Correlation of thermal analysis and pyrolysis coupled to GC-MS in the characterization of tacrolimus

摘要

In recent years, thermal analysis has assumed major role in the pharmaceutical industry because it can be used to evaluate the stability both in the control of raw materials and the finished product, having employment potential in the development and characterization of new products and assessment processes. Tacrolimus (TCR) is a macrolide lactone with potent immunosuppressive activity. The purpose of this study was to characterize tacrolimus raw material using Thermal analysis and Pyrolysis coupled to Gas chromatography-Mass spectrometry (Pyr-GC-MS). It was analyzed four samples of tacrolimus named TCR A, B, C and D. Thermal analysis experiments was performed in Shimadzu equipment, under nitrogen and synthetic air atmosphere in different heating rate. Pyrolysis analysis was conducted in isothermal conditions of 300 degrees C and 400 degrees C coupled to GC-MS, in which the mass spectrometer was operated in scan mode to detect ions in the range of mass of m/z 25-900. The thermal studies by DSC, DTA and DSC-Photovisual showed desolvation process for all tacrolimus raw materials and TG-dynamical demonstrated two pseudo-polymorphic forms (monohydrate and sesquihydrate) of tacrolimus. It was observed good correlation between the stoichiometric mass losses of the TG-dynamical and identification of product ion in Pyr-GC/MS technique. It was possible to correlate the five pyrolytic product ions with the Ozawa kinetic analysis from the thermal decomposition of TG-dynamical. The thermal studies (DSC, DSC-Photovisual, DTA and TG-dynamical) were applied in the thermal characterization of the raw materials of tacrolimus which showed pseudo-polymorphic forms, which must be monitored by pharmaceutical industry, avoiding future problems in pharmaceutical process, chemical stability and bioavailability of the tacrolimus product. (C) 2012 Elsevier B.V. All rights reserved.