Pharmaceutical Distribution Research Articles

Comprehensive profiling of the distribution, risks and priority of pharmaceuticals and personal care products: A large-scale study from rivers to coastal seas

Pharmaceuticals and personal care products (PPCPs) have captured global concern due to their detrimental effects on aquatic organisms. Thirty PPCPs were analyzed in the water of the Jiaozhou Bay watershed, the Yellow Sea (YS) and the East China Sea (ECS) in China to investigate the distribution and risk of PPCPs from rivers to coastal seas, which are not yet well documented. The results showed the prevalence of the target PPCPs with a downward trend in detection frequencies and total concentrations from rivers (675 ng/L on average) to bay (166 ng/L) and to coastal seas (103 ng/L). Antibiotics and personal care products (PCPs) were dominated by amoxicillin (AMOX) and p-hydroxybenzoic acid, respectively, while the dominant estrogens were inconsistent in different regions. Spatially, the total PPCP concentrations were higher in the ECS than that in the YS due to the larger quantity of sewage flowing into the ECS. Additionally, higher total PPCP concentrations were appeared in the southeastern waters outside the Yangtze estuary and Hangzhou Bay of the ECS. The PPCP mixtures might pose medium to high risk to aquatic organisms in general. The total risk quotient (RQT) of antibiotics and PCPs to algae was higher than that to crustacean and fish, while estrogens may cause the greatest damage to fish. Despite the higher PPCP concentrations in river water than in seawater, the RQT of PPCPs in bay water was generally higher than that in river water, which may be associated with the susceptibility of marine organisms. Furthermore, the high-risk pollutants that need special concern in different regions were clarified, showing that AMOX, 17ß-estradiol, and estriol deserve the highest-priority in rivers, bay, and coastal waters, respectively.

Research on Corporate Social Responsibility Evaluation Based on Improved CRITIC-TOPSIS—A Case Study of Listed Companies in China’s Pharmaceutical Distribution Industry

Corporate social responsibility (CSR) has garnered considerable attention from countries, institutions, enterprises and social groups. However, the lack of research on CSR evaluation system for industries has impeded its development and construction across various industries. Therefore, given the close association of pharmaceutical distribution enterprises with personal health, there exists a pressing need to explore the CSR in this domain. This paper establishes a CSR evaluation index system for pharmaceutical distribution enterprises, employing a combination of documentary analysis and in-depth interviews. This index system comprises 7 CSR criterion layers (e.g., responsible governance and employee responsibility) and 56 index layers. 25 listed companies in China’s pharmaceutical distribution industry are chosen as research objects, and this study also establishes an evaluation model for the CSR of pharmaceutical distribution companies through the improved Criteria Importance Though Intercrieria Correlation (CRITIC) method combined with The Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) method. The empirical analysis reveals that the responsible governance criterion layer and the social development criterion layer demonstrate the best performance, while the supplier, customer and patient responsibility criterion layer exhibit the worst performance.

Assessment Of Bacterial And Fungal Contamination In Common Pharmaceuticals And Their Public Health Implications

Pharmaceutical contamination by microorganisms, including bacteria and fungi, poses significant public health risks, as contaminated drugs can lead to severe infections, treatment failures, and compromised patient safety. This study investigates microbial contamination in a range of commonly used pharmaceutical products. For bacterial contamination, Troycaine, Synim, Methdilazine, and Vericose Vein were analyzed using nutrient agar. The results indicated the presence of Gram-positive bacteria in all samples: Troycaine was contaminated with Gram-positive cocci, while Synim and Methdilazine were found to contain Gram-positive rods. The study further extended to fungal contamination in pharmaceuticals, including Troycaine, Methdilazine, Vericose Vein, Ambroxl Kufril, Montair, Dextromethorphan, and Mefenamic Acid + Paracetamol. Troycaine tested positive for fungal contamination, with Rhizopus stolonifer and Aspergillus niger being identified as contaminants. These fungal species are known for their potential to cause serious infections, particularly in immunocompromised individuals. The presence of microbial contamination in pharmaceuticals not only compromises the therapeutic efficacy of the drugs but also presents a significant public health threat, increasing the risk of drug-resistant infections, allergic reactions, and other complications. These findings emphasize the critical need for stringent microbial quality control in pharmaceutical manufacturing, storage, and distribution to mitigate these risks and ensure patient safety.

Design, Development, and Validation of a Culture-Independent Nucleic Acid Diagnostics Method for the Rapid Detection and Quantification of the Burkholderia cepacia Complex in Water with an Equivalence to ISO/TS 12869:2019.

In the wake of a series of outbreaks of finished pharmaceutical product-related Burkholderia cepacia complex (Bcc) human infections worldwide, the United States Food and Drug Administration (FDA) in 2017, and subsequently in 2021, issued advisory notifications to the pharmaceutical industry for stringent Bcc testing requirements for pharmaceutical manufacturing processes and for finished pharmaceutical products prior to release to the marketplace. The advisory notifications highlight non-sterile aqueous finished pharmaceutical products as being a major culprit associated with many of these human infection events. As such, there has been a significant number of Bcc-contaminated finished product recalls resulting in company revenue losses, delayed finished product release, finished product shortages for patients, and manufacturing plant shutdowns coupled with company reputational damage. With many of the finished product recall events, pharmaceutical grade water and/or manufacturing facility water distribution systems were identified as the primary origin source of Bcc contamination. Testing and monitoring regimes currently employed to identify Bcc contamination of water associated with pharmaceutical manufacturing are often limited by costly, laborious, lengthy, and nonspecific traditional microbial culture-based methodologies. Presently FDA approved, European Conformity (CE) marked, and International Organization for Standardization (ISO) standard microbial culture-independent rapid, quantitative, specific, and sensitive nucleic acid diagnostics (NAD) methodologies are now gaining greater widespread acceptance in their routine usage in testing laboratories. Here we present the development of a rapid (<4 hours from sample in to result out) single test culture-independent Bcc NAD method, incorporating a quantitative real-time polymerase chain reaction (qPCR) assay. This method can be used for the detection and simultaneous identification of all 24 Bcc species currently assigned, directly from water samples. This culture-independent Bcc NAD method is validated to the testing method equivalent of the ISO/TS 12869:2019 standard, which is a widely used rapid culture-independent NAD method for detecting Gram-negative Legionella species in water.

Determinants of operational performance of pharmaceutical wholesalers’ companies in Bali province

Pharmaceutical distribution companies or also known as Pharmaceutical Drug Wholesalers (PBF) play a significant role in the distribution of pharmaceutical products in Indonesia. Without the role of PBF, the drug will not reach the patients from the manufacturer. The PBF appointed by the manufacturer to distribute the product, has operational performance targets that must be achieved. However, like other businesses, PBF operational performance is also affected by external factors, such as the COVID-19 pandemic, government regulations and competition intensity. The impact of internal factors such as limited company resources is also investigated in this research. This research tries to explore the impact of external factors, those are: the pandemic of COVID-19, government regulations, competition intensity and internal factors that are the company's limited resources to PBF operational performance. Sales strategy is also used as mediating variables from external and internal factors to operational performance, thus operational control as moderating variable from sales strategy to operational performance respectively. Data collection was obtained by questionnaires and interviews with 44 PBF operational leaders in Bali, Indonesia. Data analyzing using SmartPLS 3.0. The COVID-19 pandemic, government regulations, competition intensity and company’s limited resources have a negative impact on the company's operational performance. Sales strategy serves as a mediating variable from external and internal factors to operational performance. Operational control plays a significant role in moderating sales strategy and the performance of operational. The theoretical implication of this research is to enhance The Contingency Theory, which claims that the business environment, strategy, and control are three major contingency elements that are linked. The findings of this study also strengthen the concept of Transaction Cost Theory, which states that the relationship between the parties in a transaction is associated with rights and obligations that are poured into a very detailed agreement. The operational performance required by the principal to PBF is also included in the agreement and PBF should strive to achieve that operational performance.

Establishment of Corporate Social Responsibility Evaluation Index System of Chinese Pharmaceutical Distribution Enterprises &amp;lt;br/&amp;gt;—Based on Grounded Theory

Establishment of Corporate Social Responsibility Evaluation Index System of Chinese Pharmaceutical Distribution Enterprises &amp;lt;br/&amp;gt;—Based on Grounded Theory

Management of Macrolide Antibiotics (Erythromycin, Clarithromycin and Azithromycin) in the Environment: A Case Study of Environmental Pollution in Lithuania

Of all the antibiotics used today for human treatment in the world, macrolide antibiotics—erythromycin, clarithromycin and azithromycin—stand out the most for misuse, and they were included as high-risk substances in the monitoring Watch List of Regulation 2018/840/EU. The aim of the present research was to investigate the level of target human pharmaceuticals’ prevalence in the environment by the substance flow analysis (SFA) approach and to determine the potential risks of the antibiotics for the environment. The target for the environmental investigations was Lithuania. For SFA, 2021 consumption input data were used, and such key processes as the consumption rate, disposal and distribution of pharmaceuticals in the environment were analyzed. The analysis revealed that the largest part of pharmaceutical contaminants (80.1%) enters wastewater treatment plants. The risk quotient approach was based on the determination of predicted environmental concentrations (PECs), measured environmental concentrations (MECs) and their ratio to the predicted no-effect environmental concentrations (PNECs). The analysis revealed that clarithromycin causes a high potential risk for the aquatic environment in effluents from the wastewater treatment plants (WWTP); PEC/PNEC &gt; 7. For azithromycin and erythromycin, the estimated PEC values were between 0.1 and 1. Clarithromycin concentration in the effluents of two target WWTPs showed a significant risk quotient (MEC/PNEC) of higher than 7. Recommendations on how to reduce the release of pharmaceutical residues into the environment have been proposed in the framework of the environmental management system.

A Review of In Situ Methods-Solid Phase Adsorption Toxin Tracking (SPATT) and Polar Organic Chemical Integrative Sampler (POCIS) for the Collection and Concentration of Marine Biotoxins and Pharmaceuticals in Environmental Waters.

Solid Phase Adsorption Toxin Tracking (SPATT) and Polar Organic Chemical Integrative Sampler (POCIS) are in situ methods that have been applied to pre-concentrate a range of marine toxins, pesticides and pharmaceutical compounds that occur at low levels in marine and environmental waters. Recent research has identified the widespread distribution of biotoxins and pharmaceuticals in environmental waters (marine, brackish and freshwater) highlighting the need for the development of effective techniques to generate accurate quantitative water system profiles. In this manuscript, we reviewed in situ methods known as Solid Phase Adsorption Toxin Tracking (SPATT) and Polar Organic Chemical Integrative Sampler (POCIS) for the collection and concentration of marine biotoxins, freshwater cyanotoxins and pharmaceuticals in environmental waters since the 1980s to present. Twelve different adsorption substrates in SPATT and 18 different sorbents in POCIS were reviewed for their ability to absorb a range of lipophilic and hydrophilic marine biotoxins, pharmaceuticals, pesticides, antibiotics and microcystins in marine water, freshwater and wastewater. This review suggests the gaps in reported studies, outlines future research possibilities and guides researchers who wish to work on water contaminates using Solid Phase Adsorption Toxin Tracking (SPATT) and Polar Organic Chemical Integrative Sampler (POCIS) technologies.

Occurrence, distribution, and environmental risk of pharmaceutical residues in Mombasa peri-urban creeks, Kenya

The information on pharmaceutical compounds' distribution and their possible risks in marine ecosystems along the Kenya coast is limited especially in the peri-urban creeks. Hence, this study aimed to determine pharmaceutical residue levels and distribution in selected peri-urban creeks in Mombasa and Gazi bay. The target compounds were analgesic (acetaminophen), antibiotics (trimethoprim and sulfamethoxazole), antiepileptic (carbamazepine), and antiretroviral (nevirapine). Pharmaceutical residues in grab surface seawater in wet and dry seasons ranged from below detection limit (BDL)-1065.6 μg L−1 and BDL-71.3 μg L−1, respectively. The concentration of the pharmaceutical residues was high in Tudor creek in the dry and wet seasons with a mean concentration of 63.3 μg L−1 and 233.1 μg L−1 respectively compared to Makupa creek (dry season, 54.2 μg L−1; wet season 16.2 μg L), and Mtwapa creek (dry season, 43.1 μg L−1; wet season, 15.0 μg L−1). Gazi Bay being used as a control site had a mean concentration of 21.3 μg L−1 and 3.1 μg L−1 during the dry season and wet season respectively. Acetaminophen and nevirapine were the most ubiquitous compounds in seawater since they were found in all seawater samples collected. Risk quotients (RQ) for invertebrates and algae based on the mean concentrations of the analytes were estimated to provide a preliminary environmental risk assessment. The results suggest that the studied acetaminophen, trimethoprim, sulfamethoxazole, and carbamazepine in seawater pose low (0.01 ≤ RQ < 0.1) to medium (0.1 ≤ RQ < 1) ecological risk whereas nevirapine poses medium to high (RQ ≥ 1) ecological risk to the ecosystems of Mombasa periurban creeks and Gazi bay. Further research, however, is encouraged on the distribution of pharmaceuticals in the marine environment and the long-term synergistic effects of mixtures of these compounds on marine biota.

Selective Strategy Differential Evolution for Stochastic Internal Task Scheduling Problem in Cross-Docking Terminals.

This study proposed an algorithm called selective strategy differential evolution (SSDE) to handle the complexity of the stochastic internal task scheduling problem in cross-docking terminals. The aims of this study are to assign workers and transfer equipment to internal operations and sequence those operations under randomness and uncertainty with the purpose to minimise total tardiness. The main feature of SSDE is its ability to adapt itself in order to execute the best search strategy. The proposed algorithm was tested on 16 instances using generated data based on real-case scenarios of a pharmaceutical distribution centre. The results showed the significant performance of SSDE to other existing algorithms in terms of solution quality and computational time. The key success factors of SSDE are the use of various search strategies in a single run and the application of suitable termination conditions.

Leveraging the Potential of SME Capital Markets: Evidence from Small and Medium-Sized Enterprises in Jammu Region, India

The paper intends to explore the potential for developing Small and Medium-sized Enterprise (SME) capital markets in India by analyzing the business conditions of SMEs, the priority, reasons, necessary actions and critical factors needed for developing capital markets for SMEs, and to offer strategies for development of new SME capital market. Besides, the status of the SME capital market in India has also been analyzed. The study has been restricted to 114 non-financial firms consisting of 43 SMEs engaged in manufacturing activities and limited to five selected major industrial areas surrounding suburbs of Jammu city. The study covered 71 SMEs engaged in service activities and confined to hotel and restaurant, computer and electronics, offset printing, pharmaceutical distribution, wine trade, motor parts, gold jewelry, and wholesale general merchant in the commercial areas of Jammu city in Jammu and Kashmir. The study has used a life cycle approach to analyze the sources of finance in different stages of the SME. A simple descriptive technique has been used to analyze the data. The study reveals that there are various challenges to establish direct growth capital financing for SMEs. Looking at numerous viewpoints on the development of SME capital market, a specialized market infrastructure of non -exchange foundation equity market for SMEs can be developed. The establishment of a separate foundation equity market for SMEs from exchange market can be advantageous. There is a need to develop a preliminary market for growing SMEs. This should ultimately integrate into the regular SME stock exchange market. A preliminary market is expected to endow SMEs with a chance to understand clearly SME capital market rules and responsibilities linked to disclosures before integrating into the organized capital market. It will imbibe the corporate culture through knowledge regarding the significance of enhanced corporate value for the growth and development of firms. The foundation market should evolve into a robust system for carrying SMEs in equity finance from various dimensions. These dimensions can be the promotion of the venture capital market to provide initial risk capital for SMEs, the development of a strong base of capital market professionals to train and goad the SME disclosure process through a network of certified public accountants, and the development of a blueprint for government policy support measures including tax incentives for SME issuers and investors.

Antibiotic consumption in the public sector of the Limpopo province, South Africa, 2014-2018.

Antibiotic consumption (ABC) surveillance is a critical component of the strategic priority response to the increasing antibiotic resistance threat. Levels of ABC at the national and provincial levels in South Africa are unknown because of inadequate ABC surveillance systems and literature. Antibiotic consumption in the public sector of Limpopo province, South Africa, 2014-2018. This retrospective study used sales data retrieved from a pharmaceutical warehouse distribution database to quantify ABC. Antibiotic consumption was measured by the defined daily dose (DDD) per 1000 inhabitants per day (DID) and 75% drug utilisation index (DU75%). Change in consumption was measured by the compound annual growth rate (CAGR). Between 2014 and 2018, the mean ABC was 4.6 ± 1.0 DID, with an overall decrease of 1.6% in the CAGR. Penicillins (2.3 ± 0.8; 50.0%), sulphonamide and trimethoprim combinations (1.4 ± 0.3 DID; 30.4%) were the most consumed antibiotics. Macrolides had the highest relative increase in consumption during the study period, with a CAGR of 18.5%. In contrast, tetracyclines had the highest relative decrease in consumption, with a CAGR of 100.0%. The CAGR ratio for broad- to narrow-spectrum increased by 39.3%, from 0.4 in 2014 to 2.1 in 2018. The DU75% comprised amoxicillin (28.4%), sulphamethoxazole and trimethoprim (SMX-TMP) (27.2%), doxycycline (12.3%) and azithromycin (9.2%). While ABC remained relatively stable throughout the study, there was an increase in broad-spectrum ABC that requires further investigation. This study contributes ABC surveillance data in Southern Africa, described by ATC classification, which is essential for monitoring and evaluating antibiotic stewardship programmes.

Seasonal variation and ecological risk assessment of Pharmaceuticals and Personal Care Products (PPCPs) in a typical semi-enclosed bay — The Bohai Bay in northern China

The Bohai Bay as a typical semi-enclosed bay in northern China with poor water exchange capacity and significant coastal urbanization, is greatly influenced by land-based inputs and human activities. As a class of pseudo-persistent organic pollutants, the spatial and temporal distribution of Pharmaceuticals and Personal Care Products (PPCPs) is particularly important to the ecological environment, and it will be imperfect to assess the ecological risk of PPCPs for the lack of systematic investigation of their distribution in different season. 14 typical PPCPs were selected to analyze the spatial and temporal distribution in the Bohai Bay by combining online solid-phase extraction (SPE) and HPLC-MS/MS techniques in this study, and their ecological risks to aquatic organisms were assessed by risk quotients (RQs) and concentration addition (CA) model. It was found that PPCPs widely presented in the Bohai Bay with significant differences of spatial and seasonal distribution. The concentrations of ∑PPCPs were higher in autumn than in summer. The distribution of individual pollutants also showed significant seasonal differences. The high values were mainly distributed in estuaries and near-shore outfalls. Mariculture activities in the northern part of the Bohai Bay made a greater contribution to the input of PPCPs. Caffeine, florfenicol, enrofloxacin and norfloxacin were the main pollutants in the Bohai Bay, with detection frequencies exceeding 80 %. The ecological risk of PPCPs to algae was significantly higher than that to invertebrates and fish. CA model indicated that the potential mixture risk of total PPCPs was not negligible, with 34 % and 88 % of stations having mixture risk in summer and autumn, respectively. The temporary stagnation of productive life caused by Covid-19 weakened the input of PPCPs to the Bohai Bay, reducing the cumulative effects of the pollutants. This study was the first full-coverage investigation of PPCPs in the Bohai Bay for different seasons, providing an important basis for the ecological risk assessment and pollution prevention of PPCPs in the bay.

Spatial aerosol deposition correlated to anatomic feature development in 6-year-old upper airway computational models

The upper airways of children undergo developmental changes around age 6, yielding differences between adult and pediatric anatomies. These differences include the cricoid ring area shape, the location of narrowest constriction, and the angle of the epiglottis, all of which are expected to alter local fluid dynamic profiles and subsequent upper airway deposition and downstream aerosol delivery of inhaled therapeutics. In this work, we quantify “pediatric”-like and “adult”-like geometric and fluid dynamic features of two computed tomography (CT)-scan derived models of 6-year-old upper airways in healthy subjects and compare to an idealized model. The two CT-scan models had a mixture of “adult”- and “pediatric”-like anatomic features, with Subject B exhibiting more “pediatric”-like features than Subject A, while the idealized model exhibited entirely “adult”-like features. By computational fluid-particle dynamics, these differences in anatomical features yielded distinct local fluid profiles with altered aerosol deposition between models. Notably, the idealized model better predicted deposition characteristics of Subject A, the more “adult”-like model, including the relationship between the impaction parameter, dp2Q and the fraction of deposition across a range of flow rates and particle diameters, as well as deposition of an approximate pharmaceutical particle size distribution model. Our results with even this limited dataset suggest that there are key personalized metrics that are influenced by anatomical development, which should be considered when developing pediatric inhalable therapeutics. Quantifying anatomical development and correlating to aerosol deposition has the potential for high-throughput developmental characterization and informing desired aerosol characteristics for pediatric applications.

Distribution and ecological risks of pharmaceuticals and personal care products with different anthropogenic stresses in a coastal watershed of China.

The occurrences of pharmaceutical and personal care products (PPCPs) in both freshwater and sea have been widely reported. However, pollution control requires further information on riverine discharges with influence of land-based activities and associated risks to estuarine ecosystems. This study investigated the spatial occurrences and the relationship to sociodemographic parameters of 30 PPCPs in 67 rivers along the Bohai coastal region. The results showed that PPCPs were mainly deposited in aquatic phase, and the partitioning coefficient between water and sediment was highly determined by chemical properties. The levels of 30 PPCPs in rivers ranged from 8.33 to 894.48ng/L, showing a large variance among regions. Caffeine, sulfamethoxazole, sulfamethazine, ofloxacin, anhydro-erythromycin, and trimethoprim were found to be the major pollutants. Multivariable analysis method was used to assess the correlation of PPCPs markers to socio-economic parameters. The results indicated that domestic emissions contributed most to the occurrences of PPCPs in the riverine water. Risk assessment result indicated that sulfamethoxazole, caffeine, tetracycline, and carbamazepine ranked top four with the highest risks to the most sensitive aquatic organisms. The results identified caffeine and carbamazepine with high detection frequency and concentration as the priority chemicals, while sulfamethoxazole and erythromycin should also be concerned due to their potential threats in specific rivers. This study provides valuable information for pollution control over PPCPs riverine discharges in estuarine regions.

Analysis, stability and distribution of pharmaceuticals and drugs of abuse over a period of one year in formalin-fixed liver and formalin solutions

The aim of the present study was to develop, validate and apply an analytical method for the determination of a large number (84 target analytes) of drugs of abuse and pharmaceuticals in formalin- fixed human liver and formalin solution to investigate their fate within a period of one year (1, 3, 6 and 12 months). A UPLC-MS/MS method was developed, on a reversed-phase column (C18) and a gradient of MeOH over H2O with a 13 minutes run for 84 drugs and pharmaceuticals. MRM mode was applied for the detection and quantification of all 84 analytes of interest by monitoring selected transitions. The target compounds comprise opiates, cocaine, cannabinoids, amphetamines, benzodiazepines, antipsychotics, antidepressants and NPSs. Sample pretreatment process was also studied. The results showed that a number of the detected compounds in the first month was significantly lower than the compounds found in fresh tissues. The effect of formalin was catalytic, and few substances could be detected. Specifically, out of the 86 positive detections of the monitored drugs and pharmaceuticals substances in the fresh tissues (in which 25 different substances were found), only 32 (37%) remained detectable 3 months after, 20 (23%) 6 months after and 15 (17%) 12 months after. In the present study a UHPLC-MS/MS method for determination of 84 drugs in fixed-liver tissues and formalin solutions has been developed, validated and applied to 14 forensic cases. Totally 25 drugs were found in the fresh liver tissue in 16 cases and their detectability and stability during 12 months in respective fixed-liver tissues and formalin solutions were studied. Useful findings were found for forensic toxicologists to properly evaluate the results of toxicological analysis in cases, where the only available samples to be examined are fixed-liver tissues and formalin solutions.

Analysis, Stability and Distribution of Pharmaceuticals and Drugs of Abuse over a Period of One Year in Formalin-Fixed Liver and Formalin Solutions.

The present study reports a thorough research on the stability of drugs of abuse and pharmaceuticals over a time period of 12 months. Fixed-liver tissues and formalin solutions where the tissues were preserved were analyzed using an ultra high performance liquid chromatography--tandem mass spectrometry method that has been developed and validated for this purpose. The method monitors 84 drugs in a 13-minute run. The concentrations of the drugs found were compared with their concentrations determined in the fresh liver tissues in a previous study. In the study, 14 cases with forensic interest were included with the main objective of the analysis and the study of the stability and the distribution of drugs of abuse and pharmaceuticals in the human liver and the formalin solution during preservation. The results showed that the number of detected compounds in the first month was significantly lower than the compounds found in fresh tissues. The effect of formalin was catalytic, and few substances could be detected. Specifically, out of the 86 positive detections of the monitored substances in the fresh tissues (in which 25 different substances were found), only 32 (37%) remained detectable3 months after, 20 (23%) 6 months after and 15 (17%) 12 months after.

Recent Advances in the Practical Synthesis of C1 Deuterated Aromatic Aldehydes Enabled by Catalysis and Beyond.

C1 -selective deuteration of aromatic aldehydes is of great importance for isotopic labeling and for improving the characteristics of drug molecules. Due to the recent increase in the use of deuterated pharmacological drugs, there is a pressing need for synthetic procedures that are efficient to produce deuterated aromatic aldehyde analouges. Deuterium labeling approaches are typically used as an effective tool for researching pharmaceutical absorption, distribution, metabolism, and excretion (ADME). Furthermore, deuterium-labeled pharmaceuticals are intended to increase therapeutic effectiveness and reduce side effects by extending the half-life of drug response. In the last few years, several catalytic or non-catalytic methods have been developed to synthesize deuterated aromatic aldehydes. In this concern, we offer a brief overview of the various synthetic strategies and practical methods for the formyl-selective deuterium labeling of aromatic aldehydes using different deuterium sources.

Evaluation of the pharmaceutical distribution and warehousing companies through an integrated Fermatean fuzzy entropy-WASPAS approach

PurposePharmaceutical supply chains (PSCs) need a well-operating and faultless logistics system to successfully store and distribute their medicines. Hospitals, health institutes, and pharmacies must maintain extra stock to respond requirements of the patients. Nevertheless, there is an inverse correlation between the level of medicine stock and logistics service level. The high stock level held by health institutions indicates that we have not sufficiently excellent logistics systems presently. As such, selecting appropriate logistics service providers (drug distributors) is crucial and strategic for PSCs. However, this is difficult for decision-makers, as highly complex situations and conflicting criteria influence such evaluation processes. So, a robust, applicable, and strong methodological frame is required to solve these decision-making problems.Design/methodology/approachTo achieve this challenging issue, the authors develop and apply an integrated entropy-WASPAS methodology with Fermatean fuzzy sets for the first time in the literature. The evaluation process takes place in two stages, as in traditional multi-criteria problems. In the first stage, the importance levels of the criteria are determined by the FF-entropy method. Afterwards, the FF-WASPAS approach ranks the alternatives.FindingsThe feasibility of the proposed model is also supported by a case study where six companies are evaluated comprehensively regarding ten criteria. Herewith, total warehouse capacity, number of refrigerated vehicles, and personnel are the top three criteria that significantly influence the evaluation of pharmaceutical distribution and warehousing companies. Further, a comprehensive sensitivity analysis proves the robustness and effectiveness of the proposed approach.Practical implicationsThe proposed multi-attribute decision model quantitatively aids managers in selecting logistics service providers considering imprecisions in the multi-criteria decision-making process.Originality/valueA new model has been developed to present a sound mathematical model for selecting logistics service providers consisting of Fermatean fuzzy entropy and WASPAS methods. The paper's main contribution is presenting a comprehensive and more robust model for the ex ante evaluation and ranking of providers.

Ripple effect mitigation capabilities of a hub and spoke distribution network: an empirical analysis of pharmaceutical supply chains in India

In this study, we focus on ripple effect mitigation capability of the Indian pharmaceutical distribution network during disruptions like COVID-19 pandemic. To study the mitigation capabilities, we conduct a multi-layer analysis (network, process, and control levels) using Bayesian network, mathematical optimisation, and discrete event simulation methodologies. This analysis revealed an associative relationship between ripple effect mitigation capabilities and network design characteristics of upstream supply chain entities. Using stochastic optimisation and Lagrangian relaxation, we then find ideal candidates for regional distribution centres at the downstream level. We then integrate these downstream locations with other supply chain entities for building the network optimisation and simulation model to analyse overall performance of the system. We demonstrate utility of our proposed methodology using a case study involving distribution of N95 masks to ‘Jan Aushadhi’ (peoples’ medicines) stores in India during COVID-19 pandemic. We find that supply chain reconfiguration improves service level to 95.7% and reduces order backlogs by 10.7%. We also find that regional distribution centres and backup supply sources provide overall flexibility and improve occupational health and safety. We further investigate alternate mitigation capabilities through fortification of suppliers’ workforce by vaccination. We offer recommendations for policymakers and managers and implications for academic research.