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Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism

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The Hofmann and Curtius rearrangement reactions can be applied to synthesize primary amines from carboxylic acid derivatives such as amides and acyl azides. In the Hofmann rearrangement, a primary amide undergoes deprotonation in the presence of a base, followed by halogenation to generate an N-haloamide. A second proton abstraction produces a stabilized anionic species, which rearranges to an isocyanate intermediate via an alkyl group migration from the carbonyl carbon to the neighboring...

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Updated: Sep 13, 2025

Versatile CO2 Transformations into Complex Products: A One-pot Two-step Strategy

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Published on: November 9, 2019

Cutting-Edge Approaches in the Co-Amorphization Process.

Azza A K Mahmoud¹, Géza Regdon¹, Katalin Kristó¹

¹Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary.

|July 30, 2025

Summary

Co-amorphization enhances drug bioavailability. This review highlights amino acids like arginine and tryptophan as effective co-formers for poorly soluble drugs, detailing their selection and system evaluation.

Keywords:

amino acids co-former density functional theory drug–drug co-amorphization principal component analysis

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Area of Science:

Pharmaceutical Sciences
Materials Science

Background:

Co-amorphization is a key technique for improving the bioavailability of poorly soluble drugs.
It offers advantages over traditional amorphization methods.

Purpose of the Study:

To systematically review co-former classes and selection strategies for co-amorphous systems.
To evaluate the characteristics of drug co-amorphous systems.

Main Methods:

Systematic literature search across PubMed, Scopus, and Web of Science (2016-2024).
Keywords: co-amorphous, co-former, drug.
Inclusion criteria: studies on co-amorphous systems; exclusion criteria: other amorphization techniques, crystallization.

Main Results:

127 peer-reviewed articles were selected and summarized.
Amino acids are the most common co-formers, with arginine and tryptophan frequently used for acidic and basic drugs.
Various co-amorphous systems, their dissolution, and stability were reported.

Conclusions:

Amino acids, particularly arginine and tryptophan, are effective co-formers for enhancing drug properties.
The review provides insights into co-former selection and evaluation using various methods, including computational tools.