Advances in Study on Three-dimensional Printing in Pharmaceutics

Three dimensional printing（3DP） is a solid freeform fabrication technology which employs powder processing and a liquid binder material in the construction of parts in a layer-wise manner. 3DP can accommodate much geometric outline and be made with many materials due to its unprecedented flexibility. The technology can control over the material composition, microstructure and surface texture so it attracts great attentions in the pharmaceutics field. 3DP can offer many novel strategies and approaches for the research and is widely focused in the field of the controlled-release drug delivery systems. Through consulting a large number of documents the current development and the technical characteristics of 3DP in pharmaceutics field are discussed and reviewed. It is expected that 3DP technique may play a tremendous role in pharmaceutics field in the future.Three dimensional printing （3DP） is a solid freeform fabrication technology which employs powder processing and a liquid binder material in the construction of parts in a layer-wise manner. 3DP can accommodate much geometric outline and be made with many materials due to its unprecedented flexibility. The technology can control over the material composition, microstructure and surface texture so it attracts great attentions in the pharmaceutics field. 3DP can offer many novel strategies and approaches for the research and is widely focused in the field of the controlled-release drug delivery systems. Through consulting a large number of documents the current development and the technical characteristics of 3DP in pharmaceutics field are discussed and reviewed. It is expected that 3DP technique may play a tremendous role in pharmaceutics field in the future.

Modeling solubility of oxaprozin and irbesartan in biorelevant complex solutions based on a combination of pH-dependent and micellar solubilization models

Biological solubility is one of the important basic parameters in the development process of poorly soluble drugs,but the current measurement methods are mainly based on a large number of experiments,which are time-consuming and cost-intensive.There is still a lack of effective theoretical models to accurately describe and predict the biological solubility of drugs to reduce costs.Therefore,in this study,osaprazole and irbesartan were selected as model drugs,and their solubility in solutions containing surfactants and biorelevant media was measured experimentally.By calculating the parameters of each component using the perturbed-chain statistical associating fluid theory(PC-SAFT)model,combined with pH-dependent and micellar solubilization models,the thermodynamic phase behavior of the two drugs was successfully modeled,and the predicted results were in good agreement with the experimental values.These results demonstrate that the model combination used provides important basic parameters and theoretical guidance for the development and screening of poorly soluble drugs and related formulations.

Potentials of ribosomopathy gene as pharmaceutical targets for cancer treatment

Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality.Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic,collectively known as ribosomopathy genes.Emerging data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to cancer.Abnormal ribosome biogenesis and dysregulation of some ribosomopathy genes have also been found to be intimately associated with cancer development.The correlation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well established.This work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile,to excavate the potential role of these genes,which have not or rarely been reported in cancer,in the disease development across cancers.We plan to establish a theoretical framework between the ribosomopathy gene and cancer development,to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.

Evaluation of Phytochemical Contents and Antimicrobial Activities of Pandiaka heudelotii

The work investigated the secondary metabolites present in different parts of the Pandiaka heudelotii plant harvested from Ezira, Orumba south local government area of Anambra state, southeastern Nigeria as well as their antimicrobial activity. The objectives were to extract, determine the phytochemicals present, evaluate the antimicrobial potential and determine the zones of inhibition of the root, stem and leaf extracts of the plant. The emergence of antibiotics has decreased the spread and severity of a wide range of diseases. Plant extracts were tested for antibacterial and antifungal activities against Staphylococcus aureus, Escherichia coli, Proteus vulgaris, Streptococcus pyogenes, Bacillus subtelis, Pseudomonas aerogenes, Salmonella typhi, Aspergillus flavus, Aspergillus niger and Candida albicans. The zone of inhibition of extracts was compared with that of standard drugs like Erythromycin, Ciprofloxacin, Fulcin and Fluconazole. The result revealed the inhibition of bacterial and fungal growth with some test organisms. The microbial activity of the plant parts may be due to the presence of various secondary metabolites. The ethyl acetate extracts of Pandiaka heudelotii stood out with a minimum inhibitory concentration (MIC) range of 5 - 10 mg/mL and a minimum bactericidal concentration (MBC)/minimum fungicidal concentration (MFC) of 10 - 20 mg/ml against some test organisms. The plant can thus be worked upon to discover biologically active natural products that may serve as a prelude to the development of new pharmaceutical research undertakings.

Digital Transformation Trend of the Pharmaceutical Distribution Industry in the Context of New Infrastructure in China

Objective To study the pharmaceutical distribution industry against the background of new infrastructure construction since it is vital to the health and life of the public,and to offer some suggestions to further improve the industry quality and achieve industry upgrading.Methods The national strategies for new infrastructure as well as the underlying logic for enterprise digital transformation were analyzed to provide the outlook on the digital transformation trend of the pharmaceutical distribution industry.Results and Conclusion In the future,the pharmaceutical distribution industry shall transform the pattern,channel,management and control,and experience in the entire business chain in a digital way by focusing on connection efficiency,data efficiency and decision-making efficiency.

Research on the Threshold Effect of China’s Pharmaceutical Export Trade on Internal and External R&D Investment

Objective To study the threshold effect of export trade on internal and external R&D investment in China’s pharmaceutical industry,and to provide reference for some pharmaceutical enterprises to improve the investment.Methods The panel data of pharmaceutical industry in 25 provinces and cities in China from 2009 to 2019 were selected to conduct empirical analysis by establishing a threshold regression model,and a better export trade interval was obtained.Results and Conclusion There is a threshold value for the effect of new product export on both internal and external R&D expenditures,and the threshold values are 845.2788 million yuan and 318.4198 million yuan,respectively.There is a single threshold effect of export trade on both internal and external R&D investment in China’s pharmaceutical industry,and the effect of export trade on internal and external R&D investment changes from negative to positive as the export trade develops from low to high.

A Framework for Cloud Validation in Pharma

The pharmaceutical industry’s increasing adoption of cloud-based technologies has introduced new challenges in computerized systems validation (CSV). This paper explores the evolving landscape of cloud validation in pharmaceutical manufacturing, focusing on ensuring data integrity and regulatory compliance in the digital era. We examine the unique characteristics of cloud-based systems and their implications for traditional validation approaches. A comprehensive review of current regulatory frameworks, including FDA and EMA guidelines, provides context for discussing cloud-specific validation challenges. The paper introduces a risk-based approach to cloud CSV, detailing methodologies for assessing and mitigating risks associated with cloud adoption in pharmaceutical environments. Key considerations for maintaining data integrity in cloud systems are analyzed, particularly when applying ALCOA+ principles in distributed computing environments. The article presents strategies for adapting traditional Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ) models to cloud-based systems, highlighting the importance of continuous validation in dynamic cloud environments. The paper also explores emerging trends, including integrating artificial intelligence and edge computing in pharmaceutical manufacturing and their implications for future validation strategies. This research contributes to the evolving body of knowledge on cloud validation in pharmaceuticals by proposing a framework that balances regulatory compliance with the agility offered by cloud technologies. The findings suggest that while cloud adoption presents unique challenges, a well-structured, risk-based approach to validation can ensure the integrity and compliance of cloud-based systems in pharmaceutical manufacturing.

Countermeasures and Suggestions for Strengthening Human Resource Management in China’s Pharmaceutical Industry

Objective To provide reference and enlightenment for the development of human resource management in China’s pharmaceutical industry and to put forward some suggestions to promote the further development of pharmaceutical industry.Methods The method of literature review was used to analyze the current situation and existing problems of human resource management in China’s pharmaceutical industry.Results and Conclusion Only by continuously improving the human resource management skills and innovating management methods can pharmaceutical enterprises achieve long-term benefits with sustainable development.The formulation of human resource management strategy in pharmaceutical industry must be conducive to the realization of the business goals of enterprises.To achieve this overall goal,the human resources management department of enterprises must make the plan from a strategic perspective,formulate talent strategic planning which serves the overall strategic goal of the enterprise.As a result,human resource management will play an important role in the development of China’s pharmaceutical industry.

Comparative Analysis of Profit Model of Typical Pharmaceutical O2O Enterprises in China

Objective To study the profit model of Chinese pharmaceutical O2O enterprises.Methods A case study of three typical pharmaceutical O2O enterprises was conducted,and their profit models were compared.Results and Conclusion The pharmaceutical O2O enterprises in China are divided into three categories according to the profit models.It is found that the current pharmaceutical O2O enterprises have problems such as simple profit model and low corporate profits.Based on these problems,it is recommended that relevant enterprises develop various business models to increase profit channels.Besides,they should establish and improve internal cost control systems.

Research on the Status Quo and Countermeasures of Human Resource Management Outsourcing in China’s Pharmaceutical Enterprises

Objective To explore the current situation of human resource management outsourcing in China’s pharmaceutical enterprises,and to put forward some suggestions for enterprises and the government.Methods The current situation of human resource management outsourcing in China’s pharmaceutical enterprises was analyzed through the method of literature research.Results and Conclusion At present,the status of human resource management outsourcing in China’s pharmaceutical companies is that the level of human resource outsourcing companies is not high,and there are no relevant industry norms and laws.The information asymmetry between pharmaceutical enterprises and outsourcing companies results in adverse selection and moral hazard.Besides,the different culture of pharmaceutical enterprises and outsourcing companies leads to inefficient communication between enterprises and employee.To solve these problems,the government should promote and improve industry norms and laws to regulate the market.In addition,enterprises should clarify the motivation for outsourcing and make good decision on the outsourcing content.Meanwhile,enterprises should strengthen communication with employees to eliminate employees’concerns.

上海药物研发行业职业健康管理现状与改进策略

目的 了解上海药物研发行业职业健康管理现状及面临的挑战,为制订行业职业健康管理策略,促进行业健康发展提供参考。方法 采用问卷调查法对上海48家药物研发公司的职业健康风险、管理现状及存在的问题进行梳理,采用现场调研法对5家代表性公司实地了解行业职业危害防护和新业态的管理需求,探讨可行的解决方案。结果 问卷调查结果显示半数以上的药物研发公司从事小分子药物和抗肿瘤药物研发,面临着研发试剂、研发中的药物、病原微生物和实验动物等多重健康风险。职业病防护设施“三同时”工作完成率为43.8%,职业病危害因素检测和职业健康监护的开展率分别为89.6%和79.2%。现场调研发现药物研发行业的建筑通风、职业危害防护以及新业态的职业健康管理面临挑战。结论 随着药物研发行业的快速发展,潜在职业健康风险不容忽视,职业危害防护和管理工作亟待细化和完善。

Microneedle-based interstitial fluid extraction for drug analysis:Advances,challenges,and prospects

Similar to blood,interstitial fluid(ISF)contains exogenous drugs and biomarkers and may therefore substitute blood in drug analysis.However,current ISF extraction techniques require bulky instruments and are both time-consuming and complicated,which has inspired the development of viable alternatives such as those relying on skin or tissue puncturing with microneedles.Currently,microneedles are widely employed for transdermal drug delivery and have been successfully used for ISF extraction by different mechanisms to facilitate subsequent analysis.The integration of microneedles with sensors enables in situ ISF analysis and specific compound monitoring,while the integration of monitoring and delivery functions in wearable devices allows real-time dose modification.Herein,we review the progress in drug analysis based on microneedle-assisted ISF extraction and discuss the related future opportunities and challenges.

Online pharmaceutical process analysis of Chinese medicine using a miniature mass spectrometer: Extraction of active ingredients as an example

The automation of traditional Chinese medicine(TCM)pharmaceuticals has driven the development of process analysis from offline to online.Most of common online process analytical technologies are based on spectroscopy,making the identification and quantification of specific ingredients still a challenge.Herein,we developed a quality control(QC)system for monitoring TCM pharmaceuticals based on paper spray ionization miniature mass spectrometry(mini-MS).It enabled real-time online qualitative and quantitative detection of target ingredients in herbal extracts using mini-MS without chromatographic separation for the first time.Dynamic changes of alkaloids in Aconiti Lateralis Radix Praeparata(Fuzi)during decoction were used as examples,and the scientific principle of Fuzi compatibility was also investigated.Finally,the system was verified to work stably at the hourly level for pilot-scale extraction.This mini-MS based online analytical system is expected to be further developed for QC applications in a wider range of pharmaceutical processes.

Leveraging Blockchain with Optimal Deep Learning-Based Drug Supply Chain Management for Pharmaceutical Industries

Due to its complexity and involvement of numerous stakeholders,the pharmaceutical supply chain presents many challenges that companies must overcome to deliver necessary medications to patients efficiently.The pharmaceutical supply chain poses different challenging issues,encompasses supply chain visibility,cold-chain shipping,drug counterfeiting,and rising prescription drug prices,which can considerably surge out-of-pocket patient costs.Blockchain(BC)offers the technical base for such a scheme,as it could track legitimate drugs and avoid fake circulation.The designers presented the procedure of BC with fabric for creating a secured drug supplychain management(DSCM)method.With this motivation,the study presents a new blockchain with optimal deep learning-enabled DSCM and recommendation scheme(BCODL-DSCMRS)for Pharmaceutical Industries.Firstly,Hyperledger fabric is used for DSC management,enabling effective tracking processes in the smart pharmaceutical industry.In addition,a hybrid deep belief network(HDBN)model is used to suggest the best or top-rated medicines to healthcare providers and consumers.The spotted hyena optimizer(SHO)algorithm is used to optimize the performance of the HDBN model.The design of the HSO algorithm for tuning the HDBN model demonstrates the novelty of the work.The presented model is tested on the UCI repository’s open-access drug reviews database.

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.

Role of 7-methylxanthine in myopia prevention and control: a mini-review

·Myopia is becoming increasingly common. By 2050 around 10% of the world’s population is expected to be highly myopic(<-5 diopters) and therefore particularly at risk of suffering from sight-threatening complications. Currently used myopia control treatments, such as multifocal soft contact lenses or spectacle lenses, orthokeratology, and atropine eyedrops, either do not completely arrest myopia progression or are associated with significant ocular and possibly systemic side effects. A new candidate for pharmaceutical control of myopia progression and excessive eye elongation, the non-selective adenosine antagonist 7-methylxanthine(7-MX), appears to be nontoxic and effective in reducing myopia progression and axial eye growth in experimental and clinical studies. The latest findings regarding 7-MX for myopia control and evaluate its potential as a supplement to existing treatment options were reviewed.

Impact of H1N1, H7N9, ASFV, dengue virus and COVID-19 on pharmaceutical manufacturing firms' R&D investments and economic consequences: Evidence from China

Objective:To determine the impact of major disease epidemics on pharmaceutical manufacturing firms'Research&Development(R&D)investments and economic consequences.Methods:The sample consists of 1582 firm-year observations from 2009 to 2022 in China,of which,26.6%of pharmaceutical companies are involved in the diagnosis and treatment of prevalent diseases.Linear models using R&D investments,patent applications,operating performances and stock returns as dependent variables are constructed separately to examine the response of pharmaceutical companies to disease epidemics and the resulting economic consequences.Results:The prevalence of five major diseases led to a 17.5%increase in the amount of R&D investment and an 87.8%rise in the ratio of R&D investment to total assets by disease-related pharmaceutical companies,compared to unrelated pharmaceutical companies.Further evidence indicated that the patent applications for disease-related firms increased by 44.3%relative to unrelated firms after the epidemics.Though the impacts of the epidemics on firms’operating performances were insignificant in the short term,a major disease epidemic was associated with an increase in stock returns of 67.4%and 44.6%,respectively,as measured by the capital asset pricing model and Fama-French five-factor model.Additional analysis revealed that the impacts of the epidemics on R&D investments and patent applications were more pronounced for non-state-owned enterprises than state-owned enterprises.Conclusions:This study demonstrates that disease-related pharmaceutical firms respond to the disease epidemics through increasing R&D investment.More patent applications and higher market value are the main gains from the firms’increased investments in R&D following the epidemic,rather than the improvements of short-term operating performances.

Emerging novel targets for nonalcoholic fatty liver disease treatment: Evidence from recent basic studies

Nonalcoholic fatty liver disease(NAFLD),a leading chronic disease worldwide,affects approximately a quarter of the global population.Nonalcoholic steatohepatitis(NASH)is an advanced form of NAFLD and is more likely to progress to liver fibrosis than simple steatosis.NASH is also identified as the most rapidly growing cause of hepatocellular carcinoma.Although in the past decade,several phase II/III clinical trials have shown promising results in the use of novel drugs targeting lipid synthase,farnesoid X receptor signaling,peroxisome proliferatoractivated receptor signaling,hepatocellular injury,and inflammatory signaling,proven pharmaceutical agents to treat NASH are still lacking.Thus,continuous exploration of the mechanism underlying the pathogenesis of NAFLD and the identification of novel therapeutic targets remain urgent tasks in the field.In the current review,we summarize studies reported in recent years that not only provide new insights into the mechanisms of NAFLD development but also explore the possibility of treating NAFLD by targeting newly identified signaling pathways.We also discuss evidence focusing on the intrahepatic targets involved in the pathogenesis of NAFLD as well as extrahepatic targets affecting liver metabolism and function.

Anti-tumor Activity of Isovanillin and Its Molecular Mechanism

Taking isovanillin and the important products synthesized from raw materials of isovanillin as objects,this paper reviews its pharmacological effects and molecular mechanisms,including inhibiting tumor angiogenesis,blocking cancer cell self-repair,inducing cancer cell DNA fragmentation,cytotoxicity,inhibiting tumor growth,regulating brain nerves,inhibiting renin and other pharmacological effects,etc.,which provide new ideas for the in-depth research and development of isovanillin.

A review on cocrystal of active ingredients in traditional Chinese medicine

In the development of new drugs products,especially the development of traditional Chinese medicine active ingredients,solubility and oral bioavailability are the main factors which are restricting the development of new drugs,whereas the physicochemical properties of active ingredients are the key element to affecting these factors.Pharmaceutical cocrystal provides an excellent opportunity to develop new drugs with excellent physical and chemical properties such as melting point,solubility,stability and bioavailability while retaining the pharmacological properties of individuals active pharmaceutical ingredients among pharmaceutical cocrystal compounds.Traditional Chinese herbal medicine has the characteristics of multiple pathways and multiple targets,mainly because it contains many active ingredients,like cocrystals thereof with many components.The active ingredients extracted from traditional Chinese herbal medicine have a wide range of pharmacological activities,but most of the active ingredients affect the development of traditional Chinese medicine active ingredients due to their physical and chemical properties such as solubility.Traditional Chinese medicine pharmaceutical cocrystals can not only improve the physical and chemical properties of drugs without changing the internal structure of drugs,so as to provide a new scheme for the development of traditional Chinese medicine active ingredients.This paper reviews the research progress of active ingredients of traditional Chinese medicine pharmaceutical cocrystal.The preparation methods of cocrystals are summarized and the advantages of cocrystals are illustrated with examples.