Applications of pressure differential scanning calorimetry in the study of pharmaceutical hydrates. II. Ampicillin trihydrate

Jun Han, Sangeeta Gupte, Raj Suryanarayanan

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32 Scopus citations


The dehydration of ampicillin trihydrate (C16H19N3O4S.3H2O) was studied by both conventional differential scanning calorimetry (DSC) and by pressure differential scanning calorimetry (PDSC). The solid state of the anhydrous phase formed was influenced by the DSC conditions. At ambient pressure, dehydration resulted in the formation of X-ray amorphous anhydrous ampicillin, while at elevated pressures a crystalline anhydrate was obtained. These conclusions were based on variable temperature X-ray powder diffractometry (VTXRD) which was used as a complementary technique. PDSC was a reliable technique to quantify the relative amounts of ampicillin trihydrate and anhydrous ampicillin when they occur as a mixture. Grinding-induced alterations in the degree of crystallinity of ampicillin trihydrate were also quantified by PDSC. The changes in crystallinity induced after milling for just 1 min were detected and quantified with a high degree of precision. PDSC appears to be an excellent technique not only for the characterization but also for obtaining quantitative information about the solid state of pharmaceutical hydrates. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)63-72
Number of pages10
JournalInternational journal of pharmaceutics
Issue number1
StatePublished - Aug 1 1998

Bibliographical note

Funding Information:
JH was partially supported by the International Student Work Opportunity Program of the University of Minnesota. We thank Laura Connor and Dr Murti Vemuri of Rhone-Poulenc Rorer for their assistance in the HPLC experiments.

Copyright 2004 Elsevier Science B.V., Amsterdam. All rights reserved.


  • Ampicillin trihydrate
  • Degree of crystallinity
  • Dehydration
  • Hydrate
  • Powder X-ray diffractometry
  • Pressure differential scanning calorimetry (PDSC)


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