Pharmaceutical Industry Research Articles

Kinetics of the mechanically induced ibuprofen-nicotinamide co-crystal formation by in situ X-ray diffraction.

Mechanochemistry is drawing attention from the pharmaceutical industry given its potential for sustainable material synthesis and manufacture. Scaling mechanochemical processes to industrial level remains a challenge due to an incomplete understanding of their underlying mechanisms. We here show how time-resolved in situ powder X-ray diffraction data, coupled with analytical kinetic modelling, provides a powerful approach to gain mechanistic insight into mechanochemical reactions. By using the ibuprofen-nicotinamide co-crystal mechanosynthesis as a benchmark system, we investigate the behaviour of the solids involved and identify the factors that promote the reaction. As mechanochemical mechanisms become increasingly clear, it promises to become a breakthrough in the industrial preparation of advanced pharmaceuticals.

Metal-organic framework-enabled biomass conversion technologies for microalgae bio-refinery in the food industry.

Biomass is a valuable renewable energy adapted as an alternative to traditional fossil fuels. Apart from fuels, biomass is synthesized into highly valuable products that are used in various forms including biofuels, biochemical, bioproducts, packing material, and find practice in pharmaceutical, cosmetics, and nutraceuticals industries. Particularly, microalgae a third-generation feedstock known for its rich carbon content possesses protein lipids and carbohydrates produces a variety of green products such as bioethanol, biohydrogen, biodiesel, and biomethane, and also fixes carbon emission to a certain amount in the atmosphere. However, microalgae conversion in the presence of a catalyst such as a metal-organic framework (MOF) yields high-quality valuable products. A MOF is a porous crystalline material where the structure and pore size can be controlled making it suitable for catalytic reactions and appropriate conversion paths. This review briefly explains the prevailing status of microalgae as a sustainable biomass and features its components for microalgae biorefinery into valuable products and its application in the food industry. MOF properties, characteristics and various MOF-based conversion technologies for biomass conversion with its application are elaborated. In addition, usage of value products produced from microalgae biorefinery in the food industry and its importance is elucidated. In addition, the challenges in integrating biorefinery processes with food industry operations and their solutions are also presented. © 2024 Society of Chemical Industry.

Surface Acidic Species-Driven Reductive Amination of Furfural with Ru/T-ZrO2.

Catalyst development for upgrading bio-based chemicals towards primary amines has increasingly attracted owing to their applications in the pharmaceutical and polymer industries. The surface acidic sites in metal oxide-based catalysts play a key role in the reductive amination of aldehydes/ketones involving H2 and NH3; however, the crucial role of the type of surface acidic species and their strength remains unclear. Herein, this study exhibits the catalytic reductive amination of furfural (FUR) to furfurylamine (FUA) with Ru supported on tetragonal (Ru/T-ZrO2) and monoclinic (Ru/M-ZrO2) ZrO2. Ru/T-ZrO2 exhibited an 11.8-fold higher rate of reductive amination than Ru/M-ZrO2, giving a quantitative yield of FUA (99%) at 80 °C in 2.5 h and is recyclable up to four runs. Catalyst surface investigation using spectroscopic techniques, like X-ray photoelectron, electron paramagnetic resonance, and Raman, confirm higher oxygen vacancy sites (1.6 times) on the surface of Ru/T-ZrO2 compared to Ru/M-ZrO2. Moreover, in-situ NH3-diffuse reflectance infrared Fourier transform spectroscopy studies display that Ru/T-ZrO2 has more moderate Bronsted acidic sites (surface H-bonded hydroxyl groups) than Ru/M-ZrO2. Further, the controlled experiments and poisoning studies with KSCN and 2,6-lutidine suggest the crucial role of Ov sites (Lewis acidic sites) and surface hydroxyl groups (Bronsted acidic sites) for selective FUA formation.

Inhibitory Effects, Fluorescence Studies, and Molecular Docking Analysis of Some Novel Pyridine-Based Compounds on Mushroom Tyrosinase.

Melanin biosynthesis in different organisms is performed by a tyrosinase action. Excessive enzyme activity and pigment accumulation result in different diseases and disorders including skin cancers, blemishes, and darkening. In fruits and vegetables, it causes unwanted browning of these products and reduces their appearance quality and economic value. Inhibiting enzyme activity and finding novel powerful and safe inhibitors are highly important in agriculture, food, medical, and pharmaceutical industries. In this regard, in the present study, some novel synthetic pyridine-based compounds including 2,6-bis (tosyloxymethyl) pyridine (compound 3), 2,6-bis (butylthiomethyl) pyridine (compound 4), and 2,6-bis (phenylthiomethyl) pyridine (compound 5) were synthesized for the first time, and their inhibitory potencies were assessed on mushroom tyrosinase diphenolase activity. The results showed that while all tested compounds significantly decreased the enzyme activity, compounds 4 and 5 had the highest inhibitory effects (respectively, 80 and 89% inhibition with the IC50 values of 17.0 and 9.0 μmol L-1), and the inhibition mechanism was mixed-type for both compounds. Ligand-binding studies were carried out by fluorescence quenching and molecular docking methods to investigate the enzyme-compound interactions. Fluorescence quenching results revealed that the compounds can form nonfluorescent complexes with the enzyme and result in quenching of its intrinsic emission by the static process. Molecular docking analyses predicted the binding positions and the amino acid residues involved in the interactions. These compounds appear to be suitable candidates for more studies on tyrosinase inhibition.

Unlocking the Impact of Chemicals on the Health and Safety of Pharmaceutical Workers: A Concise Review

The paper presents a concise review of the historical development of the pharmaceutical industry and the problems related to chemical exposure on the health and safety of employees. The industry has greatly improved healthcare worldwide, but it is one of the riskiest due to problems like exposure to dangerous chemicals. Herein, we provide evidence of the health repercussions of pharmaceutical exposure. The paper notes that a diversified approach is required to address these issues. Firstly, there is a need to extensively examine and understand the degree of chemical exposure and its long-term health implications. Tighter laws are necessary to implement higher environmental and safety standards, whereas employee education and training will help to raise awareness of possible hazards. Green chemistry and sustainable methods will curb or mitigate the use of hazardous chemicals and waste generation. Moreover, there is a need to promote sustainable and safer work cultures through safer behaviours, increased public awareness, and community interaction. Pharmaceutical companies must commit to continuous enhancement of their operations, decrease the risks associated with chemical exposure, and put worker and environmental health first. This strategy contributes to a safer and more sustainable pharmaceutical future by being in line with the industry’s commitment to innovation and safety.

P‐Toluene Sulphonic Acid (PTSA): An Efficient Catalyst for One‐Pot Three‐Component Synthesis of Novel 3‐Pyrazolyl‐Thiazolidin‐4‐One Derivatives

AbstractThis research article focuses on the pathway for metal‐free unprecedented one‐pot three‐component synthesis of biologically active 3‐pyrazolyl‐thiazolidin‐4‐one derivatives through cyclo‐condensation of aromatic aldehydes, 1H‐pyrazol‐3‐amine and thioglycolic acid in aqueous medium. p‐Toluene sulphonic acid (PTSA), a non‐toxic, cheaper, easily accessible, eco‐benign, organic acid‐catalyst was explored to mediate this reaction. Formation of novel 3‐pyrazolyl‐thiazolidin‐4‐one derivatives, environment‐benign conditions, quick reaction time, excellent functional group acceptance and moderate to high yield of the products are some of the chief advantages of the reaction. Further, this methodology will surely contribute in various fields of synthetic organic methodology, pharmaceutical industry and natural bio‐active product synthesis.

Extraction and Characterization of Pectin from Orange Peel

Fruit and vegetable processing waste contributes to around 30% of the total weight of the fruits and vegetables. These wastes can be converted into valuable goods for potential benefits. Therefore, this study was focused on extracting pectin from agricultural waste (orange peels) using two methods: alcohol precipitation and enzymatic extraction. The extracted pectin was compared in terms of various properties. Alcohol precipitation resulted in higher yield percentages (16.99 ± 0.8 % wet; 6.46 ± 1.01 % dry respectively) compared to the enzymatic method (16.84 ± 0.42 % wet; 3.66 ± 0.34 % dry, respectively). FT-IR and XRD spectra indicated the presence of highly methylated semi-crystalline pectin in both methods with potent antioxidant property (40.57%). This research work provides comparative extraction method of pectin from agricultural waste i.e. orange peels which has diverse applications in the food, pharmaceutical industries and biomedical applications.

Metabolite Variations during the First Weeks of Growth of Immature Citrus sinensis and Citrus reticulata by Untargeted Liquid Chromatography–Mass Spectrometry/Mass Spectrometry Metabolomics

Immature citruses are an important resource for the pharmaceutical industry due to their high levels of metabolites with health benefits. In this study, we used untargeted liquid chromatography–mass spectrometry (LC-MS) metabolomics to investigate the changes associated with fruit size in immature citrus fruits in the first weeks of growth. Three orange cultivars (Citrus sinensis ‘Navel’, Citrus sinensis ‘Valencia’, and Citrus sinensis ‘Valencia Late’) and a mandarin (Citrus reticulata Blanco ‘Fremont’) were separated into eight fruit sizes, extracted, and analyzed. Statistical analyses revealed a distinct separation between the mandarin and the oranges based on 56 metabolites, with an additional separation between the ‘Navel’ orange and the ‘Valencia’ and ‘Valencia Late’ oranges based on 21 metabolites. Then, metabolites that evolved significantly with fruit size growth were identified, including 40 up-regulated and 31 down-regulated metabolites. This study provides new insights into the metabolite modifications of immature Citrus sinensis and Citrus reticulata in the first weeks of growth and emphasizes the significance of including early sampled fruits in citrus maturation studies.

69 Adherence to the ASCO Language of Respect guidelines in renal cell carcinoma abstracts in an international oncology meeting

Abstract Background The American Society of Clinical Oncology (ASCO) Language of Respect (LoR) guidelines were developed to promote the use of patient-centered language in all communications in 2020. The Language of Respect guidelines provide a directive to encourage the highest level of respect in addressing patients with cancer. In this study, we aimed to analyze the adherence to these guidelines in renal cell carcinoma (RCC) abstracts presented at the 2023 ASCO Annual Meeting, the largest international meeting of oncologists. Methods All RCC abstracts published in the 2023 ASCO Annual Meeting were evaluated. Statements from the abstracts were collected and stratified into the three categories of the LoR guidelines: (1) “Do not blame patients”, (2) “Respect the role of patients”, and (3) “Do not dehumanize patients”. Abstract and author data were summarized using descriptive statistics, and univariable and multivariable analyses were utilized to identify factors associated with odds of noncompliance with the guidelines. Results In total, 101 RCC abstracts were assessed. Most abstracts were published as poster presentations (51.5%) followed by online publication only (44.6%) and oral abstracts (4.0%). First authors affiliated with institutions in native English-speaking countries constituted 69.3% of the abstracts. Authors affiliated with institutions from a single country comprised 67.3% of the abstracts, whereas 32.7% of the abstracts were affiliated with authors from multiple countries. 40.6% of abstracts received no funding, 36.6% of abstracts received funding from a pharmaceutical company, and 22.8% received funding from non-profit organizations, institutions, or grants. There were 34 (33.7%) abstracts associated with clinical trials versus 67 (66.3%) associated with non-clinical trials. 51.5% of abstracts remained within 5% of the character count limit. Overall, 60.4% of the abstracts contained at least one statement that violated the guidelines. Abstracts with at least one statement violating “Do not dehumanize patients”, “Do not blame patients”, and “Respect the role of patients” directives were found in 46.5%, 21.8%, and 1.0% of abstracts, respectively. Abstracts within 5% of the character count limit were associated with increased odds of guideline noncompliance in the univariable analysis (OR 0.33 [95% CI 0.14-0.75], p=0.008). By multivariable analysis, abstracts within 5% of the character count limit were also associated with higher odds of violating the guidelines (OR 0.31 [95% CI 0.13-0.71], p=0.006). Conclusions A significant portion of RCC abstracts were found to violate the LoR guidelines. Our results highlight the importance of considering the expansion of the character count limit for abstract submissions to increase adherence to the LoR guidelines. With the incorporation of LoR guidelines in all forms of communication, the scientific community can promote increased use of respectful language in addressing patients, families, and colleagues.

Treatment options applied to the preclinical studies using animal models for Chagas Disease: a systematic review and meta-analysis

Background Chagas disease (CD) is a neglected tropical disease endemic to Latin America, has emerged as a global health concern due to the migration of infected individuals. With its epidemiological complexity, by difficulty to obtain appropriate diagnoses and poor treatment, the search for novel therapeutic options remains. Methods In this context, we conducted a systematic review and meta-analysis of preclinical studies employing animal models to verify the progress in CD treatment. We searched the PubMed database for CD treatment studies published between 1990 and 2023, adhering to the PRISMA guidelines. Results Twelve papers met the inclusion criteria. The findings indicate that the fifteen treatment alternatives examined, mainly between 2010 and 2014, demonstrated efficacy in experimental CD models, evidenced by significant parasitemia reduction. Bis-triazole DO870 and VNI were effective in the acute and chronic phases, respectively. However, of these emerging therapies, only posaconazole and fexinidazole have progressed to clinical trials, yielding unsatisfactory outcomes as CD monotherapies Conclusions This meta-analysis highlights the existence of promising new drug candidates for CD treatment, but most remain in the preclinical stages. Those that reached clinical trials did not demonstrate optimal results, underscoring the ongoing challenges in CD therapy. Collaborative efforts among the academic community, pharmaceutical industries, funding agencies, and government agencies are urgently needed to accelerate the development of more effective medications against CD. Inplasy registration INPLASY202430101 (25/03/2024)

Discovery Process Chemistry: An Innovation Hub at the Interface of Academia, the Pharmaceutical Industry, and Contract Research Organizations

Discovery Process Chemistry (DPC) is an emerging intersectoral space that is characterized by the development of new chemical reactions or syntheses which enable the efficient elucidation of structure-activity relationships (SARs) and structure-property relationships (SPRs), as well as a rapid transition to process development. Drug discovery and development are accelerated by such efforts and this has led chemists in academia and industry alike to place an increasing importance on these aims. In this Short Review, we explore recent advances in DPC and the impact that it can have on SAR/SPR interrogation and downstream drug development efforts.

Advancement in constructed wetland microbial fuel cell process for wastewater treatment and electricity generation: a review.

The constructed wetland coupled with a microbial fuel cell (CW-MFC) is a wastewater treatment process that combines contaminant removal with electricity production, making it an environmentally friendly option. This hybrid system primarily relies on anaerobic bioprocesses for wastewater treatment, although other processes such as aerobic bioprocesses, plant uptake, and chemical oxidation also contribute to the removal of organic matter and nutrients. CW-MFCs have been successfully used to treat various types of wastewater, including urban, pharmaceutical, paper and pulp industry, metal-contaminated, and swine wastewater. In CW-MFC, macrophytes such as rice plants, Spartina angalica, Canna indica, and Phragmites australis are used. The treatment process can achieve a chemical oxygen demand removal rate of between 80 and 100%. Initially, research focused on enhancing power generation from CW-MFC, but recent studies have shifted towards resource recovery from wastewater. This review paper provides an overview of the development of constructed wetland microbial fuel cell technology, from its early stages to its current applications. The paper also highlights research gaps and potential directions for future research.

Breaking the Gender Imbalance: Female Presence in the Computational Chemistry Group at Viva Biotech.

The growing field of computational chemistry and artificial intelligence is drawing unprecedented attention in drug discovery. However, the underrepresentation of female scientists persists in the field. While the gender disparity is acknowledged in academic settings, the issue is less addressed and intensifies in the pharmaceutical and biotech industry both at the entry-level and leadership positions. At Viva Biotech, we challenge this norm: over 60% of the full-time employees in our computational chemistry group are women, a testament of our commitment to the pursuit of gender equality. We share our vision of the evolving role of computational chemistry in drug discovery and where women stand and rise in the field. In this article, we discuss how we engage female empowerment with tactical approaches and from personal experiences. The intention is to offer actionable guidance for female computational chemists at early career stages to bring visibility to their impacts, and ascent to senior positions.

An Empirical Assessment of Lean Readiness in Pharmaceutical Component Manufacturing SMEs

This study aims to determine the readiness and adoption scenario in Pharmaceutical Component Manufacturing (PCM) industry, particularly the SMEs based in Europe. A quantitative survey of 434 PCM SMEs from around Europe was conducted. At the same time, organizations' preparedness was assessed using key performance indicators (KPIs), and their adoption status was determined by the challenges they encountered while adopting lean and their perceived advantages. The principal component analysis and multivariate analysis of the hypotheses revealed gaps in KPIs in these businesses and significant barriers to achieving desired goals. Based on the findings, a framework that shows these companies how to be efficient was proposed. This framework includes using tools and practices to find and eliminate waste, optimize work, and enhance employee productivity. It also emphasized the permanency of continuous improvement, applying relevant tools, and employee empowerment.

Analysis of the Influence of Organizational Culture, Transformational Leadership Style and Employee Performance Assessment on Employee Satisfaction at Bio Farma

Bio Farma (Persero) is a state-owned pharmaceutical company that was established in 1890 as a bacteriology laboratory by the colonial government of the Dutch East Indies and has undergone many transformations until it became Bio Farma (Persero) in 1997. This study aims to examine the influence of leadership style, organizational culture, and performance assessment on the satisfaction of permanent employees at Bio Farma. In this scientific paper, the influence of employee participation through latent variables Power Distance Index (FOC1), IDV (FOC2), Masculinity versus Femininity (FOC3), Uncertainty Avoidance Index (FOC4), Ideal Influence (FOC5), Individual Consideration (FOC6), Inspirational Motivation (FOC7), Intellectual Stimulation (FOC8), Validity (FOC9), Approval (FOC10), Reliability (FOC11), Objective (FOC12), Salary (FOC13), Promotion (FOC14), Co-workers (FOC15), Boss (FOC16), and Employment (FOC17). The researcher used Partial Least Square to see the influence between variables by testing the outer model as well as testing the inner model. Penelitian ini dilakukan terhadap 120 responden karyawan Bio Farma. The results of the study show that the three independent variables had a direct influence on employee satisfaction (p-value < 0.05), meanwhile, the simultaneous influence of the three variables showed no real influence (p-value = 0.639) with a p-value limit of < 0.5.

Challenges of the Intellectual Property System in Pharmaceutical Innovations Resulting from Artificial Intelligence

The patent system has long been criticized for limiting access to medicines. Dramatic advances in artificial intelligence and machine learning technology present a revolutionary opportunity in drug discovery, formulation and testing of dosage forms. The pharmaceutical industry claims that patenting is necessary to encourage innovation in the risky, lengthy, and costly research and development (R&D) process. But it still does not provide logical evidence about the actual effects of patents on innovation. The increasing use of artificial intelligence in research is intensifying the debate about pharmaceutical patents. Inventions created or enabled by artificial intelligence raise questions about patentability and patent policy in general. Faster and more efficient research and development weakens the justification for pharmaceutical patents. Research findings suggest that despite the necessity of continuing incentives for drug research and development, lawmakers should consider alternative systems that prioritize access alongside incentives to advance healthcare as a human right.

Influence of the Culture Conditions on Camellia sinensis Cell Cultures

Since the last century, it has been shown that dedifferentiated cells of Camellia sinensis can produce catechins and other secondary metabolites under in vitro conditions, with potential applications in the cosmetic, pharmaceutical and food industries. In this work, cell suspension cultures of a C. sinensis cell line (LSC-5Y) were established in a liquid medium in order to optimize the biomass productivity, catechin monomer (GC, EGC, C, EC, CG, and ECG) and alkaloid (TB and CAF) productivity. The following factors were evaluated: concentration of growth regulators (BA and IBA), inoculum size, age of the cell line, light exposure, and effect of biotic elicitors (MeJA and extracts of Ciborinia camelliae). GC, EGC, and ECG increased approximately 1.80-fold when the auxin IBA concentration was increased from 0.1 to 2.0 mg/L. In addition, better productivity of EGC, C, EC, and CAF was achieved by using inoculum densities between 50 and 100 g/L. Although lower inoculum densities (25 g/L) showed a higher growth rate (0.20 d−1), the use of inoculum densities higher than 25 g/L favors a 2–4-fold increase in total catechin (TC) productivity, with maximum productivity being reached after 21 days of culture. However, the cell line showed instability in TC productivity: in the short term (in three successive subcultures), the coefficient of variation was 32.80%, and catechin production capacity was 2.5 years with maximum productivity at 0.5 years. Finally, it was observed that ethanol, used as an elicitor solvent, has a strong elicitor effect capable of increasing the accumulation of catechins up to 5.24 times compared to the treatment without an elicitor.

СОЦИАЛЬНО-ЭКОНОМИЧЕСКОЕ РАЗВИТИЕ РЕГИОНОВ РОССИИ И ТЕХНОЛОГИЧЕСКИЙ СУВЕРЕНИТЕТ

The unprecedented sanctions imposed on Russia and the changing production chains in the world have set our country the task of forming its own technological base to ensure the country's security. Based on Russia's existing groundwork, social significance and multiplier effect, the pharmaceutical industry, aircraft and rocket engineering, as well as microelectronics and artificial intelligence are the most promising. Despite investments in these industries, Russia is still experiencing import dependence in each of them. To solve this problem, this article proposes the use of strategic planning with the large-scale use of state regulation tools. The scientific novelty of this article consists in proving that the control of technology in the GVC strengthens the subordinate position of developing countries. In addition, the industries that ensure technological sovereignty are identified

Reshaping the binding pocket of D-tagaturonate epimerase UxaE to improve the epimerization activity of C4-OH for enabling green synthesis of d-tagatose

d-tagatose, a rare sugar with broad applications in the food and pharmaceutical industries, can be synthesized from d-fructose by epimerases, an approach with significant biosynthesis potential. However, so far there has been only one attempt to engineer tagatose 4‑epimerase through random mutagenesis. The lack of exploration has severely restricted the application of epimerases in the industrial production of d-tagatose. The previous research primarily focused on enhancing the catalytic activity of epimerases through random mutagenesis, with limited understanding of how substrate-adjacent residues affect enzyme efficiency, which was hence the subject of this study. First, using a semi-rational design approach, after three rounds of mutagenesis and screening, the mutant (S125D/S268A/Q124E) of D-tagaturonate epimerase (UxaE) from Thermotoga neapolitana was obtained, which increased d-tagatose production efficiency by 10.8-fold compared to the wild type, with a specific activity of 1505.6 U/g, representing the highest specific activity reported for a UxaE mutant to date. Molecular dynamics simulations showed that the substitution of Ser to Asp-125 enhanced substrate-enzyme interactions, while the substitution of Glu to Gln-124 reinforced the hydrogen bond network around the catalytic residue Glu-128, further reshaping the substrate-binding pocket and enhancing catalytic activity. This study for the first time explored the enhancement of the C4 epimerization function of epimerases by reshaping their substrate-binding pockets, thereby providing a feasible route for the industrial biosynthesis of d-tagatose.

Enhancing thermodynamic performance with an advanced combined power and refrigeration cycle with dual LNG cold energy utilization

Utilizing waste heat to drive thermodynamic systems is imperative for improving energy efficiency, thereby improving sustainability. A combined cooling and power systems (CCP) utilizes heat from a temperature source to deliver both power and cooling. However, CCP systems utilizing LNG cold energy suffers from low second law efficiency due to significant temperature differences. To address this, an “Advanced Power and Cooling with LNG Utilization (ACPLU)” system is proposed, integrating a cascaded transcritical carbon dioxide (TCO2)-LNG cycle with an Organic Rankine cycle (ORC) for improved power generation and an absorption refrigeration system (ARS) for simultaneous cooling. This study evaluates the second law efficiency, net work output, and exergy destruction performance through a sensitivity analysis, optimizing variables such as heat source temperature, superheater temperature difference, ORC and CO2 turbine inlet and condenser pressures, evaporator temperature, and pinch point temperatures of heat exchangers and generator. Compared to previous studies on CCP systems, the ACPLU shows a superior performance, with a second law efficiency of 27.3 % and a net work output of 11.76 MW. Cyclopentane as an ORC working fluid resulted in the highest second law efficiency of 29.06 % and net work output of 12.27 MW. Parametric analysis suggested that heat source temperature significantly impacts net power output. The exergy analysis concluded that a high-pressure ratio and good thermal match between the heat exchangers enhance overall performance. Utilizing artificial neural network (ANN) to produce a multiple-input-multiple-output (MIMO) objective function and performing multi-objective optimization (MOO) using genetic algorithm (GA), an improved second law efficiency and net power output by 28.11 % and 14.16 MW respectively, with pentane as the working fluid, is demonstrated. An average cost rate of 9.121 $/GJ was observed through a thermo-economic analysis. The ACPLU system is promising for medium temperature waste heat recovery, such as, pharmaceutical manufacturing plants.