CN110787139A - 一种孟鲁司特钠药物组合物 - Google Patents
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Abstract
本发明为一种孟鲁司特钠药物组合物。本发明属于医药领域，提供了一种组成简单、稳定性良好的孟鲁司特钠组合物及其制备方法，组合物中含有孟鲁司特钠、甘露醇、羟丙基纤维素及硬脂酸镁，通过处方设计及制备工艺该显著降低了孟鲁司特钠降解杂质的增长，提高了其稳定性，该制备工艺重现性好，成本低，适于工业化大生产。
Description
技术领域
本发明属于药物制剂领域，具体涉及了孟鲁司特药物组合物及其制备方法。
背景技术
孟鲁司特钠具有优良的口服生物利用度、临床疗效和安全性，优于同类药物，是目前世界上最畅销的治疗哮喘的药物。孟鲁司特钠制剂是由Merck Sharp & Dohme开发用于抗哮喘，于1997年在墨西哥获得批准，商品名为Singulair®，之后在1998年获得美国食品药品管理局批准，2008年在日本获得上市批准。
由于近年来环境的恶化，特别是秋冬季节，国内外哮喘的发病率，尤其是小儿哮喘的发病率呈显著上升趋势。由于孟鲁司特的安全有效，不良反应相对较低，患者耐受性和依从性较好，故我司对孟鲁司特钠组合物进行开发。
由于孟鲁司特钠对湿、热、光敏感。多数研发案例为提高其稳定性增加抗氧剂、络合物、聚合物或全程避光进行，不但增加成本，还降低工艺可行性，本发明涉及了一种有效提高孟鲁司特钠稳定性，且降低生产成本的制备方法。
发明内容
在本发明中，孟鲁司特钠颗粒采用流化床制粒，在流化床内多为避光环境，避免了主药的光降解。制备主药颗粒的目的为提高主药的稳定性及确保产品的含量均匀度，同时控制流化床干燥温度，避免主药高温降解。主药颗粒与甘露醇的再次制粒，实现甘露醇对主药颗粒的包裹作用，还可以提高颗粒粒度、流动性及可压性，为制备成相应的制剂提供保障。
具体而言，本发明是通过以下过程达到的：
该药物组合物有孟鲁司特钠、羟丙基纤维素、甘露醇、硬脂酸镁，按如下处方比例制备而成：
孟鲁司特钠 6.0%~10.0%
羟丙基纤维素 10.0%~22.0%
甘露醇 70.0%~80.0%
硬脂酸镁 0.2%~1.0%
共计 100.0%
药物组合物的粘合剂为配置成重量比为4%~8%的羟丙基纤维素溶液，此浓度范围的粘合剂适合制粒工艺的顺应性，又有助于主药的稳定性。
该药物组合物的填充剂为喷雾干燥甘露醇或普通甘露醇，用于主药颗粒制备的填充剂为喷雾干燥甘露醇。因普通甘露醇在流化床内的流动性差，制粒时易粘连。
该药物组合物的制备方法为：
将羟丙基纤维素加入适量的纯化水中，配置成重量比为4%~8%的粘合剂。将处主药加入黏合剂中，得主药溶液，此过程尽量避光。喷雾干燥甘露醇置于流化床中，将主药溶液喷至喷雾干燥甘露醇上，进风温度及物料稳定控制在40℃以下干燥，40目整粒，得主药颗粒。主药颗粒与甘露醇湿法制粒，再与硬脂酸镁混合均匀，将此物料制备成预计的制剂。
经上述处方工艺制备的样品稳定性较强，本发明提供了一种有效提高孟鲁司特钠稳定性，且降低生产成本的制备方法。
具体实施例
以下实施例进一步描述本发明的有益效果，实施例仅用于例证的目的，不限制本发明的范围，同时本领域普通技术人员根据本发明所做的显而易见的改变和修饰也包含在本发明范围之内。
实施例1
处方组成：
制备工艺：
称取处方量的羟丙基纤维素加入纯化水，配置成重量比为8%的粘合剂；将主药加入粘合剂中搅拌溶解，得主药溶液；采用流化床将主药溶液喷至喷雾干燥甘露醇上，进风温度及物料温度控制在35℃±5℃，40目筛整粒，得主药颗粒；主药颗粒与甘露醇混合制粒，加硬脂酸镁，压片。
实施例2
处方组成：
制备工艺：
称取处方量的羟丙基纤维素加入纯化水，配置成重量比为4%的粘合剂；将主药加入粘合剂中搅拌溶解，得主药溶液；采用流化床将主药溶液喷至喷雾干燥甘露醇上，进风温度及物料温度控制在30℃±5℃，40目筛整粒，得主药颗粒；主药颗粒与甘露醇混合制粒，加硬脂酸镁，压片。
实施例3
制备工艺：
称取处方量的羟丙基纤维素加入纯化水，配置成重量比为5%的粘合剂；将主药加入粘合剂中搅拌溶解，得主药溶液；采用流化床将主药溶液喷至喷雾干燥甘露醇上，进风温度及物料温度控制在35℃±5℃，40目筛整粒，得主药颗粒；主药颗粒与甘露醇混合制粒，加硬脂酸镁，分装成颗粒剂。
对比实施例1
处方组成：
制备工艺：
称取处方量的羟丙基纤维素加入纯化水中，配置成重量比为6%的粘合剂；将孟鲁司特钠、喷雾干燥甘露醇混合均匀，加入粘合剂，20目筛制粒，40℃干燥；加入硬脂酸镁混匀，压片而成。
光热因素稳定性考察
取实施例1-3及对比实施例1的样品分别置于光照（1.2×106Lux·hr、近紫外能量不低于200w·hr/m2）和40℃10天。
有关物质：避光操作，在72小时内进行测定。取本品10袋，分别将内容物定量转移至200ml棕色量瓶中，加甲醇约130ml，超声15分钟并时时振摇，放冷至室温，用甲醇稀释至刻度，摇匀，溶液离心，取上清液（或取溶液滤过，取续滤液）作为供试品溶液。取孟鲁司特二环己胺盐对照品约 33mg，精密称定，置100ml棕色量瓶中，加甲醇约80ml，超声10分钟使溶解，放冷至室温，用甲醇稀释至刻度，摇匀，精密量取2ml置25ml棕色量瓶中，加甲醇稀释至刻度，摇匀，作为对照品溶液。用苯基键合硅胶为填充剂，0.2%的三氟乙酸溶液-0.2%的三氟乙酸乙腈溶液（1：1）为流动相，流速为0.9ml/min，柱温为50°C，检测波长为389nm，理论板数按孟鲁司特峰计算应不低于 1500。精密量取对照品溶液和0.1%的供试品溶液各10μl，分别注入液相色谱仪，记录色谱图，按外标法以峰面积计算。
有关物质检测结果
上述有关物质结果表明，将孟鲁司特钠配置成主药溶液喷至喷雾干燥甘露醇上，之后再与甘露醇制粒的方式，能改善孟鲁司特钠在光、热因素下的不稳定性。因此本发明所述的组合物制备方法取得了良好的技术效果，可为生产提供有效的制备方法。
Claims (7)
1.一种孟鲁司特钠药物组合物，其特征在于该药物组合物有孟鲁司特钠、羟丙基纤维素、甘露醇、硬脂酸镁。
2.根据权利要求1所述的药物组合物，其特征在于该药物组合物由以下原辅料按重量比制备而成：
孟鲁司特钠 6.0%~10.0%
羟丙基纤维素 10.0%~22.0%
甘露醇 70.0%~80.0%
硬脂酸镁 0.2%~1.0%
共计 100.0% 。
3.根据权利要求2所述的药物组合物，其特征在于该药物组合物的粘合剂为配置成重量比为4%~8%的羟丙基纤维素溶液。
4.根据权利要求2所述的药物组合物，其特征在于该药物组合物的填充剂为喷雾干燥甘露醇或普通甘露醇，用于主药颗粒制备的填充剂为喷雾干燥甘露醇。
5.根据权利要求2所述的药物组合物，其特征在于该药物组合物的制备方法为：
1）粘合剂配置：将适量的羟丙基纤维素加入纯化水中，配置成重量比为4%~8%的粘合剂；
2）配置主药溶液：将处方量的主药加入粘合剂中搅拌溶解，得主药溶液；
3）制备主药颗粒：将喷雾干燥甘露醇置于流化床中，将主药溶液喷至喷雾干燥甘露醇上，干燥，40目整粒，得主药颗粒；
4）将主药颗粒、甘露醇混合均匀后湿法制粒，再与硬脂酸镁混合均匀，制备成组合物。
6.根据权利要求5所述的药物组合物，其特征在于该药物组合物在制备主药颗粒加入的喷雾干燥甘露醇占总重的40%~50%。
7.根据权利要求5所述的药物组合物，其特征在于该药物组合物的制备方法中流化床进风温度、物料温度应在40℃下。
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| CN114224847A (zh) * | 2021-12-07 | 2022-03-25 | 哈尔滨珍宝制药有限公司 | 一种孟鲁司特钠颗粒的制备方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1575163A (zh) * | 2001-10-26 | 2005-02-02 | 麦克弗罗斯特(加拿大)公司 | 孟鲁司特颗粒制剂 |
| CN101365450A (zh) * | 2006-02-09 | 2009-02-11 | 特瓦制药工业有限公司 | 孟鲁司特钠的稳定药物制剂 |
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| CN1575163A (zh) * | 2001-10-26 | 2005-02-02 | 麦克弗罗斯特(加拿大)公司 | 孟鲁司特颗粒制剂 |
| CN101365450A (zh) * | 2006-02-09 | 2009-02-11 | 特瓦制药工业有限公司 | 孟鲁司特钠的稳定药物制剂 |
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|---|---|---|---|---|
| CN114224847A (zh) * | 2021-12-07 | 2022-03-25 | 哈尔滨珍宝制药有限公司 | 一种孟鲁司特钠颗粒的制备方法 |
| CN114224847B (zh) * | 2021-12-07 | 2023-09-15 | 哈尔滨珍宝制药有限公司 | 一种孟鲁司特钠颗粒的制备方法 |
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