CN115300458B - 一种无糖地氯雷他定口服溶液及其制备方法 - Google Patents
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Abstract
本发明公开了一种无糖地氯雷他定口服溶液及制备方法。本发明无糖地氯雷他定口服溶液中添加了1.5％‑2.5％的大豆卵磷脂来掩盖地氯雷他定的苦味，已达到使用少量的甜味剂就可以提高制剂口感的目的。本发明的地氯雷他定口服溶液，制备方法简单，口味良好。通过稳定性试验，该口服溶液质量稳定，适合儿童服用。
Description
技术领域
本发明属于药物制剂领域，具体涉及一种无糖地氯雷他定口服溶液及其制备方法
背景技术
地氯雷他定为第二代抗组胺药氯雷他定主要活性代谢产物，为长效三环类第三代抗组胺药，可用于治疗过敏性鼻炎和过敏性鼻炎哮喘，并且有效缓解过敏性鼻炎症状，如打喷嚏、流涕、鼻痒、鼻粘膜充血\鼻塞、眼痒、流泪、眼结膜充血和上腭痒，作用可持续24小时。
仿制药参比制剂目录(第二十二批)公布欧盟上市的Merck Sharp&Dohme B.V生产的地氯雷他定口服溶液为参比制剂，目前国内上市的地氯雷他定剂型为片剂、干混悬剂、糖浆剂。对于儿童来说，地氯雷他定较为方便的服用剂型为口服溶液、干混悬剂或糖浆剂。而为了掩盖药物的苦味，往往制剂中会加入大量蔗糖，而过多摄入蔗糖会导致儿童蛀牙及高血糖，甚至引发糖尿病。
为使儿童更为健康的服用地氯雷他定口服溶液，特提出本发明。
发明内容
本发明的目的是提供一种无糖地氯雷他定口服溶液及制备方法。
本发明所提供的无糖地氯雷他定口服溶液，含有地氯雷他定、质量体积含量为1.5-2.5％的大豆卵磷脂、丙二醇、无水枸橼酸、枸橼酸钠、山梨醇、三氯蔗糖、草莓香精、纯化水。
进一步的，所述无糖地氯雷他定口服溶液，由下述质量体积百分含量(g/100ml)的原料组成：地氯雷他定0.05％、大豆卵磷脂1.5-2.5％、丙二醇8％-12％、无水枸橼酸0.033％、枸橼酸钠0.08％、山梨醇1.65％-1.69％、三氯蔗糖0.04％-0.06％、草莓香精0.01％-0.03％，余量为纯化水。
更进一步的，所述无糖地氯雷他定口服溶液，由下述质量体积百分含量(g/100ml)的原料组成：地氯雷他定0.05％、大豆卵磷脂1.5-2.5％、丙二醇10％、无水枸橼酸0.033％、枸橼酸钠0.08％、山梨醇1.67％、三氯蔗糖0.05％、草莓香精0.02％、余量为纯化水。
本发明还提供了上述无糖地氯雷他定口服溶液的制备方法，包含如下步骤：
(1)取丙二醇加热至30-50℃，加入大豆卵磷脂，溶解后加入原料药地氯雷他定，搅拌至溶解；
(2)加入60％配液量纯化水，搅拌均匀；
(3)依次加入无水枸橼酸、枸橼酸钠、山梨醇、三氯蔗糖、草莓香精，搅拌至溶解；
(4)加纯化水至全量，即得。
与现有技术相比，本发明具有如下有益效果：
该地氯雷他定口服溶液处方中加入大豆卵磷脂可较好掩饰苦味，再加入少量山梨醇及矫味剂三氯蔗糖和香精以提高口感；该制备方法过程简便、易操作，省时节能，适合工业化大生产，制备得到的口服溶液质量稳定、口味较好、更适合儿童服用。
具体实施方式
下面结合具体实施例对本发明作进一步阐述，但本发明并不限于以下实施例。所述方法如无特别说明均为常规方法。所述原材料如无特别说明均能从公开商业途径获得。
实施例1-5：
实施例1-5、对比例1无糖地氯雷他定口服溶液的处方组成如表1。
表1无糖地氯雷他定口服溶液的处方组成
| 实施例1 | 实施例2 | 实施例3 | 实施例4 | 实施例5 | 对比例1 | |
| 地氯雷他定 | 0.05g | 0.05g | 0.05g | 0.05g | 0.05g | 0.05g |
| 大豆卵磷脂 | 1.0g | 1.5g | 2.0g | 2.5g | 3.0g | / |
| 丙二醇 | 10g | 12g | 10g | 8g | 10g | 10g |
| 无水枸橼酸 | 0.033g | 0.033g | 0.033g | 0.033g | 0.033g | 0.033g |
| 枸橼酸钠 | 0.080g | 0.080g | 0.080g | 0.080g | 0.080g | 0.080g |
| 山梨醇 | 1.69g | 1.69g | 1.67g | 1.65g | 1.67g | 1.67g |
| 三氯蔗糖 | 0.05g | 0.04g | 0.05g | 0.06g | 0.06g | 0.05g |
| 草莓香精 | 0.02g | 0.01g | 0.02g | 0.03g | 0.03g | 0.02g |
| 纯化水加至 | 100ml | 100ml | 100ml | 100ml | 100ml | 100ml |
实施例1-5无糖地氯雷他定口服溶液的制备工艺相同，具体为：
(1)处方量丙二醇加热至30-50℃，加入大豆卵磷脂，溶解后加入原料药，搅拌至溶解；
(2)加入60％配液量纯化水，搅拌均匀；
(3)依次加入无水枸橼酸、枸橼酸钠、山梨醇、三氯蔗糖、草莓香精，搅拌至溶解；
(4)加纯化水至全量。
对比例1无糖地氯雷他定口服溶液的制备工艺同实施例1-5，区别在于步骤(1)中不加入大豆卵磷脂。
实施例1-5、对比例1无糖地氯雷他定口服溶液产品质量评价
1、模糊数学评价法进行口感评价
由20名评价员(身体健康，男7名，女13名，年龄23-45岁)对实施例1-5及对比例1制备的无糖地氯雷他定口服溶液的口感进行评价，根据口感调查表对所品尝的药液进行打分，汇总统计结果见下表。选择苦味、口腔余味、粘稠度、总体口感作为评价指标，权重分别为0.3、0.15、0.15、0.4；以很好(5分)、好(4分)、中(3分)、差(2分)、很差(1分)作为口感评价等级，即评语集。根据口感评定统计结果，建立矩阵，采用模糊数学评价模型进行分析。
表2口感评定结果
结果处理：
将综合评价的结果用Y表示。模糊关系综合评价集Y＝H×M，其中权重集为：H＝(0.3、0.15、0.15、0.4)，模糊矩阵为M。将表2中苦味、口腔余味、粘稠度、总体口感评价结果初一总评价人数，可得各试验的模糊矩阵。如
同理
根据模糊变换原理，采用普通矩阵乘法对各类因素的综合结果进行计算，即Y＝H×M。
如
同理Y2＝(0.15 0.5125 0.465 0.0225 0)，Y3＝(0.1675 0.645 0.2075 0 0)，Y4＝(0.14 0.735 0.1175 0.0075 0)，Y5＝(0.08 0.4075 0.3175 0.1275 0)，Y对1＝(0 0.0150.2025 0.4025 0)
将各评语集对应的分值与模糊综合评价的结果相乘、相加，得到各实施例的综合评分结果。如Q1＝0×5+0.12×4+0.08×3+0.605×2+0.195×1＝2.125，同理Q2＝4.24，Q3＝4.04，Q4＝4.0075，Q5＝3.2375，Q对1＝1.4725。
由各实施例综合评分的结果可知，综合排序为：实施例2＞3＞4＞5＞1＞对比例1，其中实施例2、3、4得分大于4分，为“好”，说明评价组对这三个实施例的口感评价认可度高，为无糖地氯雷他定口服溶液的最优处方，即加入1.5-2.5％的大豆卵磷脂的无糖地氯雷他定口服溶液的口味较好。
2、稳定性考察
将未加大豆卵磷脂的对比例1与实施例2-4进行质量对比及稳定性考察，结果如下：
表3地氯雷他定口服溶液0天检测结果
结论：本发明处方制备的含有大豆卵磷脂的无糖地氯雷他定口服溶液0天杂质水平同不加大豆卵磷脂的无糖地氯雷他定口服溶液相当。
表4地氯雷他定口服溶液光照(照度4500lx±500lx)30天试验结果
表5地氯雷他定口服溶液高温(60℃±2℃)30天试验结果
结论：影响因素试验结果表明，实施例2-4的含有大豆卵磷脂的无糖地氯雷他定口服溶液及参比制剂在光照、高温条件下，性状、pH值、有关物质均未发生显著变化，稳定性良好。且与未加入大豆卵磷脂的样品相比无明显差别。
表6地氯雷他定口服溶液长期稳定性(25℃，60％RH)12个月试验结果
结论：实施例2-4的含有大豆卵磷脂无糖地氯雷他定口服溶液及参比制剂，性状、pH值、有关物质均未发生显著变化，产品质量稳定。且与未加入大豆卵磷脂的样品相比，未发生显著变化。
实施例6-8添加大豆卵磷脂含量均匀性考察
实施例6-8无糖地氯雷他定口服溶液的处方组成如表7。
表7无糖地氯雷他定口服溶液的处方组成
| 实施例 | 6 | 7 | 8 |
| 地氯雷他定 | 1.00g | 1.00g | 1.00g |
| 大豆卵磷脂 | 30g | 40g | 50g |
| 丙二醇 | 200g | 200g | 200g |
| 无水枸橼酸 | 0.66g | 0.66g | 0.66g |
| 枸橼酸钠 | 1.60g | 1.60g | 1.60g |
| 山梨醇 | 33.4g | 33.4g | 33.4g |
| 三氯蔗糖 | 1.0g | 1.0g | 1.0g |
| 草莓香精 | 0.4g | 0.4g | 0.4g |
| 纯化水加至 | 2000ml | 2000ml | 2000ml |
实施例6-8无糖地氯雷他定口服溶液的制备工艺相同，具体为：
(1)处方量丙二醇加热至30-50℃，加入大豆卵磷脂，溶解后加入原料药，搅拌至溶解；
(2)加入60％配液量纯化水，搅拌均匀；
(3)依次加入无水枸橼酸、枸橼酸钠、山梨醇、三氯蔗糖、草莓香精，搅拌至溶解；
(4)加纯化水至全量。
(5)全量后，分别在搅拌5、10分钟时，在药液的上层、中层、下层取样对含量均匀性进行研究。
表8含量均匀性考察结果
结论：采用本发明处方及方法制备的无糖地氯雷他定口服溶液，全量后搅拌5-10分钟即可使含量均匀。
采用本发明处方及方法制备的无糖地氯雷他定口服溶液，质量稳定、口味较好、更适合儿童服用。
Claims (3)
1.一种无糖地氯雷他定口服溶液，含有地氯雷他定、丙二醇、无水枸橼酸、枸橼酸钠、山梨醇、三氯蔗糖、草莓香精、纯化水；其特征在于：所述无糖地氯雷他定口服溶液，由下述质量体积百分含量的原料组成：地氯雷他定0.05％、大豆卵磷脂1.5-2.5％、丙二醇8％-12％、无水枸橼酸0.030％-0.036％、枸橼酸钠0.07％-0.09％、山梨醇1.65％-1.69％、三氯蔗糖0.04％-0.06％、草莓香精0.01％-0.03％，余量为纯化水。
2.根据权利要求1所述的无糖地氯雷他定口服溶液，其特征在于：所述无糖地氯雷他定口服溶液，由下述质量体积百分含量的原料组成：地氯雷他定0.05％、大豆卵磷脂1.5-2.5％、丙二醇10％、无水枸橼酸0.033％、枸橼酸钠0.08％、山梨醇1.67％、三氯蔗糖0.05％、草莓香精0.02％、余量为纯化水。
3.权利要求1或2所述无糖地氯雷他定口服溶液的制备方法，包含如下步骤：
(1)取丙二醇加热至30-50℃，加入大豆卵磷脂，溶解后加入原料药地氯雷他定，搅拌至溶解；
(2)加入60％配液量纯化水，搅拌均匀；
(3)依次加入无水枸橼酸、枸橼酸钠、山梨醇、三氯蔗糖、草莓香精，搅拌至溶解；
(4)加纯化水至全量，即得。
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