Chemical Pharmaceutical Industry Research Articles

Ivermectin-based products in the context of green pharmaceutical analysis

Abstract Background Ivermectin (IVE), a broad-spectrum antiparasitic, is used in human and animal health. Analytical methods for evaluating IVE in pharmaceutical products are found in the literature and in official compendiums. However, the vast majority of them do not have an eco-friendly approach. Objective and Method The aim of this review is to present an overview of existing analytical methods for evaluating IVE in pharmaceutical matrices in the context of Green Analytical Chemistry (GAC) and show possibilities for increasing their greenness. Results GAC is a current alternative to promote sustainable development in laboratories and chemical-pharmaceutical industries, therefore, through its principles, such as reducing the use of aggressive solvents, it is possible to make processes more ecological. However, the vast majority of analytical methods available in the literature and official compendiums do not present an eco-friendly approach. 70% of the methods are by HPLC. Among the various pharmaceutical matrices, the most evaluated are tablets (37%). Of all the solvents used in HPLC, UPLC, HPLC-MS/MS, UV and TLC methods, the combination of methanol and acetonitrile is the most chosen, accounting for more than 50% of occurrences. Conclusions Analytical methods for evaluating IVE-based products can be leveraged within the scope of GAC, bringing sustainable work opportunities to analytical development laboratories around the world. Highlights This review shows an overview of the analytical methods present in the literature and official compendiums to evaluate pharmaceutical IVE matrices, in the context of green analytical chemistry.

The problem of professional adaptation of young specialists in the chemical-pharmaceutical industry (on the example of graduates of St. Petersburg State Chemical and Pharmaceutical University)

Based on the results of the survey of SPCPU graduates, the peculiarities of professional adaptation of young specialists in the chemical-pharmaceutical industry were identified in terms of two factors: internal readiness of a young specialist for professional ad­aptation and external environment support aimed at the implementation of the adaptation process. It is concluded that, in general, the process of adaptation of young specialists at workplaces is quite successful. Most of them have no problems in finding employment in their speciality and are confidently established in organisations. The difficulties identified in the course of the study indicate the need for closer cooperation between higher education and industry.

Innovation Capacity, Entrepreneurial Orientation, and Flexibility: An Analysis from Industrial SMEs in Ecuador

Through the methodology of a case study, this paper presents a holistic analysis of the relationship between innovation capacity, entrepreneurial orientation, flexibility, and environmental factors. Three studies were conducted in the context of chemical-pharmaceutical industries, SMEs, in a small economy. Likewise, they analyze the relationship between the innovation capacity and internationalization of those companies. The studies provide further evidence of the relationships between areas of interest, where links among entrepreneurial orientation, flexibility, externalities (local and international), and innovation capacity are clear. Finally, this paper contributes to the theory-building on innovation capacity and internationalization from a scholarly perspective while presenting a practical view for practitioners.

Role of Export Credit Insurance and the Development of Russian Export Trade

Since the Russian Agency for Export Credit and Investment Insurance (EXIAR) was established in 2011, only a few scientists have bothered to substantiate of the Agency’s economic policy. The aim of the paper is to investigate the role of EXIAR economic policy in promoting the growth of Russia’s export trade. The current study conducts methods such as statistical, comparative and empirical analysis of panel data on the basis of econometric models. The results of the research suggest that export credit insurance can be useful for the development of Russian export trade, especially for exports to high-risk developing countries and to high-value-added Russian exporting enterprises, such as machinery, electrical and chemical-pharmaceutical industries. The authors suggest that Russia should raise the status of export credit insurance, increase the penetration rate of high-tech goods into key countries-importers, improve the foreign trade oppor tunities of exporting enterprises.

Quantitative analysis of pharmaceutical products by spectrophotometry in the infrared region: a practical review

Quality control in the chemical-pharmaceutical industry to identify and quantify the active ingredient has fundamental importance to guarantee the quality of the final product. Its lack can generate irreparable consequences, and therefore its existence is extremely important. However, currently, in this process there is an ecologically correct need beyond the choice of the ideal method and the ideal conditions. This mini-review contemplates the current technological vision of pharmaceutical analysis through Green Analytical Chemistry (GAC). Green and sustainable methods have a main focus providing economic, environmental and social benefits. An example is spectrophotometry in the infrared region for quantitative purposes. The purpose of this mini-review is to show a practical guide for the quantitative analysis of raw materials and pharmaceutical products by spectrophotometry in the infrared region in order to contribute to a sustainability cycle, where the guarantee of product quality and the analytical awareness about health, time, waste generation, environment and cost coexist. A practical review for quantitative analysis by spectrophotometry in the infrared region was shown. It is useful for routine analysis of pharmaceutical products in general, and it can be used by chemical-pharmaceutical laboratories around the world.

Synthesis of Lobeglitazone intermediates seeking for continuous drug production in flow capillary microreactor

Continuous flow synthesis in microreactors has been integrated into chemical-pharmaceutical industry in recent years as an alternative to the batch process due to its advantages, especially process intensification, which can reduce the time for a new drug to be placed on the market on a large scale. This work aimed to transpose the synthesis of Lobeglitazone, a drug employed in the treatment of diabetes mellitus type 2, from batch to flow process in a microreactor as well as to determine the reaction kinetics of each step. The synthesis was carried out in five-steps, being synthesized intermediates 4-chloro-6-(4-methoxyphenoxy)pyrimidine (I1), 2-{[6-(4-methoxyphenoxy)pyrimidin-4-yl]methylamino}ethanol (I2), 4-(2-{[6-(4-methoxyphenoxy)pyrimidin-4-yl]methylamino}ethoxy)benzaldehyde (I3), 5-[4-(2-{[6-(4-methoxyphenoxy)pyrimidin-4-yl]methylamino}ethoxy)benzylidene]thiazolidine-2,4-dione (I4) and Lobeglitazone. Intermediates I1 and I4 were synthesized in flow, while I4 was synthesized either in a continuous flow multistep synthesis or in a one-pot batch process. The flow syntheses of I1, I2 and I4 showed 28.0 %, 61.8 % and 32.0 % yields at 25, 160 and 120 °C, respectively, while the yield of I3 in batch process was 73.3 % at 60 °C. In one-pot batch process and continuous flow multistep synthesis, I2 was obtained with 13 and 16 % yields, respectively. These preliminary results constitute a starting point for the synthesis of this drug in flow on an industrial scale, with the aim of improving reaction performance using this new technology.

Development of Concepts for a Climate-Neutral Chemical–Pharmaceutical Industry in 2045

Global primary energy consumption has increased tenfold over the course of the 20th Century, the availability of non-renewable energy is becoming scarce, and the burning of fossil fuels is leading to global warming. Climate change has now become tangible. The will to act against fossil fuels has become apparent in the western world, and in Germany in particular. This poses a particular challenge for the chemical and pharmaceutical industry, since, in the future, not only will the energy input, but also the feedstock, have to come from non-fossil sources. They must be replaced by carbon capture and utilization, and the exploitation of a circular economy. Concepts for a climate-neutral chemical–pharmaceutical industry have been developed and evaluated. Due to a high predicted consumption of renewable energies and an insufficient expansion of these, Germany will remain an energy importer in the future. The largest consumer in a climate-neutral chemical–pharmaceutical industry will be electrolysis for hydrogen (up to 81%, 553 TWh/a). This can be circumvented by importing green ammonia and cracking. This will require investments of EUR 155 bn. An additional benefit will be increased independence from fossil resource imports, as green ammonia can be produced in a multitude of nations with strong potential for renewable energies and a diversified set of exporting nations.

Climate Neutrality Concepts for the German Chemical–Pharmaceutical Industry

This paper intends to propose options for climate neutrality concepts by taking non-German international experiences and decisions made into account. Asia-Pacific and Arabic countries do have already same lessons learned by large-scale projects with regard to economic evaluations. Quite a few conceptual studies to generate the climate neutrality of the chemical–pharmaceutical industry in Germany have been published recently. Most of the studies differ even in magnitude but do not refer to or evaluate the other ones. These are all first theoretical feasibility studies. Experimental piloting is not far developed; only few and only stand-alone parts are operated, with no overall concepts. Economic evaluation is missing nearly completely. Economic analysis shows a factor 3 more expensive green technologies. Even if a large optimization potential of about 30% during manufacturing optimization is assumed as significant, cost increases would result. To make green products nevertheless competitive, the approach is to increase the carbon-source cost analogue, e.g., by CO2/ton taxes by around EUR 100, which would lead to about factor 3 higher consumer prices regarding the material amount. Furthermore, some countries would not participate in such increases and would have benefits on the world market. Whether any customs-duties policy could balance that is generally under question. Such increasing costs are not imaginable for any social-political system. Therefore, the only chance to realize consequent climate neutrality is to speed up research on more efficient and economic technologies, including, e.g., reaction intensification technologies such as plasma ionization, catalyst optimization, section coupling to cement, steel and waste combustion branches as well as pinch technology integration and appropriate scheduling. In addition, digital twins and process analytical technologies for consequent process automation would help to decrease costs. All those technologies seem to lead to even less personnel, but who need to be highly educated to deal with complex integrated systems. Research and education/training has to be designed for those scenarios. Germany as a resource-poor country could benefit from its human resources. Germany is and will be an energy importing country.

Current state of the chemical-pharmaceutical industry in the national economic system of the Republic of Kazakhstan

The rapid development of the pharmaceutical market is determined by its life priority, since from the very beginning of life, humanity requires the regular consumption of drugs and medical devices to maintain the level of health necessary for a full life. The pharmaceutical market is an important sector of the economy of any country as a criterion for economic and social development, the well-being of the population. The developed pharmaceutical industry of a country is a highly innovative indicator of its economy. Pharmaceuticals have become the most profitable industry for investors today. The pharmaceutical market in Kazakhstan is the largest and most structured in Central Asia. However, it is weaker compared to the CEE (Central and Eastern Europe) market in terms of the business environment and its volume. This article summarizes how some of the current pharmaceutical companies were formed and how they reached maturity. There are a number of challenges facing the drug discovery industry as a whole, whether the company is a large pharmaceutical company or a biotech company that is just getting started. The purpose of this study is to analyze the current state of the pharmaceutical market in Kazakhstan, including a brief excursion into the history of its development and immediate prospects, based on the data of the following international and domestic organizations. The article examines the pharmaceutical market of Kazakhstan, including the production of basic pharmaceutical products, and also conducts a SWOT analysis of the pharmaceutical industry in Kazakhstan, describes the concept of a medicine market, analyzes the economic laws used in the market and its features.

Technical Potential for Energy and GWP Reduction in Chemical–Pharmaceutical Industry in Germany and EU—Focused on Biologics and Botanicals Manufacturing

European policy demands climate neutrality by the year 2050. Therefore, any manufacturing optimization needs to be achieved in the well-known pareto of global warming potential (GWP) reduction combined with cost of goods (COG) reduction at increasing product amounts, while still being able to compete in the world market. The chemical–pharmaceutical industry is one of the most energy-intensive industries. The pharmaceutical industry operates with low batch sizes, but high margins. This study analyzes, based on the literature and Bundesministerium für Wirtschaft und Energie (BMWi; English: Federal Ministry for Economic Affairs and Energy)-funded project results, the technical potentials for energy and GWP reduction, while focusing on biologics and botanicals, because those are already widely based on natural raw material resources. The potential impact for green technologies is pointed out in relation to climate-neutral manufacturing.

Microwave-Assisted Catalytic Method for a Green Synthesis of Amides Directly from Amines and Carboxylic Acids.

Amide bonds are among the most interesting and abundant molecules of life and products of the chemical pharmaceutical industry. In this work, we describe a method of the direct synthesis of amides from carboxylic acids and amines under solvent-free conditions using minute quantities of ceric ammonium nitrate (CAN) as a catalyst. The reactions are carried out in an open microwave reactor and allow the corresponding amides to be obtained in a fast and effective manner when compared to other procedures of the direct synthesis of amides from acids and amines reported so far in the literature. The amide product isolation procedure is simple, environmentally friendly, and is performed with no need for chromatographic purification of secondary amides due to high yields. In this report, primary amines were used in most examples. However, the developed procedure seems to be applicable for secondary amines as well. The methodology produces a limited amount of wastes, and a catalyst can be easily separated. This highly efficient, robust, rapid, solvent-free, and additional reagent-free method provides a major advancement in the development of an ideal green protocol for amide bond formation.

Определение аварийного загрязнения антибиотиками сточных вод

The way for solving the task of enterprises sewage treatment from emergency discharge of antibiotics is offered. Emergency discharge of antibiotics into sewage can arise at enterprises of chemical-pharmaceutical and processing industry. Emergency discharge happens in a short period that gives the chance for its detection and utilization into a settler. Standards for emergency discharges have been presented. The main form for detection of antibiotics in water, their kind and concentration identification is analysis of flowing sewage. This analysis includes two elements: obtaining information on the actual existence of antibiotics (their qualitative and quantitative characteristics), and comparison of obtained information with available indicators for the purpose of definition of their compliance. The control procedure includes operations of measurement and identification. Determination of numerical values for indicators of quantitative characteristics is based on information obtained when using technical means of measurements. For the task solution have been considered characteristics of various methods for detection of antibiotics in sewage. Classification of methods according to quantitative and qualitative indicators of sewage on antibiotics existence has been carried out. Have been allocated methods providing the real time control, among which a specific place is occupied by optical-electronic control methods with use of laser radiation. For implementation of real spectroscopy it is offered to use laser radiation with radiation wavelength corresponding to antibiotic range extremes. In such a case, a spectral characteristic of an antibiotic, which can appear in emergency discharge of enterprise’s sewer, is a priori known. For verification of this technical offer an experiment was set up, which had showed a possibility to use a direct method of spectroscopy — translucency on laser radiation’s chosen wavelength for definition of emergency discharge of antibiotic into enterprise’s sewage.

As formas político-jurídicas do Estado no capitalismo contemporâneo e as renúncias fiscais em saúde

RESUMO Analisando-se a situação da saúde no Brasil, é perceptível o reforço de uma lógica que torna o direito a ela refém da dinâmica do capitalismo contemporâneo. Nesta perspectiva, destaca-se a renúncia de arrecadação fiscal em saúde no Estado brasileiro, trazendo as renúncias fiscais decorrentes da dedução dos gastos com planos de saúde e símiles no imposto de renda, como também as concessões fiscais às entidades privadas sem fins lucrativos (hospitais filantrópicos) e à indústria químico-farmacêutica. Assim, este artigo realiza uma crítica a estes dispositivos legais, que acentuam a relação de subserviência do Estado à lógica do capital, identificando, socio-historicamente, como tais formas vêm dilapidando, direta e indiretamente, o financiamento do Sistema Único de Saúde.

La construcción de una industria farmacéutica autosuficiente en la España de la Autarquía: entre la necesidad, la utopía y la propaganda franquista

La historia de la industria farmacéutica española está condicionada por su adscripción a un modelo de corte mediterráneo, de menor empaque económico y mayor presencia de la componente artesana y profesional. La industria de las materias primas, al menos las de carácter químico-orgánico y fermentativo, no apareció hasta la dictadura franquista. Durante la Autarquía parece evidenciarse un cierto interés por promocionar este sector; en primer lugar, potenciando las industrias de productos naturales, algo que ya se venía haciendo con anterioridad a la Guerra Civil, con el propósito de obtener principios activos de acción medicinal y evitar así su importación; en segundo lugar, a más largo plazo, estableciendo en España una industria química integral, de tipo orgánico, capaz de obtener fármacos a partir del carbón; finalmente, tras conocerse la síntesis a escala industrial de la penicilina, entró un escena un nuevo objetivo que acabaría convirtiéndose en prioritario: la fabricación nacional de esta sustancia. Sin embargo hubo una serie de factores que frenaron el desarrollo de la industria químico-farmacéutica, como las propias limitaciones de las políticas autárquicas, el excesivo número de laboratorios y de productos comercializados, la escasa capitalización de estas empresas así como su tímida implicación en tareas investigadoras, y la insuficiente capacitación científico-técnica necesaria para esta actividad.

Organization of the Soviet armed forces medical supply in 1950’s and 1960’s

A historical analysis of the development of troops (forces) medical supply system after the Great Patriotic War finished in 1950’s and 1960’s has been given. Steps to restore country’s medical and chemical-pharmaceutical industry, that stimulated the improvement of the medical equipment supply of the military units and institutions, have been shown. It was found that the five-years targets of the national economy for the post-war recovery and development plan during 1946-1950, which provides increasing of drug, medical products, medical devices and equipment production have been achieved, and in many cases exceeded. Transferring troops (forces) medical supply system to work under new conditions has been studied. It was revealed that in spite of the specificity and existing difficulties in the state and military construction in the 1950’s and 1960’s of the 20th century, it was possible to establish planned medical supply system in the Soviet Army and Navy in short time. The contribution of the Military Medical Academy of S.M. Kirov to develop official documents, create new models of medical supply and training the military pharmaceutical personnel has been shown. Special attention is given to the role of war members who contributed a lot in scientific and educational work on the issue of supplying troops (forces) with medical equipment. It is established that the reorganization of troops (forces) medical supply system made it possible not only to increase the effectiveness of military health care, but also to contribute strengthening the country’s defense toward the global confrontation and «cold war» started.

A simulation-optimization approach to integrate process design and planning decisions under technical and market uncertainties: A case from the chemical-pharmaceutical industry

This study addresses the product-launch planning problem in the chemical-pharmaceutical industry under technical and market uncertainties, and considering resource limitations associated to the need of processing in the same plant products under development and products in commercialization. A novel approach is developed by combining a mixed integer linear programming (MILP) model and a Monte Carlo simulation (MCS) procedure, to deal with the integrated process design and production planning decisions during the New Product Development (NPD) phase. The Monte Carlo simulation framework was designed as a two-step sampling procedure based on Bernoulli and Normal distributions. Results show the unquestionable influence of the uncertainty parameters on the decision variables and objective function, thus highlighting the inherent risks associated to the deterministic models. Process designs and scale-ups that maximize expected profit were determined, providing a valuable knowledge frame to support the long-term decision-making process, and enabling earlier and better decisions during NPD.

Removal of AOX in Activated Sludge of a Chemical Pharmaceutical Industry with Fenton Oxidation

This study aimed to remove AOX (adsorbable organic halogens) with Fenton oxidation from activated sludge in a chemical pharmaceutical industry. The influences of H2O2 dosage, Fe2+ dosage and reaction time were investigated, based on which the reaction conditions for AOX removal were optimized, and the reaction mechanism was discussed. The optimized reaction conditions were as follows:0.90 mol·L-1 of H2O2, 0.045 mol·L-1 of Fe2+[n (Fe2+):n (H2O2) of 1:20] and reaction time of 2 h. Under the optimized conditions, 70.7% of AOX in the sludge and 78.5% of AOX in the supernatant were removed. GC-MS analysis revealed that eleven organic halides were detectable in the original sludge. After Fenton reaction, only three organic halides were detectable, and their peak areas were reduced by 40%-50%. Toxic and hazardous non-AOX organic matters such as xylene, diisobutyl phthalate were also effectively removed.

No‐Regret Solutions – Modular Production Concepts for Times of Complexity and Uncertainty

AbstractGlobal competition, shorter product cycles, individualized products, and faster technology innovation lead to more complex production systems. For the product life cycle, forecast of product demand, resource availability, and technology chances becomes a mission impossible. Applying a modularization strategy, future production systems are designed as no‐regret‐solutions that add risk minimization to profit maximization. Additive manufacturing and the Internet of Things will significantly improve economics of modular designs for the chemical‐pharmaceutical Industry.

Solution Methodology for Scheduling Problems in Batch Plants

This paper proposes a solution methodology for the production scheduling of batch plants. The methodology is defined by an integrated approach that simultaneously considers the representation of the scheduling problem, the optimization model, and the decision-making process. A problem representation and a mixed integer linear programing (MILP) model are developed and applied to solve a real world scheduling problem from the chemical–pharmaceutical industry. The main advantage of this approach is that it includes a general process representation that can be used across several departments of the company. Moreover, we also discuss development and implementation challenges of optimization methods for the process industry, and we provide some guidelines to mitigate existing problematic issues in this domain.

Simultaneous regular and non-regular production scheduling of multipurpose batch plants: A real chemical–pharmaceutical case study

Regular and non-regular production can often be found in multipurpose batch plants, requiring two distinct operating strategies: campaign and short-term production. This paper proposes a solution approach for simultaneous scheduling of campaign and short-term products in multipurpose batch plants. Regular products follow a cyclic schedule and must cover several product deliveries during the scheduling horizon, while non-regular products have a non-cyclic schedule. The proposed approach explores the Resource-Task Network (RTN) discrete-time formulation. Moreover, a rolling horizon approach, and reformulation and branching strategies have been applied to deal with the computational complexity of the scheduling problem. Real case instances of a chemical–pharmaceutical industry are solved, showing the applicability of the solution approach.