完整的NMR方法快速揭示了同步的微观结构变化在油在水纳米乳液配方
Deyun Wang1, Jiayi Li2, Kang Chen3
1Division of Liquid Based Products II, Office of Lifecycle Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.
The AAPS journal
|July 9, 2024
概括
完整的核磁共振 (NMR) 方法精确地测量了油在水纳米乳液中的药物相分布和油球体大小. 这些技术为配方开发和质量保证提供了独特的诊断工具.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 分析化学 分析化学
背景情况:
- 软核油在水 (O/W) 纳米乳液 (NEs) 是关键的药物输送系统.
- 包括药物阶段分布 (DPD) 和油球体大小 (OGS) 在内的NE微结构的非侵入性表征具有挑战性.
- 了解这些属性对于配方开发和质量控制至关重要.
研究的目的:
- 为了证明完整的19F核磁共振 (NMR) 和1H扩散有序光谱法 (DOSY) 的NMR对表征o/w NEs的实用性.
- 调查NE配方中DPD和OGS之间的相关性.
- 评估配方变化和机械扰动对NE微观结构的影响.
主要方法:
- 使用完整的19F核磁共振来测量药物阶段分布 (DPD).
- 采用1H扩散有序光谱 (DOSY) NMR来确定油球体大小 (OGS).
- 分析了三种具有不同表面活性剂度的NE配方,并受到机械扰动.
主要成果:
- 通过NMR方法准确而非侵入性地测量DPD和OGS.
- 配方变化,例如增加表面活性剂,改变DPD和减少OGS.
- 机械干扰诱导了向微乳液 (ME) 的相位过渡,影响了DPD和OGS.
- 1D 1H NMR和动态光散射 (DLS) 在描述这些微观结构变化方面存在局限性.
结论:
- 完整的NMR技术对于测量软核NE系统中的关键微观结构属性是特定的和必不可少的.
- 经过证明的NMR方法是O/WNE配方开发和质量保证的独特诊断工具.
- 这些方法提供了快速,准确和非侵入性的NE分子排列和Q3属性的洞察.
相关概念视频
01:13¹H NMR: Complex Splitting
A proton M that is coupled to a proton X results in doublet signals for M. However, NMR-active nuclei can be simultaneously coupled to more than one nonequivalent nucleus. When M is coupled to a second proton A, such as in styrene oxide, each peak in the doublet is split into another doublet.
Splitting diagrams or splitting tree diagrams are routinely used to depict such complex couplings. While drawing splitting diagrams, the splitting with the larger coupling constant is usually applied first.
Splitting diagrams or splitting tree diagrams are routinely used to depict such complex couplings. While drawing splitting diagrams, the splitting with the larger coupling constant is usually applied first.
01:02¹H NMR: Interpreting Distorted and Overlapping Signals
Spin systems where the difference in chemical shifts of the coupled nuclei is greater than ten times J are called first-order spin systems. These nuclei are weakly coupled, and their chemical shifts and coupling constant can generally be estimated from the well-separated signals in the spectrum.
As Δν decreases and the signals move closer, the doublets appear increasingly distorted. The intensities of the inner lines increase at the cost of those of the outer lines as the signals are slanted or...
As Δν decreases and the signals move closer, the doublets appear increasingly distorted. The intensities of the inner lines increase at the cost of those of the outer lines as the signals are slanted or...
00:52¹H NMR of Conformationally Flexible Molecules: Temporal Resolution
At room temperature, the chair conformer of cyclohexane undergoes rapid ring flipping between two equivalent chair conformers at a rate of approximately 105 times per second. These two chair conformers are in equilibrium. The rapid ring flipping results in the interconversion of the axial proton to an equatorial proton and an equatorial to the axial proton. Such interconversions are too rapid and cannot be detected on the NMR timescale. Hence, the NMR spectrometer cannot distinguish between the...
01:15¹H NMR of Conformationally Flexible Molecules: Variable-Temperature NMR
The axial and equatorial protons in cyclohexane can be distinguished by performing a variable-temperature NMR experiment. In this process, except for one proton, the remaining eleven protons are replaced by deuterium. The deuterium substitution avoids the possible peak splitting caused by the spin-spin coupling between the adjacent protons. The remaining proton flips between the axial and equatorial positions.
01:04¹³C NMR: ¹H–¹³C Decoupling
The probability of having two carbon-13 atoms next to each other is negligible because of the low natural abundance of carbon-13. Consequently, peak splitting due to carbon-carbon spin-spin coupling is not observed in spectra. However, protons up to three sigma bonds away split the carbon signal according to the n+1 rule, resulting in complicated spectra.
A broadband decoupling technique is used to simplify these complex, sometimes overlapping, signals. Broadband decoupling relies on a...
A broadband decoupling technique is used to simplify these complex, sometimes overlapping, signals. Broadband decoupling relies on a...
01:25Applications Of NMR In Biology
Nuclear magnetic resonance (NMR) spectroscopy is a very valuable analytical technique for researchers. It has been used for more than 50 years as an analytical tool. F. Bloch and E. Purcell formulated NMR in 1946 and won the 1952 Nobel Prize in Physics for their work. Biological macromolecules such as proteins, nucleic acids, lipids, and organic molecules including pharmaceutical compounds, can be studied using this versatile tool that exploits the magnetic properties of certain nuclei.
The...
The...