Old Polymorph, New Technique: Assessing Ritonavir Crystallinity Using Low-Frequency Raman Spectroscopy

拉曼光谱 利托那韦 结晶度 结晶 化学 粉末衍射 溶解度 无定形固体 分析化学(期刊) 多态性(计算机科学) 结晶学 色谱法 有机化学 人类免疫缺陷病毒(HIV) 光学 物理 病毒载量 基因型 基因 家庭医学 医学 抗逆转录病毒疗法 生物化学
作者
Manolya Kukut Hatipoglu,Yeakub Zaker,Daniel Willett,Nirzari Gupta,Jason D. Rodriguez,Suhas V. Patankar,Peter Capella,Huzeyfe Yılmaz
出处
期刊:Analytical Chemistry [American Chemical Society]
卷期号:95 (41): 15325-15332 被引量:2
标识
DOI:10.1021/acs.analchem.3c02781
摘要

Two decades ago, postmarket discovery of a second crystal form of ritonavir with lower solubility had major implications for drug manufacturers and patients. Since then, ritonavir has been reformulated via the hot–melt–extrusion process in an amorphous form. Here, quantitative low- and mid-frequency Raman spectroscopy methods were developed to characterize polymorphs, form I and form II, in commercial ritonavir 100 mg oral tablets as an alternate analysis approach compared to X-ray powder diffraction (XRPD). Crystallization in three lots of ritonavir products obtained from four separate manufacturers was assessed after storage under accelerated conditions at 40 °C and 75% relative humidity (RH). Results were compared with quantitative XRPD methods developed and validated according to ICH Q2 (R1) guidelines. In a four-week open-dish study, form I crystallization occurred in two of the four products and form II crystallization was detected in another ritonavir product. The limits of detection for XRPD, low-frequency Raman (LFR), and mid-frequency Raman (MFR) were determined to be 0.7, 0.8, and 0.5% for form I and 0.6, 0.6, and 1% for form II, respectively. Root-mean-squared-error of predictions were 0.6–1.0 and 0.6–2.5% for LFR- and MFR-based partial least-squares models. Further, ritonavir polymorphs could also be identified and detected directly from ritonavir tablets using transmission LFR. In summary, LFR was applied for the assessment of polymorphism in real-world samples. While providing analytical performance similar to conventional techniques, LFR reduced the single measurement time from 66 min (XRPD) to 10 s (LFR) without the need for tedious sample preparation procedures.
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
PDF的下载单位、IP信息已删除 (2025-6-4)

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
Milktea123发布了新的文献求助10
1秒前
彭于晏应助徐志成采纳,获得10
2秒前
量子星尘发布了新的文献求助10
5秒前
Theo完成签到,获得积分10
10秒前
大气的哈密瓜完成签到,获得积分10
11秒前
11秒前
彭于晏应助victorchen采纳,获得10
12秒前
雪白卿完成签到,获得积分10
12秒前
13秒前
15秒前
Theo发布了新的文献求助10
15秒前
16秒前
w_donghui完成签到,获得积分10
19秒前
鲤鱼安青发布了新的文献求助10
20秒前
快飞飞完成签到 ,获得积分10
23秒前
叶夜南完成签到 ,获得积分10
25秒前
29秒前
WJM完成签到,获得积分10
30秒前
JAJ完成签到 ,获得积分10
32秒前
所所应助小郑采纳,获得10
33秒前
独特冰安发布了新的文献求助10
33秒前
liyuxuan发布了新的文献求助10
33秒前
34秒前
戴佳伟彩笔完成签到,获得积分10
34秒前
劉浏琉完成签到,获得积分10
36秒前
领导范儿应助勤恳紫霜采纳,获得10
36秒前
Luu完成签到 ,获得积分10
38秒前
38秒前
39秒前
灵魂发布了新的文献求助10
40秒前
高挑的若剑完成签到,获得积分10
41秒前
mt13完成签到,获得积分10
41秒前
科研通AI2S应助科研通管家采纳,获得10
42秒前
yar应助科研通管家采纳,获得10
42秒前
田様应助科研通管家采纳,获得10
42秒前
科研通AI5应助科研通管家采纳,获得10
42秒前
共享精神应助科研通管家采纳,获得10
42秒前
42秒前
Owen应助科研通管家采纳,获得10
42秒前
42秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 700
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
热门求助领域 (近24小时)
化学 材料科学 医学 生物 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 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3975378
求助须知:如何正确求助?哪些是违规求助? 3519775
关于积分的说明 11199621
捐赠科研通 3256067
什么是DOI,文献DOI怎么找? 1798124
邀请新用户注册赠送积分活动 877386
科研通“疑难数据库(出版商)”最低求助积分说明 806305