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

Basicity of Heterocyclic Aromatic Amines01:25

Basicity of Heterocyclic Aromatic Amines

Heterocyclic amines, where the N atom is a part of an alicyclic system, are similar in basicity to alkylamines. Interestingly, the heterocyclic amine having a nitrogen atom as part of an aromatic ring has much less basicity than its corresponding alicyclic counterpart. For this reason, as presented in Figure 1, piperidine (pKb = 2.8) is significantly more basic than pyridine (pKb = 8.8).
Solvating Effects02:12

Solvating Effects

An understanding of the solvating effect helps rationalize the relation between solvation and acidity of the compound. In addition, this also explains the relative stability of conjugate bases for compounds with different pKa values. This lesson details, in-depth, the principle of solvating effects. The strength of an acid and the stability of its corresponding conjugate base are determined using pKa values. This observed relationship is a consequence of solvation, which is the interaction...
Molecular Structure and Acidity02:34

Molecular Structure and Acidity

An acid can be deprotonated to form a conjugate base or an anion. If the produced anion is more stable, then the acid is stronger. On the contrary, if the anion is unstable, then the acid is weaker. Hence, to determine the acidity of the compound, the stability of its conjugate base is studied using various factors.
The size effect explains the change in atomic size on acidity. When comparing the acids formed from elements that belong to the same column in the periodic table, their atomic sizes...
Leveling Effect01:29

Leveling Effect

In acid-base chemistry, the leveling effect refers to the limitation imposed by the solvent on the strength of acids and bases in solution. When a base stronger than the solvent's conjugate base is used, it deprotonates the solvent until the base is entirely consumed, making it ineffective against weaker acids. Conversely, an acid stronger than the solvent's conjugate acid protonates the solvent until the acid is depleted, rendering it ineffective against weaker bases. Essentially, the solvent...
Leveling Effect and Non-Aqueous Acid-Base Solutions02:11

Leveling Effect and Non-Aqueous Acid-Base Solutions

This lesson defines the leveling effect in acidic and basic solutions and its role in aqueous and non-aqueous solutions. It is essential to understand the competing nature of various species in a chemical system.
The Leveling Effect of a Solvent
A generic acid (HA) reacts with the generic base (B-) to yield the corresponding conjugate base (A-) and conjugate acid (HB):
Basicity of Aliphatic Amines01:21

Basicity of Aliphatic Amines

Amines can behave as Brønsted–Lowry bases by accepting a proton from the acid to form corresponding conjugate acids. Due to a lone pair of nonbonding electrons, aliphatic amines can also act as Lewis bases by forming a covalent bond with an electrophile.
To measure the basicity of amines, two conventions are generally used. The first defines Kb as the basicity constant for the deprotonation reaction of water by the amine, as presented in Figure 1. Conventionally, lower Kb indicates higher...

You might also read

Related Articles

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

Sort by
Same author

Challenges and opportunities to include patient-centric product design in industrial medicines development to improve therapeutic goals.

British journal of clinical pharmacology·2020
Same author

Reduced Crystallization Temperature Methodology for Polymer Selection in Amorphous Solid Dispersions: Stability Perspective.

Molecular pharmaceutics·2016
Same author

A prodrug strategy for the oral delivery of a poorly soluble HCV NS5B thumb pocket 1 polymerase inhibitor using self-emulsifying drug delivery systems (SEDDS).

Bioorganic & medicinal chemistry letters·2014
Same author

Origin of two modes of non-isothermal crystallization of glasses produced by milling.

Pharmaceutical research·2011
Same author

Miscibility/stability considerations in binary solid dispersion systems composed of functional excipients towards the design of multi-component amorphous systems.

Journal of pharmaceutical sciences·2009
Same author

Crystallization of cephalothin sodium during lyophilization from tert-butyl alcohol-water cosolvent system.

Pharmaceutical research·2005

Related Experiment Video

Updated: Jun 29, 2026

Controlling the Size, Shape and Stability of Supramolecular Polymers in Water
16:24

Controlling the Size, Shape and Stability of Supramolecular Polymers in Water

Published on: August 2, 2012

Improved physical stability of amorphous state through acid base interactions.

Chitra Telang1, Siddharthya Mujumdar, Michael Mathew

  • 1Pharmaceutical R&D, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, Connecticut 06877, USA. chitra.telang@boehringer-ingelheim.com

Journal of Pharmaceutical Sciences
|October 7, 2008
PubMed
Summary

Specific interactions, like amorphous salt formation between indomethacin (IMC) and meglumine (MU), significantly enhance drug stabilization in dispersions. This chemical interaction improves physical stability, even with low glass transition temperatures.

More Related Videos

How to Stabilize Protein: Stability Screens for Thermal Shift Assays and Nano Differential Scanning Fluorimetry in the Virus-X Project
07:22

How to Stabilize Protein: Stability Screens for Thermal Shift Assays and Nano Differential Scanning Fluorimetry in the Virus-X Project

Published on: February 11, 2019

Sedimentation Equilibrium of a Small Oligomer-forming Membrane Protein: Effect of Histidine Protonation on Pentameric Stability
09:49

Sedimentation Equilibrium of a Small Oligomer-forming Membrane Protein: Effect of Histidine Protonation on Pentameric Stability

Published on: April 2, 2015

Related Experiment Videos

Last Updated: Jun 29, 2026

Controlling the Size, Shape and Stability of Supramolecular Polymers in Water
16:24

Controlling the Size, Shape and Stability of Supramolecular Polymers in Water

Published on: August 2, 2012

How to Stabilize Protein: Stability Screens for Thermal Shift Assays and Nano Differential Scanning Fluorimetry in the Virus-X Project
07:22

How to Stabilize Protein: Stability Screens for Thermal Shift Assays and Nano Differential Scanning Fluorimetry in the Virus-X Project

Published on: February 11, 2019

Sedimentation Equilibrium of a Small Oligomer-forming Membrane Protein: Effect of Histidine Protonation on Pentameric Stability
09:49

Sedimentation Equilibrium of a Small Oligomer-forming Membrane Protein: Effect of Histidine Protonation on Pentameric Stability

Published on: April 2, 2015

Area of Science:

  • Physical Chemistry
  • Materials Science
  • Pharmaceutical Science

Background:

  • Amorphous solid dispersions are crucial for improving the solubility and bioavailability of poorly soluble drugs.
  • Understanding the role of specific molecular interactions is key to designing stable amorphous formulations.
  • Indomethacin (IMC) is a model weakly acidic drug, meglumine (MU) a base, and polyvinyl pyrollidone (PVP) a common polymer excipient.

Purpose of the Study:

  • To investigate the role of specific interactions in the formation and stabilization of amorphous states in drug dispersions.
  • To compare the stabilization effects in binary (drug-polymer) and ternary (drug-base-polymer) systems.
  • To elucidate the mechanism of stabilization imparted by specific interactions, including salt formation.

Main Methods:

  • Preparation of dispersions via solvent evaporation and cryo-milling.
  • Characterization using X-ray powder diffraction (XRPD), polarized light microscopy (PLM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier-transform infrared spectroscopy (FTIR).
  • Analysis of drug-excipient interactions and solid-state properties.

Main Results:

  • Meglumine (MU) exhibits a high crystallization tendency and a low glass transition temperature (T(g) ~17°C).
  • Indomethacin (IMC) crystallization was effectively inhibited in ternary dispersions with MU compared to binary IMC/PVP systems.
  • Spectroscopic data confirmed the formation of an IMC-MU amorphous salt, indicating solid-state proton transfer and improved physical stability.
  • The IMC-MU amorphous salt (T(g) ~50°C) demonstrated enhanced physical stability, resisting crystallization even in stoichiometric excess of MU.

Conclusions:

  • Specific chemical interactions, particularly amorphous salt formation between IMC and MU, play a dominant role in the physical stabilization of amorphous drug dispersions.
  • The formation of an IMC-MU amorphous salt disrupts the local structure of amorphous IMC, enhancing its physical stability.
  • Salt formation can be induced both thermally and mechanically, offering versatile formulation strategies.
  • Improved physical stability of IMC in polymer dispersions containing MU highlights the importance of chemical interactions over solely relying on high T(g) excipients.