New processing technique for viscous amorphous materials and characterisation of their stickiness and deformability.

This paper reports on a technique using ultrasound-assisted equipment to characterise and handle stickiness of viscous amorphous blends of citric acid and paracetamol after melt mixing and during processing. Deformability and stickiness were studied using a specially designed sample measurement compartment. An ultrasound-assisted nozzle and knife for pharmaceutical applications were studied. The application of ultrasound was found to increase the mass flow through a nozzle connected to a pressurized tank. This effect was found to be separate from the increased mass transport resulting from the reduced viscosity as the temperature was increased. Ultrasound was also found to have a favourable influence on cutting through melt extrudates. The stickiness and resistance to deformation of samples were observed to be dependent on the amount of paracetamol in the blend and temperature that was in agreement with the glass transition temperature and viscosity. Other influencing factors, such as time-dependent wetting and surface energetics, are discussed. We conclude that it is possible to characterise stickiness and resistance to deformation of viscous amorphous materials with a specially designed probe test, and the stickiness of amorphous material can be handled during processing with ultrasound-assisted equipment.

Characterization of ultrasound extrudated and cut citric acid/paracetamol blends.

The purpose of the present work was to study the effect of ultrasound extrusion and cutting on the physical stability of a viscous and sticky supercooled melt containing (50/50, w/w, %) citric acid anhydrate and paracetamol. Samples were extrudated at temperatures of 50, 60, and 70 degrees C using power levels of 0, 50, 100, and 150 W. Similarly, extrudates prepared at 60 degrees C were cut at temperatures ranging from 25-60 degrees C with an ultrasound knife in the range 0, 50, and 100 W. The characterization methods used were: high performance liquid chromatography, differential scanning calorimetry, Karl Fischer titration, X-ray powder diffraction, Fourier transform infrared microscopy, optical- and stereomicroscopy. There was no physical difference in extrudates or cut surfaces whether processed with or without ultrasound. During 1-year aging time in dry conditions, all the samples were observed to crystallize slowly and ultrasound processing did not enhance the crystallization. Ultrasound thus holds some promise for processing of viscous and sticky pharmaceuticals, provided the material is physically stable enough to withstand mechanical and thermal stress. Processing of sticky and viscous material would be difficult without ultrasound with the methods currently used in pharmaceutical industry.

A solid-state NMR study of phase structure, molecular interactions, and mobility in blends of citric acid and paracetamol.

Citric acid anhydrate (CAA) and paracetamol (PARA), prepared as crystalline physical mixtures and as amorphous blends, were studied using (13)C solid-state cross polarization magic angle spinning (CPMAS) NMR. Amorphous blends showed significant line broadening from the conformational distribution as compared to the crystalline samples. Also, chemical shift variations were observed between crystalline and amorphous blends, which were attributed to differences in intermolecular interactions. Averaging of proton rotating-frame spin-lattice relaxation times (T(1rho)) probed via different (13)C sites in the amorphous blends confirmed molecular level mixing. For some, initially amorphous, sample compositions the onset of crystallization was evident directly from spectra and from the significantly longer T(1rho) relaxations. Thus, crystallization caused phase separation with properties of the two phases resembling those of pure CAA and PARA, respectively. (13)C spectra of amorphous 50/50 (w/w, %) CAA/PARA recorded from above the glass transition temperature broadened as the temperature increased to a maximum at T approximately T(g) + 33 K. This was the result of a dynamic interference between the line narrowing techniques being applied and the time scale of molecular reorientation in the miscible melt. The derived average correlation time was found to correspond well with previous results from melt rheology. We conclude that the underlying reasons for physical instability (i.e., crystallization from the miscible melt, including molecular interactions and dynamics) of this class of amorphous binary mixtures can be effectively evaluated using NMR spectroscopy.