Diclofenac Salts. V. Examples of Polymorphism among Diclofenac Salts with Alkyl-hydroxy Amines Studied by DSC and HSM.

Adamo Fini,Francesca Ospitali,Cristina Cavallari

doi:10.3390/pharmaceutics2020136

Abstract

Nine diclofenac salts prepared with alkyl-hydroxy amines were analyzed for their properties to form polymorphs by DSC and HSM techniques. Thermograms of the forms prepared from water or acetone are different in most cases, suggesting frequent examples of polymorphism among these salts. Polymorph transition can be better highlighted when analysis is carried out by thermo-microscopy, which in most cases made it possible to observe the processes of melting of the metastable form and re-crystallization of the stable one. Solubility values were qualitatively related to the crystal structure of the salts and the molecular structure of the cation.

Highlights

A number of papers dealing with the preparation or the structure of some diclofenac salts revealed that some of them precipitate as hydrates when crystallized from water
Diclofenac salts prepared with hydroxy amines proved to be highly soluble in water [11]: it was demonstrated that, in the case of the pyrrolidine ethanol diclofenac salt, the equilibrium solubility concerns the bi-hydrate polymorph form, the one which is stable in aqueous solution
High solubility values may possibly be found since aqueous solutions of this salt tend to oversaturate and the equilibrium is very slowly reached: in these cases the estimate of the solubility of the metastable forms could be obtained by means of measurement of the intrinsic dissolution rate [13]

Summary

Introduction

A number of papers dealing with the preparation or the structure of some diclofenac salts revealed that some of them precipitate as hydrates when crystallized from water. The interesting behavior of diclofenac/pyrrolidine ethanol salt, which forms polymorphs with different extents of hydration [3,4]; and the easiness of dehydration of some alkaline diclofenac salts [5] suggested better examination of the nature of the solid state of these salts soon after their preparation or after equilibration with water in order to state the formation of hydrates and their stoichiometry or the presence of polymorphs, by suitable techniques. Since most of the salts were previously prepared in organic solvents to obtain crystalline material, in this paper we prepared a series of these salts in water and, by means of thermal analysis (differential scanning calorimetry - DSC and thermomicroscopy - HSM), assessed the formation of polymorphs, measured the solubility in water and related the solubility to the physical form of the salt present at the equilibrium

Methods

Results

Conclusion