Document Detail

Polymorph Formation and Nucleation Mechanism of Tolfenamic Acid in Solution: An Investigation of Pre-nucleation Solute Association.
MedLine Citation:
PMID:  21879384     Owner:  NLM     Status:  Publisher    
PURPOSE: Crystallization from solution involves nucleation and growth; growth conditions greatly influence self-association behaviors of solute molecules in these steps, affecting crystal packing of organic molecules. We examined the role of pre-nucleation association to provide insights into the mutual influence between molecular conformation in solution and packing in the solid state. METHODS: Crystallization experiments of tolfenamic acid were conducted in ethanol under different supersaturation conditions. UV spectroscopy was performed to study self-association of solute molecules in ethanol as a function of concentration. Intermolecular interaction energies of tolfenamic acid dimers were calculated with quantum mechanical methods. RESULTS: As supersaturation increased, growth of the most stable polymorph outpaced the metastable one, contradicting Ostwald's Rule of Stages. UV spectroscopy measurement suggests solute molecules exist as hydrogen-bonded dimers and more dimers form as total concentration increases. Hydrogen bonding in the most stable form is significantly stronger than that in the metastable form. CONCLUSIONS: With the fact that molecular conformation is different in the two polymorphs, as concentration increases, solute molecules rearrange their conformations to form stronger hydrogen-bonded dimers in solution, resulting in nucleation of the most stable form.
Alessandra Mattei; Tonglei Li
Related Documents :
3539884 - Serum stability of 67cu chelates: comparison with 111in and 57co.
24005524 - 2-[anilino(diphenylphosphoryl)methyl]phenol from a three-component kabachnik-fields rea...
24548994 - Photoresponsive metallo-hydrogels based on visual discrimination of the positional isom...
23634094 - (z)-9-(1,2-dichloro-vin-yl)-9h-carbazole.
19217164 - Probing for missing links in the binary and ternary v(v)-citrate-(h2o2) systems: synthe...
22239984 - Morphological determination of face-centered-cubic metallic nanoparticles by x-ray diff...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-31
Journal Detail:
Title:  Pharmaceutical research     Volume:  -     ISSN:  1573-904X     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-8-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  White matter abnormalities and their impact on attentional performance in adult attention-deficit/hy...
Next Document:  OMIT: A Domain-Specific Knowledge Base for MicroRNA Target Prediction.