CN113230235B - 含地氯雷他定的复方缓释胶囊及其制备方法 - Google Patents
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Abstract
本申请提供了一种含地氯雷他定的复方缓释胶囊,其中地氯雷他定以微片形式存在,并与苹果酸和水杨酸熔融混合;本申请的复方缓释胶囊可以有效解决胃酸不足情况下氯雷他定溶出速度慢的问题。
Description
技术领域
本申请属于抗过敏药物领域和药剂领域,具体的,本申请提供了一种含地氯雷他定的复方缓释胶囊。
背景技术
氯雷他定(Loratadine)为第二代组胺H1-受体拮抗剂,具有选择性的对抗外周受体的作用,临床常以片剂、混悬液、胶囊等剂型用于过敏性皮炎、过敏性结膜炎、过敏性鼻炎、花粉症和荨麻疹等的治疗。将氯雷他定作为常释成分与缓释成分硫酸伪麻黄碱组合后(如先灵葆雅的开瑞能)用于缓解过敏性鼻炎和感冒症状也有良好的效果,此类缓释剂一般每24小时服用一次。
氯雷他定在pH2左右的胃酸中溶解迅速,但其溶解性能,特别是非强酸性溶液中的溶解性能不佳,造成在胃液pH低的情况下(例如胃部疾病、饮水过多、饭后服用等情况,此类情况在数日中多次服用的情况下会相当常见)不能快速溶出发挥作用。
针对此问题,发明人发现氯雷他定与适合的固体酸(如柠檬酸、苹果酸)熔融混合,为地氯雷他定的溶解/溶出制造适合的酸性环境可以明显优化氯雷他定的高pH溶出性能,更好地适应胃酸不足患者的需求,并基于此发现申请了片剂和混悬剂专利。随后,发明人尝试将此技术用于改进先前研制的氯雷他定和伪麻黄碱的复方缓释胶囊(CN200410025666.9),以改进此复方胶囊的性能,但实际溶出实验和血药浓度实验中均未取得预期的效果。
发明内容
如上所述,申请人将熔融氯雷他定和苹果酸用于氯雷他定和伪麻黄碱的复方缓释胶囊时未实现类似片剂中的快速溶出效果。为解决此问题,申请人尝试了不同的有机酸种类和辅料配方,发现熔融的有机酸中进一步加入水杨酸并在素片成分中加入少量琼脂粉可以有效的解决这一问题。
一方面,本申请提供了一种地氯雷他定和硫酸伪麻黄碱的复方缓释胶囊,其特征在于,每胶囊中包含地氯雷他定2.5mg、硫酸伪麻黄碱120mg,地氯雷他定与有机酸熔融混合。
进一步地,所述有机酸为选自苹果酸、柠檬酸、水杨酸中的一种或多种。
进一步地,所述有机酸为苹果酸和水杨酸。
进一步地,地氯雷他定、苹果酸、和水杨酸以2:1:1的质量比熔融混合。
进一步地,所述熔融混合为在160摄氏下加热至熔融,维持熔融状态5分钟。
进一步地,所述胶囊中的地氯雷他定存在于微片中。
进一步地,微片包含琼脂。
进一步地,琼脂为微片素片质量的1%。
进一步地,微片素片的配方为:熔融混合的质量比2:1:1的地氯雷他定、苹果酸和水杨酸50g、淀粉260g、磷酸氢钙80g、聚维酮K30 10g、羧甲基淀粉钠85g、琼脂5g、微粉硅胶5g、硬脂酸镁5g;制备方法为:原料过筛;将熔融混合的地氯雷他定和苹果酸、淀粉、磷酸氢钙和一半羧甲基淀粉钠在配制10%的聚维酮K30醇溶液中混合;制成软材,过筛制粒;烘干整粒,加入剩余的羧甲基淀粉钠、琼脂、微粉硅胶、硬脂酸镁;压制成50mg素片,硬度3kg;以尤特奇E100 12.5g、硬脂酸镁5g、PEG6000 1g、水2g、乙醇160g配制包衣液并包衣素片。
另一方面,本申请提供了上述复方缓释胶囊在制备治疗过敏性鼻炎和感冒中的用途。
本申请中的辅料不限于实施例中实际使用的种类,本领域技术人员可以根据具体需要和规定使用各种常规药用辅料,包括但不限于微晶纤维素、果胶、滑石粉、玉米淀粉等。可以根据药剂学领域技术人员的常识和简单实验选用其他类似性能的赋形剂或溶剂取代本申请实施例中的辅料,各种赋形剂和溶剂可以选用各厂家的市售产品或生产厂家自制产品。
本申请的复方缓释胶囊可用于治疗治疗各种氯雷他定/伪麻黄碱定已知/待发现的可以治疗的疾病,包括但不限于荨麻疹、瘙痒性皮肤病、过敏性皮肤病、过敏性鼻炎、发热、感冒等或制备治疗上述疾病的药品。
附图说明
图1为多种产品的血药浓度曲线变化图。
具体实施方式
主要试剂和仪器
地氯雷他定、硫酸伪麻黄碱:海南普利制药股份有限公司自制;
苹果酸:安徽山河药用辅料股份有限公司;
琼脂粉:西安晋湘药用辅料有限公司;
其他药用辅料(包括蔗糖型药用微丸丸芯产品):自制或购自有相关资质的企业如安徽山河药用辅料股份有限公司、连云港德邦精细化工有限公司、湖州展望药业有限公司、FMC等。
实施例1 地氯雷他定和硫酸伪麻黄碱的复方缓释胶囊的制备
参照CN200410025666.9(此申请申请人为本申请人企业董事长)的方法制备地氯雷他定和硫酸伪麻黄碱的复方缓释胶囊(以下简称为产品):
按10000粒胶囊计算,配方和制备过程如下:
地氯雷他定微片:
熔融混合的地氯雷他定、苹果酸和水杨酸(将质量比2:1:1的地氯雷他定、苹果酸、和水杨酸混匀后在160摄氏下加热至熔融,维持熔融状态5分钟)50g、淀粉260g、磷酸氢钙80g、聚维酮K30 10g、羧甲基淀粉钠85g、琼脂5g、微粉硅胶5g、硬脂酸镁5g。
制备过程为:
原料过筛;将熔融混合的地氯雷他定和苹果酸、淀粉、磷酸氢钙和一半羧甲基淀粉钠在配制10%的聚维酮K30醇溶液中混合;制成软材,过筛制粒;烘干整粒,加入剩余的羧甲基淀粉钠、琼脂、微粉硅胶、硬脂酸镁;压制成50mg素片,硬度3kg;配制包衣液(尤特奇E10012.5g、硬脂酸镁5g、PEG6000 1g、水2g、乙醇160g)并包衣素片。
硫酸伪麻黄碱缓释微丸:
蔗糖型药用微丸丸芯600g、硫酸伪麻黄碱1000g、聚维酮K30 60g、羟丙甲纤维素10g、75%乙醇1400mL。
制备过程为:
以75%乙醇溶解硫酸伪麻黄碱、聚维酮K30和羟丙甲纤维素;将溶液侧喷加载到蔗糖型药用微丸丸芯表面并顶喷干燥,成素丸;配制包衣液1(Aquacoat ECD 570mL、柠檬酸三乙酯25g、水550mL,混合3小时),侧喷加载到素丸表面并顶喷干燥,成第一层包衣微丸;配制包衣液2(Aquacoat ECD 570mL、柠檬酸三乙酯25g、水550mL,硫酸伪麻黄碱200g,混合3小时),侧喷加载到第一层包衣微丸表面并顶喷干燥成第二层包衣微丸;60摄氏度衣膜固化。
复方胶囊:
将得到的地氯雷他定包衣片和硫酸伪麻黄碱缓释微丸装入明胶胶囊壳中,每粒胶囊含地氯雷他定2.5mg、硫酸伪麻黄碱120mg。
同时参照上述方法在上述配方的基础上分别做出以下变化制备对照产品:以1:1熔融混合苹果酸的地氯雷他定为原料制备对照产品1;不熔融混合任何有机酸的氯雷他定为原料制备对照产品2;不加入琼脂制备对照产品3(制备上述产品时适量微调其他辅料用量以保障胶囊中地氯雷他定和硫酸伪麻黄碱含量不变)。
参比药剂选用先灵葆雅的开瑞能,每片含氯雷他定5mg、硫酸伪麻黄碱120mg。
实施例2 复方缓释胶囊溶出实验
含量测定:参照中国药典2010年版第二部,附录VD以及“地氯雷他定的生物利用度研究”部分的HPLC法:使用安捷伦1100高效液相色谱仪***,安捷伦C18柱(4.6mm×150mm、5μm);流动相为乙腈:20毫摩尔/升醋酸铵缓冲液:1%甲酸80:20:3,流速:0.5毫升/分钟,柱温20摄氏度,检测波长247nm。
参考中国药典(2010版第二部附录XC的方法)进行地氯雷他定溶出实验:500毫升溶出介质,50转/分钟,于5、10、15、30分钟时,取溶液5毫升(补加等量溶出介质),滤过,取滤液HPLC检测;称取干燥至恒重的地氯雷他定对照品适量,加溶出介质溶解并定量稀释成含氯雷他定10微克/毫升的溶液作为对照品。溶出仪为天津市天大天发科技发展有限公司生产。结果如下:
pH 2的盐酸中溶出效果
样品 | 5分钟(%) | 10分钟(%) | 20分钟(%) | 30分钟(%) |
产品 | 94.1 | 96.7 | 100.1 | 100.5 |
对照产品1 | 93.7 | 95.8 | 100.2 | 100.2 |
对照产品2 | 92.9 | 93.9 | 99.9 | 99.9 |
对照产品3 | 93.4 | 94.2 | 99.7 | 100.2 |
参比药剂 | 95.1 | 96.9 | 100.3 | 100.4 |
可见在模拟一般胃液的pH 2的环境下,各种药剂均能实现快速溶出。
pH 4.5的PBS缓冲液中溶出效果
样品 | 5分钟(%) | 10分钟(%) | 20分钟(%) | 30分钟(%) |
产品 | 93.7 | 95.9 | 99.3 | 100.1 |
对照产品1 | 59.8 | 63.7 | 71.2 | 79.4 |
对照产品2 | 55.7 | 62.1 | 69.8 | 74.2 |
对照产品3 | 73.4 | 77.4 | 79.6 | 88.1 |
参比药剂 | 55.7 | 64.9 | 72.0 | 80.2 |
pH 6.8的纯净水中溶出效果
样品 | 5分钟(%) | 10分钟(%) | 20分钟(%) | 30分钟(%) |
产品 | 69.6 | 74.8 | 83.2 | 92.8 |
对照产品1 | 47.8 | 57.4 | 63.5 | 69.4 |
对照产品2 | 39.3 | 47.4 | 56.8 | 64.2 |
对照产品3 | 63.3 | 72.7 | 74.5 | 82.2 |
参比药剂 | 44.9 | 54.7 | 59.2 | 66.1 |
在pH为4.5的情况下,除产品之外的其他对照和参比药品的溶解性能都受到了明显的影响,除对照产品3外,其他药剂(包括熔融混合苹果酸的对照产品1)在30分钟后溶出都仍然达不到80%。这样的情况在pH 6.7的情况下更为严重。pH 4-7的胃酸pH在大量饮水、进食或疾病情况下都可能出现,溶出效果变差意味着这些情况下药剂中的氯雷他定起效时间明显变慢,不能充分适应治疗过敏、感冒、鼻炎等问题的要求。
我们认为相比先前片剂复方胶囊产品中的溶出效果变差的问题可能源于苹果酸和最初溶出的一部分硫酸伪麻黄碱在氯雷他定片芯附近的局部环境中有沉淀/成盐倾向而使得苹果酸无法形成类似单独氯雷他定片剂中预期的酸性环境。熔融部分其他有机酸减少了这种沉淀/成盐倾向,压片中加入琼脂粉的效果可能源于其成膜性能(推测的机理尚未安排详细验证)。
实施例3 服用复方缓释胶囊后的血药浓度变化
为上述药物产品和参比药剂征集20名男性志愿受试者(年龄22-29岁,体重59-78kg)。受试者经常规体检确认心、肝、肺功能正常,主要相关血生化指标正常,无重大疾病或病史。受试前1个月内未使用过其他药物(部分志愿者用于其他剂型实验,并非全部用于复方缓释胶囊)。
受试者随机分为4组(每组3人),分别在进食面包250g并饮水300mL后服用产品、对照产品1、对照产品3的复方缓释胶囊2粒,或开瑞能1片;另有2人在空腹情况(未进食8h,未饮水2小时以上)下服用开瑞能1片。
在服药前以及服药后10、20、30、40、60分钟取肘静脉血5mL,离心3000转15分钟分离血浆贮存于零下20摄氏度冰箱中,作为分析样品检测血药浓度。
具体结果见图1所示:虽然差异不及溶出实验明显,但仍然可以看出本申请产品的在进食饮水后的血药浓度曲线已经接近空腹服用时的开瑞能水平,明显由于在进食饮水后的两种对照以及开瑞能。本申请的产品有望实现在更宽泛的服用条件下实现良好的过敏、感冒、鼻炎等治疗效果。
Claims (3)
1.一种含地氯雷他定的复方缓释胶囊,其特征在于,每个胶囊中包含地氯雷他定2.5mg、硫酸伪麻黄碱120mg;所述胶囊中的地氯雷他定存在于微片中,所述微片素片的配方为:每10000片中含50g熔融混合的质量比2:1:1的地氯雷他定、苹果酸和水杨酸、淀粉260g、磷酸氢钙80g、聚维酮K30 10g、羧甲基淀粉钠85g、琼脂5g、微粉硅胶5g、硬脂酸镁5g。
2.根据权利要求1所述的胶囊,所述胶囊中的硫酸伪麻黄碱存在于缓释微丸中,所述微丸的制备过程为:微丸原料为蔗糖型药用微丸丸芯600g、硫酸伪麻黄碱1000g、聚维酮K3060g、羟丙甲纤维素10g、75%乙醇1400mL;以75%乙醇溶解硫酸伪麻黄碱、聚维酮K30和羟丙甲纤维素;将溶液侧喷加载到蔗糖型药用微丸丸芯表面并顶喷干燥,成素丸;配制包衣液1:Aquacoat ECD 570mL、柠檬酸三乙酯25g、水550mL,混合3小时;侧喷加载到素丸表面并顶喷干燥,成第一层包衣微丸;配制包衣液2:Aquacoat ECD 570mL、柠檬酸三乙酯25g、水550mL,硫酸伪麻黄碱200g,混合3小时;侧喷加载到第一层包衣微丸表面并顶喷干燥成第二层包衣微丸;60摄氏度下衣膜固化。
3.根据权利要求1或2所述的复方缓释胶囊在制备治疗过敏性鼻炎或感冒的药物中的用途。
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1246794A (zh) * | 1997-02-07 | 2000-03-08 | 塞普拉科公司 | 脱乙氧羰基氯雷他定的无乳糖、非吸湿性及无水的药物组合物 |
CN1593413A (zh) * | 2004-07-01 | 2005-03-16 | 范敏华 | 一种复方缓释胶囊及其制备方法 |
CN102940617A (zh) * | 2012-11-21 | 2013-02-27 | 北京润德康医药技术有限公司 | 一种地氯雷他定口腔分散膜剂 |
CN104983708A (zh) * | 2015-06-24 | 2015-10-21 | 万特制药(海南)有限公司 | 一种地氯雷他定硫酸伪麻黄碱缓释片及其制备方法 |
CN109846843A (zh) * | 2019-04-15 | 2019-06-07 | 浙江普利药业有限公司 | 地氯雷他定口腔崩解片 |
CN109925289A (zh) * | 2019-04-11 | 2019-06-25 | 海南普利制药股份有限公司 | 地氯雷他定分散片 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AR025711A1 (es) * | 1999-09-21 | 2002-12-11 | Schering Corp | El uso de la desloratadina para la preparacion de un medicamento para tratar y prevenir estados alergicos e inflamatorios |
AU2276801A (en) * | 1999-12-20 | 2001-07-03 | Schering Corporation | Extended release oral dosage composition |
EP1507774A1 (en) * | 2003-03-12 | 2005-02-23 | Biogal Gyogyszergyar Rt. | Processes for preparation of polymorphic forms of desloratadine |
US20070014855A1 (en) * | 2005-07-12 | 2007-01-18 | Rahul Gawande S | Stable desloratadine compositions |
WO2008008434A1 (en) * | 2006-07-11 | 2008-01-17 | Mutual Pharmaceutical Company, Inc. | Controlled-release formulations |
CN1994278A (zh) * | 2006-11-21 | 2007-07-11 | 北京润德康医药技术有限公司 | 一种以对乙酰氨基酚、地雷他定和硫酸伪麻黄碱为活性成分的缓释制剂及其制备方法 |
EP2164470A1 (en) * | 2007-05-11 | 2010-03-24 | ratiopharm GmbH | Pharmaceutical composition comprising desloratadine |
-
2021
- 2021-04-15 CN CN202110404015.4A patent/CN113230235B/zh active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1246794A (zh) * | 1997-02-07 | 2000-03-08 | 塞普拉科公司 | 脱乙氧羰基氯雷他定的无乳糖、非吸湿性及无水的药物组合物 |
CN1593413A (zh) * | 2004-07-01 | 2005-03-16 | 范敏华 | 一种复方缓释胶囊及其制备方法 |
CN102940617A (zh) * | 2012-11-21 | 2013-02-27 | 北京润德康医药技术有限公司 | 一种地氯雷他定口腔分散膜剂 |
CN104983708A (zh) * | 2015-06-24 | 2015-10-21 | 万特制药(海南)有限公司 | 一种地氯雷他定硫酸伪麻黄碱缓释片及其制备方法 |
CN109925289A (zh) * | 2019-04-11 | 2019-06-25 | 海南普利制药股份有限公司 | 地氯雷他定分散片 |
CN109846843A (zh) * | 2019-04-15 | 2019-06-07 | 浙江普利药业有限公司 | 地氯雷他定口腔崩解片 |
Non-Patent Citations (3)
Title |
---|
优选氯雷他定胶囊制粒工艺;徐鹏等;《机电信息》;20150915(第26期);全文 * |
复方氯雷他定缓释微丸胶囊的药代动力学与相对生物利用度;田媛等;《中国药科大学学报》;20060225(第01期);全文 * |
氯雷他定伪麻黄碱双层缓释片的制备及体外释药的影响因素;胡建平等;《广西中医学院学报》;20041215(第04期);全文 * |
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