CN116421575A - 盐酸罗匹尼罗缓释片及其制备方法 - Google Patents
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Abstract
本发明公开了盐酸罗匹尼罗缓释片及其制备方法。所述的盐酸罗匹尼罗缓释片采用单一凝胶骨架阻滞剂作为缓释材料,进行干法制粒,压片,随后外加缓释衣膜进行膜控联合控制的方式制备出缓释片,能够有效控制释放速率。此外,还公开了该缓释片的制备方法。
Description
技术领域
本发明涉缓释药物控制释放速率的方法,具体涉及一种含活性成分盐酸罗匹尼罗的缓释片剂药物控制释放速率的方法。
背景技术
盐酸罗匹尼罗(结构式如下)是一种非麦角类多巴胺受体激动剂,BCS分类为1类。体外试验表明本品对多巴胺D2和D3受体具有相对高的选择性和内在活性,与D3受体的亲合力比D2或D4高。体外研究表明本品与阿片受体具有中度程度的亲合力,原型及其代谢物与多巴胺D1受体,5-HT1,5-HT2,苯二氮卓的,GABA,蕈毒碱的,α1,α2和β肾上腺素受体没有亲合力;
作为盐酸罗匹尼罗缓释片控制释放速率的方法,人们进行了各种研究。例如,1、多层片剂的口服剂型,其中的一层中负载有生理活性物质,使用羟丙甲纤维素阻滞剂和空白层包夹活性层的方法控制释放速率(中国专利CN1198598C),此方法对压片设备要求较高;2、用含缓释材料的包衣液包衣含活性物质的颗粒,以形成包衣颗粒进而控制释放速率,此方法工艺较复杂;等等。
发明内容
本发明的目的是提供一种盐酸罗匹尼罗缓释片的制备方法。
本发明采用单一凝胶骨架阻滞剂作为缓释材料,进行干法制粒,压片,随后外加缓释衣膜进行膜控的联合控制方式制备出缓释片。
一方面,本发明提供了一种盐酸罗匹尼罗缓释片,所述的盐酸罗匹尼罗缓释片是由活性部分颗粒和空白部分颗粒混合、压片和包衣制得:
所述活性部分颗粒的组成为:盐酸罗匹尼罗、糖醇类填充剂1和亲水凝胶骨架材料1;
所述空白部分颗粒的组成为:糖醇类填充剂2和亲水凝胶骨架材料2;
所述片芯的组成为:活性部分颗粒、空白部分颗粒和润滑剂;
所述包衣的材料包含不溶性材料和可溶性材料。
作为进一步技术方案,所述糖醇类填充剂1和糖醇类填充剂2各自独立地选自乳糖、甘露醇和木糖醇中的1种或2种以上,优选地,所述糖醇类填充剂1和糖醇类填充剂2为乳糖。
作为进一步技术方案,所述亲水凝胶骨架材料1和亲水凝胶骨架材料2各自独立地选自羟丙纤维素、羟丙甲纤维素、海藻酸钠和聚维酮中的1种或2种以上,优选地,所述亲水凝胶骨架材料1和亲水凝胶骨架材料2为羟丙甲纤维素。
作为进一步技术方案,所述润滑剂选自二氧化硅和硬脂酸镁;优选地,所述润滑剂为硬脂酸镁。
作为进一步技术方案,所述缓释包衣中不溶性材料选自乙基纤维素及其衍生物中的1种或2种以上,优选地,为乙基纤维素。
作为进一步技术方案,所述缓释包衣中可溶性材料的主要成分选自羟丙甲纤维素、羟丙纤维素、聚维酮中的1种或2种以上,优选地,为羟丙甲纤维素。
作为进一步技术方案,相对于活性部分颗粒的总重量,糖醇类填充剂1的含量为10~50的重量%;优选地,糖醇类填充剂1的含量为15~25的重量%。
作为进一步技术方案,相对于活性部分颗粒的总重量,亲水凝胶骨架材料1的含量为30~90的重量%;优选地,亲水凝胶骨架材料1的含量为70~80的重量%。
作为进一步技术方案,相对于空白部分颗粒的总重量,糖醇类填充剂2的含量为10~50的重量%;优选地,糖醇类填充剂1的含量为15~25的重量%。
作为进一步技术方案,相对于活空白部分颗粒的总重量,亲水凝胶骨架材料2的含量为30~90的重量%;优选地,亲水凝胶骨架材料1的含量为70~80的重量%。
作为进一步技术方案,相对于包衣片剂的总重量,包衣剂的含量为1~15的重量%;优选地,所述包衣剂的含量为3~5的重量%。
作为进一步技术方案,相对于缓释包衣剂的总重量,不溶性材料的含量为30~70的重量%;优选地,所述缓释包衣剂的含量为50~60的重量%。
作为进一步技术方案,相对于缓释包衣剂的总重量,可溶性材料的含量为30~60的重量%;优选地,所述缓释包衣剂的含量为35~45的重量%。
作为进一步技术方案,相对于所述片剂的总重量,所述活性颗粒的含量为5~50重量%;优选地,所述活性颗粒的含量为15~25重量%。
另一方面,本发明提供了一种盐酸罗匹尼罗缓释片的制备方法,所述的制备方法包括步骤如下:
步骤1,将糖醇类填充剂1、亲水凝胶骨架材料1、盐酸罗匹尼罗混合均匀,得到活性部分混合物;将糖醇类填充剂2和亲水凝胶骨架材料2混合均匀,得到空白部分混合物;
步骤2,将步骤1得到活性部分混合物和空白部分混合物分别加入制粒机中制粒,得到活性部分颗粒和空白部分颗粒;
步骤3,将步骤2得到的活性部分颗粒和空白部分颗粒混合均匀,加入润滑剂再混合均匀;
步骤4,压片;
步骤5,压片后进行缓释包衣,任选地还进行薄膜包衣,即得成品。
作为进一步技术方案,还包括步骤5,压片后先进行缓释包衣,再进行薄膜包衣,或直接进行缓释包衣。
作为进一步技术方案,还包括步骤2,制粒方式为干法制粒、湿法制粒或流化床制粒,优选干法制粒。
作为进一步技术方案,还包括步骤1和2,制粒方式为将物料分为多部分分别混合后制粒,或整体混合后制粒。
该方法的有益效果能够有效控制释放速率,且采用普通的旋转压片机降低了设备成本。
附图说明
图1为本发明各实施例和参比制剂在pH1.0盐酸溶液(关键介质)中的释放曲线对比图。
图2为本发明各实施例和参比制剂在pH4.0柠檬酸-三羟甲基氨基甲烷缓冲溶液中的释放曲线对比图。
图3为本发明各实施例和参比制剂在pH 6.8磷酸盐缓冲液中的释放曲线对比图。
实施方式
下面,将参考实施例详细描述本发明。但是,本发明无论如何不旨在限于这些实施例:
具体实施过程:
实施例1~3
将活性部分的盐酸罗匹尼罗、乳糖和羟丙甲纤维混合均匀,得活性部分混合物;空白部分的乳糖和羟丙甲纤维混合均匀,得空白部分混合物。
将活性部分混合物和空白部分混合物分别加入干法制粒机中进行制粒,得活性颗粒和空白颗粒。
活性部分颗粒和空白部分颗粒混合均匀,加入润滑剂再混合均匀,得总混颗粒。
将总混颗粒进行压片,然后将压制的片剂进行缓释包衣,控制缓释包衣增重为3%~5%。
实施例4
将盐酸罗匹尼罗、乳糖和羟丙甲纤维混合均匀,得混合物。
将混合物加入干法制粒机中进行制粒,得制得颗粒。
将制得颗粒和润滑剂混合均匀,得总混颗粒。
将总混颗粒进行压片,然后将压制的片剂进行缓释包衣,控制缓释包衣增重为3%~5%。
将盐酸罗匹尼罗缓释片(实施例、参比制剂)在三种介质pH1.0盐酸溶液(关键介质)、pH4.0柠檬酸-(三羟甲基)氨基甲烷缓冲溶液、pH 6.8磷酸盐缓冲液中,以500ml桨法+沉降篮进行释放曲线检测。将溶出量计算为6个片剂的平均溶出百分数,进行对比:
由实施例和参比制剂的溶出曲线对比表可知,在pH1.0盐酸溶液(关键介质)中,实施例1~4释放曲线与参比制剂相似。在pH4.0柠檬酸溶液、pH6.8磷酸溶液中的释放曲线与参比制剂有差异,但实施例1~4间相似:
由实施例和参比制剂的溶出曲线对比表可知,实施例1~3的稳定性与参比制剂相当,实施例4的稳定性明显叫参比制剂差。
综合判断,实施例1~3采用单一凝胶骨架阻滞剂作为缓释材料,进行干法制粒,压片,随后外加缓释衣膜进行膜控联合控制的方式制备出缓释片,能够有效控制释放速率,达到与参比制粒相似的释放速率。
Claims (8)
1.一种缓释包衣片剂,其通过下述包衣剂对下述片剂进行包衣而得,
(1)所述包衣剂含有:
(A)不溶性材料,所述不溶性材料选自乙基纤维素及其衍生物中的1种或2种以上,和
(B)可溶性材料,所述可溶性材料选自羟丙甲纤维素、羟丙纤维素、聚维酮中的1种或2种以上;
(2)所述片剂含有:
下述式表示的4-[2-(二丙基氨基)乙基]-1,3-二氢-2H-吲哚-2-酮盐酸盐:
(B)糖醇类,所述糖醇类选自乳糖、甘露醇和木糖醇中的1种或2种以上;和
(C)亲水凝胶骨架材料,所述亲水凝胶骨架材料选自羟丙甲纤维素、羟丙纤维素、海藻酸钠和聚维酮中的1种或2种以上;
(D)活性颗粒由4-[2-(二丙基氨基)乙基]-1,3-二氢-2H-吲哚-2-酮盐酸盐、糖醇类填充剂1和亲水凝胶骨架材料1制得;
(E)空白颗粒由糖醇类填充剂2和亲水凝胶骨架材料2制得;
(F)所述片剂由活性颗粒和空白颗粒混合压制而得。
2.权利要求1所述的缓释包衣片剂,其中包衣剂的不溶性材料为乙基纤维素分散体。
3.权利要求1所述的缓释包衣片剂,其中包衣剂的可溶性材料为羟丙甲纤维素。
4.权利要求1或2或3所述的缓释包衣片剂,其中相对于包衣片剂的总重量,包衣剂的含量为1~15的重量%。
5.权利要求1或2或3所述的缓释包衣片剂,其中糖醇类填充剂1和糖醇类填充剂2为乳糖。
6.权利要求1或2或3所述的缓释包衣片剂,其中亲水凝胶骨架材料1和亲水凝胶骨架材料2为羟丙甲纤维素,其中所述羟丙甲纤维素的黏度范围为4000Cps~100000Cps。
7.权利要求1或2或3所述的缓释包衣片剂,其中相对于片剂的总重量,活性颗粒的含量为5~50%。
8.一种缓释包衣片剂,其通过含有乙基纤维素和羟丙甲纤维素的包衣剂对下述片剂进行包衣而得,
所述片剂含有:4-[2-(二丙基氨基)乙基]-1,3-二氢-2H-吲哚-2-酮盐酸盐、乳糖以及羟丙甲基纤维素制的活性颗粒,与乳糖以及羟丙甲基纤维素制的空白颗粒混合压制而得。
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