Quantification of Polymorphic Mixtures by Whole Pattern Rietveld Analysis with and without Crystal Structure Models



Quantification of Polymorphic Mixtures by  Whole  Pattern Rietveld Analysis with and without  Crystal  Structure  Models


Antonietta Guagliardi
Rocco Caliandro
Giuseppe Chita
Rocco Lassandro


Commessa:  PM.P04.011 / Diffrazione e imaging a raggi x per l'ingegneria di materiali nanostrutturati e tessuti biologici e per la biodiagnostica
Modulo: PM.P04.011.001 / Sviluppo di metodi e caratterizzazione di materiali cristallini alla nano, micro e mesoscala


Rietveld Quantitative Phase analysis, Polymorphism, Pharmaceuticals

Institute on Membrane Technology, ITM, CNR, Cosenza, Italy.
Department of Chemical and Materials Engineering, University of Calabria, Cosenza, Italy.

Polymorphism, that is the ability of a compound to adopt more than one crystal form, is a fundamental issue in many fields, some of which have enormous economic and social impacts: Pharmaceuticals, Food and Agrochemicals, Pigments, Explosive, etc. As an example, two important aspects of polymorphism are relevant to the development of drugs: the medical aspect, because crystalline powder drugs that are orally administered, have a dissolution rate depending on the crystal form; the patent aspect, because drugs receive a regulatory approval for a specific polymorph. The expertise in phase quantification of polymorphic mixtures can play a relevant role in most of the aforementioned fields. Powder diffraction and the "standard" Rietveld method, which can be applied only when all the crystal structure models of polymorphs are available, is by far the most accurate approach to the problem and, for this reason, largely used. It is implemented in the program QUANTO (link webpage distribution), developed by the IC team, and successfully applied (as an example) to quantify and, indirectly, to control, the antisolvent membrane crystallization process used to influence the polymorphic composition of L-histidine aminoacid (in favour of the less thermodynamically stable form B) or to address the co-crystallization of carbamazepine with nicotinamide, isonicotinamide, saccharin and aspirin.

A problematic aspect of polymorphic quantification, especially for pharmaceuticals, is that the crystal structure of some polymorphs is not available by single crystal and often too complex to be solved by ab initio powder diffraction methods. These cases have been already successfully dealt with by using QUANTO on (undisclosable) pharmaceutical compounds, by adopting a non standard Rietveld approach that, in case of unknown or imperfectly known crystal structure, takes advantage of the experimental pattern of the pure phase.


Guagliardi Antonietta
Email : antonietta.guagliardiATic.cnr.it
Tel : +39 031-2386636


Last Updated (Thursday, 02 December 2010 16:22)