えば、(A)成分以外の機能性成分、(B)成分以外の滑沢剤、(C)成分以外の賦形剤、油性成分、崩壊剤、流動化剤、結合剤、薬効成分、植物抽出物、色素、香料等を挙げることができる。具体的には、下記成分を挙げることができる。なお、重複した役割を有する成分は、重複して記載される。
・ラクトフェリン:森永乳業(株)製、ラクトフェリンMLF−FG(中位径:80μm)
・ヒハツエキス:丸善製薬(株)製、Tie2ヒハツエキスパウダーMF
・結晶セルロース:旭化成ケミカルズ(株)製、セオラスUF-F711
・マルチトール:三菱商事フードテック(株)製、粉末マルチトールG-3
・イソマルト:フロイント産業(株)製、イソマルトグラニュー
・エリスリトール:マイクロフーズジャパン(株)製、エリスリトール顆粒
・ソルビトール:三菱商事フードテック(株)製、ソルビット
・キシリトール:三菱商事フードテック(株)製、キシリット
・乳糖:フロイント産業(株)製、乳糖グラニュー
・カルボキシメチルセルロースカルシウム:ニチリン化学工業(株)製、E.C.G-F A
・微粒二酸化ケイ素:DSL.ジャパン(株)製、カープレックスFPS-500
富士シリシア化学(株)製、サイロページ720
・ステアリン酸カルシウム:太平化学産業(株)製、ステアリン酸カルシウム
・ステアリン酸マグネシウム:太平化学産業(株)製、ステアリン酸カルシウム
・ショ糖脂肪酸エステル:三菱化学フーズ(株)製、リョートーシュガーエステルS-370F
・グリセリン脂肪酸エステル:阪本薬品工業(株)製、SYグリスター
・ラブレ菌末:ラブレ創健(株)製、ナノ型ラブレ菌(60億個/10mg)
・ヒドロキシプロピルメチルセルロース:メトローズ、信越化学工業(株)製、SE-06
・グリセリン:阪本薬品工業(株)製、食品添加物グリセリン
・アルギン酸ナトリウム:(株)キミカ製、キミカアルギンIL−2
・タルク:キハラ化成(株)、リスブラン
[1]錠剤の調製
下記表1〜4に記載されたそれぞれの原料を秤量、混合し、ロータリー式打錠機を用いて錠剤硬度が8〜15kgf以上になるように打錠した。次いで、パン回転式コーティング機を用いて、得られた素錠をコーティングした。なお、コーティング剤は、下記表1〜3に記載した組成のものを使用した。なお、錠剤形状は、2段R錠(R1=3.6mm、R2=10.5mm、H=1.5mm)であった。
製造直後(初期)の錠剤、及びプラスチックボトルに充填し、40℃、75%RHの恒温槽にて4か月間保存した後の錠剤について、第十六改正日本薬局方に収載された錠剤の崩壊試験法に従って崩壊試験を行った。錠剤の崩壊時間(分)を測定し、測定回数6回の平均値を算出し、下記評価基準に従って崩壊性を評価した。結果を表1〜3に併記する。
崩壊時間40分未満:◎
崩壊時間40分以上50分未満:○
崩壊時間50分以上60分未満:△
崩壊時間60分以上:×
製造直後(初期)の錠剤、及びプラスチックボトルに充填し、40℃、75%RHの恒温槽にて4か月間保存した後の錠剤について、第十六改正日本薬局方に収載される錠剤の溶出試験法に準じて溶出試験を行い、ラクトフェリンの溶出率(%)を測定した。具体的には、試験液として溶出試験第2液(pH約6.8)を用い、パドル法により、毎分50回転で試験を行った。錠剤は1個、溶出試験第2液は900mL使用した。溶出試験開始2時間後の溶出液をとり、溶出したラクトフェリンをHPLC法により定量し、溶出率を算出した。測定は3回行い、溶出率の平均値を算出し、下記評価基準に従って溶出性を評価した。結果を表1〜3に併記する。
2時間後の溶出率80%以上:◎
2時間後の溶出率70%以上80%未満:○
2時間後の溶出率60%以上70%未満:△
2時間後の溶出率60%未満:×
50mLメスフラスコに標準ラクトフェリン75mgを入れ、溶出試験溶液でメスアップした。この標準溶液の1/5、1/20、1/50の標準溶液を作製し、各標準溶液を高速液体クロマトグラフィー(HPLC)により測定し、それぞれの標準液のラクトフェリンピーク面積を求め、検量線を作成した。
溶出試験開始2時間後の溶出液をHPLCにより測定し、ラクトフェリンピーク面積を求めた。検量線を用いて各試料溶液中のラクトフェリン濃度を求め、ラクトフェリン含量を求めた。
<HPLC測定条件>
・検出器:紫外吸光光度計(測定波長:280nm)
・カラム:Shodex Asahipak C4P-50 4D(ポリマー系逆相クロマトグラフィ用カラム)
ブチル基(5μm×4.6×150)
Shodex Asahipak C4P-50 4D:ガードカラム
カラム温度35℃
導入量:20μL
流量:0.8mL/min
・移動層A:トリフルオロ酢酸を0.03質量%含むアセトニトリル/塩化ナトリウム溶液(3→100)混液(10:90)
・移動層B:トリフルオロ酢酸を0.03質量%含むアセトニトリル/塩化ナトリウム溶液(3→100)混液(50:50)
・濃度勾配:A:B(50:50)から(0:100)までの直線濃度勾配を30分間行った。
2時間の連続打錠を行い、打錠用臼杵と盤面を観察し、以下の評価基準で評価した。結果を表1〜3に併記する。
○:臼杵・盤面に打錠末の付着が認められなかった
×:臼杵・盤面に打錠末の付着が認められた
○:崩壊性、溶出性、付着性評価の全てが△〜◎
×:崩壊性、溶出性、付着性評価でいずれかが×
Claims (8)
- (A)30〜70質量%のラクトフェリン、(B)0.12〜1.0質量%のステアリン酸塩、及び(C)マルチトール、イソマルト及びエリスリトールから選ばれる糖アルコールを含み、(B)/(A)×100で表される(A)成分と(B)成分との配合質量比が0.4〜1.6、かつ(C)/(A)で表される(C)成分と(A)成分との配合質量比が0.3〜0.8である錠剤組成物。
- 前記(B)ステアリン酸塩が、ステアリン酸カルシウム又はステアリン酸マグネシウムである請求項1記載の錠剤組成物。
- (C)成分の配合量が、15〜50質量%である請求項1又は2記載の錠剤組成物。
- (A)30〜70質量%のラクトフェリンを含む錠剤組成物の崩壊性及び前記ラクトフェリンの溶出性を改善する方法であって、前記錠剤組成物に(B)0.12〜1.0質量%のステアリン酸塩、及び(C)マルチトール、イソマルト及びエリスリトールから選ばれる糖アルコールを、(B)/(A)×100で表される(A)成分と(B)成分との配合質量比が0.4〜1.6、かつ(C)/(A)で表される(C)成分と(A)成分との配合質量比が0.3〜0.8となる範囲で配合することを特徴とする、錠剤組成物の崩壊性及び溶出性改善方法。
- (A)30質量%以上のラクトフェリン、及び(B1)0.12〜1.0質量%のステアリン酸カルシウムを含む錠剤組成物。
- (B1)/(A)×100で表される(A)成分と(B1)成分との配合質量比が、0.25〜3である請求項5記載の錠剤組成物。
- 更に、(C)糖又は糖アルコールを5質量%以上含む請求項5又は6記載の錠剤組成物。
- (A)30質量%以上のラクトフェリンを含む錠剤組成物の崩壊性及び前記ラクトフェリンの溶出性を改善する方法であって、前記錠剤組成物に(B1)0.12〜1.0質量%のステアリン酸カルシウムを配合することを特徴とする、錠剤組成物の崩壊性及び溶出性改善方法。
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