CN106389343A - 一种阿立哌唑口服用液体干混悬剂及其制备方法 - Google Patents
一种阿立哌唑口服用液体干混悬剂及其制备方法 Download PDFInfo
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Abstract
本发明属于医药技术领域，涉及一种用于治疗精神分裂症，对急性复发患者、慢性患者及情感性精神分裂症患者有效的阿立哌唑口服干混悬剂及其制备方法。所述的药物组成含有活性成分阿立哌唑、填充剂、助悬剂、矫味剂、粘合剂、崩解剂等其它药学上可接受的辅料。本发明提供的口服干混悬剂解决了一些吞咽能力较弱的患者服药困难、服药顺应性差的问题，而且保证质量可控，稳定性高，服用方便，口感良好，能更好地满足临床需要。该口服干混悬剂与其已知的片剂比较，具有给药速度快、起效快、吸收稳定、生物利用度高等优势。
Description
技术领域
本发明属于医药技术领域，具体涉及到阿立哌唑口服干混悬剂及其制备方法。本发明制剂主要用来治疗各类型的精神分裂症疾病，对精神分裂症的阳性和阴性症状均有明显疗效，可改善伴发的情感症状，降低精神分裂症的复发率。
背景技术
阿立哌唑（7-{4-[4-(2，3-二氯苯基)-l-哌嗪基]丁氧基}-3，4-二氢-2(1H)-喹啉酮）是多巴胺和5-羟色胺系统的稳定剂，是突触后多巴胺受体的阻滞剂，同时又是突触前自主受体的激动剂，与D2和D3受体的亲和力非常强，同时又作为D2受体的部分激动剂，在活体多巴胺功能亢进模型中显示出较强的阻滞作用，而在多巴胺功能低下的模型中则表现出较强激动作用，能够抑制多巴胺激动剂，这种抑制作用可以被氟哌啶醇完全阻滞，因此，本品有稳定多巴胺系统的作用，同时又因本品是5-HT1A受体的部分激动剂和5-HT2A受体的阻滞剂，作为世界上第一个上市的多巴胺部分激动剂，能透过血-脑屏障，与D2受体的结合随剂量的增加而增加，在抗精神分裂症的焦虑、抑郁、认知缺损和阴性症状方面有着广阔的前景。
阿立哌唑目前供临床选择的剂型有口服片剂，国内已有多家上市，胶囊剂国内上市一家，口崩片国内上市一家，注射剂，缓释注射剂，一家已发批件，口服溶液剂国内暂无上市申报信息。口服片剂、胶囊剂，不适合吞咽能力较弱的老人和小孩服用。口崩片除要求崩解迅速以外，还需要其口感好，因而在压片时要加入大量的优良崩解剂和矫味剂，使得制得的片重、片型如太大，则服用不便。注射剂由于直接迅速进入人体，无人体正常生理屏障的保护，因此若剂量不当或注射过快，或药品质量存在问题，均有可能给患者带来危害，安全性差，此外注射剂注射给药时产生疼痛、一般不能由患者自己给药，给药不方便，临床顺应性差。口服溶液剂虽然能够解决吞咽能力较弱患者的服用困难问题，但是其在服用期间稳定较差，且作为液体制剂携带服用不方便。但口服干混悬剂，以固体形式储存，而以混悬液形式供口服，性质稳定、质量好、有效成分含量高，因此具有便于携带服用、可以保证药物稳定性及疗效好的特点。另外口服干混悬剂以液体形式送入人体吸收，解决了一些患者吞咽困难的问题，容易被患者所接受，尤其适用于吞咽困难的患者、老人及儿童。口服后以液体的形态流经胃肠道，并且该制剂在进入人体到达呼吸道黏膜及胃肠道之前已经以细微颗粒形式存在，药物分散速度快，在人体内分布面积大，吸收点多，能够提高生物利用度，针对于幼儿、老年人以及难变动体位的患者，极大的提高了患者的顺应性，改善了临床的有效性以及应急性。
发明内容
本发明的目的是提供一种制备药物性质稳定，并且服用方便，对适应症起效快，应用广泛的阿立哌唑口服干混悬剂。
本发明的阿立哌唑口服干混悬剂的制备方法为：
1）将所述阿立哌唑、填充剂粉碎过100目筛备用；
2）将所述阿立哌唑及上述药学辅料填充剂、助悬剂混合均匀后加入粘合剂搅拌制粒，50℃干燥，整粒，分级得颗粒备用；
3）将矫味剂、崩解剂与上述2）中制备好的颗粒混合即得。
针对现有技术的不足，本发明提供一种阿立哌唑口服干混悬剂及其制备方法，为解决口服干混悬剂对患者的服用顺应性问题，加入了填充剂。所述的填充剂包括庶糖、淀粉、甘露醇中的一种或几种。另外助悬剂的选择对于混悬剂的稳定性起决定性作用，这种助悬剂可以确保药物制备过程中药物不会产生沉淀析出的现象，确保其分散均匀性良好。同时为改善口服干混悬剂口感，加入了矫味剂，所述矫味剂包括三氯蔗糖、阿斯巴甜、糖精钠、蔗糖、木糖醇、甘露醇、香草香精、草莓香精、蓝莓香精、橙香精的一种或多种。所得的阿立哌唑口服干混悬剂，可随身携带，随冲随服，服用方便、溶出合格、对适应症达峰早、疗效明显、口感好，适合于广泛的推广和应用。
本发明的技术方案中阿立哌唑口服干混悬剂，为提高药物释放问题，可以含有崩解剂，改善颗粒的崩解，加快颗粒的溶出。确保主药含量稳定。
具体实施方式
以下实施例仅用于进一步说明本发明，但不限制本发明。本发明的上述实施例仅仅是为清楚地说明本发明所作的举例，而并非是对本发明的实施方式的限定，对于所属领域的普通技术人员来说，在上述说明的基础上还可以做出其它不同形式的变化或变动，这里无法对所有的实施方式予以穷举，凡是属于本发明的技术方案所引伸出的显而易见的变化或变动仍处于本发明的保护范围之列。
实施例 1
制备工艺：
1）将所述阿立哌唑、蔗糖、木糖醇粉碎过100目筛备用；
2）将所述阿立哌唑及上述蔗糖、木糖醇、黄原胶混合均匀后加入粘合剂搅拌制粒，50℃干燥，整粒，分级得颗粒备用；
3）将矫味剂、羧甲基淀粉钠与上述2）中制备好的颗粒混合即得。
实施例 2
制备工艺：
1）将所述阿立哌唑、甘露醇、木糖醇过100目筛备用；
2）将所述阿立哌唑及上述甘露醇、木糖醇、黄原胶混合均匀后加入粘合剂搅拌制粒，50℃干燥，整粒，分级得颗粒备用；
3）将三氯蔗糖、草莓香精、羧甲基淀粉钠与上述2）中制备好的颗粒混合即得。
实施例3
制备工艺：
1）将所述阿立哌唑、乳糖、木糖醇过100目筛备用；
2）将所述阿立哌唑及上述乳糖、木糖醇、黄原胶混合均匀后加入粘合剂搅拌制粒，50℃干燥，整粒，分级得颗粒备用；
3）将三氯蔗糖、橙香精、羧甲基淀粉钠与上述2）中制备好的颗粒混合即得。
Claims (9)
1.一种阿立哌唑口服干混悬剂，其特征在于包括填充剂、助悬剂、矫味剂、粘合剂、崩解剂。
2.根据权利要求1所述一种阿立哌唑口服干混悬剂，其特征在于：含有主药（0.1%~1%），填充剂(30%~95%)、助悬剂(0.1%~2%)、矫味剂（0.3%~15%）、粘合剂（1～20％）、崩解剂（0～20％）等其它药学上可接受的载体。
3.根据权利要求1和2所述阿立哌唑口服干混悬剂，其特征在于：所述填充剂包括木糖醇、乳糖、庶糖、淀粉、甘露醇中的一种或几种混合物。
4.根据权利要求1和2所述阿立哌唑口服干混悬剂，其特征在于：所述助悬剂包括选黄原胶、二氧化硅、聚维酮、羧甲基纤维素钠、交联羧甲基纤维素钠等其中的一种或多种。
5.根据权利要求1和2所述阿立哌唑口服干混悬剂，其特征在于：所述矫味剂选三氯蔗糖、阿斯巴甜、糖精钠、蔗糖、木糖醇、甘露醇、香草香精、草莓香精、蓝莓香精、橙香精的一种或多种。
6.根据权利要求1和2所述阿立哌唑口服干混悬剂，其特征在于：所述粘合剂选自糊精浆、淀粉浆、PVPK30、羟丙甲纤维素或羧甲基纤维素钠等中的一种或者几种的混合物。
7.根据权利要求1和2所述阿立哌唑口服干混悬剂，其特征在于：所述崩解剂包括羧甲基淀粉钠，交联聚维酮等中的一种或者几种的混合物。
8.根据权利要求1、2所述阿立哌唑口服干混悬剂，其特征在于：所述干混悬剂可用凉水或开水冲服，可以随冲随服。
9.根据权利要求1阿立哌唑口服干混悬剂，其制备方法包括如下步骤：
1）将所述阿立哌唑、填充剂粉碎过100目筛备用；
2）将所述阿立哌唑及上述药学辅料填充剂、助悬剂混合均匀后加入粘合剂搅拌制粒，50℃干燥，整粒，分级得颗粒备用；
3）将矫味剂、崩解剂与上述2）中制备好的颗粒混合即得。
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