Issue 28, 2015

Polymorphism in anti-hyperammonemic agent N-carbamoyl-l-glutamic acid

Abstract

Carglumic acid (CGA) is used for the treatment of hyperammonaemia. The aim of this study was to investigate novel crystalline forms of CGA which can offer improved physicochemical properties and also to understand the stability relationships between such forms. We report two novel polymorphs I and II and a degradation derivative of the drug hydantoin-5-propionic acid (5-HPA). Crystallization conditions have been optimized to obtain each polymorph in reproducible crystallization batches. 5-HPA was obtained serendipitously upon crystallization of CGA in acidic medium (2-butanone : propionic acid). The X-ray crystal structures of CGA Form-I and Form-II and 5-HPA are sustained by carboxylic acid catemer and dimer, carboxamide catemer and dimer and an acid–amide heterosynthon. The two polymorphs are monotropically related. Thermodynamic stability, phase transformation, and Hirshfeld surface maps complement the structural analysis. Both forms are stable for two months under accelerated ICH conditions of 40 °C and 75% RH. Dynamic vapor sorption (DVS) showed that Form-I is more stable under moisture conditions than Form-II. Slurry crystallization, mechanical grinding and thermal measurements confirm the thermodynamic nature of CGA Form-I.

Graphical abstract: Polymorphism in anti-hyperammonemic agent N-carbamoyl-l-glutamic acid

  • This article is part of the themed collection: Polymorphism

Supplementary files

Article information

Article type
Paper
Submitted
18 जनवरी 2015
Accepted
20 फरवरी 2015
First published
20 फरवरी 2015

CrystEngComm, 2015,17, 5252-5265

Author version available

Polymorphism in anti-hyperammonemic agent N-carbamoyl-L-glutamic acid

D. Maddileti and A. Nangia, CrystEngComm, 2015, 17, 5252 DOI: 10.1039/C5CE00116A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements