Crystallization of Amorphous Indomethacin during Dissolution: Effect of Processing and Annealing

溶解 无定形固体 结晶 材料科学 化学工程 猝灭(荧光) 溶解度 结晶度 差示扫描量热法 过饱和度 成核 非晶态金属 退火(玻璃) 再结晶(地质) 核化学 化学 结晶学 冶金 复合材料 光学 工程类 物理 荧光
作者
Kristyn Greco,Robin H. Bogner
出处
期刊:Molecular Pharmaceutics [American Chemical Society]
卷期号:7 (5): 1406-1418 被引量:71
标识
DOI:10.1021/mp1000197
摘要

The crystallization of amorphous drugs during dissolution is a type of solution mediated phase transformation that can reduce the bioavailability enhancement one hoped to gain from the amorphous state. The goal of this study was to explore the effects of processing on the dissolution performance of amorphous indomethacin. The amorphous solids were prepared by four techniques, quench cooling the melted solid, cryogrinding γ indomethacin amorphous for 1 or 3 h and quench cooling the solid followed by 1 h of cryogrinding. Dissolution results assessed in a flow-through intrinsic dissolution apparatus reveal decreases in the dissolution rate of amorphous indomethacin during the experimental time frame indicating that a solution mediated phase transformation has occurred. The amorphous solids prepared by melt quenching and melt quenching followed by cryogrinding showed a significant dissolution rate advantage over the γ form of indomethacin. In contrast, indomethacin that was cryoground amorphous for 1 or 3 h did not show any dissolution rate advantage over the crystalline material. Transformation was confirmed by in situ Raman microscopy and polarized light microscopy with differences seen in the nature of the crystals apparent on the surface of the dissolving solid. A portion of the melt quenched amorphous sample was annealed at 25 °C and 0% relative humidity to induce partial crystallization of γ indomethacin. As crystallinity increased, the dissolution rate decreased. The transformation time of partially amorphous indomethacin was not dependent on the level of crystallinity present, indicating only a small fraction of crystalline material needs to be present to affect the kinetics of crystallization. The solution mediated phase transformation of amorphous indomethacin is affected by the processing method even though all solids were confirmed amorphous by polarized light microscopy and X-ray diffraction. Dissolution may distinguish differences in amorphous solids that other methods cannot discern.
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
1秒前
酷波er应助hello采纳,获得10
1秒前
1秒前
啦啦发布了新的文献求助10
1秒前
唯美发布了新的文献求助10
5秒前
hnlgdx发布了新的文献求助10
9秒前
一根完成签到,获得积分20
9秒前
七月完成签到 ,获得积分10
11秒前
xiaojiahuo完成签到,获得积分10
12秒前
13秒前
猪猪hero发布了新的文献求助10
13秒前
自信不愁完成签到,获得积分10
14秒前
潇湘雪月发布了新的文献求助10
15秒前
Arthur完成签到,获得积分10
16秒前
16秒前
量子星尘发布了新的文献求助10
17秒前
芋孟齐完成签到,获得积分20
17秒前
猪猪hero发布了新的文献求助10
19秒前
20秒前
高手发布了新的文献求助10
20秒前
20秒前
WN发布了新的文献求助10
20秒前
超级的鹅发布了新的文献求助10
23秒前
FashionBoy应助axin采纳,获得10
24秒前
胡霖完成签到,获得积分10
25秒前
流飒完成签到,获得积分10
25秒前
香蕉觅云应助牛马码字员采纳,获得10
26秒前
猪猪hero发布了新的文献求助10
26秒前
CAOHOU应助林sir采纳,获得10
26秒前
26秒前
甜甜亦巧完成签到,获得积分10
27秒前
栗惠发布了新的文献求助20
28秒前
28秒前
29秒前
31秒前
小二郎应助高手采纳,获得10
31秒前
32秒前
民科王聪发布了新的文献求助10
32秒前
32秒前
YaoZhang完成签到 ,获得积分10
33秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
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 3989242
求助须知:如何正确求助?哪些是违规求助? 3531393
关于积分的说明 11253753
捐赠科研通 3270010
什么是DOI,文献DOI怎么找? 1804868
邀请新用户注册赠送积分活动 882084
科研通“疑难数据库(出版商)”最低求助积分说明 809136