CN112843003A - 一种注射用拉氧头孢钠的冻干粉及其冻干工艺 - Google Patents
一种注射用拉氧头孢钠的冻干粉及其冻干工艺 Download PDFInfo
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Abstract
本发明提供一种注射用拉氧头孢钠的冻干粉及其冻干工艺,其中冻干粉包括以下重量份原料:拉氧头孢钠20~40份、冻干辅剂8~15份、赋形剂6~18份、水30~55份,通过对原料工艺的优化,制备冻干辅剂、两次干燥,使得原料质量稳定、杂质少、纯度高、不良反应少、药效高;同时对制剂配液工艺进行创新改进,降低配液温度,保证药液质量稳定;同时对冻干工艺采用二次干燥,使得成品水分、杂质和质量更稳定。
Description
技术领域
本发明涉及药品制备领域,特别涉及一种注射用拉氧头孢钠的冻干粉及其冻干工艺。
背景技术
注射用拉氧头孢钠,适应症为用于敏感菌引起的各种感染症,如败血症、脑膜炎、呼吸系统感染症(肺炎、支气管炎、支气管扩张症、肺化脓症、脓胸等),消化系统感染症(胆道炎、胆囊炎等),腹腔内感染症(肝脓疡、腹膜炎等),泌尿系统及生殖系统感染症(肾孟肾炎、膀胱炎、尿道炎、淋病、副睾炎、子宫内感染、子宫附件炎、盆腔炎等),皮肤及软组织感染、骨、关节感染及创伤感染。
目前,注射用拉氧头孢钠冻干粉剂由于生产时所用辅料为单一的甘露醇,它存在生产时冻干时间长,干燥温度高,能耗大,成品澄清度和溶液颜色合格率低,冻干工艺得到的注射用拉氧头孢钠水分、杂质高,质量不稳定。
发明内容
鉴于此,本发明提出一种注射用拉氧头孢钠的冻干粉及其冻干工艺,解决上述问题。
本发明的技术方案是这样实现的:一种注射用拉氧头孢钠的冻干粉:包括以下重量份原料:拉氧头孢钠20~40份、冻干辅剂8~15份、赋形剂6~18份、水30~55份,所述冻干辅剂由银杏内酯、β-葡萄糖苷酶、甘露醇组成,所述赋形剂选自乳糖、甘露醇、右旋糖苷、甘氨酸、葡萄糖中的一种或多种,
所述注射用拉氧头孢钠的冻干粉的冻干方法,包括以下步骤:
S1、制备冻干辅剂:将杏内酯、β-葡萄糖苷酶、甘露醇按比例混合,加入3~5倍体积水搅拌,搅拌速率为600~1200rpm,搅拌时间60~150s,再置于-14~10℃下放置,得到冻干辅剂;
S2、按上述重量份将拉氧头孢钠、冻干辅剂、赋形剂、水混合,用振荡器混匀,制成悬液,
S3、一次干燥:将悬液置于搁板,缓慢升至-6~-3℃,保温,待一次干燥中的制品的冰晶完全消失后,继续保温3~5小时;
S4、二次干燥:将S3干燥后的悬液升温至12~15℃,保温0.3~1.5小时,搁板继续升温至33~37℃,待二次干燥中的制品的温度达33~37℃后,继续保温3~5小时。
进一步的,一种注射用拉氧头孢钠的冻干粉,包括以下重量份原料:拉氧头孢钠30份、冻干辅剂12份、赋形剂12份、水43份,所述冻干辅剂由重量份比为1~3:0.1~2:0.6~3.9的银杏内酯、β-葡萄糖苷酶、甘露醇组成。
进一步的,所述S1中放置时间为3~8h。
进一步的,所述S3中升温速率为0.30~0.35℃/min。
进一步的,所述S4中升温速率为0.50~0.55℃/min。
进一步的,所述S4中继续升温速率为0.30~0.35℃/min。
与现有技术相比,本发明的有益效果是:
本发明经合理选择原料,科学配比,冻干辅剂中选择杏内酯、β-葡萄糖苷酶、甘露醇按比例混合,辅助冻干,避免干燥过程发生水解以及发生氧化、凝聚、融合等现象,通过对原料工艺的优化,使得原料质量稳定、杂质少、纯度高、不良反应少、药效高;同时对制剂配液工艺进行创新改进,降低配液温度,保证药液质量稳定;同时对冻干工艺采用二次干燥,使得成品水分、杂质和质量更稳定。
具体实施方式
为了更好理解本发明技术内容,下面提供具体实施例,对本发明做进一步的说明。
本发明实施例所用的实验方法如无特殊说明,均为常规方法。
本发明实施例所用的材料、试剂等,如无特殊说明,均可从商业途径得到。
实施例1
一种注射用拉氧头孢钠的冻干粉,包括以下重量份原料:拉氧头孢钠20份、冻干辅剂8份、乳糖6份、水30份,所述冻干辅剂由重量份比为1:0.1:0.6的银杏内酯、β-葡萄糖苷酶、甘露醇组成。
实施例2
一种注射用拉氧头孢钠的冻干粉,包括以下重量份原料:拉氧头孢钠40份、冻干辅剂15份、甘露醇18份、水55份,所述冻干辅剂由重量份比为3:2:3.9的银杏内酯、β-葡萄糖苷酶、甘露醇组成。
实施例3
一种注射用拉氧头孢钠的冻干粉,包括以下重量份原料:拉氧头孢钠30份、冻干辅剂12份、甘氨酸12份、水42份,所述冻干辅剂由重量份比为2:1.2:2.3的银杏内酯、β-葡萄糖苷酶、甘露醇组成。
上述实施例1~3按照以下冻干工艺:
S1、制备冻干辅剂:将杏内酯、β-葡萄糖苷酶、甘露醇按比例混合,加入3~5倍体积水搅拌,搅拌速率为900rpm,搅拌时间120s,再置于-12℃下放置5h,得到冻干辅剂;
S2、按上述重量份将拉氧头孢钠、冻干辅剂、赋形剂、水混合,用振荡器混匀,制成悬液,
S3、一次干燥:将悬液置于搁板,温度以0.33℃/min的速度缓慢升至-4℃,保温,待一次干燥中的制品的冰晶完全消失后,继续保温4小时;
S4、二次干燥:将S3干燥后的悬液再以温度以0.53℃/min的速度升至13℃,保温1小时,搁板继续以0.33℃/min的速度升至35℃,待二次干燥中的制品的温度达34℃后,继续保温4小时。
实施例4
本实施例与实施例3的区别在于,一种注射用拉氧头孢钠的冻干粉的冻干工艺,包括以下步骤:
S1、制备冻干辅剂:将杏内酯、β-葡萄糖苷酶、甘露醇按比例混合,加入3~5倍体积水搅拌,搅拌速率为600rpm,搅拌时间60s,再置于-14℃下放置,得到冻干辅剂;
S2、按上述重量份将拉氧头孢钠、冻干辅剂、赋形剂、水混合,用振荡器混匀,制成悬液,
S3、一次干燥:将悬液置于搁板,按0.30℃/min的速率缓慢升至-6℃,保温,待一次干燥中的制品的冰晶完全消失后,继续保温3小时;
S4、二次干燥:将S3干燥后的悬液按0.50℃/min的速率升温至12℃,保温0.3小时,搁板按0.30℃/min的速率继续升温至33℃,待二次干燥中的制品的温度达33℃后,继续保温3小时。
实施例5
本实施例与实施例3的区别在于,一种注射用拉氧头孢钠的冻干粉的冻干工艺,包括以下步骤:
S1、制备冻干辅剂:将杏内酯、β-葡萄糖苷酶、甘露醇按比例混合,加入3~5倍体积水搅拌,搅拌速率为1200rpm,搅拌时间150s,再置于-10℃下放置,得到冻干辅剂;
S2、按上述重量份将拉氧头孢钠、冻干辅剂、赋形剂、水混合,用振荡器混匀,制成悬液,
S3、一次干燥:将悬液置于搁板,按0.35℃/min的速率缓慢升至-3℃,保温,待一次干燥中的制品的冰晶完全消失后,继续保温5小时;
S4、二次干燥:将S3干燥后的悬液按0.55℃/min的速率升温至15℃,保温1.5小时,搁板按0.35℃/min的速率继续升温至37℃,待二次干燥中的制品的温度达37℃后,继续保温5小时。
实施例6
本实施例与实施例3的区别在于,一种注射用拉氧头孢钠的冻干粉的冻干工艺,所述S3中升温速率为0.38℃/min。
对比例1
本对比例和实施例3的区别在于,一种注射用拉氧头孢钠的冻干粉,包括以下重量份原料:拉氧头孢钠50份、冻干辅剂20份、赋形剂20份、水25份。
对比例2
本对比例和实施例3的区别在于,一种注射用拉氧头孢钠的冻干粉,所述冻干辅剂由重量份比为4:3:4的银杏内酯、β-葡萄糖苷酶、甘露醇组成。
对比例3
本对比例和实施例3的区别在于,一种注射用拉氧头孢钠的冻干粉,所述冻干辅剂由等量的右旋糖酐、β-葡萄糖苷酶、甘露醇组成。
一、稳定性
参照《中国药典》的要求,对实施例1~6和对比例1~3所制得样品的性状、pH值、含量、总杂。
由上表可知,本方法制备的注射用冻干粉针剂,呈类白色疏松块状物,pH值呈中性,含量高,总杂少,由于其他上市产品,产品质量稳定,且质量更优。
以上所述仅为本发明的较佳实施例而已,并不用以限制本发明,凡在本发明的精神和原则之内,所作的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
Claims (6)
1.一种注射用拉氧头孢钠的冻干粉,其特征在于:包括以下重量份原料:拉氧头孢钠20~40份、冻干辅剂8~15份、赋形剂6~18份、水30~55份,所述冻干辅剂由银杏内酯、β-葡萄糖苷酶、甘露醇组成,所述赋形剂选自乳糖、甘露醇、右旋糖苷、甘氨酸、葡萄糖中的一种或多种;
所述的注射用拉氧头孢钠的冻干粉的冻干方法,包括以下步骤:
S1、制备冻干辅剂:将杏内酯、β-葡萄糖苷酶、甘露醇按比例混合,加入3~5倍体积水搅拌,搅拌速率为600~1200rpm,搅拌时间60~150s,再置于-14~-10℃下放置,得到冻干辅剂;
S2、按上述重量份将拉氧头孢钠、冻干辅剂、赋形剂、水混合,用振荡器混匀,制成悬液,
S3、一次干燥:将悬液置于搁板,缓慢升至-6~-3℃,保温,待一次干燥中的制品的冰晶完全消失后,继续保温3~5小时;
S4、二次干燥:将S3干燥后的悬液升温至12~15℃,保温0.3~1.5小时,搁板继续升温至33~37℃,待二次干燥中的制品的温度达33~37℃后,继续保温3~5小时。
2.如权利要求1所述的一种注射用拉氧头孢钠的冻干粉,其特征在于:包括以下重量份原料:拉氧头孢钠30份、冻干辅剂12份、赋形剂12份、水43份,所述冻干辅剂由重量份比为1~3:0.1~2:0.6~3.9的银杏内酯、β-葡萄糖苷酶、甘露醇组成。
3.如权利要求1所述的一种注射用拉氧头孢钠的冻干粉,其特征在于:所述冻干方法S1中放置时间为3~8h。
4.如权利要求1所述的一种注射用拉氧头孢钠的冻干粉,其特征在于:所述冻干方法S3中升温速率为0.30~0.35℃/min。
5.如权利要求1所述的一种注射用拉氧头孢钠的冻干粉,其特征在于:所述S4中升温速率为0.50~0.55℃/min。
6.如权利要求3所述的一种注射用拉氧头孢钠的冻干粉,其特征在于:所述冻干方法S4中继续升温速率为0.30~0.35℃/min。
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