Abstract
Salt formation has been extensively used to improve drug properties, including solubility, stability and mechanical properties. A sweet salt of metformin with acesulfame, prepared though an anion exchange reaction, showed superior properties over the commercial hydrochloride salt. These included both remarkable improvement of taste and significant enhancement in tabletability, which is explained by the different crystal structures and lower hardness as measured by nanoindentation. The relationship among crystal structure, mechanical properties and tabletability was rationalized through an energy framework analysis. This approach led to the successful development of an orally disintegrating tablet product containing 60% of metformin-acesulfame salt by direct compaction.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 435-443 |
| Number of pages | 9 |
| Journal | International journal of pharmaceutics |
| Volume | 532 |
| Issue number | 1 |
| DOIs | |
| State | Published - Oct 30 2017 |
Bibliographical note
Funding Information:We are grateful for resources from the University of Minnesota through the Minnesota Supercomputing Institute. Some of the experiments were performed at the University of Minnesota I.T. Characterization Facility, which receives partial support from the NSF through the NNIN program. We thank Kunling Wang at Department of Pharmaceutics, University of Minnesota for collecting the Raman data and Ms. Lindsay Johnson at Department of Chemistry, University of Minnesota for collecting TGA data. This research did not receive any specific grant from funding agencies from the public, commercial, or not-for-profit sectors.
Publisher Copyright:
© 2017 Elsevier B.V.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
Keywords
- Direct compression
- Formulation development
- Metformin
- Orally disintegrating tablet
- Sweet salt