CN118059070A - 一种氯雷他定口溶膜剂及其制备方法 - Google Patents
一种氯雷他定口溶膜剂及其制备方法 Download PDFInfo
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Abstract
本发明属于医药技术领域，具体涉及一种氯雷他定口溶膜剂及其制备方法，所述氯雷他定口溶膜包括，平均粒径（D90）为3~8μm的氯雷他定、高分子成膜材料、增稠剂、增塑剂、矫味剂。本发明制备的氯雷他定口溶膜剂外观良好、韧性较好、药物含量均匀、可迅速溶化，起效快，用于缓解与过敏性鼻炎有关的症状。
Description
技术领域
本发明主要涉及医药制药技术领域，具体涉及一种氯雷他定口溶膜剂及其制备方法
背景技术
氯雷他定(Loratadine)，化学名为4-(8-氯-5,6-二氢-11H-苯并[5,6]环庚并[1,2-B]吡啶-11-亚基)-1-哌啶羧酸乙酯，属于三环类长效口服第二代抗组胺药。临床上主要用于缓解与过敏性鼻炎有关的症状，如喷嚏、流涕及鼻痒、鼻塞以及眼部痒及烧灼感。亦适用于缓解慢性荨麻疹、瘙痒性皮肤病及其他过敏性皮肤病的症状及体征。在治疗剂量范围内，无心脏毒性作用，不易通过血脑屏障，无中枢镇静作用，是抗组胶药物中使用较多的品种。
氯雷他定最初由美国先灵葆雅公司研发，FDA于1993批准上市，2002年FDA批准氯雷他定由处方药转换为非处方药(OTC)，目前市售主要剂型有普通片剂、颗粒、糖浆、泡腾片、咀嚼片、胶囊、分散片、口崩片等。普通口服制剂患者服用时，必须用水送服或本身就为液体制剂，不仅服用不方便，不易吞服，而且吸收较慢。
口溶膜是一种在口腔内快速溶解的口服药物薄膜制剂。与其他种类的口服固体制剂相比，口溶膜制剂具有诸多优势，例如外观新颖、口味独特、服用方便、口腔内快速溶解、不易吐出、吸收快速、迅速起效、辅料用量少、工艺简单、吞咽方便、不会引起窒息等等。鉴于口溶膜制剂具有诸多优点，因此已经成为国内外制剂研发的热点领域之一。目前世界上已经上市了十几种口溶膜制剂，例如昂丹司琼口溶膜、右美沙芬口溶膜、利培酮口溶膜、盐酸多奈哌齐口溶膜等等。
氯雷他定为BCS 2类药物，在纯化水中几乎不溶，呈疏水性，难以分散，即使通过搅拌均匀地分散在水中，静置后又聚集成团，极易造成成品含量和含量均匀度不合格，临床使用上存在生物利用度低等问题，因此其产品开发最大的难度在于氯雷他定的低溶解性及膜的含量均一性。
发明内容
针对以上技术难度，本发明提供了具有改善药物溶解度和含量均一性的氯雷他定口溶膜：本发明通过控制氯雷他定口溶膜中原料药的粒径，以提高药物的溶出，可使其在口腔中达到理想的溶出速度，通过搅拌和均质处理，使得原料药分散更均匀，解决了原料药极易团聚的现象，制得的口溶膜剂，外观良好、药物含量均匀、溶出度高、起效快，方便患者携带和口服。
本发明是通过以下技术方案实现，制备步骤如下：
a)采用气流粉碎机将氯雷他定原料药粉碎，使得原料药的平均粒径(D90)为3～8μm，备用；
b)将增稠剂加入到纯化水中，使增稠剂完全溶解；
c)将氯雷他定原料加入上述溶液中，使其分散均匀；
d)将其他物料加入上述溶液中，搅拌并均质，制成胶液；
e)将胶液置真空环境下进行脱气；
f)将脱气后的胶液涂至薄膜上，干燥；
g)将干燥后的药膜置干薄膜包装机中，裁切后进行包装。
具体实施方式
本发明得到的氯雷他定口溶膜具备生产工艺简单、易于服用、便于携带的特点。下面将对本发明实施例中的技术方案进行清楚、完整的描述。
所描述的实施例仅仅是本发明的一部分实施例，而不是全部实施例。实施例仅用于例证的目的，不限制本发明的范围。如无特别说明，以下实施例中所用试剂均为普通市售试剂，所用方法均为本领域常规方法。
实施例1～3：氯雷他定口溶膜
表1实施例1～3氯雷他定口溶膜剂处方
| 处方组成 | 实施例1 | 实施例2 | 实施例3 |
| 氯雷他定(平均粒径D90为3.44μm) | 3g(10.0％) | —— | —— |
| 氯雷他定(平均粒径D90为5.99μm) | —— | 3g(10.0％) | —— |
| 氯雷他定(平均粒径D90＜7.72μm) | —— | —— | 3g(10.0％) |
| 羟丙基甲基纤维素(HPMC) | 12.0g(40.0％) | 12.0g(40.0％) | 12.0g(40.0％) |
| 聚乙烯吡咯烷酮(PVP) | 4.5g(15％) | 4.5g(15％) | 4.5g(15％) |
| 黄原胶 | 2.3g(7.7％) | 2.3g(7.7％) | 2.3g(7.7％) |
| 泊洛沙姆 | 4.7g(15.7％) | 4.7g(15.7％) | 4.7g(15.7％) |
| 甘油 | 2g(6.7％) | 2g(6.7％) | 2g(6.7％) |
| 安赛蜜 | 1.0g(3.3％) | 1.0g(3.3％) | 1.0g(3.3％) |
| 阿司巴坦 | 0.5g(1.6％) | 0.5g(1.6％) | 0.5g(1.6％) |
| 纯化水 | 100g | 100g | 100g |
实施例1～3制备工艺：
(1)采用气流粉碎机将氯雷他定原料药粉碎，使得原料药的平均粒径(D90)为3～8μm，备用；
(2)首先增稠剂黄原胶、泊洛沙姆加入到纯化水中，加热搅拌使其完全溶解(3)再将气流粉碎后的氯雷他定原料加入上述溶液中，使用匀质机搅拌均质，使原料药分散均匀；
(4)然后将处方中其他物料加入上述溶液中，搅拌并均质，制成胶液，再将胶液置真空干燥箱中，在真空环境下脱气；
(5)最后将脱气后的胶液涂至薄膜制作机上，进行涂布干燥，干燥后，进行裁切和包装。
实施例4～6：氯雷他定口溶膜
表2实施例4～6氯雷他定口溶膜剂处方
实施例4～6制备工艺：
(1)采用气流粉碎机将氯雷他定原料药粉碎，使得原料药的平均粒径D90为5.99μm，备用；
(2)首先增稠剂加入到纯化水中，加热搅拌使其完全溶解
(3)再将气流粉碎后的氯雷他定原料加入上述溶液中，使用匀质机搅拌均质，使原料药分散均匀；
(4)然后将处方中其他物料加入上述溶液中，搅拌并均质，制成胶液，再将胶液置真空干燥箱中，在真空环境下脱气；
(5)最后将脱气后的胶液涂至薄膜制作机上，进行涂布干燥，干燥后，进行裁切和包装。
(6)
对比实施例1～3：氯雷他定口溶膜
表3对比实施例1～3氯雷他定口溶膜剂处方
| 处方组成 | 对比实施例1 | 对比实施例2 | 对比实施例3 |
| 氯雷他定(平均粒径D90为13.47μm) | 3g(10.0％) | —— | —— |
| 氯雷他定(平均粒径D90为21.89μm) | —— | 3g(10.0％) | —— |
| 氯雷他定(平均粒径D90＜5.99μm) | —— | —— | 3g(10.0％) |
| 羟丙基甲基纤维素(HPMC) | 12.0g(40.0％) | 17.8g(59.3％) | 9.0g(30.0％) |
| 聚乙烯吡咯烷酮(PVP) | 4.5g(15％) | —— | 4.5g(15％) |
| 黄原胶 | 2.3g(7.7％) | —— | 2.3g(7.7％) |
| 泊洛沙姆 | 4.7g(15.7％) | 4.7g(15.7％) | 4.7g(15.7％) |
| 甘油 | 2g(6.7％) | 3.0g(10.0％) | 5g(16.7％) |
| 安赛蜜 | 1.0g(3.3％) | 1.0g(3.3％) | 1.0g(3.3％) |
| 阿司巴坦 | 0.5g(1.6％) | 0.5g(1.6％) | 0.5g(1.6％) |
| 纯化水 | 100g | 100g | 100g |
对比实施例1～3的制备工艺同实施例1。
实验结果及结论：
1、外观评价，试验结果如表4：
表4外观评价检测结果
2、含量均匀度检查，试验结果如表5：
3、溶出曲线检查，试验结果如表6：
实验结论：
(1)通过实施例1～4与对比实施例1和2的检测结果比较，原料药的粒径影响样品的溶出，随着原料药的粒径逐渐增大，溶出相应变慢且由于粒径变大，原料药的分散均匀性变差，导致样品表面有气泡，不平整，影响产品的外观，因此在本发明中因严格控制原料药的粒径。
(2)通过实施例1～6与对比实施例2发现，增塑剂的用量超出了本权利要求的用量范围后，样品的韧性不合格，可见应合理控制增塑剂的用量。
Claims (7)
1.一种氯雷他定口溶膜剂及其制备方法，其特征在于，包含由以下占膜剂重量百分比的各组分组成：
氯雷他定＜20%
高分子成膜材料40%~60%
增稠剂19%~32%
增塑剂6%~10%
矫味剂0.5%~5%。
2.根据权利要求1所述的氯雷他定口溶膜，其特征在于，氯雷他定原料药的平均粒径（D90）为3~8μm。
3.根据权利要求1所述的氯雷他定口溶膜，其特征在于，所述高分子成膜材料包括羟丙基甲基纤维素(HPMC)、羟丙基纤维素(HPC)、聚乙烯吡咯烷酮(PVP)、聚氧乙烯(PEO)中的一种或多种。
4.根据权利要求1所述的氯雷他定口溶膜，其特征在于，所述增稠剂选自黄原胶、卡拉胶、阿拉伯胶、羧甲基纤维素钠、泊洛沙姆、卡波姆中的一种或多种。
5.根据权利要求1所述的氯雷他定口溶膜，其特征在于，所述增塑剂选自柠檬酸三乙酯、甘油或聚乙二醇中的一种或多种。
6.根据权利要求1所述的氯雷他定口溶膜，其特征在于，所述矫味剂为安赛密、三氯蔗糖、阿司巴坦中的一种或多种。
7.一种如权利要求1所述的氯雷他定口溶膜的制备方法，其特征在于，包括如下步骤：
采用气流粉碎机将氯雷他定原料药粉碎，使得原料药的平均粒径（D90）为3~8μm，备用；
将增稠剂加入到纯化水中，使增稠剂完全溶解；
将氯雷他定原料加入上述溶液中，使其分散均匀；
将其他物料加入上述溶液中，搅拌并均质，制成胶液；
将胶液置真空环境下进行脱气；
将脱气后的胶液涂至薄膜上，干燥；
将干燥后的药膜置干薄膜包装机中，裁切后进行包装。
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