CN111437256A - 一种利鲁唑缓释口服混悬液 - Google Patents
一种利鲁唑缓释口服混悬液 Download PDFInfo
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- 229960004181 riluzole Drugs 0.000 title claims abstract description 56
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Abstract
本发明属于药物制剂技术领域，公开一种利鲁唑缓释口服混悬液，同时解决药物平缓释放及老年儿童等吞咽困难人群给药顺应性问题。公开的的缓释混悬液由利鲁唑缓释微球分散于包含稀释剂、矫味剂、助悬剂、防腐剂、pH缓冲剂的溶液中制备而成，所述利鲁唑缓释微球由利利鲁唑溶于乙基纤维素水分散体经喷雾干燥制备而成。本发明的利鲁唑缓释口服混悬液与目前市场上的普通片剂、胶囊、口服混悬液相比，药物释放平缓，给药次数减少，质量稳定，口感良好，给药顺应性高，适用于老人和儿童等吞咽困难人群。
Description
技术领域
本发明属于药物制剂技术领域，具体涉及一种具有缓释作用的利鲁唑缓释口服混悬液，药物释放平稳，口感良好，适合老人及儿童等吞咽困难人群给药。
背景技术
利鲁唑为谷氨酸盐拮抗剂，可抑制脑内神经递质的释放，对谷氨酸能神经突触传递有抑制作用，并抑制γ氨基丁酸(GABA)、多巴胺、谷氨酸的再摄取；还可明显抑制兴奋性氨基酸的活性；可稳定电压依赖性钠通道的失活状态，具有明显的神经保护作用，其主要用于运动神经元疾病的治疗，用于治疗肌萎缩性脊髓侧索硬化症 (ALS， 有时亦称作鲁格利克氏征、夏科氏征或运动神经元疾病 ) 的药物。肌萎缩性脊髓侧索硬化症是一种由于运动神经退化所导致的致命的渐行性神经退化症，以控制横纹肌运动的中枢神经系统神经细胞的逐渐退化为表征。 由于运动神经元退化， 它们不能再向日常控制肌肉运动的肌纤维传递神经脉冲。肌萎缩性脊髓侧索硬化症的早期症状通常包括肌无力现象严重化， 特别是手臂部、腿部及与言语、吞咽和呼吸有关的肌肉群。对于依赖呼吸机或接受气管造口术的特定患者，其服药间隙还需延长。
利鲁唑是一种难溶性的化合物，由于其亲脂性和低水溶性，利鲁唑是制备悬浮剂的优良候选物。利鲁唑的上市剂型有片剂、胶囊剂、口服混悬液，口服固体制剂对于需要长期服药且具有吞咽困难人群给药顺应性较差。而普通口服混悬液每日2次给药，对于ALS患者，给药过于频繁。基于此，缓释口服混悬液与目前市场上的普通片剂、胶囊、口服混悬液相比，药物释放平缓，给药次数减少，质量稳定，口感良好，给药顺应性高，适用于老人和儿童等吞咽困难人群。
发明内容
针对现有技术中存在的缺陷，本发明的目的在于提供一种利鲁唑缓释口服混悬液，能够较长时间维持平稳的血药浓度，并适用于老年和儿童等具有吞咽困难人群。
为达到上述目的，本发明采取的技术方案是：
一种利鲁唑缓释口服混悬液，包括利鲁唑缓释微球、稀释剂、矫味剂、助悬剂、防腐剂、pH缓冲剂，其特征在于：
所述的利鲁唑缓释微球由利鲁唑溶于乙基纤维素水分散体经喷雾干燥制备而成，按照重量百分比计，所述的各组分含量如下：
利鲁唑缓释微球 5%-25%
稀释剂 30%-60%
矫味剂 1%-2%
助悬剂 5%-15%
防腐剂 0.05-0.1%
pH缓冲剂 0.5%-2%
溶剂 25%-55%
其中，所述利鲁唑缓释微球由赖诺普利溶于乙基纤维素水分散体经喷雾干燥技术制备而成，利鲁唑与乙基纤维素水分散体固含量比例为1:1-1:3。
其中，所述利鲁唑缓释微球平均粒径为20-50微米。
其中，所述稀释剂为甘露醇或木糖醇。
其中，所述矫味剂为安赛蜜、阿斯巴甜和三氯蔗糖中的一种或多种。
其中，所述助悬剂为黄原胶、阿拉伯胶、羧甲基纤维素钠、羟丙基纤维素中的一种或多种。
其中，所述的防腐剂为羟苯甲酯、羟苯乙酯、羟苯丙酯、苯甲酸、苯甲酸钠中的一种或多种。
其中，所述pH缓冲剂为柠檬酸和柠檬酸钠。
其中，所述溶剂为纯化水。
具体实施方式
以下是本发明的具体实施例，对本发明的技术方案做进一步描述，但是本发明的保护范围并不限于这些实施例。凡是不背离本发明构思的改变或等同替代均包括在本发明的保护范围之内。
实施例1
处方组成
制备工艺：
（1）将利鲁唑溶于乙基纤维素水分散体中，其中利鲁唑与乙基纤维素水分散体固含量比例为1:3，喷雾干燥制备乙基纤维素微球；
（2）称取处方量木糖醇、安赛蜜、柠檬酸和柠檬酸钠溶于一定量溶剂中，得含有稀释剂、矫味剂和缓冲剂的溶液；
（3）称取处方量黄原胶、苯甲酸钠和利鲁唑缓释微球，分散于一定量溶剂中，得含有助悬剂、防腐剂和活性成分的混悬液；
（4）将上述溶液与混悬液混合充分搅拌，并用剩余溶剂定容至刻度。
实施例 2
处方组成
制备工艺：
（1）将利鲁唑溶于乙基纤维素水分散体中，其中利鲁唑与乙基纤维素水分散体固含量比例为1:1，喷雾干燥制备乙基纤维素微球；
（2）称取处方量木糖醇、三氯蔗糖、柠檬酸和柠檬酸钠溶于一定量溶剂中，得含有稀释剂、矫味剂和缓冲剂的溶液；
（3）称取处方量羧甲基纤维素钠、苯甲酸钠和利鲁唑缓释微球，分散于一定量溶剂中，得含有助悬剂、防腐剂和活性成分的混悬液；
（4）将上述溶液与混悬液混合充分搅拌，并用剩余溶剂定容至刻度。
实施例 3
制备工艺：
（1）将利鲁唑溶于乙基纤维素水分散体中，其中利鲁唑与乙基纤维素水分散体固含量比例为1:2，喷雾干燥制备乙基纤维素微球；
（2）称取处方量甘露醇、阿斯巴甜、柠檬酸和柠檬酸钠溶于一定量溶剂中，得含有稀释剂、矫味剂和缓冲剂的溶液；
（3）称取处方量黄原胶、羟苯乙酯和利鲁唑缓释微球，分散于一定量溶剂中，得含有助悬剂、防腐剂和活性成分的混悬液；
（4）将上述溶液与混悬液混合充分搅拌，并用剩余溶剂定容至刻度。
实施例 4
制备工艺：
（1）将利鲁唑溶于乙基纤维素水分散体中，其中利鲁唑与乙基纤维素水分散体固含量比例为1:2，喷雾干燥制备乙基纤维素微球；
（2）称取处方量木糖醇、阿斯巴甜、柠檬酸和柠檬酸钠溶于一定量溶剂中，得含有稀释剂、矫味剂和缓冲剂的溶液；
（3）称取处方量阿拉伯胶、苯甲酸钠和利鲁唑缓释微球，分散于一定量溶剂中，得含有助悬剂、防腐剂和活性成分的混悬液；
（4）将上述溶液与混悬液混合充分搅拌，并用剩余溶剂定容至刻度。
实施例 5
制备工艺：
（1）将利鲁唑溶于乙基纤维素水分散体中，其中利鲁唑与乙基纤维素水分散体固含量比例为1:2，喷雾干燥制备乙基纤维素微球；
（2）称取处方量甘露醇、阿斯巴甜、柠檬酸和柠檬酸钠溶于一定量溶剂中，得含有稀释剂、矫味剂和缓冲剂的溶液；
（3）称取处方量黄原胶、羟苯甲酯和利鲁唑缓释微球，分散于一定量溶剂中，得含有助悬剂、防腐剂和活性成分的混悬液；
（4）将上述溶液与混悬液混合充分搅拌，并用剩余溶剂定容至刻度。
选取上述实施例1、3、5中得到的利鲁唑缓释混悬液，进行体外释放度测定：采用《中国药典》2015版四部通则0931第二法（桨法），以0.1mol/L 的盐酸溶液900mL 为释放介质，搅拌桨转速为50r/min，介质温度为36.5℃～37.5℃，取上述实施例中得到的利鲁唑缓释混悬液投入溶出杯中进行测定，系每隔一定时间取样10mL，同时补加同体积、同温度的溶出介质，将所取样立即用0.45μm 微孔滤膜过滤，续滤液用高效液相色谱测定其浓度，计算利鲁唑的累积释放度，结果见表1。
表1 部分实施例所得利鲁唑缓释混悬液体外累积释放度测定结果
从上表中可得，利鲁唑缓释混悬液在2h内药物释放量仍小于10%，且所得缓释混悬液能够平缓释放，能持续释药16h以上。
Claims (9)
1.一种利鲁唑缓释口服混悬液，包括利鲁唑缓释微球、稀释剂、矫味剂、助悬剂、防腐剂、pH缓冲剂，其特征在于：
所述的利鲁唑缓释微球由利鲁唑溶于乙基纤维素水分散体经喷雾干燥制备而成，按照重量百分比计，所述的各组分含量如下：
利鲁唑缓释微球 5%-25%
稀释剂 30%-60%
矫味剂 1%-2%
助悬剂 5%-15%
防腐剂 0.05-0.1%
pH缓冲剂 0.5%-2%
溶剂 25%-55%。
2.如权利要求1所述的利鲁唑缓释口服混悬液，其特征在于：所述利鲁唑缓释微球由利鲁唑溶于乙基纤维素水分散体经喷雾干燥技术制备而成，利鲁唑与乙基纤维素水分散体固含量比例为1:1-1:3。
3.如权利要求1所述的利鲁唑缓释口服混悬液，其特征在于：所述利鲁唑缓释微球平均粒径为20-50微米。
4.如权利要求1所述的利鲁唑缓释口服混悬液，其特征在于：所述稀释剂为甘露醇或木糖醇。
5.如权利要求1所述的利鲁唑缓释口服混悬液，其特征在于：所述矫味剂为安赛蜜、阿斯巴甜和三氯蔗糖中的一种或多种。
6.如权利要求1所述的利鲁唑缓释口服混悬液，其特征在于：所述助悬剂为黄原胶、阿拉伯胶、羧甲基纤维素钠、羟丙基纤维素中的一种或多种。
7.如权利要求1所述的利鲁唑缓释口服混悬液，其特征在于：所述的防腐剂为羟苯甲酯、羟苯乙酯、羟苯丙酯、苯甲酸、苯甲酸钠中的一种或多种。
8.如权利要求1所述的利鲁唑缓释口服混悬液，其特征在于：所述pH缓冲剂为柠檬酸和柠檬酸钠。
9.如权利要求1所述的利鲁唑缓释口服混悬液，其特征在于：所述溶剂为纯化水。
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