CN117442573A - 一种右佐匹克隆药物组合物 - Google Patents
一种右佐匹克隆药物组合物 Download PDFInfo
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Abstract
本发明涉及一种右佐匹克隆口崩片药物组合物及其制备方法,属于药物制剂技术领域。本发明的技术方案是:一种右佐匹克隆口崩片的药物组合物,其特征在于每片含有右佐匹克隆1mg、聚丙烯酸树脂Ⅳ2‑4mg、黄原胶0.2‑0.4mg、甘露醇70mg、微晶纤维素20mg、交联聚维酮5mg、柠檬酸0.1mg、柠檬味香精3mg、纽甜2mg、硬脂酸镁1mg。本发明提供了一种适合商业化生产的右佐匹克隆口崩片处方工艺,所选用的辅料在不影响溶出度的前提下,可以很好地起到掩味效果,提高了患者服药的顺应性。
Description
技术领域
本发明属于药物制剂技术领域,具体涉及一种右佐匹克隆口崩片的药物组合物。
背景技术
失眠是临床常见病症之一,虽不属于危重疾病,但妨碍人们正常生活、工作、学习和健康,并能加重或诱发心悸、胸痹、眩晕、头痛、中风病等病症。顽固性的失眠,给病人带来长期的痛苦,会引起人的疲劳感、不安、全身不适、无精打采、反应迟缓、头痛、注意力不能集中,它的最大影响是精神方面的,严重一点会导致精神分裂和抑郁症、焦虑症、植物神经功能紊乱等功能性疾病,以及各个系统疾病,如心血管系统、消化系统等等。
目前常用治疗失眠的药物有镇静催眠药(包括巴比妥类、苯二氮类、非典型苯二氮类)、抗抑郁药、抗组胺药(目前极少用于催眠)和中药。此类治疗失眠的药物大多需要用开水送服,对于老人等吞咽困难的患者十分不便。
右佐匹克隆是由美国Sepracor公司开发一种非苯二氮卓类催眠药,是通过作用于苯二氮䓬受体偶联的GABA受体复合物,起到镇静催眠的作用。长期使用无明显耐药性,且停药后无明显反跳现象。该产品于2004年获美国FDA批准上市,剂型为片剂,规格有3mg、2mg、1mg。现为临床上最常用的镇静催眠药。然而,右佐匹克隆在口腔中可产生极为强烈而持久的苦味,该缺点使得右佐匹克隆口服制剂的开发受到极大限制。目前已上市右佐匹克隆普通片剂虽然为右佐匹克隆的应用提供了一种选择, 但常规的普通片缺点和使用局限性也非常明显:1、不能够有效掩盖药物的不良味道, 崩解和药物溶出时间较长, 发挥疗效慢;薄膜包衣片虽在一定程度上的掩味效果,但其崩解和药物溶出可能更差;2、药物崩解后局部浓度高,容易造成胃肠道不良反应;3、必须完整吞服, 老人、儿童及其他吞咽困难的患者使用顺应性较差;4、吞服的药片可能粘滞在食管,引起异物感甚至药物性食管损伤。总之,普通片剂难以最大限度发挥右佐匹克隆的应用优势。CN1418631A公开了一种佐匹克隆口腔崩解片,虽然实现了片剂在口腔中溶解便于吞服的效果, 但该崩解片不能有效的掩盖佐匹克隆苦味, 患者对此存在一定的排斥感。
CN102232953A提到一种含有右佐匹克隆的药物组合物及其制备方法,该专利主要通过对主药粒径大小、预混方法及辅料的控制,获得具有高溶出度及含量均匀度的药物组合物。该专利需要对原料药进行特定处理以达到所需原料,且这个制备过程中没有考虑到右佐匹克隆的特殊苦味,所得片剂不能很好地掩盖其苦味。
CN107669647A提到一种右佐匹克隆口崩片及其制备方法,该专利采用甜菊苷为掩味剂,无法对原料药进行有效包裹,该方法制备的口崩片崩解后虽然对苦味有所改善,但还是不能很好地掩盖右佐匹克隆的特殊苦味;再次在制备过程中需要将右佐匹克隆和辅料进行粉碎过筛粉末使用,增加了繁琐的操作。
目前市面上右佐匹克隆为普通片剂,普通片剂需要吞咽,不利于吞咽困难者等特殊人群吞服,且在用水送服过程中由于包衣层破裂,右佐匹克隆会快速与口腔接触,且因其特殊持久的苦味,会引起服用者严重不适,口中苦味持久。
发明内容
本发明的目的是提供一种口感较好、能够快速分散且与原研制剂溶出曲线相似的右佐匹克隆口崩片的物组合物及其制备方法。
本发明采用现代药物制剂技术,右佐匹克隆与聚丙烯酸树脂Ⅳ号溶于柠檬酸水溶液中,与甘露醇流化床制粒后再采用黄原胶、柠檬香精溶液流化床制粒后采用40目筛整粒,加入微晶纤维素、交联聚维酮、纽甜、硬脂酸镁混合均匀后压片。
申请人发现右佐匹克隆与聚丙烯酸树脂Ⅳ、柠檬酸、黄原胶、柠檬味香精、甘露醇制粒后,避免了右佐匹克隆口崩片崩解后迅速与口腔接触特殊苦味的产生;干燥后的颗粒与微晶纤维素、交联聚维酮、纽甜、硬脂酸镁混合压片后,保证了片剂在口腔中的快速崩解。
本发明的技术方案是:一种右佐匹克隆口崩片的药物组合物,其特征在于每片含有右佐匹克隆1mg、聚丙烯酸树脂Ⅳ2-4mg、黄原胶0.2-0.4mg、甘露醇70mg、微晶纤维素20mg、交联聚维酮5mg、柠檬酸0.1mg、柠檬味香精3mg、纽甜2mg、硬脂酸镁1mg。
优选的,本发明所述右佐匹克隆药物组合物,其特征在于每片含有右佐匹克隆1mg、聚丙烯酸树脂Ⅳ3mg、黄原胶0.3mg、甘露醇70mg、微晶纤维素20mg、交联聚维酮5mg、柠檬酸0.1mg、柠檬味香精3mg、纽甜2mg、硬脂酸镁1mg。
本发明所述组合物的制备方法,包括以下步骤:
第一步:称取处方量的右佐匹克隆、聚丙烯酸树脂Ⅳ,加入0.1%的柠檬酸水溶液中溶解后备用;
第二步:称取处方量的黄原胶、柠檬味香精溶于纯化水中备用;
第三步:称取处方量的甘露醇投入流化床中,采用第一步制备的溶液制粒,制粒后干燥5min后再采用第二步制备的溶液制粒;
第四步:流化床制备的颗粒采用40目筛整粒;
第五步:将整粒后的颗粒与微晶纤维素、交联聚维酮、纽甜、硬脂酸镁混合均匀后压片。
本发明的有益效果是:
通过制剂学手段创新了一种新的右佐匹克隆药物组合物及制备方法,有效掩盖了右佐匹克隆特殊苦味的弊端,同时保证了片剂口中的快速崩散及溶出曲线与参比制剂相似,提高了吞咽困难患者的顺应性。
具体实施方式
以下通过具体实施方式对本发明作进一步的详细说明,但不应将此理解为本发明的范围仅限于以下的实例。在不脱离本发明上述方法思想的情况下,根据本领域普通技术知识和惯用手段做出的各种替换或变更,均应包含在本发明的范围内。
实施例1:
按技术方案所述制备方法制备1000片,包括以下步骤:
第一步:称取处方量的右佐匹克隆、聚丙烯酸树脂Ⅳ,加入0.1%的柠檬酸水溶液中溶解后备用;
第二步:称取处方量的黄原胶、柠檬味香精溶于纯化水中备用;
第三步:称取处方量的甘露醇投入流化床中,采用第一步制备的溶液制粒,制粒后干燥5min后再采用第二步制备的溶液制粒;
第四步:流化床制备的颗粒采用40目筛整粒;
第五步:将整粒后的颗粒与微晶纤维素、交联聚维酮、纽甜、硬脂酸镁混合均匀后压片。
实施例2:
按实施例1所述制备方法制备1000片。
实施例3:
按实施例1所述制备方法制备1000片。
对比例1:
按下述制备方法制备1000片:
第一步:将右佐匹克隆过80目筛后备用,将其余辅料过30目筛备用;
第二步:按处方量称取右佐匹克隆、甘露醇、微晶纤维素、交联聚维酮、甜菊苷混合10min;
第三步:在第二步混合物中加入处方量硬脂酸镁混合20min;
第四步:将第三步制备的物料采用压片机压片。
对比例2:
按实施例1所述制备方法制备1000片。
对比例3:
按实施例1所述制备方法制备1000片。
试验例1口感测试:
将实施例1-3及对比例1-3样品分别10人逐一品尝打分,10分为最佳,1分为最差,具体结果如下:
由上表评分可以看出,采用右佐匹克隆与聚丙烯酸树脂Ⅳ、黄原胶、柠檬酸、柠檬味香精、甘露醇制粒后能够很好地掩盖原料药的苦味;因对比例1口感差,故不再进行后续考察研究。
试验例2 崩解时限考察:
参照2020年版《中国药典》四部0921崩解时限检查法相关规定,对实施例1-3和对照例2-3进行崩解时限考察,具体结果如下:
试验例3 溶出曲线考察:
参照2020年版《中国药典》四部0931溶出度与释放度测定法相关规定,以pH6.8磷酸盐缓冲液为溶出介质,体积为900mL,桨法,转速为每分钟50rpm,分别测定实施例1-3和对比例2-3产品在5min、15min、45min、90min的溶出量,计算与原研制剂的溶出相似因子f2,具体结果如下:
注:当f2≥50时,判定溶出曲线相似。
由上表溶出曲线数据可以看出,当聚丙烯酸树脂Ⅳ及黄原胶用量在专利保护范围内能够保证溶出曲线与原研制剂相似。
Claims (5)
1.种右佐匹克隆口崩片药物组合物,其特征在于,每片含右佐匹克隆1mg、聚丙烯酸树脂Ⅳ2-4mg、黄原胶0.2-0.4mg、甘露醇70mg、微晶纤维素20mg、交联聚维酮5mg、柠檬酸0.1mg、柠檬味香精3mg、纽甜2mg、硬脂酸镁1mg。其中聚丙烯酸树脂Ⅳ与黄原胶比例为10:1。
2.根据权利要求1所述右佐匹克隆口崩片药组合物,其特征在于,每袋含右佐匹克隆1mg、聚丙烯酸树脂Ⅳ3mg、黄原胶0.3mg、甘露醇70mg、微晶纤维素20mg、交联聚维酮5mg、柠檬酸0.1mg、柠檬味香精3mg、纽甜2mg、硬脂酸镁1mg。
3.根据权利要求1所述右佐匹克隆口崩片药组合物,其特征在于,每片0.1㎎柠檬酸。
4.根据权利要求1所述右佐匹克隆口崩片药合物,其特征在于,每片含有2mg纽甜。
5.权利要求1所述右佐匹克隆口崩片药组合物的制备方法,其特征在于,包含以下步骤:
第一步:称取处方量的右佐匹克隆、聚丙烯酸树脂Ⅳ,加入0.1%的柠檬酸水溶液中溶解后备用;
第二步:称取处方量的黄原胶、柠檬味香精溶于纯化水中备用;
第三步:称取处方量的甘露醇投入流化床中,采用第一步制备的溶液制粒,制粒后干燥5min后再采用第二步制备的溶液制粒;
第四步:流化床制备的颗粒采用40目筛整粒;
第五步:将整粒后的颗粒与微晶纤维素、交联聚维酮、纽甜、硬脂酸镁混合均匀后压片。
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