Spinoff, 1992

This publication is intended to foster the aim of the NASA Technology Transfer Program by heightening awareness of the NASA technology available for reapplication and its potential for public benefit. The publication is organized in three main sections. Section 1 outlines NASA's mainline effort, the major programs that generate new technology and therefore replenish and expand the bank of knowledge available for transfer. Section 2 contains a representative sampling of spinoff products that resulted from secondary application of technology originally developed to meet mainline goals. Section 3 describes the various mechanisms NASA employs to stimulate technology transfer and lists, in an appendix, contact sources for further information about the Technology Transfer Program

Non-destructive detection of counterfeit and substandard medicines using X-ray diffraction

The prevalence of counterfeit and substandard medicines has been growing rapidly over the past decade, and fast, non-destructive techniques for their detection are urgently needed to counter this trend. In this thesis, both energy-dispersive X-ray diffraction (EDXRD) and pixelated diffraction (“PixD”) combined with chemometric methods were assessed for their effectiveness in detecting poor-quality medicines within their packaging. Firstly, a series of caffeine, paracetamol and cellulose mixtures of known concentrations were pressed into tablets. EDXRD spectra of each tablet were collected both with and without packaging. Principal component analysis (PCA) and partial least-squares regression (PLSR) were used to study the data and construct calibration models for quantitative analysis. The concentration prediction errors for the packaged data were found to be very similar to those obtained in the unpackaged case, and were also on a par with reported values in the literature using higher-resolution angular-dispersive X-ray diffraction (ADXRD). Following this, soft independent modelling by class analogy (SIMCA) classification was used to compare EDXRD spectra from a test set of over-the-counter (OTC) medicines containing various combinations of active pharmaceutical ingredients (APIs) against PCA models constructed using spectra collected for paracetamol and ibuprofen samples. The test samples were selected to emulate different levels of difficulty in authenticating medicines correctly, ranging from completely different APIs (easy) to those with a small quantity of additional API (difficult). This classification study found that the sensitivity and specificity were optimal at data acquisition times on the order of 75~150s, and regardless of whether layers of blister and card packaging surrounded the tablet in question. This experiment was repeated on a novel, compact system incorporating a pixellated detector, which was found to reduce the required data acquisition times for optimal classification by a factor of five

Pharmachk: robust device for counterfeit and substandard medicines screening on developing regions

Thesis (Ph.D.)--Boston UniversityCounterfeit and substandard medicines are a grave public health concern that comprises a $75B black market and claims over 100,000 lives every year. The World Health Organization estimates that 10-50% of medicines in countries around the world are adulterated, and their presence imposes serious financial and economic burdens while also contributing to the rise of drug-resistant pathogens. Although a plethora of technologies are available for field-based quality screening, none reliably quantify active pharmaceutical ingredient (API) content or kinetic release from a dissolving tablet. The United States Pharmacopeia, a global leader in medicines standards for over 150 years, indicates that these quality measures are vitally important yet remain outside of the reach ofexisting screening tools. The current field standard relies on thin layer chromatography to only provide qualitative results that make it difficult to discern between tablets that contain 80% and 100% API. Meanwhile, international standards set the threshold for substandard medicines at 90%. This clear lack of appropriately quantitative and field- ready analytical tools poses a serious problem for national and international policymakers who are plagued with wildly variable information that prevents focused and deliberate action against the spread ofthese medications. This work presents an alternative analytical technique that can specifically and accurately quantify drug API content and kinetic release. PharmaChk provides an orthogonal approach to existing technologies using a portable, inexpensive, and easy-to-use platform. We demonstrate that aptamers can provide a simple and effective way to target a wide range of APis, while maintaining high quantitative precision and accuracy. A microfluidic, flow-through system is employed to obtain valuable drug quality information using a single step procedure. Through our research, we demonstrate the development of the PharmaChk platform from the proof-of-concept stage to beta prototyping and field-testing. By providing a portable, robust, and quantitative approach to medicines testing, PharmaChk can enable the collection of important drug quality information throughout pharmaceutical supply chains and ultimately save the lives of millions that are not afforded safe and essential medicines

Novel approaches to the detection of substandard medicines

This thesis addresses the serious implications of substandard medicines to public health care and describes attempts to bridge the apparent gap of detecting substandard medicines by exploring new detection approaches in pharmacovigilance and in analytical technologies as well as validating these methods in a field study. Substandard medicines (SSMs) are licensed medicines, that most commonly contain either too little or too much active pharmaceutical ingredient (API). SSMs may be the result of negligence, error and/or low standard of quality control of the manufacturing process (non-good manufacturing accredited status) and/or distribution process (degradation of medicinal products through bad storage). The use of SSMs may result in severe adverse events (AEs) and even death and may promote antimicrobial resistance. Evidence of high increases of SSMs, predominantly in developing countries, reveals that there is a need for easy, rapid and affordable detection tools. Currently, there is no portable screening device in the market that can accurately measure the content of API of medicinal samples. The only available device, currently under development, is PharmaChk, an innovative analytical instrument, that is able to quantify the amount of a number of APIs (e.g. artemisinin, tetracycline) and evaluate their dissolution profile. In collaboration with the Biomechanical Department of Boston University, we conducted further research on this device. The assay for essential antimalarial drug Coartem® (artemether and lumefantrine) was developed and used for a field study in Zimbabwe. In addition to analytical detection, pharmacovigilance signal detection techniques have been shown to be effective in detecting SSMs. Preliminary research (conducted by the WHO Uppsala Monitoring Centre) exists on using data mining algorithms on the WHO Vigibase® data set of global individual case safety reports to identify SSMs. After validation of this pharmacovigilance screening tool and the assay of Coartem® on the PharmaChk device and in order to assess the efficiency of these two detection approaches of SSMs in real world practice, we initiated a field study on Coartem® and its generic versions in Zimbabwe. Malaria is a major health burden in this country with 8,000,000 people at risk (50% of the population). Previous studies have shown that Zimbabweans are at high risk from substandard and falsified medicines, resulting in increased mortality, morbidity, financial strain and long-term antimicrobial resistance. We collected samples from sites of the private health sector as well as from sites that were conveniently accessible. The purchase of samples was performed in 18 cities in areas with high risk for malaria. The quality of purchased samples was tested through qualitative and quantitative measurements using different screening field devices including Raman, Near-Infrared spectrometry and X-Ray Fluorescence as well as spectrophotometer and high performance liquid chromatography (HPLC) analysis for confirmatory analysis in analytical laboratories in Zimbabwe, Switzerland and the United States. Data mining for the antimalarial drug Coartem® identified no excess reporting of AEs in Zimbabwe. Analyses of all screening and confirmatory analytical technologies revealed a good quality of all collected samples. The PharmaChk device demonstrated comparable results of the collected samples to HPLC, which is the gold standard method. The analytical screening tool PharmaChk was able to determine that there was no unexpected risk with essential medicine artemether/lumefantrine in Zimbabwe. This pilot study highlighted the potential of these two detection methods (pharmacovigilance screening tool and analytical detection tool using the PharmaChk device). However, further research on a larger scale of samples and other therapeutic areas is required to validate these findings. This thesis highlights the need and importance of collaborations in identifying SSMs. Without the partnership between academia, industry and private laboratory institutions this research may have not been possible. The complex issue of SSMs requires this kind of engagement to enhance safe and effective medical treatment by decreasing the number of circulating SSMs worldwide

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 301)

This bibliography lists 217 reports, articles, and other documents introduced into the NASA scientific and technical information system in August, 1987

FORENSIC PHARMACEUTICAL ANALYSIS OF COUNTERFEIT MEDICINES

The World Health Organisation suggests that falsified and substandard medicines (FSMs) constitute approximately 10% of medicines globally with higher figures expected in low and middle income countries (LMICs). To combat the proliferation of FSMs, this study is aimed at developing simple and rapid instrumental methods for the identification and quantification of these medicines. Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopy, Raman spectroscopy and two probe Mass Spectrometry (MS) methods were assessed for the rapid screening of tablet dosage forms. These systems were chosen because NO solvent extraction of the sample was required. Comparison with analyses of the tablets by accepted but more time consuming methods (UV-Vis and LC-MS) assessed the quality of the data obtained. Analgesic/antipyretic and antimalarial medicines tablet dosage forms are commonly falsified and for this study tablets were obtained opportunistically from different countries around the world. Reference spectra of appropriate active pharmaceutical ingredients (APIs) and excipients were created, for each method, as part of the identification process. Currently only Raman and ATR-FTIR delivered quantitative results which were based on automated multivariate analysis. For tablets with a single API, Raman and ATR-FTIR provided the simplest route to API confirmation and for tablets with multiple APIs or APIs present at <10%w/w, in the tablet, probe MS methods were superior. Quantitative screening using ATR-FTIR required the samples to be weighed and crushed to produce reproducible data. Comparison of API confirmation tests between trial methods and LC-MS showed complete agreement and the quantitative results were within ±15% of the UV-Vis data. Each of the new tests can be completed in under five minutes and a survey of 69 paracetamol tablets, from around the world, showed that 10% were suspect. Subsequent probe MS showed the presence of a second undeclared API in different samples. More complex tablet formulations, for example the antimalarials were difficult to quantify rapidly. Raman and PCA methods provide a rapid approach to tablet identification within a limited range of possibilities. Factors that may affect Raman spectra of tablets include the expected API, the API levels, different excipients, colours or surface coatings for the tablets. The simplicity, speed and cost effectiveness of the proposed analytical methods make them suitable for use in LMICs. The potential use of these simple analytical methods in addition to already established pharmacopoeia approved (solvent extraction) techniques could help provide more comprehensive data about FSMs globally

Space station systems: A bibliography with indexes (supplement 6)

This bibliography lists 1,133 reports, articles, and other documents introduced into the NASA scientific and technical information system between July 1, 1987 and December 31, 1987. Its purpose is to provide helpful information to the researcher, manager, and designer in technology development and mission design according to system, interactive analysis and design, structural and thermal analysis and design, structural concepts and control systems, electronics, advanced materials, assembly concepts, propulsion, and solar power satellite systems. The coverage includes documents that define major systems and subsystems, servicing and support requirements, procedures and operations, and missions for the current and future Space Station

Teachers, teams and technology: Investigating a team approach for supporting teachers\u27 uptake of ICT

This study sought to explore the professional development of elementary school teachers who were keen to use Information and Communications (ICT) in their teaching and learning. The main object of the study was to investigate a model of professional development that would support teachers as they adopted ICT. At the same time a simple framework to help locate teachers on some typology of ICT uptake was desirable, on the grounds that such a typology could help teachers, professional development planners and schools in their use of and support for ICT and its associated professional development.A review of the literature suggests two factors were of particular significance to teachers in Western Australia. The first was collaboration, and the second was an outcomes orientation. Collaboration is shorthand for the myriad ways that teachers worked together and an outcomes orientation embodies, in short, a student-centred approach to learning. Outcomes orientation is a current major initiative of the WA Department of Education and of keen relevance to educators in Western Australian schools