CN112587493A - 一种双氯芬酸钠的口服缓释制剂及其制备方法 - Google Patents
一种双氯芬酸钠的口服缓释制剂及其制备方法 Download PDFInfo
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Abstract
本发明属于医药制剂技术领域,具体涉及一种含有双氯芬酸钠的口服缓释制剂,并公开了其制备方法:双氯芬酸钠与内层载体溶于内层溶剂中,外层载体溶于外层溶剂中,经同轴静电喷雾法制备而得双氯芬酸钠微囊,后加入填充剂混匀,制粒,加其他药用辅料压片即得,本发明创造性的将静电喷雾技术应用于双氯芬酸钠缓释制剂,缓释效果良好,可有效降低胃肠道副反应,提高了患者的顺应性,适合临床用药发展的需要。
Description
技术领域
本发明属于药物制剂领域,涉及一种双氯芬酸钠的口服缓释制剂及其制备方法。
背景技术
关节炎和类风湿性关节炎是一种累及多关节滑膜炎病变的自身免疫疾病,全世界发病率大约1%,其发病机制复杂,受遗传和环境因素的影响。类风湿性关节炎的基本病变是滑膜细胞增生,衬里层增厚,多种炎性细胞浸润,血管翳形成及软骨与骨组织的破坏,最终导致关节畸形和功能丧失。关节炎和类风湿性关节炎严重影响着人们的身心健康。
双氯芬酸钠是一种止痛剂,主要用于治疗关节炎或者风湿病,其作用机理为抑制环氧化酶活性,从而阻断花生四烯酸向前列腺素的转化,同时,它也能促进花生四烯酸与甘油三脂结合,降低细胞内游离的花生四烯酸浓度,而间接抑制白三烯的合成,双氯芬酸钠添加到药物后,被制成双氯芬酸钠肠溶片,用于消炎。
双氯芬酸钠为淡黄色结晶,无臭,其口服吸收迅速,但其半衰期较短(约1.5h),故需日服3-4次才能维持药效,加上双氯芬酸钠的胃肠道的刺激性,极大的限制了其在临床的广泛应用。现有的双氯芬酸钠缓释剂型往往缓释效果欠佳,使得患者服用双氯芬酸钠缓释剂后,短时间内血液中的有效浓度就达到很高浓度,缓释效果较差,导致治疗效果较差。
目前,双氯芬酸钠口服缓释制剂主要有缓释胶囊和缓释片剂,缓释片剂分为凝胶型、溶蚀型、非溶蚀性骨架缓释片三种形式,而国内绝大部分为亲水凝胶骨架缓控释片、溶蚀型骨架缓释片,是目前口服缓、控释制剂的主要类型,约占上市骨架片品种的60%~70%。双氯芬酸钠口服缓释制剂大多采用湿法制粒工艺、直接压片工艺,或者进行包衣采用膜控释工艺进行生产,但制备步骤多,过程复杂,导致生产收率较低,而且制得的双氯芬酸钠口服缓释制剂存在药物释放前期偏快或后期释放不完全的问题,释放较不稳定。
现有技术中,CN 112022813 A公开了一种双氯芬酸钠缓释微丸及微丸片的制备方法,其将双氯芬酸钠、蜡质材料、填充剂混合,加热制得泥浆状的混合物,然后经干冰或液氮冷却,制得缓释微丸或微丸片,其生产过程复杂且能耗较高。专利CN 110101686 A公开了一种双氯芬酸钠缓释胶囊及其制备工艺,但包衣时间较长,有机溶剂难以去除,且收率较低,难以实现大生产。因此如何在保证药物稳定性的前提下提高收率,保证药物的缓释效果和生物利用度,是目前急需解决的问题。
发明内容
在本研究过程中,发明人发现静电喷雾技术可应用于缓释制剂的制备,并且创新性的发现同轴静电喷雾可极大的避免药物突释现象。同轴静电喷雾可使两种溶液分别进入核层或壳层,在高压静电作用下产生稳定的射流,射流破裂后可形成一种单分散性液滴气溶胶,外层液体将内层物质包裹起来形成缓释微囊,进一步制成缓释片剂。该缓释制剂缓释效果良好,极大降低了胃肠道副反应,提高了患者的顺应性,且稳定性,收率高,适用于产业化生产。
本发明的目的在于提供一种含有双氯芬酸钠的缓释口服制剂及其制备方法,该缓释片剂工艺简单可行,有效降低了胃肠道副反应,缓释效果良好,提高了患者的顺应性,适合临床用药发展的需要。
为实现上述发明目的,本发明所述的一种双氯芬酸钠的缓释口服制剂及其制备方法,其具体实施方案为:
所述的一种双氯芬酸钠的口服缓释制剂,该口服缓释制剂由双氯芬酸钠微囊和药用辅料压片而成。
所述的一种双氯芬酸钠的口服缓释制剂,其特征在于,所述的双氯芬酸钠微囊主要由双氯芬酸钠、内层载体、外层载体组成。
所述的一种双氯芬酸钠的口服缓释制剂,所述的内层载体材料为PVP K25,外层载体为PLGA75/25。
所述的一种双氯芬酸钠的口服缓释制剂,所述的双氯芬酸钠微囊的制备方法为:双氯芬酸钠与内层载体溶于内层溶剂乙醇中,外层载体溶于外层溶剂丙酮,经同轴静电喷雾法制备而得。
所述的一种双氯芬酸钠的口服缓释制剂,所述的双氯芬酸钠微囊含有双氯芬酸钠、内层载体、外层载体的重量份比例为1:2-6:0.6~8。
所述的一种双氯芬酸钠的口服缓释制剂,所述的药用辅料为填充剂、崩解剂和润滑剂,其中双氯芬酸钠微囊与填充剂、崩解剂和润滑剂的重量份比例为1-1.5:2-3:0.05-0.15:0.05-0.1。
所述的一种双氯芬酸钠的口服缓释制剂,其所述的填充剂为:微晶纤维素、预胶化淀粉、乳糖、淀粉中的一种或几种。
所述的一种双氯芬酸钠的口服缓释制剂,其所述的崩解剂为:交联聚维酮、交联羧甲基纤维素钠、羧甲基淀粉钠、低取代羟丙基纤维素中的一种。
所述的一种双氯芬酸钠的口服缓释制剂,其所述的润滑剂为硬脂酸镁。
所述的一种双氯芬酸钠的口服缓释制剂,其制备方法为:双氯芬酸钠与内层载体溶于内层溶剂中,外层载体溶于外层溶剂中,经同轴静电喷雾法制备而得双氯芬酸钠微囊,后加入填充剂混匀,制粒,加其他药用辅料压片即得。
本发明通过,静电喷雾技术制备双氯芬酸钠缓释制剂,可有效降低了胃肠道副反应,缓释效果良好,提高了患者的顺应性,适合临床用药发展的需要。
与现有技术相比,本发明的优势在于:
(1)有机溶剂干燥迅速,约不到1s;
(2)工艺过程简单,操控方便,成本低廉;
(3)通过同轴静电喷雾形成的缓释微囊缓释效果良好,且收率较高。
具体实施方式
下面实施例只为进一步说明本发明,不以任何形式限制本发明。
实施例1
本实施例提供一种含有双氯芬酸钠的口服缓释制剂及其制备方法,所述的缓释制剂由以表1和表2处方制备步骤得到:
表1
表2
制备工艺:
将双氯芬酸钠、PVP K25溶解在内层溶剂乙醇中,得内层溶液;将PLGA75/25溶解在外层溶剂丙酮中,得外层溶液;以同轴静电喷雾法分别将内层溶液和外层溶剂置于注射器中,由恒流泵缓慢输出,在高压电场作用下经同轴喷头喷出,铝箔纸收集后即得该双氯芬酸钠微囊。取适量微囊,向其中加入乳糖、硬脂酸镁、交联羧甲基纤维素钠混合均匀,压制成片,即得。
实施例2
本实施例提供一种含有双氯芬酸钠的口服缓释制剂及其制备方法,所述的缓释制剂由以表3表4处方和制备步骤得到:
表3
表4
制备工艺:
将双氯芬酸钠、PVP K25溶解在内层溶剂乙醇中,得内层溶液;将PLGA75/25溶解在外层溶剂丙酮中,得外层溶液;以同轴静电喷雾法分别将内层溶液和外层溶剂置于注射器中,由恒流泵缓慢输出,在高压电场作用下经同轴喷头喷出,铝箔纸收集后即得该双氯芬酸钠微囊。取适量微囊,向其中加入微晶纤维素、硬脂酸镁、交联聚维酮混合均匀,压制成片,即得。
实施例3
本实施例提供一种含有双氯芬酸钠的口服缓释制剂及其制备方法,所述的缓释制剂由以表5和表6处方制备步骤得到:
表5
表6
制备工艺:
将双氯芬酸钠、PVP K25溶解在内层溶剂乙醇中,得内层溶液;将PLGA75/25溶解在外层溶剂丙酮中,得外层溶液;以同轴静电喷雾法分别将内层溶液和外层溶剂置于注射器中,由恒流泵缓慢输出,在高压电场作用下经同轴喷头喷出,铝箔纸收集后即得该双氯芬酸钠微囊。取适量微囊,向其中加入乳糖、微晶纤维素、硬脂酸镁、羧甲基淀粉钠混合均匀,压制成片,即得。
对比实施例1(未采用静电喷雾技术制备微囊)
表7
物料 | 重量 |
双氯芬酸钠 | 10kg |
微晶纤维素 | 40kg |
硬脂酸镁 | 2kg |
交联羧甲基纤维素钠 | 1.2kg |
羟丙基纤维素 |
制备工艺:
按表7处方,称取处方量的双氯芬酸钠、微晶纤维素、羟丙基纤维素混合均匀,即得预混粉末。取适量纯化水,加入预混粉末中用湿法制粒机制备软材,整粒得含药颗粒,并干燥,加入交联羧甲基纤维素钠、硬脂酸镁混匀,压片即得。
对比实施例2(参考专利CN112022813)
表8
物料 | 重量 |
双氯芬酸钠 | 25kg |
十六醇 | 6.25Kg |
单硬脂酸甘油脂 | 6.25Kg |
乳糖 | 8kg |
淀粉 | 4.5kg |
波拉克林钾 | 5Kg |
硬脂酸钙 | 1Kg |
按表8处方,在湿法制粒机中,将双氯芬酸钠、十六醇、单硬脂酸甘油脂、乳糖和淀粉混合,加热至70℃,搅拌,得混合物后冷却,至形成圆整的微丸,出料,制得双氯芬酸钠缓释微丸。将微丸与乳糖和淀粉、波拉克林钾在混合机中混合10分钟,然后加入硬脂酸钙,混合压片,得双氯芬酸钠缓释微丸片。
验证实施例
稳定性试验
应用本发明实施例1-3得到的片剂与对比实施例1-2进行了质量对比,并进行了加速和长期稳定性试验考察,对比结果如下:
表9稳定性数据对比-0天
注:—代表未检出
表10稳定性数据对比(40℃,75%RH加速6个月)
从结果看出,本发明实施例1-3在体外溶出24h内释放完全,且不存在突释现象,缓释效果明显优于对比实施例1-2;稳定性试验表明,本发明实施例1-3在加速过程中有关物质、含量均未有明显变化,而对比实施例1-2加速过程中出现含量降低、有关物质升高的情况,稳定性不如本发明。
由上述数据可知,本发明使用静电喷雾技术制备双氯芬酸钠缓释制剂,缓释效果良好,同时,药物被载体材料包裹,有效降低了胃肠道副反应,提高了患者的顺应性,适合临床用药发展的需要。
Claims (9)
1.一种双氯芬酸钠的缓释口服制剂,特征在于,所述的缓释口服制剂由双氯芬酸钠微囊和药用辅料制成,所述双氯芬酸钠微囊由双氯芬酸钠、内层载体、外层载体组成。
2.如权利要求1所述双氯芬酸钠的口服缓释制剂,其特征在于,所述的内层载体材料为PVP K25,外层载体为PLGA75/25。
3.如权利要求2所述双氯芬酸钠的口服缓释制剂,其特征在于,所述的双氯芬酸钠微囊的制备方法为:双氯芬酸钠与内层载体溶于内层溶剂乙醇中,外层载体溶于外层溶剂丙酮,经同轴静电喷雾法制备而得。
4.如权利要求1所述双氯芬酸钠的口服缓释制剂,其特征在于,所述的双氯芬酸钠微囊含有双氯芬酸钠、内层载体、外层载体的重量份比例为1:2-6:0.6~8。
5.如权利要求1所述双氯芬酸钠的口服缓释制剂,其特征在于,所述的药用辅料为填充剂、崩解剂和润滑剂,其中双氯芬酸钠微囊与填充剂、崩解剂和润滑剂的重量份比例为1-1.5:2-3:0.05-0.15:0.05-0.1。
6.如权利要求5所述双氯芬酸钠的口服缓释制剂,其特征在于,其所述的填充剂为:微晶纤维素、预胶化淀粉、乳糖、淀粉中的一种或几种。
7.如权利要求1所述双氯芬酸钠的口服缓释制剂,其特征在于,其所述的崩解剂为:交联聚维酮、交联羧甲基纤维素钠、羧甲基淀粉钠、低取代羟丙基纤维素中的一种。
8.如权利要求1所述双氯芬酸钠的口服缓释制剂,其特征在于,其所述的润滑剂为硬脂酸镁。
9.如权利要求1所述双氯芬酸钠的口服缓释制剂,其特征在于,制备方法为:双氯芬酸钠与内层载体溶于内层溶剂乙醇中,外层载体溶于外层溶剂丙酮中,经同轴静电喷雾法制备而得双氯芬酸钠微囊,后加入填充剂混匀,制粒,加其他药用辅料压片即得。
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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-
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Non-Patent Citations (1)
Title |
---|
YAO-YAO YANG等: "Colon-specific pulsatile drug release provided by electrospun shellac nanocoating on hydrophilic amorphous composites", 《INTERNATIONAL JOURNAL OF NANOMEDICINE》 * |
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