INVESTIGATION OF CHEMICAL DIFFERENCES IN MEDICATIONS OBTAINED FROM DIVERSE SOURCES USING NOVEL SPECTROSCOPIC AND STATISTIC APPROACHES

Generic medications are those medicines manufactured by a pharmaceutical company without a license from the company that has first invented and patented the same drug, when the related patent and other exclusivity rights have expired. Only studies of bioequivalence are requested as requirements to introduce a new generic medication in clinics, making easier and financially attractive for many pharmaceutical companies to participate in this typology of market. Organised criminality is strongly attracted by this market both for the high profitability, and for the high similarity to the production and trafficking of illegal controlled substances associated to the extreme difficulties faced by the law enforcement authorities in effectively investigating the online market, because of its anonymity. A significant paradigm continuously frequented in pharmacology is the confliction between views on generic medications that can be used interchangeably with the original medicines. Several clinical studies conducted in certain medical areas have shown as the generic medications present an overlapping therapeutic equivalence to the original ones. On the contrary, for certain other generics, both pharmacokinetics and pharmacodynamics issue have been reported. Also, in some cases issues on the stability of generics have been raised. Despite the numerous research articles and reviews published on the matter of clinical equivalence among generic and original medications, no study to the scientific community has been presented on an analytical evaluation of the chemical composition of the different generic drugs that could shed some lights on the reason of the different clinical performances reported. The main aim of this research was to develop a non-destructive quick qualitative analytical methodology to be able to discriminate differences in the chemical composition from generic medicines that have been reported not presenting similar therapeutic equivalence in clinical comparison studies, obtained from authorised pharmacies and non-authorised online sellers. From the cardio-vascular area, digoxin (with the related cardiac glycosides digitoxin and digoxigenin) and amlodipine (in its different salts maleate, mesylate and besylate used in therapies). In the gastroenterology area, omeprazole both in its racemic and isomeric forms, have been selected as samples to be analysed. In the antihistamine area, cetirizine, in its racemic and isomeric forms, equally for the same reasons as before, have been considered. As starting analytical approaches, voltammetry, FT-IR, Raman spectroscopies and NMR have been considered and a statistical data analysis approach of the analytical data obtained based on multivariate analysis such as principal component analysis, cross validation, correlation scatter plots and factor loadings has been implemented. This work has matched the aims initially set, generating novel methods of analysis to investigate differences in the chemical composition within different groups of generic medications. This study has led to the creation and interpretation of new knowledge, through a systematic acquisition and understanding of a substantial body of scientific literature and through original research, and adjusting the project design in the light of unforeseen problems, conceptualizing, designing and implementing the research project for the generation of novel knowledge

An investigation of digoxin by cyclic voltammetry using gold and silver solid electrodes and chemometric analysis

Digoxin, one of the main cardiac glycosides medication, has shown to have a strong analytical response under investigation by voltammetric analysis using mercury electrodes, achieving nanomole sensitivity. In this study we investigated the suitability of solid electrodes as gold and silver electrodes in voltammetric analysis of this active pharmaceutical ingredient. The scope of the investigation was to evaluate if the use of these solid electrodes, more practical and especially less dangerous, under an operative and environmental aspects could represent a valid further possibility to add to the use of the mercury ones. Both of the solid electrodes have been tested at different pH of 5, 7.4, 10, and 11. PCA analysis has been performed and specific responses achieved. Micromole sensitivity has been achieved for both of the electrodes, showing that the use of these sensors could represent a preliminary analytical approach when the more accurate alternative choice is not necessary, being more practical and less environmental impacting than using mercury

Periodontal Care as a Fundamental Step for an Active and Healthy Ageing

In the industrialized part of the world, an increasing number of people live the old age without too many restrictions due to illness or physiological impairment. This group is known as the young elderly. On the contrary, a consistent part of seniors develops a greater number of medical conditions and become more and more dependent, these are the old elderly. The first cause of tooth lost in industrialized word is periodontitis that generally strikes people older than 40 years and determines serious detriment of the stomatognatic organ. Smoking and stress are risk factors for periodontitis that are common and shared between young, adult, and older age. Diabetes mellitus, obesity, and osteoporosis are very frequent pathological situations in older age. They have been identified as cofactors in the progression of periodontitis. Many dental associations recognize the importance of continued research on oral fluids diagnostics and welcome the development of rapid point-of-care tests providing accurate measurements of clinically validated biomarkers. At present, well-studied molecules associated with host response factors and with derived tissue destruction mediators have been proposed as diagnostic biomarkers for periodontitis detected in the oral fluids

Analysis of omeprazole and esomeprazole obtained from traditional pharmacies and unlicensed internet websites using Raman spectroscopy, 1H-NMR and chemometric analysis

The relevant therapeutic outcomes obtained with the use of proton pump inhibitors for the treatment of gastric conditions have an important reflection on the prescribing habits of clinicians of primary and secondary care organizations. With the attempt to reduce their financial impact on the health systems, generic medications, obtained both from tradition distribution chain and from parallel import, have represented the main type of proton pump inhibitors used in clinics recently. The effect of parallel import and the use of the internet as an international distribution network significantly facilitates the entry of falsified medicines in the official channels of distribution. Since the interchangeability of different omeprazole preparations has been previously questioned, in this study we used Raman and 1H-NMR to characterise different omeprazole and esomeprazole formulations produced by different manufacturers and obtained from both traditional pharmacies and from unlicensed internet market in order to establish if any differences could be found to substantiate any different clinical performances. A chemometric study of Raman spectra allowed partial separation indicating that there are not sufficient chemical differences for PCA groups to be established using this analytical approach and for these specific medications. On the contrary, NMR investigations allowed the identification of impurities in internet samples, not detected by the Raman analyses, making this technique a valid candidate analytical tool to adopt for the investigation of falsified medicines

The test method of composting in vermiculite is unaffected by the priming effect

Glucose, starch, and cellulose can increase the biodegradation of the compost used as a solid matrix in the biodegradation test under composting conditions (priming effect). The enhanced evolution of carbon dioxide determines an overestimation of the biodegradation of the starch- and cellulose-based materials and, in some cases, values higher than 100% can be reached. The work has verified that using activated vermiculite, an inorganic matrix, the priming effect can be reduced, improving the reliability of the test method. Glucose, the most effective primer, causes the attainment of biodegradation values significantly higher than 100% in mature compost while this does not happen in activated vermiculite. Since all the initial carbon present in the activated vermiculite is converted into CO2 within the test period, we conclude that a substantial priming effect cannot occur for the lack of organic carbon. Furthermore, by measuring in parallel both the consumption of glucose and the CO2 evolution, the yield of CO2 production ( ) was determined. In no case a value higher than 1, a clear indication of priming effect, was found

Degradability of plastics. Standard methods developed in Italy

Degradability of plastics. Standard methods developed in Ital

Activated Vermiculite, a Solid Bed for Testing Biodegradability under Composting Conditions

Vermiculite, a clay mineral, can be activated and used as a solid matrix in place of mature compost in the controlled composting test, a respirometric essay widely applied to assess biodegradability of plastics. The results obtained with two materials (cellulose and a starch-based blend) indicate that activated vermiculite affects neither the biodegradation rate nor the final biodegradation level. On the other hand, possible metabolic intermediates and polymeric residues left after biodegradation can be recovered more easily from activated vermiculite than from mature compost, a very complex organic matter. Therefore, at test termination it was possible to determine the carbon balance taking into account both the evolved CO2 and a polymeric residue extracted from vermiculite, totalling 101% of the carbon present originally in the test material. This work was partly financed by the European Commission (DGXII) with the SMT “Labelling biodegradable products” project SMT4-CT97-2187

Detection of toxicity released by a biodegradable plastic after composting in activated vermiculite

The composting test method based on activated vermiculite is a comprehensive system for the assessment of the environmental impact of biodegradable plastics. It allows, in a single test, (i) the measurement of the mineralization of the polymer under study; (ii) the retrieval of the final polymeric residues and (iii) determination of the biomass (to make a final mass balance); (iv) detection of breakdown products of the original polymer. In this study it is shown that the vermiculite test method is also suitable to perform ecotoxicological studies. The Flash test is a method based on kinetic measurement of bioluminescence by Vibrio fischeri, and was applied to evaluate the toxicity of compost samples and vermiculite samples after the biodegradation of a polyurethane (PU) based plastic material. Toxicity was detected in vermiculite samples contaminated by 4,4′ diamino diphenyl methane (MDA), a toxic breakdown product released by the PU moiety, as shown by HPLC. On the other hand, neither toxicity nor the presence of MDA was detected in mature compost. A recovery experiment previously performed had shown a 10% MDA recovery yield from mature compost. The possibility of testing the ecotoxicity of extracts obtained from mineral matrix after biodegradation makes the vermiculite test system particularly interesting for the overall assessment of the environmental impact of biodegradable plastics

Economic and Environmental Sustainability of Olive Production: A Case Study

This paper aims to achieve an economic feasibility and life cycle assessment of three different olive cultivation systems in the Mediterranean area through the joint use of economic and environmental indicators, in order to identify the key elements to optimize their economic performance and a lower environmental impact. Three different management systems of olive cultivation were analysed by distinguishing Treatment 1—Fully Irrigated, Treatment 2—Partially Irrigated, and Treatment 3—Non-Irrigated, which were conducted through different levels of irrigation strategies. The three scenarios were examined using a Life Cycle Assessment methodology to assess the environmental impacts, and the impact in terms of water footprint was investigated using the Water Scarcity Index approach. The economic sustainability evaluation of olive cultivation was carried out through economic indicators, taking into account all of the cost and revenue factors of the olive cultivation in each management system. The results showed, overall, a suitable level of profitability of different scenarios, except for the Partially Irrigated treatment, as the investment costs of the irrigation system are not economically sustainable with regard to the revenue obtained. Furthermore, the findings highlighted the importance of irrigation management strategies to decrease agricultural practice costs and the negative environmental impact of olive production

Dynamic Lighting Strategies with Load Modulation Purposes to Reduce Peak Electrical Demand

This paper proposes a study about the feasibility to modulate the indoor artificial lighting, taking into account both achievable energy savings and comfort conditions, in order to reduce lighting electric loads. In particular, it focuses on the possibility, on one hand, to decrease the luminous flux and, on the other hand, to change the Correlated Colour Temperature (CCT), in order to decrease the absorbed power. Moreover, the impact of daylight-linked control systems was considered. Finally, the possibility to combine the different technical solutions was analysed. The paper proposes the definition of daily scheduling referred to lighting energy management, in order to modulate the maximum load value, maintaining a minimum during the rest of the time for an office end use