An investigation into the structure and bioavailability of a-tocopherol dispersions in Gelucire 44/14

In this investigation we describe the preparation, physical characterisation and in vivo behaviour of solid dispersions of a liquid nutraceutical, ±-tocopherol, in Gelucire 44/14 with a view to establishing whether dispersion in this matrix may provide a means of formulating a liquid drug in a solid dosage form while also improving the oral bioavailability. Using Vitamin E Preparation USP as the source of ±-tocopherol, dispersions were prepared using a melt-fusion method with active loadings up to 50% (w/w) and characterised using differential scanning calorimetry and optical microscopy. Capsules containing 300 IU ±-tocopherol were manufactured and the absorption profiles compared to a commercial soft gelatin capsule preparation in healthy human volunteers. Confocal laser scanning microscopy (CLSM) studies were performed in order to elucidate the mechanism by which drug release may be occurring. Differential scanning calorimetry studies indicated that the presence of the active had a negligible effect on the melting profile of the carrier, indicating limited miscibility between the two components, a conclusion supported by the microscopy studies. Similarly, the dispersions were shown to exhibit a glass transition corresponding to the incorporated drug, indicating molecular cooperativity and hence phase separation from the lipid base. Despite the phase separation, it was noted that capsules stored for 18 months under ambient conditions showed no evidence of leakage. Bioavailability studies in six healthy male volunteers indicated that the Gelucire 44/14 formulation showed an approximately two-fold increase in total ±-tocopherol absorption compared to the commercial preparation. Confocal laser scanning microscopy studies indicated that, on contact with water, the dispersions formed two interfacial layers, from which the Gelucire 44/14 disperses in the liquid medium as small particles. Furthermore, evidence was obtained for the dispersed material becoming incorporated into the hydrated lipid. In conclusion, the dispersion of the liquid drug in Gelucire 44/14 appears to allow the dual advantages of the preparation of a solid formulation and improved bioavailability of this material.

Presence of cave bears in western Austria before the onset of the Last Glacial Maximum: new radiocarbon dates and palaeoclimatic considerations

Tischoferhohle and Pendling-Barenhohle near Kufstein, Tyrol, are among the only locations where remains of cave bear, Ursus spelaeus-group, were found in the western part of Austria. One sample from each site was radiocarbon-dated four decades ago to ca. 28 C-14 ka BP. Here we report that attempts to date additional samples from Pendling-Barenhohle have failed due to the lack of collagen, casting doubts on the validity of the original measurement. We also unsuccessfully tried to date flowstone clasts embedded in the bone-bearing sediment to provide maximum constraints on the age of this sediment. Ten cave bear bones from Tischoferhohle showing good collagen preservation were radiocarbon-dated to 31.1-39.9 C-14 ka BP, again pointing towards an age underestimation by the original radiocarbon-dated sample from this site. These new dates from Tischoferhohle are therefore currently the only reliable cave bear dates in western Austria and constrain the interval of cave occupation to 44.3-33.5 cal ka BP. We re-calibrate and re-evaluate dates of alpine cave bear samples in the context of available palaeoclimate information from the greater alpine region covering the transition into the Last Glacial Maximum, eventually leading to the demise of this megafauna.

Electron-impact excitation of W 44+ and W 45+

Plans to employ tungsten in the divertor region of the International Thermonuclear Experimental Reactor require radiative and collisional data for modelling x-ray emissions of highly ionized stages of tungsten. In an earlier paper, we reported on the results of fully relativistic R -matrix calculations for W 46+ that included the effects of radiation damping on the resonance contributions. In this paper, we present the results of similar fully relativistic, radiatively damped R -matrix calculations for W 44+ and W 45+ . Radiation damping is found to be small for W 45+ , but is appreciable for many of the excitations from the ground and metastable levels of W 44+ . Rates from the present calculations will be combined with those from the calculations for W 46+ and employed for collisional-radiative modelling for these ions.