Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2486716 | Journal of Pharmaceutical Sciences | 2009 | 11 Pages |
Abstract
Five crystal forms of the amide-type local anesthetic S-bupivacaine hydrochloride (levobupivacaine) were prepared and characterized by means of thermal analytical methods, FTIR- and Raman-spectroscopy, powder X-ray diffractometry, and moisture sorption analysis. Commercial lots of the substance may consist of form A°, the thermodynamically stable form at 20°C, and/or the metastable form C. Form A° shows a highly reversible transformation into form B (Ttrs: 85.3°C) with a transition enthalpy of 4.6 kJ molâ1. The hysteresis between the experimental transition temperatures is 3.5 K, indicating a very weak kinetic control. The hydrate shows a variable water content (0.71-1.14 mol/mol) between 10% and 90% relative humidity (RH) and dehydrates to form C under dry conditions or at elevated temperatures. All anhydrous forms transform to the hydrate at and above 90% RH (25°C). Form C slowly converts to form A° on storage and is the polymorph with the highest hygroscopicity. At higher temperatures all forms transform into form D, which is kinetically stable at 20°C. It is concluded that the forms A°, B, and D are enantiotropically related, whereas form C shows a monotropic relationship to these forms and is metastable in the entire temperature range.
Keywords
Related Topics
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Drug Discovery
Authors
V. Niederwanger, F. Gozzo, U.J. Griesser,