Journal
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 17, Issue 1-2, Pages 13-21Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0928-0987(02)00129-X
Keywords
orthorhombic paracetamol; crystal morphology; solvent mediated transformation
Categories
Ask authors/readers for more resources
Orthorhombic paracetamol (form 11) can be obtained from ethanolic solution when seeding technique is applied although it converts to monoclinic (form 1) upon contact with the solvent. In the present work different cooling temperature T-C (-20, - 10 and 0 degreesC) was applied under fixed agitation (700 rpm) and the crystalline product was harvested after different crystallization time t(H) (20, 30 and 40 min). Crystal yield (Y%), micromeritic properties and orthorhombic content of the crystalline product were evaluated and related to T, and t(H). Conditions for optimal crystal yield and orthorhombic content were elucidated and kinetic parameters of solvent mediated transformation (induction times, t(it), and activation energy, E-a) were determined. It was found that crystal yield (Y%) increases with t(H) and decreases with T-C. The mean crystal size and size distribution is affected linearly by T-C, probably due to alterations in the nucleation and growth processes. The effects on the crystal shape can be elucidated only after size classification. As the crystals grow, they become more elongated, with rougher surface due to secondary nucleation and alteration in growth rate of different crystal faces. Induction times for solvent mediated transformation (t(it)), were remarkably longer than those corresponding to appearance of monoclinic form, when large scale collection and drying of crystalline product was applied, probably due to residual solvent evaporation. The activation energy of solvent mediated transformation (E-a=62.9 kJ/mol) is between those for nucleation in the solid state and in a solvent, indicating the operation of a mixed mechanism. (C) 2002 Published by Elsevier Science B.V..
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available