A quest to find the cause of unknown peaks in cleaning verification chromatography following the manufacture of pharmaceutical preparations

Cleaning equipment following the manufacture of pharmaceutical products is of paramount importance to ensure that the following batch of product manufactured is not contaminated with therapeutic levels of the prior manufactured product. The patient must only receive the therapeutic effect expected from the drug they take. During a number of cleaning verification studies, it was discovered that unknown peaks were present in the chromatography, the source of which was unclear. A study was performed to examine a theory that the gloves used by the operator during the cleaning procedure, in combination with the solvent based cleaning products were responsible for the unknown peaks that were evident in the chromatography. NASA had performed a similar study for the critical parts of the space shuttle in the space shuttle program. The following poster examines the conclusions that were made from the data that was attained for the study. The data will answer the question: ‘Are the gloves themselves responsible by way of leachables for the unknown peaks in the cleaning verification chromatography.

Liquid-filled hard gelatin capsules : excipient/capsule compatibility studies

Encapsulation of pharmaceutical formulations as liquids or semisolids, within hard gelatin capsules, presents an important oral dosage strategy for poorly water-soluble drugs, resulting in good bioavailability and reproducible drug absorption. In addition, this technology offers an inherently safer process than powder filled capsules and tablets for highly potent or cytotoxic drugs by avoiding dust generation. Here we present a compatibility study of hard gelatin capsules with common excipients in absence of active pharmaceutical

Awareness of Meningococcal disease among travelers from the United Kingdom to the meningitis belt in Africa

Meningococcal disease causes considerable morbidity and has a high case-fatality rate. In the United Kingdom, the meningococcal quadrivalent vaccine is recommended for travelers visiting the meningitis belt of Africa. We analyzed 302 responses to a cross-sectional study conducted in 2010 of travelers who had visited the meningitis belt recently or were shortly due to travel there. Using the results of an online questionnaire, we assessed knowledge and understanding of meningococcal disease and likelihood of uptake of meningococcal immunization before travel. Meningococcal vaccine uptake was 30.1%. Although global scores in the questionnaire did not correlate with vaccine uptake, knowledge of the meningitis belt and knowledge of certain key symptoms or signs were statistically associated with high vaccine uptake. We conclude that improved education of travelers may improve vaccine uptake before travel to the meningitis belt in Africa

Explosivity : an unusual challenge in drug development

There remains an urgent global need for new drugs to combat diseases such as malaria, tuberculosis and cancer, as well as overcoming increasing antibiotic resistance. Chemists are moving into ‘new chemical space’ for drug design (1,2) and with this comes the possibility of traditional (and stable) ‘carbon-carbon’ bond structures being replaced by more ‘exotic’ bonding arrangements. While the implication of this on pharmaceutical stability can often be mitigated by suitable formulation and storage strategies, we came across an unusual case of chemical stability: the possibility that the drug was an explosive! By pushing drug designing into uncharted chemical space it could be argued that the possibility of finding explosive molecules of pharmaceutical interest will increase

The Birmingham Boron Neutron Capture Therapy (BNCT) project : developments towards selective internal particle therapy

This paper will review progress on two aspects of the Birmingham BNCT project. Firstly on evaluation of the effects of high and low LET radiations when delivered simultaneously, and secondly on attempts to optimise delivery of the boron carrier compound BPA through pharmacokinetic studies. Simultaneous or non-simultaneous irradiations of V79 cells with alpha-particle and X-ray irradiations were performed. Alpha doses of 2 and 2.5 Gy were chosen and the impact on survival when delivered separately or simultaneously with variable doses of X-rays was evaluated. The pharmacokinetics of the delivery of a new formulation of BPA (BPA-mannitol) are being investigated in brain tumour patients through a study with 2 × 2 design featuring intravenous and intracarotid artery infusion of BPA, with or without a mannitol bolus. On the combined effect of low and high LET radiations, a synergistic effect was observed when alpha and X-ray doses are delivered simultaneously. The effect is only present at the 2.5 Gy alpha dose and is a very substantial effect on both the shape of the survival curve and the level of cell killing. This indicates that the alpha component may have the effect of inhibiting the repair of damage from the low LET radiation dose delivered simultaneously. On the pharmacokinetics of BPA, data on the first three cohorts indicate that bioavailability of BPA in brain ECF is increased substantially through the addition of a mannitol bolus, as well as by the use of intracarotid artery route of infusion. In both cases, for some patients the levels after infusion approach those seen in blood, whereas the ECF levels for intravenous infusion without mannitol are typically less than 10% of the blood values

‘Engage the World’: examining conflicts of engagement in public museums

Public engagement has become a central theme in the mission statements of many cultural institutions, and in scholarly research into museums and heritage. Engagement has emerged as the go-to-it-word for generating, improving or repairing relations between museums and society at large. But engagement is frequently an unexamined term that might embed assumptions and ignore power relationships. This article describes and examines the implications of conflicting and misleading uses of ‘engagement’ in relation to institutional dealings with contested questions about culture and heritage. It considers the development of an exhibition on the Dead Sea Scrolls by the Royal Ontario Museum, Toronto in 2009 within the new institutional goal to ‘Engage the World’. The chapter analyses the motivations, processes and decisions deployed by management and staff to ‘Engage the World’, and the degree to which the museum was able to re-think its strategies of public engagement, especially in relation to subjects,issues and publics that were more controversial in nature

Quantum Tunneling in Nuclear Fusion

Recent theoretical advances in the study of heavy ion fusion reactions below the Coulomb barrier are reviewed. Particular emphasis is given to new ways of analyzing data, such as studying barrier distributions; new approaches to channel coupling, such as the path integral and Green function formalisms; and alternative methods to describe nuclear structure effects, such as those using the Interacting Boson Model. The roles of nucleon transfer, asymmetry effects, higher-order couplings, and shape-phase transitions are elucidated. The current status of the fusion of unstable nuclei and very massive systems are briefly discussed.Comment: To appear in the January 1998 issue of Reviews of Modern Physics. 13 Figures (postscript file for Figure 6 is not available; a hard copy can be requested from the authors). Full text and figures are also available at http://nucth.physics.wisc.edu/preprints

Delays Associated with Elementary Processes in Nuclear Reaction Simulations

Scatterings, particularly those involving resonances, and other elementary processes do not happen instantaneously. In the context of semiclassical nuclear reaction simulations, we consider delays associated with an interaction for incident quantum wave-packets. As a consequence, we express delays associated with elementary processes in terms of elements of the scattering matrix and phase shifts for elastic scattering. We show that, to within the second order in density, the simulation must account for delays in scattering consistently with the mean field in order to properly model thermodynamic properties such as pressure and free-energy density. The delays associated with nucleon-nucleon and pion-nucleon scattering in free space are analysed with their nontrivial energy dependence. Finally, an example of s-channel scattering of massless partons is studied, and scattering schemes in nuclear reaction simulations are investigated in the context of scattering delays.Comment: 45 pages, 5 uuencoded Postscript figure