Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

X-ray Diffraction of Biological Samples01:10

X-ray Diffraction of Biological Samples

3.8K
X-ray diffraction or XRD is an analytical tool that utilizes X-rays to study ordered structures such as crystalline organic and inorganic samples, polycrystalline materials, proteins, carbohydrates, and drugs.
According to Bragg's law, when X-rays strike the sample positioned on a stage, the rays are  scattered by the electron clouds around the sample atoms. The  X-ray diffraction or scattering is caused by constructive interference of the X-ray waves that reflect off the internal...
3.8K
X-ray Crystallography02:18

X-ray Crystallography

24.0K
The size of the unit cell and the arrangement of atoms in a crystal may be determined from measurements of the diffraction of X-rays by the crystal, termed X-ray crystallography.
Diffraction
Diffraction is the change in the direction of travel experienced by an electromagnetic wave when it encounters a physical barrier whose dimensions are comparable to those of the wavelength of the light. X-rays are electromagnetic radiation with wavelengths about as long as the distance between neighboring...
24.0K
¹H NMR: Complex Splitting01:13

¹H NMR: Complex Splitting

1.3K
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...
1.3K
¹H NMR of Conformationally Flexible Molecules: Temporal Resolution00:52

¹H NMR of Conformationally Flexible Molecules: Temporal Resolution

870
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...
870
2D NMR: Overview of Homonuclear Correlation Techniques01:16

2D NMR: Overview of Homonuclear Correlation Techniques

215
Homonuclear correlation spectroscopy (COSY) is a powerful technique used in Nuclear Magnetic Resonance (NMR) spectroscopy to study the correlations between nuclei of the same type within a molecule. It provides information about scalar couplings between adjacent nuclei, which helps determine connectivity and structural information. There are several COSY variants, each with its unique strengths and experimental parameters.
COSY90 is the standard two-dimensional (2D) COSY experiment that...
215
NMR Spectroscopy Of Amines01:19

NMR Spectroscopy Of Amines

8.9K
In proton NMR spectroscopy, primary amines and secondary amines showcase their N–H protons as a broad signal in the chemical shift range between δ 0.5 and 5 ppm. The exact position in this range depends on several factors, including sample concentration, hydrogen bonding, and the type of solvent used. Since amine protons undergo fast proton exchange in solution, the protons are labile and therefore do not participate in any splitting with adjacent protons. Thus, the observed peak is...
8.9K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Call For Papers: Molecular Understanding and Formulation Design for Peptide Delivery.

Molecular pharmaceutics·2026
Same author

Nirmatrelvir methyl <i>tert</i>-butyl ether solvate.

Acta crystallographica. Section E, Crystallographic communications·2026
Same author

Impact of Amino Acid Excipients on icIEF Method Development in Protein Therapeutics: A Formulation-Aware Analytical Framework.

AAPS PharmSciTech·2026
Same author

ASB7 promotes osteosarcoma lung metastasis through ubiquitin-mediated degradation of ATF2.

Cell discovery·2026
Same author

The Molecular Structures of Liquid and Glassy Nifedipine and Felodipine and Their Incorporation into PVP.

Pharmaceuticals (Basel, Switzerland)·2026
Same author

Quantitative Solid-State NMR Spectroscopy for Pharmaceutical Analysis.

Analytical chemistry·2026

Related Experiment Video

Updated: Jul 14, 2025

Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy
14:55

Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy

Published on: September 17, 2017

15.5K

Probing Molecular Packing of Amorphous Pharmaceutical Solids Using X-ray Atomic Pair Distribution Function and

Zhenxuan Chen1, Haichen Nie2,3, Chris J Benmore4

  • 1Analytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.

Molecular Pharmaceutics
|October 6, 2023
PubMed
Summary

High-resolution structural analysis of amorphous pharmaceuticals like posaconazole is crucial for stability. This study combined X-ray PDFs and ssNMR to reveal molecular packing and interactions in amorphous posaconazole and its solid dispersion.

Keywords:
amorphous solid dispersionsmolecular interactionpair distribution functionsphysical stabilitysolid-state nuclear magnetic resonancesynchrotron X-ray

More Related Videos

A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients
11:27

A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients

Published on: August 9, 2022

2.1K
Mass Spectrometric Approaches to Study Protein Structure and Interactions in Lyophilized Powders
11:14

Mass Spectrometric Approaches to Study Protein Structure and Interactions in Lyophilized Powders

Published on: April 14, 2015

16.1K

Related Experiment Videos

Last Updated: Jul 14, 2025

Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy
14:55

Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy

Published on: September 17, 2017

15.5K
A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients
11:27

A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients

Published on: August 9, 2022

2.1K
Mass Spectrometric Approaches to Study Protein Structure and Interactions in Lyophilized Powders
11:14

Mass Spectrometric Approaches to Study Protein Structure and Interactions in Lyophilized Powders

Published on: April 14, 2015

16.1K

Area of Science:

  • Pharmaceutical sciences
  • Materials science
  • Analytical chemistry

Background:

  • Understanding amorphous pharmaceutical structures is key to predicting physicochemical stability.
  • Limited high-resolution analytical tools have hindered detailed structural investigations of amorphous drugs.
  • Amorphous solid dispersions are vital for improving drug solubility and bioavailability.

Purpose of the Study:

  • To investigate the molecular packing and intermolecular interactions of amorphous posaconazole and its amorphous solid dispersion.
  • To demonstrate the synergistic power of X-ray pair distribution functions (PDFs) and solid-state nuclear magnetic resonance (ssNMR) for high-resolution amorphous structure analysis.
  • To elucidate the drug-polymer interactions in amorphous solid dispersions.

Main Methods:

  • Synchrotron X-ray pair distribution functions (PDFs) were employed to analyze atomic-level structure.
  • Solid-state nuclear magnetic resonance (ssNMR) 19F-13C distance measurements provided complementary structural information.
  • Empirical Potential Structure Refinement (EPSR) methodology was used to model the amorphous structures.
  • Principal Component Analysis (PCA) was applied to integrate PDF and ssNMR data.

Main Results:

  • A rigid conformation and short-range intermolecular C-F contacts were identified in amorphous posaconazole.
  • ssNMR 19F-13C distance measurements corroborated the findings from X-ray PDF analysis.
  • PCA revealed insights into the chemical nature of drug-polymer interactions in the amorphous solid dispersion.
  • The study successfully achieved high-resolution structural insights into amorphous systems.

Conclusions:

  • The combined use of X-ray PDF and ssNMR, along with advanced modeling, provides a powerful approach for high-resolution structural characterization of amorphous pharmaceuticals.
  • Understanding the molecular packing and intermolecular interactions is essential for controlling the physicochemical stability of amorphous drugs and their dispersions.
  • This methodology offers a pathway to better comprehend and optimize amorphous solid dispersion formulations.