CN105456205A - 一种恩诺沙星缓释颗粒剂的制备工艺 - Google Patents
一种恩诺沙星缓释颗粒剂的制备工艺 Download PDFInfo
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Abstract
一种恩诺沙星缓释颗粒剂的制备工艺,涉及抗生素缓释剂制备领域,所述恩诺沙星颗粒剂由质量比2-10%的恩诺沙星、20-30%的羧甲基纤维素钠、20-30%的乙基纤维素、20-40%的无水乙醇及适量的淀粉与淀粉浆组成,盖缓释颗粒剂以羧甲基纤维素钠为亲水骨架,乙基纤维素为阻滞剂,通过淀粉浆粘连进而烘干成恩诺沙星缓释颗粒剂,该颗粒剂4h释药量约为50%,8h释药量不足70%,缓释效果明显,能够达到稳定血药浓度、减少临床给药次数以及改善药物的适口性的目的。
Description
技术领域
本发明涉及抗生素缓释剂制备领域,尤其是涉及一种恩诺沙星缓释剂的制备工艺。
背景技术
恩诺沙旱(ENRO)是第一个畜禽专用的氟喹诺酮类药物,具有抗菌潜广、杀菌活性强、体内分布广泛、与其他抗菌药物无交义耐药性等特点。目前ENRO在兽医临床上已得到广泛应用,生产中已将其制成多种剂型,如片剂、粉剂、注射剂、普通颗粒剂等,但这些剂型多以普通制剂为主,临床上往往给药次数多,体内作用时间短,而且有血药浓度峰谷现象,副作用较大,成本高。因此开发符合实际生产需要的长效缓释制剂具有十分重要的意义。
常用的恩诺沙星颗粒剂是将ENRO与载体混合后,用淀粉浆粘连,干燥成粒,该工艺虽能在一定程度上降低血药浓度峰谷现象,但其仍不能有效延长药物缓慢平稳释放的时间。
发明内容
本发明旨在针对现有技术的缺陷,提供一种能延长恩诺沙星缓慢平稳释放时间的缓释颗粒剂,以解决现有技术中存在的给药次数多,体内作用时间短,而且有血药浓度峰谷现象,副作用较大,成本高等问题。
为实现以上技术目的,本发明采用以下技术方案:
一种恩诺沙星缓释颗粒剂的制备工艺,其特征在于:所述恩诺沙星颗粒剂由质量比2-10%的恩诺沙星、20-30%的羧甲基纤维素钠、20-30%的乙基纤维素、20-40%的无水乙醇及适量的淀粉与淀粉浆组成;所述制备工艺的配制步骤如下:
1)将称取的恩诺沙星、羧甲基纤维素钠及少许淀粉混合均匀;
2)将称取的乙基纤维素溶于无水乙醇;
3)将步骤2)的乙醇溶液均匀喷洒在步骤1)的混合粉末上并搅拌均匀;
4)将淀粉浆分批少量加入至步骤3)的混合产物制成软材;
5)将软材过16目分样筛制成湿粒;
6)湿粒烘干即得恩诺沙星缓释颗粒剂。
本发明制备恩诺沙星缓释颗粒剂的工艺,所述的恩诺沙星为恩诺沙星原药或恩诺沙星的盐酸盐、乳酸盐、甲磺酸、苹果酸等形式的盐或其水合物。
本发明制备恩诺沙星缓释颗粒剂的工艺,所述的恩诺沙星与羧甲基纤维素钠的质量比为1:3-1:10。
本发明制备恩诺沙星缓释颗粒剂的工艺,所述的乙基纤维素钠与乙醇溶液的质量比为1:1-1:2。
本发明制备恩诺沙星缓释颗粒剂的工艺,所述的湿粒烘干温度为40-70℃,烘干时间为1-4h。
由于采用了上述技术方案,本发明具有如下有益效果:
本发明以羧甲基纤维素钠为亲水骨架,乙基纤维素为阻滞剂,通过淀粉浆粘连进而烘干成恩诺沙星缓释颗粒剂,该颗粒剂4h释药量约为50%,8h释药量不足70%,缓释效果明显,能够达到稳定血药浓度、减少临床给药次数以及改善药物的适口性的目的。
具体实施方式
以下将对本发明的具体实施方式进行详细描述。为了避免过多不必要的细节,在以下实施例中对属于公知的结构或功能将不进行详细描述。
实施例1
制备恩诺沙星缓释颗粒剂
制备通法:称取适量恩诺沙星、羧甲基纤维素钠及少许淀粉均匀混合后制成恩诺沙星混合粉末;称取乙基纤维素溶于无水乙醇制成乙醇混合液;将乙醇混合液均匀喷洒至恩诺沙星混合粉末并搅拌均匀制成恩诺沙星混合物;将备好的淀粉浆少量分批加入恩诺沙星混合物制成软材;软材过16目筛后制成湿粒;湿粒烘干后即得恩诺沙星缓释颗粒剂。
以同样方法,采用以下不同的五种配比方案出可分别制备五份恩诺沙星缓释颗粒剂(合计100%):
方案1:恩诺沙星2%,羧甲基纤维素钠20%,乙基纤维素20%,无水乙醇30%,余为淀粉和淀粉浆。
方案2:恩诺沙星4%,羧甲基纤维素钠28%,乙基纤维素20%,无水乙醇20%,余为淀粉和淀粉浆。
方案3:恩诺沙星6%,羧甲基纤维素钠24%,乙基纤维素30%,无水乙醇30%,余为淀粉和淀粉浆。
方案4:恩诺沙星8%,羧甲基纤维素钠30%,乙基纤维素25%,无水乙醇30%,余为淀粉和淀粉浆。
方案5:恩诺沙星10%,羧甲基纤维素钠30%,乙基纤维素20%,无水乙醇30%,余为淀粉和淀粉浆。
实施例2
本发明中恩诺沙星缓释颗粒剂与普通恩诺沙星颗粒剂体外释放度的对比
1、恩诺沙星颗粒剂的制备:
恩诺沙星缓释颗粒剂按实施例1中的方案3制备;
普通恩诺沙星颗粒的制备方法为:称取0.6g恩诺沙星,0.25g羧甲基淀粉钠,加适量干淀粉混合均匀,接着向其中加入适当淀粉浆,制成软材,通过16目分样筛制成均匀的湿粒,在60℃干燥4小时即得普通恩诺沙星颗粒。
2、体外释放度检测:
量取蒸馏水500ml注入溶出杯中,加热至37℃左右;精密称取缓释颗粒剂2g加入其中,用电子恒速搅拌器在转速为200r/min条件下测定其体外释放度;以颗粒剂接触溶出介质开始计时,分别于0.25、0.5、1、2、4、8、12、16h等不同时间点按时取样,每次取样10mL(每次取样后随即补加0.1mol/L氢氧化钠溶液10ml),过滤,取5ml续滤液置于50ml的容量瓶;用0.1mol/LNaOH溶液稀释至刻度,摇匀,用紫外分光光度计在271nm外测定吸光度。然后按下式计算出累积释药百分率:累积释药百分率(%)=测定介质ENRO量(μg/ml)×稀释倍数/缓释颗粒ENRO含量×100。
表1缓释颗粒剂与普通颗粒剂的累积释药百分率(%)
如上表所示,普通颗粒2h累积释药率即达到80%以上,8h后累积释药率达到最大值;而缓释颗粒2h的累积释药率为46.15%,8h的累积释药率仅为59.55%,16h的累积释药率仍不足80%。
Claims (5)
1.一种恩诺沙星缓释颗粒剂的制备工艺,其特征在于:所述恩诺沙星颗粒剂由质量比2-10%的恩诺沙星、20-30%的羧甲基纤维素钠、20-30%的乙基纤维素、20-40%的无水乙醇及适量的淀粉与淀粉浆组成;所述制备工艺的配制步骤如下:
1)将称取的恩诺沙星、羧甲基纤维素钠及少许淀粉混合均匀;
2)将称取的乙基纤维素溶于无水乙醇;
3)将步骤2)的乙醇溶液均匀喷洒在步骤1)的混合粉末上并搅拌均匀;
4)将淀粉浆分批少量加入至步骤3)的混合产物制成软材;
5)将软材过16目分样筛制成湿粒;
6)湿粒烘干即得恩诺沙星缓释颗粒剂。
2.根据权利要求1所述的制备恩诺沙星缓释颗粒剂的工艺,其特征在于:所述的恩诺沙星为恩诺沙星原药或恩诺沙星的盐酸盐、乳酸盐、甲磺酸、苹果酸等形式的盐或其水合物。
3.根据权利要求1所述的制备恩诺沙星缓释颗粒剂的工艺,其特征在于:所述的恩诺沙星与羧甲基纤维素钠的质量比为1:3-1:10。
4.根据权利要求1所述的制备恩诺沙星缓释颗粒剂的工艺,其特征在于:所述的乙基纤维素钠与乙醇溶液的质量比为1:1-1:2。
5.根据权利要求1所述的制备恩诺沙星缓释颗粒剂的工艺,其特征在于:所述的湿粒烘干温度为40-70℃,烘干时间为1-4h。
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CN111617056A (zh) * | 2020-05-18 | 2020-09-04 | 四川省欧邦动物药业有限公司 | 一种恩诺沙星缓释颗粒剂的制备工艺 |
CN112390754A (zh) * | 2020-11-17 | 2021-02-23 | 华南农业大学 | 一种恩诺沙星盐水合物及其制备方法和应用 |
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CN111617056A (zh) * | 2020-05-18 | 2020-09-04 | 四川省欧邦动物药业有限公司 | 一种恩诺沙星缓释颗粒剂的制备工艺 |
CN112390754A (zh) * | 2020-11-17 | 2021-02-23 | 华南农业大学 | 一种恩诺沙星盐水合物及其制备方法和应用 |
CN112390754B (zh) * | 2020-11-17 | 2022-12-09 | 华南农业大学 | 一种恩诺沙星盐水合物及其制备方法和应用 |
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