Effect of Packaging Materials and the Leached Iron on the Stability of Butorphanol Tartrate Injection

安瓿 布托啡诺 氧气 酒石酸盐 柠檬酸 化学 核化学 无机化学 有机化学 医学 外科
作者
Zijun Dai,Zhu Chang,Jinyuan Lyu,Chunfeng Liu,Jiajian Xu,Haoxiang Wu,Fuli Zhang
出处
期刊:Aaps Pharmscitech [Springer Nature]
卷期号:22 (5) 被引量:1
标识
DOI:10.1208/s12249-021-02060-4
摘要

The aim of this study was to investigate the effect of various parameters on the stability of butorphanol tartrate injection and to screen the optimal packaging material. The effect of the headspace oxygen levels, ampoule color, manufacturer, and size on the stability of butorphanol tartrate formulation were evaluated. The headspace oxygen levels controlled by nitrogen purging were found to be particularly effective in improving stability of the butorphanol formulation, especially below 2%. Although it is a photolabile drug, butorphanol tartrate was getting degraded at much higher extent in amber color ampoules in comparison to clear ampoules. The degradation by oxidation was found to be a free radical-mediated process catalyzed by the presence of iron ions leached from the amber ampoules. The ampoule manufacturers also had a significant effect on the stability of butorphanol. Two-milliliter ampoules provided a better stability of the butorphanol tartrate injection than 1mL ampoules as 2-mL ampoules had the lower headspace oxygen level at the same level of oxygen content. The oxidation mechanism of the butorphanol tartrate injection was investigated under various conditions, which include iron powder spiking, removal of excipients, exposure to oxygen/nitrogen, exposure to stainless steel and at different pH. Iron powder spiking, presence of citric acid, exposure to oxygen, exposure to stainless steel, and high pH accelerated the oxidative degradation. The effect of oxygen, iron ion and citric acid is in agreement with a metal-catalyzed oxidation mechanism called Udenfriend reaction. Based on the formulation test results, limiting headspace oxygen level, ampoule color, manufacturer, size, controlling iron ion contamination, and pH are recommended for formulation development. In conclusion, it can be suggested that this study can lead to a better understanding of the degradation mechanism of butorphanol tartrate; hence, it would contribute to the development of butorphanol tartrate injection with improved stability. Virous packaging materials have different effects on the stability of butorphanol tartrate injection, and the leached iron of packaging ampoules and stainless steel can trigger Udenfriend reaction with butorphanol tartrate and citric acid (CA), which lead to the oxydative degradation of butorphanol tartrate injection.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
星辰大海应助可乐采纳,获得10
1秒前
科研通AI2S应助luojie采纳,获得10
1秒前
2秒前
2秒前
桐桐应助adgfasdvz采纳,获得10
4秒前
4秒前
4秒前
5秒前
5秒前
研友_VZG7GZ应助LHW采纳,获得10
6秒前
6秒前
7秒前
鱼鱼片片发布了新的文献求助10
8秒前
SUMMER完成签到,获得积分20
8秒前
8秒前
小蘑菇应助小杜采纳,获得10
8秒前
wyvern114发布了新的文献求助10
9秒前
9秒前
9秒前
veraonly发布了新的文献求助10
10秒前
10秒前
Funnymudpee发布了新的文献求助10
10秒前
默茗发布了新的文献求助10
11秒前
有点IS完成签到,获得积分10
12秒前
13秒前
领导范儿应助认真的连虎采纳,获得10
14秒前
小二郎应助浩西采纳,获得10
14秒前
14秒前
14秒前
西扬发布了新的文献求助10
15秒前
15秒前
ding应助鱼鱼片片采纳,获得10
15秒前
16秒前
zcc发布了新的文献求助10
16秒前
lovestudy发布了新的文献求助10
16秒前
17秒前
wenx发布了新的文献求助30
17秒前
1234发布了新的文献求助10
17秒前
77777发布了新的文献求助10
17秒前
科研通AI2S应助仁爱的灵松采纳,获得10
17秒前
高分求助中
Spray / Wall-interaction Modelling by Dimensionless Data Analysis 2000
Evolution 3rd edition 1500
保险藏宝图 1000
Lire en communiste 1000
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 700
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 700
Mathematics and Finite Element Discretizations of Incompressible Navier—Stokes Flows 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3185487
求助须知:如何正确求助?哪些是违规求助? 2835818
关于积分的说明 8006526
捐赠科研通 2498268
什么是DOI,文献DOI怎么找? 1333365
科研通“疑难数据库(出版商)”最低求助积分说明 636828
邀请新用户注册赠送积分活动 604465