CN104510730B - 小体积双氯芬酸钠利多卡因冻干粉针及其制备方法和生产装置 - Google Patents

小体积双氯芬酸钠利多卡因冻干粉针及其制备方法和生产装置 Download PDF

Info

Publication number
CN104510730B
CN104510730B CN201310461339.7A CN201310461339A CN104510730B CN 104510730 B CN104510730 B CN 104510730B CN 201310461339 A CN201310461339 A CN 201310461339A CN 104510730 B CN104510730 B CN 104510730B
Authority
CN
China
Prior art keywords
lidocaine
freeze
dried powder
small size
preparation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201310461339.7A
Other languages
English (en)
Other versions
CN104510730A (zh
Inventor
苗得足
张光明
白先杰
司吉晖
张国明
宋忠国
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Reyoung Pharmaceutical Co Ltd
Original Assignee
Reyoung Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Reyoung Pharmaceutical Co Ltd filed Critical Reyoung Pharmaceutical Co Ltd
Priority to CN201310461339.7A priority Critical patent/CN104510730B/zh
Publication of CN104510730A publication Critical patent/CN104510730A/zh
Application granted granted Critical
Publication of CN104510730B publication Critical patent/CN104510730B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/196Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/16Amides, e.g. hydroxamic acids
    • A61K31/165Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biochemistry (AREA)
  • Pain & Pain Management (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

本发明属于冻干粉针及其制备配制方法和设备领域,特别涉及双氯芬酸钠利多卡因冻干粉针及其制备方法和设备领域。所述的小体积双氯芬酸钠利多卡因冻干粉针装在7ml棕色管制西林瓶中,其水痕位置以下体积为2.0ml,其生产装置依次由保温管道连接的保温配药罐、第二格兰富泵、泵棒过滤器、第二除菌滤芯、无菌保温液储罐、第一格兰富泵、第一除菌滤芯、灌装机和冻干机组成。

Description

小体积双氯芬酸钠利多卡因冻干粉针及其制备方法和生产 装置
技术领域
本发明属于冻干粉针及其制备配制方法和设备领域,特别涉及双氯芬酸钠利多卡因冻干粉针及其制备方法和设备领域。
背景技术
目前市售的(规格:双氯芬酸钠75mg、利多卡因20mg)双氯芬酸钠利多卡因冻干粉针使用10ml棕色管制西林瓶灌装,从而存在内包装容器体积大,造成每批生产的产品产量低的缺点,由于双氯芬酸钠利多卡因本身的水溶性不好,因而在制备过程中需要用大量的溶剂才可溶解,以便制成双氯芬酸钠利多卡因冻干粉针。原先的配制工艺没有使用超声波助溶,在浓配时溶剂的用量加大,而且加入水量也较大(为主药的100倍水)导致双氯芬酸钠利多卡因析出,从而增大了灌装量致使产品的溶解性不理想、产量降低、冻干含水多能耗增大、包装和运输成本增加。
发明内容
本发明的目的是提供一种小体积双氯芬酸钠利多卡因冻干粉针、制备方法及其生产装置。
本发明所述的一种小体积双氯芬酸钠利多卡因冻干粉针装在7ml棕色管制西林瓶中,其水痕位置以下体积为2.0ml。
本发明所述小体积双氯芬酸钠利多卡因冻干粉针的制备方法,包括以下步骤:
(1)在20℃~25℃将盐酸利多卡因、甘露醇和亚硫酸钠加入水中溶解,得浓配液A;
(2)聚乙二醇4000溶于丙二醇后加双氯芬酸钠,超声波超声30分钟使药物溶解,得B液;
(3)将B液缓慢倒入浓配液A中,调节pH控制在7.5-8.5,搅拌均匀;加入活性炭,搅拌吸附20~40min,用钛棒脱碳过滤,精滤;
(4)20℃~25℃将步骤(3)得到的溶液加水制成稀配液,保温,灌装于7ml棕色管制西林瓶中,冻干,压塞、轧盖即得。
浓配液A中各组分的质量分数为:盐酸利多卡因2%~4%;甘露醇10%~15%;亚硫酸钠0.15%~1%和水82%~86%。
聚乙二醇4000、丙二醇和双氯芬酸钠的质量比为12~18∶4~6∶1。
本发明所述的小体积双氯芬酸钠利多卡因冻干粉针的生产装置,依次由保温管道连接的保温配药罐、第二格兰富泵、泵棒过滤器、第二除菌滤芯、无菌保温液储罐、第一格兰富泵、第一除菌滤芯、灌装机和冻干机组成。
与现有技术相比,本发明具有以下有益效果:
提高了产品质量、有效地增加了产量降低了能耗,减小了包装体积,从而降低了包装、运输成本;降低了灌装量仅为2.0ml,大大降低了冻干蒸发能耗,进一步降低了成本。
附图说明
图1是本发明生产线结构示意图。
图中:1、保温配液罐;2、钛棒过滤器;3、无菌液储罐;4、冻干机;5、灌装机;6、第一格兰富泵;7、第一除菌滤芯;8、第二除菌滤芯;9、第二格兰富泵;10、保温管道。
具体实施方式
以下结合实施例对本发明做进一步描述。
实施例1
针对双氯芬酸钠利多卡因在水中溶解度的性质,筛选不同用量的溶剂、亚硫酸钠、聚乙二醇4000、丙二醇、甘露醇、注射用水和不超声进行对比,结果见表1,并考察溶剂用量改变后、超声对双氯芬酸钠利多卡因和辅料混合溶液稳定性的影响,结果见表2。
表1在不同量的溶剂下溶解24.65g盐酸利多卡因和双氯芬酸钠75g,制成1000支,超声和不超声的那个最好。
表2充分溶解后,相同溶剂不同用量下对主药双氯芬酸钠利多卡因稳定性的影响(含量、有关物质)
从上表可以看出,双氯芬酸钠利多卡因在相同溶剂不同用量的溶剂中溶解通过试验考察超声的2#处方稳定性最好,所以我们选择此处方为最终处方双氯芬酸钠75g盐酸利多卡因24.65g、聚乙二醇-4000730g、丙二醇155g、亚硫酸钠1g、甘露醇75g注射用水800ml。
加入70%处方量注射用水,冷却至20℃,取处方量的盐酸利多卡因、甘露醇和亚硫酸钠,加入容器内开启搅拌溶解,在23±3℃充分搅拌使溶解,得浓配液A;另取一容器称取处方量的聚乙二醇4000、丙二醇,搅拌使聚乙二醇4000熔融后加双氯芬酸钠,超声波超声30分钟使药物溶解(为B液)。将B液缓慢倒入A液中,调节pH控制在8±1,搅拌均匀;称取0.1%(W/V)的活性炭加入,搅拌吸附30min,用钛棒脱碳过滤,精滤,将剩余配制量的注射用水,水温23±3℃)加入配液罐中,通过钛棒过滤后精滤,并与精滤后的浓配液混合制成稀配液,保温23±3℃,灌装于7ml棕色管制西林瓶中,冻干,压塞、轧盖即得。
降制品温度均将至-40℃,制品-40℃维持2小时,将冷凝筒温度降至-45℃后,设定载冷剂温度为-10℃,维持30小时。再升介质25℃,制品到20℃维持2小时,最后干燥后打开箱体的气源开关输入无菌空气,按《冻干机标准操作规程》压塞。
采用此方法制得的小体积双氯芬酸钠利多卡因冻干粉针产品装在7ml棕色管制西林瓶中,达到水痕位置以下体积为2.0ml。

Claims (1)

1.一种小体积双氯芬酸钠利多卡因冻干粉针的制备方法,其特征在于,所述的小体积双氯芬酸钠利多卡因冻干粉针装在7ml 棕色管制西林瓶中,其水痕位置以下体积为2.0ml;
所述的小体积双氯芬酸钠利多卡因冻干粉针的制备方法包括以下步骤:
(1)在20℃~25℃将盐酸利多卡因、甘露醇和亚硫酸钠加入水中溶解,得浓配液A;
(2)聚乙二醇4000溶于丙二醇后加双氯芬酸钠,超声波超声30分钟使药物溶解,得B液;
(3)将B 液倒入A液中,调节pH控制在7.5-8.5,搅拌均匀;加入活性炭,搅拌吸附20~40min,用钛棒脱碳过滤,精滤;
(4)20℃~25℃将步骤(3)得到的溶液加水制成稀配液,保温,灌装于7ml 棕色管制西林瓶中,冻干,压塞、轧盖即得;
各物质用量为:双氯芬酸钠 75g、盐酸利多卡因 24.65g、聚乙二醇-4000 730g、丙二醇155g、亚硫酸钠 1g、甘露醇 75g、水800ml 。
CN201310461339.7A 2013-09-30 2013-09-30 小体积双氯芬酸钠利多卡因冻干粉针及其制备方法和生产装置 Active CN104510730B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201310461339.7A CN104510730B (zh) 2013-09-30 2013-09-30 小体积双氯芬酸钠利多卡因冻干粉针及其制备方法和生产装置

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201310461339.7A CN104510730B (zh) 2013-09-30 2013-09-30 小体积双氯芬酸钠利多卡因冻干粉针及其制备方法和生产装置

Publications (2)

Publication Number Publication Date
CN104510730A CN104510730A (zh) 2015-04-15
CN104510730B true CN104510730B (zh) 2016-09-07

Family

ID=52786969

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201310461339.7A Active CN104510730B (zh) 2013-09-30 2013-09-30 小体积双氯芬酸钠利多卡因冻干粉针及其制备方法和生产装置

Country Status (1)

Country Link
CN (1) CN104510730B (zh)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115682646B (zh) * 2022-11-22 2024-05-14 中玉制药(海口)有限公司 注射用双氯芬酸钠利多卡因冻干设备及其制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1689561A (zh) * 2004-04-30 2005-11-02 济南百诺医药科技开发有限公司 含有双氯芬酸盐和利多卡因的冻干制剂及其制备方法
CN102743344A (zh) * 2012-06-25 2012-10-24 瑞阳制药有限公司 小体积炎琥宁冻干粉针及其制备方法、生产装置
CN102743346A (zh) * 2012-06-25 2012-10-24 瑞阳制药有限公司 小体积脂溶性维生素冻干粉针制备方法及其制备装置

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1689561A (zh) * 2004-04-30 2005-11-02 济南百诺医药科技开发有限公司 含有双氯芬酸盐和利多卡因的冻干制剂及其制备方法
CN102743344A (zh) * 2012-06-25 2012-10-24 瑞阳制药有限公司 小体积炎琥宁冻干粉针及其制备方法、生产装置
CN102743346A (zh) * 2012-06-25 2012-10-24 瑞阳制药有限公司 小体积脂溶性维生素冻干粉针制备方法及其制备装置

Also Published As

Publication number Publication date
CN104510730A (zh) 2015-04-15

Similar Documents

Publication Publication Date Title
CN101953803B (zh) 小体积多索茶碱冻干粉针制备方法及其生产设备
CN101199851A (zh) 一种以高固含量甘露醇为辅料的冻干粉针剂的制备方法
CN104510730B (zh) 小体积双氯芬酸钠利多卡因冻干粉针及其制备方法和生产装置
CN107836723A (zh) 一种益生元添加剂及其制备方法和应用
CN103520121B (zh) 注射用维库溴铵冻干粉针剂及其制备方法
CN105602793A (zh) 桂花酒制备方法
CN102743346B (zh) 小体积脂溶性维生素冻干粉针制备方法及其制备装置
CN103694727B (zh) 一种从速溶茶排渣废弃液中分离茶色素的方法
CN104510709A (zh) 小体积棓丙酯冻干粉针及其制备方法和生产装置
Cai et al. Novel natural deep eutectic solvent-based supramolecular solvents designed for extracting phytochemicals from pigeon pea leaves and its scale-up and recovery process
CN105412008B (zh) 一种阿胶益寿口服液的制备方法
CN102743349A (zh) 小体积葛根素冻干粉针、其制备方法及其生产装置
CN102743345B (zh) 小体积氨甲环酸冻干粉针、其制备方法及其生产装置
CN103494779B (zh) 一种注射用炎琥宁粉针制剂及其制备方法
CN105343156A (zh) 一种归芪颗粒及其制备方法
CN102743344A (zh) 小体积炎琥宁冻干粉针及其制备方法、生产装置
CN105079015A (zh) 曲克芦丁冻干粉针剂及其制备方法
CN104095816A (zh) 叶黄素酯纳米颗粒及其制备方法
CN102743348B (zh) 小体积左卡尼汀冻干粉针及其制备方法、生产装置
CN104510711A (zh) 小体积细辛脑冻干粉针及其制备方法和生产装置
CN105055340A (zh) 制备氨甲环酸冻干粉针剂的工艺配方和方法
CN103505423A (zh) 盐酸溴己新冻干粉针剂及其制备方法
CN102743347B (zh) 小体积多索茶碱冻干粉针及其制备方法、生产装置
CN209931390U (zh) 一种搅拌蒸煮装置
CN102697753B (zh) 一种罗红霉素软胶囊的制备方法

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CP01 Change in the name or title of a patent holder

Address after: 256100 No. 6 Erlang Road, Yiyuan County, Zibo, Shandong

Patentee after: Ruiyang Pharmaceutical Co., Ltd

Address before: 256100 No. 6 Erlang Road, Yiyuan County, Zibo, Shandong

Patentee before: REYOUNG PHARMACEUTICAL Co.,Ltd.

CP01 Change in the name or title of a patent holder