CN112438968A - 一种复方马来酸右旋溴苯那敏固体制剂及其制备方法 - Google Patents
一种复方马来酸右旋溴苯那敏固体制剂及其制备方法 Download PDFInfo
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Abstract
本发明含有盐酸去氧肾上腺素的复方固体制剂的制备方法,是以α肾上腺素受体激动药盐酸去氧肾上腺素和抗组胺药马来酸右旋溴苯那敏为活性成分,配以包裹剂、粘合剂、填充剂、润滑剂等辅料制备而成的一种固体制剂,所述固体制剂为片剂。本发明中因盐酸去氧肾上腺素可在氧、醛、某些酸和金属存在下降解,所以本发明先将盐酸去氧肾上腺素用包裹剂进行包裹后进行制粒,为进一步防止药品被氧化而降解,本发明还在制备中加入了抗氧化剂。本发明具有暂时缓解由于普通感冒、花粉症(过敏性鼻炎)或其他上呼吸道过敏引起的以下症状:鼻充血、减少鼻道的肿胀、流鼻涕、打喷嚏、鼻子或喉咙痒、眼睛发痒和流眼泪等。
Description
技术领域
本发明属药物技术研发领域,具体涉及一种复方马来酸右旋溴苯那敏固体制剂及其制备方法,具体的讲是马来酸右旋溴苯那敏和盐酸去氧肾上腺素组合,与适宜的辅料经科学方法制备而成的固体片剂。
背景技术
感冒是全世界上最常见的疾病之一,据统计感冒每年的发病率为15~33%,其症状主要有:鼻塞、流鼻涕、打喷嚏、咳嗽、发热、全身酸痛等。病程通常在1~2周,若治疗不及时可诱发咽炎、中耳炎、支气管炎、肺炎、急性肾炎、风湿及心肌炎等疾病。
现治疗上述感冒症状的药物有很多,有中药或化药,有内服、外用、注射剂等。
右旋马来酸溴苯那敏,是马来酸溴苯那敏的具有药理活性的右旋异构体,是一种比较强的抗组胺药,但持续时间短,有镇静作用,可治疗慢性荨麻疹等皮肤瘙痒症。同马来酸溴苯那敏比较,都具有相同的功效,但是不含无效的左旋异构体成分,可有效减少药物毒副作用。
盐酸去氧肾上腺素为α-肾上腺素受体激动药,具有收缩血管,升高血压作用;是一种很强的血管收缩剂,被用作鼻减充血剂和心电剂,去氧肾上腺素还会导致肺血管收缩,以及随后的肺动脉压力增加,呼吸道黏膜下的血管收缩等,常与抗过敏药、祛痰药、镇咳药、退热剂等组成组合物治疗因感冒引起的发热、鼻塞、流涕、咳嗽、打喷嚏或头痛等症状。
发明内容
发明内容简述:
本发明是将右旋马来酸溴苯那敏与盐酸去氧肾上腺素合用,具有暂时缓解由于普通感冒、花粉症(过敏性鼻炎)或其他上呼吸道过敏引起的以下症状:鼻充血、减少鼻道的肿胀、流鼻涕、打喷嚏、鼻子或喉咙痒、眼睛发痒和流眼泪等。
本发明一种复方马来酸右旋溴苯那敏固体制剂及其制备方法,是以抗组胺药马来酸右旋溴苯那敏、α肾上腺素受体激动药盐酸去氧肾上腺素为活性成分,配以包裹剂、填充剂、润滑剂等辅料,制备而成的一种固体制剂,所述固体制剂为片剂。
采用本发明制备的片剂,稳定性好,制备方法简单,含量均匀,储存时间长。
发明内容详述:
因盐酸去氧肾上腺素可在氧、醛、某些酸和金属存在下降解,所以本发明先将盐酸去氧肾上腺素用包裹剂进行包裹后,与马来酸右旋溴苯那敏以及填充剂等辅料混合,采用干法制粒、压片,即得。
除非另外指明,本文所有重量均是在18-25℃条件下,对组合物中的活性药物成分和所需的辅料进行称量的。
除非另外指明,本文中所有百分比按重量计算,所有百分比均基于总组合物计算。
本发明说明书实施例中公开了多种实施方案,这些实施方案所有组合,对于同领域的技术人员来说都是可以实施的,有的是优选的。
实现本发明的具体技术方案如下:
一种复方马来酸右旋溴苯那敏固体制剂及其制备方法,其特征在于按重量百分比包括以下组分:马来酸右旋溴苯那敏7.0-10.0%、盐酸去氧肾上腺素0.1-5.0%、填充剂80.0-90.0%、包裹剂2.5-10%、润滑剂0.4-0.8%,
如上所述一种复方马来酸右旋溴苯那敏固体制剂及其制备方法,其特征在于按重量百分比包括以下组分:马来酸右旋溴苯那敏8.3%、盐酸去氧肾上腺素0.5%、蔗糖80.0%、PEG8000 8%、抗氧化剂2.9%、微粉硅胶0.3%。
如上所述填充剂包括但不限于糊精、蔗糖、淀粉中的一种或两种以上混合物。
如上所述包裹剂为PEG8000。
如上所述抗氧化剂包括但不限于苯甲酸、苯甲酸钠、三梨酸、山梨酸钾。
如上所述润滑剂包括但不限于微粉硅胶或滑石粉或硬脂酸镁。
如上所述一种复方马来酸右旋溴苯那敏固体制剂及其制备方法,其制备方法如下:
a、将包裹剂70-85℃加热溶化后,加入盐酸去氧肾上腺素,搅拌均匀,放冷,粉碎,过筛,得包裹物,备用;
b、将所制备的包裹物与马来酸右旋溴苯那敏与填充剂、粘合剂等辅料混合均匀,干法制粒,整粒,加入润滑剂,混合均匀,压片,即得。
所述过筛,是指用80-120筛网过筛;
所述干法制粒,是指采用干法制粒机制备成20-24目的颗粒;
所述混合,是指用混合机混合时间为60-120min。
有益效果
本发明一种复方马来酸右旋溴苯那敏固体制剂及其制备方法,是以α肾上腺素受体激动药盐酸去氧肾上腺素和抗组胺药马来酸右旋溴苯那敏为活性成分,配以包裹剂、填充剂、润滑剂等辅料,采用干法制粒制备而成的一种固体制剂,所述固体制剂为片剂。
本发明具有暂时缓解由于普通感冒、花粉症(过敏性鼻炎)或其他上呼吸道过敏引起的以下症状:鼻充血、减少鼻道的肿胀、流鼻涕、打喷嚏、鼻子或喉咙痒、眼睛发痒和流眼泪等。
本发明制备方法简单,药物均匀度好,稳定性好,储存时间长,符合药物的质量标准要求。
本发明中因盐酸去氧肾上腺素可在氧、醛、某些酸和金属存在下降解,所以本发明先将盐酸去氧肾上腺素用包裹剂进行包裹后进行制粒,增加了盐酸去氧肾上腺素的稳定性。
具体实施方式
下述实施例进一步描述和证明了本发明范围内的实施方案,所给出的这些实施例为了例举说明目的,不可看作是对本发明的限制。
实施例1
处方组成:马来酸右旋溴苯那敏8.3%、盐酸去氧肾上腺素0.5%、蔗糖80.0%、PEG8000 8%、苯甲酸钠2.9%、微粉硅胶0.3%。
制备方法:
1、将组分中的PEG8000,55-70℃加热溶化后,搅拌状态下加入盐酸去氧肾上腺素,搅拌均匀,放冷,粉碎,用80目筛网过筛,得包裹物,备用;
2、将包裹物、马来酸右旋溴苯那敏、蔗糖和苯甲酸钠混合均匀,用干法制粒机制粒,24目筛网整粒,得颗粒,备用;
3、将上述颗粒置混合机中,加入微粉硅胶,混合均匀,压片,即得。
实施例2
处方组成:马来酸右旋溴苯那敏10.0%、盐酸去氧肾上腺素0.1%、糊精78.6%、PEG8000 10.0%、苯甲酸1.0%、硬脂酸镁0.3%。
制备方法:
1、将组分中的PEG8000,60-70℃加热溶化后,搅拌状态下加入盐酸去氧肾上腺素,搅拌均匀,放冷,粉碎,用100目筛网过筛,得包裹物,备用;
2、将包裹物、马来酸右旋溴苯那敏、糊精和苯甲酸混合均匀,用干法制粒机制粒,24目筛网整粒,得颗粒,备用;
3、将上述颗粒置混合机中,加入微粉硅胶,混合均匀,压片,即得。
实施例3
处方组成:马来酸右旋溴苯那敏9.0%、盐酸去氧肾上腺素0.4%、蔗糖78.6%、PEG8000 8.5%、苯甲酸钠1.0%、微粉硅胶0.3%。
制备方法:
1、将组分中的PEG8000,60-70℃加热溶化后,搅拌状态下加入盐酸去氧肾上腺素,搅拌均匀,放冷,粉碎,用100目筛网过筛,得包裹物,备用;
2、将包裹物、马来酸右旋溴苯那敏、蔗糖和苯甲酸钠混合均匀,用干法制粒机制粒,24目筛网整粒,得颗粒,备用;
3、将上述颗粒置混合机中,加入微粉硅胶,混合均匀,压片,即得。
实施例4
考察盐酸去氧肾上腺素未包裹制备的片剂和包裹后制备的片剂的稳定性。
a、盐酸去氧肾上腺素未包裹制备的片剂(A表示):
处方:马来酸右旋溴苯那敏8.3%、盐酸去氧肾上腺素0.5%、蔗糖88.0%、苯甲酸钠2.9%、微粉硅胶0.3%。
制备方法:
1、取盐酸去氧肾上腺素、马来酸右旋溴苯那敏、蔗糖和苯甲酸钠混合均匀,用干法制粒机制粒,24目筛网整粒,得颗粒,备用;
2、将上述颗粒置混合机中,加入微粉硅胶,混合均匀,压片,即得。
b、盐酸去氧肾上腺素包裹后制备的片剂(B表示):
处方组成:马来酸右旋溴苯那敏8.3%、盐酸去氧肾上腺素0.5%、蔗糖80.0%、PEG8000 8%、苯甲酸钠2.9%、微粉硅胶0.3%。
制备方法:
1、将组分中的PEG8000,55-70℃加热溶化后,搅拌状态下加入盐酸去氧肾上腺素,搅拌均匀,放冷,粉碎,用80目筛网过筛,得包裹物,备用;
2、将包裹物、马来酸右旋溴苯那敏、蔗糖和苯甲酸钠混合均匀,用干法制粒机制粒,24目筛网整粒,得颗粒,备用;
3、将上述颗粒置混合机中,加入微粉硅胶,混合均匀,压片,即得。
试验方法:分别取上述(A)30片和(B)30片,分成三份,每份10片,分别置白色洁净的容器中,密封,分别在高温(45℃)、高湿(95%±2%)和光照(照度4500Lx±500Lx)条件下放置30天,以盐酸去氧肾上腺素含量为检测指标,分别在第10天和30天取样检测。结果见表一。
表一:
结论:盐酸去氧肾上腺素未包裹和盐酸去氧肾上腺素包裹后制备的片剂,分别在高温、高湿和光照条件下进行稳定性试验,结果经包裹的盐酸去氧肾上腺素除高温条件下降解比较明显,在其他两种条件下,含量变化不明显,而未包裹的盐酸去氧肾上腺素在三种条件下,含量变化较大,降解快。
实施例5
考察本发明在高湿、高热和光照条件下,其稳定性情况。
试验方法:取实施例1制得的样品10份,每份10片,置密封袋中,密封,分别在高温(60℃)、高湿(95%±2%)和光照(照度4500Lx±500Lx)条件下放置60天,以马来酸右旋溴苯那敏(A);盐酸去氧肾上腺素(B)含量为检测指标,分别在第10天、30天和第60天取样检测。结果见表二。
表二:
试验表明:上述产品在高温条件下,马来酸右旋溴苯那敏、盐酸去氧肾上腺素含量下降明显,
并且在60天时,药片变微黄色;在强光、高湿条件下,有效成分变化不明显。其含量在90-110%之间,符合稳定性研发要求。
Claims (11)
1.一种复方马来酸右旋溴苯那敏固体制剂及其制备方法,其特征在于是由下列按重量百分比的原料和辅料组成:马来酸右旋溴苯那敏7.0-10.0%、盐酸去氧肾上腺素0.1-5.0%、填充剂80.0-90.0%、包裹剂2.5-10%、润滑剂0.4-0.8%。
2.根据权利要求1所述一种复方马来酸右旋溴苯那敏固体制剂及其制备方法,其特征在于是由下列按重量百分比的原料和辅料组成:马来酸右旋溴苯那敏8.3%、盐酸去氧肾上腺素0.5%、蔗糖80.0%、PEG8000 8%、抗氧化剂2.9%、微粉硅胶0.3%。
3.根据权利要求1或2所述一种复方马来酸右旋溴苯那敏固体制剂及其制备方法,其特征在于所述填充剂包括但不限于糊精、蔗糖、淀粉中的一种或两种以上混合物。
4.根据权利要求1或2所述一种复方马来酸右旋溴苯那敏固体制剂及其制备方法,其特征在于所述包裹剂为PEG8000。
5.根据权利要求1或2所述一种复方马来酸右旋溴苯那敏固体制剂及其制备方法,其特征在于所述抗氧化剂包括但不限于苯甲酸、苯甲酸钠、三梨酸、山梨酸钾。
6.根据权利要求1或2所述一种复方马来酸右旋溴苯那敏固体制剂及其制备方法,其特征在于所述润滑剂包括但不限于微粉硅胶或滑石粉或硬脂酸镁。
7.根据权利要求1或2所述一种复方马来酸右旋溴苯那敏固体制剂及其制备方法,其特征在于制备方法如下:
7.1将包裹剂70-85℃加热溶化后,加入盐酸去氧肾上腺素,搅拌均匀,放冷,粉碎,过筛,得包裹物,备用;
7.2将所制备的包裹物与马来酸右旋溴苯那敏与填充剂、粘合剂等辅料混合均匀,干法制粒,整粒,加入润滑剂,混合均匀,压片,即得。
8.根据权利要求7所述一种复方马来酸右旋溴苯那敏固体制剂及其制备方法,其特征在于所述过筛,是指用80-120筛网过筛。
9.根据权利要求7所述一种复方马来酸右旋溴苯那敏固体制剂及其制备方法,其特征在于所述干法制粒,是指采用干法制粒机制备成20-24目的颗粒。
10.根据权利要求7所述一种复方马来酸右旋溴苯那敏固体制剂及其制备方法,其特征在于所述混合,是指用混合机混合时间为60-120min。
11.根据权利要求1所述一种复方马来酸右旋溴苯那敏固体制剂及其制备方法,其特征在于本发明具有暂时缓解由于普通感冒、花粉症(过敏性鼻炎)或其他上呼吸道过敏引起的以下症状:鼻充血、减少鼻道的肿胀、流鼻涕、打喷嚏、鼻子或喉咙痒、眼睛发痒和流眼泪等。
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