Potential of Cyclodextrin Complexation and Liposomes in Topical Delivery of Ketorolac: In Vitro and In Vivo Evaluation

The objective of this investigation was to evaluate the effect of delivery strategies such as cyclodextrin complexation and liposomes on the topical delivery of ketorolac acid (KTRA) and ketorolac tromethamine. Ketorolac acid–hydroxypropyl-β-cyclodextrin solid dispersions (KTRA-CD) were prepared by kneading method. The liposomes containing ketorolac tromethamine (KTRM) and KTRA-CD were prepared. The in vitro permeation of KTRM solution, KTRA solution, KTRA-CD, and liposomes containing KTRM or KTRA-CD through guinea pig skin was evaluated. The anti-inflammatory activity of the topically applied KTRA-CD gel (containing 1% w/w KTRA) was compared to that of orally delivered KTRM solution. The KTRA-CD demonstrated significantly higher transdermal transport of ketorolac as compared to all other systems whereas liposomes significantly reduced the transport of ketorolac. The anti-inflammatory activity of the topically applied KTRA-CD gel was similar to that of the orally administered KTRM. Thus, cyclodextrin complexation enabled effective transdermal delivery of the ketorolac

Fusion Energy-Production from a Deuterium-Tritium Plasma in the Jet Tokamak

The paper describes a series of experiments in the Joint European Torus (JET), culminating in the first tokamak discharges in deuterium-tritium fuelled mixtures. The experiments were undertaken within limits imposed by restrictions on vessel activation and tritium usage. The objectives were: (i) to produce more than one megawatt of fusion power in a controlled way; (ii) to validate transport codes and provide a basis for accurately predicting the performance of deuterium-tritium plasma from measurements made in deuterium plasmas; (iii) to determine tritium retention in the torus systems and to establish the effectiveness of discharge cleaning techniques for tritium removal; (iv) to demonstrate the technology related to tritium usage; and (v) to establish safe procedures for handling tritium in compliance with the regulatory requirements. A single-null X-point magnetic configuration, diverted onto the upper carbon target, with reversed toroidal magnetic field was chosen. Deuterium plasmas were heated by high power, long duration deuterium neutral beams from fourteen sources and fuelled also by up to two neutral beam sources injecting tritium. The results from three of these high performance hot ion H-mode discharges are described: a high performance pure deuterium discharge; a deuterium-tritium discharge with a 1% mixture of tritium fed to one neutral beam source; and a deuterium-tritium discharge with 100% tritium fed to two neutral beam sources. The TRANSP code was used to check the internal consistency of the measured data and to determine the origin of the measured neutron fluxes. In the best deuterium-tritium discharge, the tritium concentration was about 11% at the time of peak performance, when the total neutron emission rate was 6.0 x 10(17) neutrons/s. The integrated total neutron yield over the high power phase, which lasted about 2 s, was 7.2 x 10(17) neutrons, with an accuracy of +/- 7%. The actual fusion amplification factor, Q(DT), was about 0.15. With an optimum tritium concentration, this pulse would have produced a fusion power of almost-equal-to 5 MW and a nominal Q(DT) almost-equal-to 0.46. The same extrapolation for the pure deuterium discharge would have given almost-equal-to 11 MW and a nominal Q(DT) = 1.14, so that the total fusion power (neutrons and alpha-particles) would have exceeded the total losses in the equivalent deuterium-tritium discharge in these transient conditions. Techniques for introducing, tracking, monitoring and recovering tritium were demonstrated to be highly effective: essentially all of the tritium introduced into the neutral beam system and, so far, about two thirds of that introduced into the torus have been recovered