Thermal stability of amorphous nimesulide: from glass formation to crystal growth and thermal degradation.

Thermally induced physico-chemical transformations in amorphous nimesulide were studied by means of differential scanning calorimetry (DSC), thermogravimetry, and Raman microscopy. The equilibrium glass transition temperature was found to be Tg0 = 10-15 °C, and the relaxation motions were found to be temperature-dependent. Crystal growth from the amorphous phase was found to be crucially dependent on the presence of mechanical defects that serve as centers for heterogeneous nucleation. The large amounts of mechanical defects significantly decrease the activation energy of the macroscopic crystallization; the positions of the crystallization peaks and their asymmetry/shape remain however almost unchanged. At laboratory temperature, powdered nimesulide fully crystallizes within several hours, with an absolute majority of the crystalline phase being formed as the thermodynamically stable form I polymorph. Amorphous nimesulide does not crystallize from the free smooth surface (no trace of formed crystallites was found by optical microscopy after 30 days at laboratory temperature). Nimesulide was found to be very stable at temperatures above its melting point of 147.5 °C; thermal degradation starts to proceed slowly at 200 °C. Mutual correlations between the macroscopic and microscopic crystal growth processes and between the viscous flow and structural relaxation motions were discussed based on the values of the corresponding activation energies. A link between the cooperativity of structural domains, parameters of the Tool-Narayanaswamy-Moynihan relaxation model, and microscopic crystal growth was proposed.

Thermal degradation of Affinisol HPMC: Optimum Processing Temperatures for Hot Melt Extrusion and 3D Printing.

PURPOSE: Affinisol HPMC HME is a new popular form of hypromellose specifically designed for the hot melt extrusion and 3D printing of pharmaceutical products. However, reports of its thermal stability include only data obtained under inert N2 atmosphere, which is not consistent with the common pharmaceutical practice. Therefore, detailed investigation of its real-life thermal stability in air is paramount for identification of potential risks and limitations during its high-temperature processing. METHODS: In this work, the Affinisol HPMC HME 15LV powder as well as extruded filaments will be investigated by means of thermogravimetry, differential scanning calorimetry and infrared spectroscopy with respect to its thermal stability. RESULTS: The decomposition in N2 was proceeded in accordance with the literature data and manufacturer's specifications: onset at ~260°C at 0.5°C·min-1, single-step mass loss of 90-95%. However, in laboratory or industrial practice, high-temperature processing is performed in the air, where oxidation-induced degradation drastically changes. The thermogravimetric mass loss in air proceeded in three stages: ~ 5% mass loss with onset at 150°C, ~ 70% mass loss at 200°C, and ~ 15% mass loss at 380°C. Diffusion of O2 into the Affinisol material was identified as the rate-determining step. CONCLUSION: For extrusion temperatures ≥170°C, Affinisol exhibits a significant degree of degradation within the 5 min extruder retention time. Hot melt extrusion of pure Affinisol can be comfortably performed below this temperature. Utilization of plasticizers may be necessary for safe 3D printing.