NMR relaxometry in the investigation of the kinetics of the recrystallization of felodipine

The method of Nuclear Magnetic Resonance (NMR) relaxometry is proposed to be applied to investigate the kinetics of the recrystallization of a substance from the amorphous phase. The method is based on the determination and analysis of nuclear magnetization recovery Mz obtained from spin-lattice T1 relaxation time measurements as a function of time since sample amorphization. The formation of a biphasic (crystalline and amorphous) system in the process of recrystallization implies that the magnetization recovery Mz is biexponential and that the amplitudes of its components are proportional to the number of spins (protons) in the crystalline and amorphous phases, and, thus, also to the volume occupied by the phases. The method was tested for amorphous felodipine samples with grain sizes close to 0.1 or 1 mm, and the recrystallization process was confirmed by using Powder X-ray Diffraction (PXRD) and Fourier-Transform Infrared (FTIR) methods. Qualitative comparison of the results obtained with the data obtained earlier by PXRD and Raman methods for felodipine samples with grain sizes of 0.2 and 0.6 mm [U. S. Kestur, I. Ivanesivic, D. E. Alonzo, L. S. Taylor, Influence of particle size on the crystallization kinetics of amorphous felodipine powders, Powder Technology 236 (2013) 197–204] showed reasonable agreement. The method is fully extensive and can be applied to amorphous samples prepared in different ways, such as grinding, milling or melting, as well as for co-amorphous or amorphous solid dispersion samples.