CN116585314A - 一种地氯雷他定口服制剂及其制备工艺 - Google Patents
一种地氯雷他定口服制剂及其制备工艺 Download PDFInfo
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Abstract
本发明公开了一种地氯雷他定口服溶液制剂及其制备工艺，属于药物制剂领域。组合物包括：作为活性成分的地氯雷他定和药学上可接受的载体。本发明解决了地氯雷他定在水中溶解度低及稳定性差的问题，口感适宜，适用于儿童给药，用于缓解1‑11儿童、12岁以上青少年及成人的慢性特发性荨麻疹及过敏性鼻炎的全身及局部症状。
Description
技术领域
本发明属于药物制剂领域，具体涉及一种地氯雷他定口服制剂及其制备工艺。
背景技术
地氯雷他定为第二代新型H1抗组胺药，与第一代相比，无中枢神经系统和心脏毒性，具有安全性高、起效快、作用持久等优势，是荨麻疹和过敏性鼻炎的一线治疗药物。
由于工业化和生活方式的改变，过敏性疾病已成为21世纪常见疾病之一，全球儿童过敏性鼻炎的发病率呈逐年递增的趋势，我国最新的流行病学调查提示儿童过敏性鼻炎的发病率为8-20％之间，因此为满足临床需求，需要开发一款适用于儿童用药的地氯雷他定相关制剂产品。口服液体制由于其易于吞咽，口感适宜等优点，适用于儿童给药。但是，地氯雷他定在水中的溶解度小，且上市口服溶液在长期贮藏过程中会发生药物的降解。
现有上市产品中多加入丙二醇作为增溶剂，用以提高产品的溶解度，该方式虽然解决了地氯雷他定在水系溶液中溶解度低的问题，但处方中加入丙二醇，增加了该过敏人群的过敏机率，受众人群减少，且未解决地氯雷他定降解的问题，因此一种不含丙二醇，且质量稳定的地氯雷他定口服液体制剂有待开发。
发明内容
本发明提供了一种地氯雷他定口服溶液制剂及其制备工艺，以期得到一种不含丙二醇，且口感适宜、质量稳定的产品。
一种地氯雷他定口服制剂，包括活性成分地氯雷他定以及药学上可接受的辅料载体。其中，药学上可接受的辅料载体包括两亲性材料、增稠剂、稳定剂、甜味剂、矫味剂以及溶剂等。
优选的，一种地氯雷他定口服液体制包含如下组分：以100ml计，含地氯雷他定0.03-0.07g、两亲性材料3-5g、助溶剂3-5g、稳定剂0.1-0.2g、增稠剂0.2-0.5g、甜味剂0.05-0.1g、矫味剂0.3-0.5g及适宜水。
其中，所述两亲性材料为大豆卵磷脂、蛋黄卵磷脂一种或两种；所述增稠剂为羟丙甲纤维素、羟乙纤维素中的一种或两种；所述稳定剂为生育酚；所述甜味剂为三氯蔗糖、阿斯巴甜中的一种或两种、矫味剂为石榴香精；所述助溶剂为胆酸盐类非离子表面活性剂；所述溶剂为乙醇、丙酮中的一种。
本发明的另一目的是提供了一种地氯雷他定口服制剂的制备工艺，包括以下步骤：
(1)取地氯雷他定、卵磷脂、胆酸盐、生育酚加入有机溶剂搅拌溶解，旋转蒸发除去有机溶剂，形成含药膜；所述溶剂为乙醇、丙酮中的一种；
(2)取纯化水适量，加入甜味剂、矫味剂，搅拌溶解，备用；
(3)将(2)所得溶液加入(1)中水化，超声分散均匀，加入适量的增稠剂，搅拌混匀，定容混匀，过滤即得。
本发明取得以下有益效果：
(1)产品中不含稳定剂及增溶剂丙二醇，为丙二醇过敏患者提供了用药可能性，增加了临床受众人群。
(2)产品中使用少量甜味剂改善口感，减少了蔗糖、葡萄糖等甜味剂使用，降低儿童龋齿发生机率。
(3)产品中加入稳定剂生育酚，有效减少了地氯雷他定口服溶液在长期放置过程中降解，提高了用药安全性。
(4)使用人体内源性物质卵磷脂及胆酸盐作为药物载体材料制备成混合胶束制剂，其安全性高，且提高了地氯雷他定在水系溶液中的溶解度，解决了其溶解度低的问题，更方便临床用药。
具体实施方式
为使本发明的目的、技术方案和优点更加清楚，下面将对本发明实施例中的技术方案进行清楚、完整地描述，以下各实施例仅用以说明本发明的技术方案，而非对其限制。显然，所描述的实施例是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
实施例1
处方：
工艺：
(1)取地氯雷他定0.03g、蛋黄卵磷脂3g、胆酸钠3g、生育酚0.1g加入30ml乙醇搅拌溶解，旋转蒸发除去乙醇，形成含药膜；
(2)取纯化水适量，加入三氯蔗糖0.05g、香精0.3g，搅拌溶解，备用；
(3)将(2)所得溶液加入(1)中水化，超声分散均匀，加入羟乙纤维素0.2g，搅拌混匀，定容混匀，过滤即得。
实施例2
处方：
| 组分 | 含量 |
| 地氯雷他定 | 0.07g |
| 蛋黄卵磷脂 | 5g |
| 胆酸钠 | 5g |
| 生育酚 | 0.2g |
| 阿斯巴甜 | 0.1g |
| 香精 | 0.5g |
| 羟丙甲纤维素 | 0.5g |
| 纯化水 | 定容100mL |
工艺：
(1)取地氯雷他定0.07g、大豆卵磷脂5g、胆酸钠5g、生育酚0.2g加入65ml丙酮搅拌溶解，旋转蒸发除去丙酮，形成含药膜；
(2)取纯化水适量，加入阿斯巴甜0.1g、香精0.5g，搅拌溶解，备用；
(3)将(2)所得溶液加入(1)中水化，超声分散均匀，加入羟丙甲纤维素0.5g，搅拌混匀，定容混匀，过滤即得。
实施例3
处方：
工艺：
(1)取地氯雷他定0.05g、大豆卵磷脂4g、胆酸钠4g、生育酚0.2g加入50ml丙酮搅拌溶解，旋转蒸发除去丙酮，形成含药膜；
(2)取纯化水适量，加入阿斯巴甜0.05g、香精0.4g，搅拌溶解，备用；
(3)将(2)所得溶液加入(1)中水化，超声分散均匀，加入羟乙纤维素0.5g，搅拌混匀，定容混匀，过滤即得。
对比例1
| 组分 | 含量 |
| 地氯雷他定 | 0.05g |
| 丙二醇 | 10mL |
| 枸橼酸 | 0.3g |
| 枸橼酸钠 | 0.11g |
| 蔗糖 | 10g |
| 香精 | 0.3g |
| 羟丙甲纤维素 | 0.3g |
| 纯化水 | 定容100mL |
工艺：
(1)取地氯雷他定0.05g，溶解于10ml丙二醇中；
(2)取枸橼酸0.3g、枸橼酸钠0.11g，使用纯化水搅拌溶解；
(3)将(1)所得溶液缓慢加入(2)中，搅拌混匀，加入蔗糖10g、香精0.3g，羟丙甲纤维素0.3g，搅拌混匀，定容混匀，过滤即得。
将以上所得产品进行质量对比研究，结果见下表：
Claims (10)
1.一种地氯雷他定口服制剂，其特征在于，包括以下组分：地氯雷他定，两亲性材料，助溶剂，增稠剂，稳定剂，甜味剂。
2.如权利要求1所述的口服制剂，其特征在于，还包括矫味剂。
3.如权利要求1所述的口服制剂，其特征在于，所述两亲性材料为大豆卵磷脂、蛋黄卵磷脂一种或两种。
4.如权利要求1所述的口服制剂，其特征在于，所述增稠剂为羟丙甲纤维素、羟乙纤维素中的一种或两种。
5.如权利要求1所述的口服制剂，其特征在于，所述稳定剂为生育酚。
6.如权利要求1所述的口服制剂，其特征在于，所述甜味剂为三氯蔗糖、阿斯巴甜中的一种或两种，所述助溶剂为胆酸盐类非离子表面活性剂。
7.如权利要求2所述的口服制剂，其特征在于，所述矫味剂为香精。
8.如权利要求1所述的口服制剂，其特征在于，以100ml计，含地氯雷他定0.03-0.07g、两亲性材料3-5g、助溶剂3-5g、稳定剂0.1-0.2g、增稠剂0.2-0.5g、甜味剂0.05-0.1g、矫味剂0.3-0.5g及适宜水。
9.如权利要求1-8任意一项所述口服制剂的制备工艺，其特征在于，包括以下步骤：
（1）取地氯雷他定、卵磷脂、胆酸盐、生育酚加入适量有机溶剂搅拌溶解，旋转蒸发除去有机溶剂，形成含药膜；
（2）取纯化水适量，加入甜味剂、矫味剂，搅拌溶解，备用；
（3）将（2）所得溶液加入（1）中水化，超声分散均匀，加入适量的增稠剂，搅拌混匀，定容混匀，过滤即得。
10.如权利要求9所述的制备工艺，其特征在于，包括以下步骤：
（1）取地氯雷他定0.03-0.07g、卵磷脂3-5g、胆酸钠3-5g、生育酚0.1-0.2g加入适量有机溶剂搅拌溶解，旋转蒸发除去乙醇，形成含药膜；所述卵磷脂为大豆卵磷脂和蛋黄卵磷脂中的一种；所述有机溶剂为乙醇、丙酮中的一种；
（2）取纯化水适量，加入三氯蔗糖0.05-0.1g、香精0.3-0.5g，搅拌溶解，备用；
（3）将（2）所得溶液加入（1）中水化，超声分散均匀，加入羟乙纤维素0.2-0.5g，搅拌混匀，定容至100mL混匀，过滤即得。
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