Dear Syaiful,

The best and efficient way is by x-ray diffraction.

For similar cases to your case, please use the following link:

http://pubs.acs.org/doi/abs/10.1021/cg9001994

Although the following paper is not directly deals with your problem but it might be interesting to read it:

Polymorphs, Salts, and Cocrystals: What’s in a Name?

Cryst. Growth Des., 2012, 12 (5), pp 2147–2152

DOI: 10.1021/cg3002948

Publication Date (Web): April 12, 2012

Copyright © 2012 American Chemical Society

*E-mail: [email protected] (M.Z.); [email protected] (G.R.D.); [email protected] (P.K.); [email protected](R.K.T).

Synopsis

Names can mean everything when classifying solid forms of active pharmaceutical ingredients as exemplified by fluoxetine HCl, the active ingredient of Prozac, left, and its carboxylic acid cocrystals, for example, right. Whereas Prozac is a salt, how should one classify cocrystals of salts? This perspective addresses such issues in light of recently proposed regulatory guidelines for classification of active pharmaceutical ingredients.

Abstract

he December 2011 release of a draft United States Food and Drug Administration (FDA) guidance concerning regulatory classification of pharmaceutical cocrystals of active pharmaceutical ingredients (APIs) addressed two matters of topical interest to the crystal engineering and pharmaceutical science communities: (1) a proposed definition of cocrystals; (2) a proposed classification of pharmaceutical cocrystals as dissociable “API-excipient” molecular complexes. The Indo–U.S. Bilateral Meeting sponsored by the Indo–U.S. Science and Technology Forum titled The Evolving Role of Solid State Chemistry in Pharmaceutical Science was held in Manesar near Delhi, India, from February 2–4, 2012. A session of the meeting was devoted to discussion of the FDA guidance draft. The debate generated strong consensus on the need to define cocrystals more broadly and to classify them like salts. It was also concluded that the diversity of API crystal forms makes it difficult to classify solid forms into three categories that are mutually exclusive. This perspective summarizes the discussion in the Indo–U.S. Bilateral Meeting and includes contributions from researchers who were not participants in the meeting.

http://pubs.acs.org/doi/abs/10.1021/cg3002948

Hoping this will be helpful,

Rafik

XRD analysis is ultimate way to detect crystallinity of a poweder..

XRD analysis is ultimate way to detect crystallinity of a poweder..

XRD analysis is ultimate way to detect crystallinity of a poweder..

Thank Mr. Ravik Karaman and Mr.Jagadecappa S Patil, but using PXRD how do you use it? whether compare to the diffraction angel? it's not provide suffient reason because either salt or co crystal formation provide peaks in diffractogram, and it is difficult to distunguish either salt or co crystal formation

XRD gives you the whole structure; how atoms are connected together, distances between all atoms, torsion angles and dihedral angles. Therefore it will be very easy to validate if the structure is co-crystal or salt. Try for example to draw co crystal and salt using ChemDraw. The same picture will be seen using XRD.

Rafik

that mean using single XRD?

Yes.

ok thanks a lot, is there any other methods except single X-ray?

The proton transfer can be in principle estimated by solid-state NMR and/or IR spectra. However, the interpretation of the results in a particular system may be tricky. Still, the SC X-Ray is an ultimate method for salt/cocrystal determination, while the others are indirect and are easy to misinterpret.

You can use the values from delta pKa analysis..and also FTIR analysis...just search the publication in crystal growth and design (authors name : Ashwini Nangia, Gautam Desiraju and Reginald Tan)..you can also read my publication in Int. J. Pharmaceutics..hope this can help...Regards

In general, in order to understand the obtained solid form:

IR helps to distinguish a salt and cocrystal: For salt frequency variation is larger (greater than 10cm-1)

DSC: In general melting point of salt is greater than the two coformers (but, note that there are some higher melting cocrystals as well)

NMR gives you the information about the proton transfer

In final and the well-known prediction method is rule of pKa: If the pKa difference between the starting materials is greater than 3 then it is likely to form a salt, it is between 0-3 it could be any solid forms (salt/cocrystal), if it lies less than 0 then it can only be a cocrystal/eutectic or no solid form.

Hope this helps.

Yes,  1H NMR gives the information about proton transfer.

For better distinguish, generating the single crystal and get the single crystal analysis.