Influence of process temperature and residence time on the manufacturing of amorphous solid dispersions in hot melt extrusion.

The manufacturing of amorphous solid dispersions via hot melt extrusion is a topic of high interest in pharmaceutical development. By this technique, the drug is dissolved in the molten polymer above solubility temperature within the process time. In this study, an experimental framework is proposed determining the minimum required process temperature and the residence time using particularly low quantities of material. Drug/polymer mixtures in different ratios were processed in a micro-scale extruder while the process temperature and residence time were varied systematically. The phase situation was assessed by the turbidity of the final extrudate. Four different drug/polymer mixtures were investigated in three drug/polymer ratios. The minimum required process temperature was close to solubility temperature for each specific formulation. Moreover, an influence of residence time on the phase situation was found. About three minutes were required in order to dissolve the drug in the polymer at these process conditions.

The relaxation behavior of supercooled and glassy imidacloprid.

Employing dielectric spectroscopy, oscillatory shear rheology, and calorimetry, the present work explores the molecular dynamics of the widely used insecticide imidacloprid above and below its glass transition temperature. In its supercooled liquid regime, the applied techniques yield good agreement regarding the characteristic structural (alpha) relaxation times of this material. In addition, the generalized Gemant-DiMarzio-Bishop model provides a good conversion between the frequency-dependent dielectric and shear mechanical responses in its viscous state, allowing for an assessment of imidacloprid's molecular hydrodynamic radius. In order to characterize the molecular dynamics in its glassy regime, we employ several approaches. These include the application of frequency-temperature superposition (FTS) to its isostructural dielectric and rheological responses as well as use of dielectric and calorimetric physical aging and the Adam-Gibbs-Vogel model. While the latter approach and dielectric FTS provide relaxation times that are close to each other, the other methods predict notably longer times that are closer to those reflecting a complete recovery of ergodicity. This seemingly conflicting dissimilarity demonstrates that the molecular dynamics of glassy imidacloprid strongly depends on its thermal history, with high relevance for the use of this insecticide as an active ingredient in technological applications.

Occurrence of 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate (Texanol) in foods packed in polystyrene and polypropylene cups.

After simultaneous distillation-extraction (SDE) of foods packed in polystyrene (n = 77) and polypropylene cups (n = 42) from 61 different suppliers, coupled capillary gas chromatography-mass spectrometric (HRGC-MS) analyses indicated the presence of diastereomers of 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate (TMPD-MIB; Texanol), a known coalescent of paints and printing inks. The contaminant was found in 55 and 50% of the polystyrene and polypropylene packed samples, respectively. Amounts ranged 1.2-64.5 microg kg(-1) in polystyrene cups (average 25.1 microg kg(-1)) and 0.9-45.7 microg kg(-1) in polypropylene cups (average 10.8 microg kg(-1)). The origin of Texanol in the printed plastic cups was demonstrated by separate HRGC-MS analysis, showing amounts in the higher microg kg(-1) range. In addition, the presence of two pairs of enantiomers, both found to be racemic by enantioselective multi-dimensional gas chromatography-mass spectrometry (enantio-MDGC-MS), excluded it being of natural origin. The detection limit of overall procedure (DLOP) and the reliable quantification limit (RQL) were 0.2 and 0.9 microg kg(-1), respectively. As the diester, 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB), is on the EU list of regulated substances (restricted to single-use gloves only) with a migration limit of 5 mg kg(-1) in food and is metabolised rapidly by hydrolysis, the observed migration of the monoester Texanol at the microg kg(-1) level poses no risk of adverse effects.