Diclofenac salts, part 7: are the pharmaceutical salts with aliphatic amines stable?

Abstract

Eight cyclic aliphatic amines, pyrrolidine (Py), piperidine (Pp), morpholine (M), piperazine (Pz), and the N-hydroxyethyl (HE) analogues, were employed to prepare a salt with acidic diclofenac (D). These salts were examined by thermal [differential scanning calorimetry (DSC), thermogravimetric analysis, and hot-stage microscopy (HSM)] and spectroscopic [Fourier transform infrared (FTIR), Raman, (1) H NMR, and ultraviolet] analysis. The results show the thermal instability of these salts: the thermal dissociation leaves the starting acidic D, evidenced by the FTIR and Raman spectra inside the molten mass of the salts with M and HEM. The nature of the salt with Pz (1:1 or 1:2) and HEPy (anhydrous or hydrate polymorph), but not for the salt with HEPz and Py, depends on the polarity of the solvent used for the preparation of the salt. Incomplete dehydration of the hydrate Py and Pz salts progressively modifies the thermogram profiles and originates false information. Melting of the salts with Pp, M, and HEM could be demonstrated by HSM, but not with DSC. The difficulty of providing a description of these salts in a simple way originates doubts on the utility of a wide application of aliphatic amines to prepare pharmaceutical salts with D, whose solubility in water does not significantly differ from that of the common sodium D.

• Authors: Adamo Fini, Cristina Cavallari, Glenda Bassini, Francesca Ospitali, Rita Morigi
• Journal: Journal of pharmaceutical sciences (J Pharm Sci) Vol. 101 Issue 9 Pg. 3157-68 (Sep 2012) ISSN: 1520-6017 [Electronic] United States
• PMID: 22234897 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc.

Chemical References

• Amines
• Anti-Inflammatory Agents, Non-Steroidal
• Solvents
• Diclofenac

Topics

• Amines (chemistry)
• Anti-Inflammatory Agents, Non-Steroidal (chemistry)
• Calorimetry, Differential Scanning
• Chemistry, Pharmaceutical
• Diclofenac (analogs & derivatives, chemistry)
• Drug Stability
• Hydrogen-Ion Concentration
• Magnetic Resonance Spectroscopy
• Microscopy
• Models, Chemical
• Solubility
• Solvents (chemistry)
• Spectrophotometry, Ultraviolet
• Spectroscopy, Fourier Transform Infrared
• Spectrum Analysis, Raman
• Technology, Pharmaceutical (methods)
• Thermogravimetry
• Transition Temperature