Search Results (55)

The present study describes the ten-year (2014–2024) validation of a Class 100,000ISO 8 qualified air system used in the manufacture of non-sterile pharmaceutical dosage forms in a GMP-certified facility. The lifecycle evaluation included design, installation, qualification, continuous operation, environmental monitoring, cleaning and disinfection verification, and annual third-party validation. The system was assessed for critical parameters, including air renewal rates, airflow directionality, the integrity of high-efficiency particulate air (HEPA) filters and ultra-low penetration air (ULPA) filters, environmental recovery times, and non-viable particle counts. Particle monitoring focused on 0.5 μm and 1.0 μm channels within the 0.5–5 μm range specified by ISO 14644-1 for ISO 8 areas. The 0.5–1.0 μm range was prioritized because it provides higher statistical representativeness for evaluating filter performance and controlling fine particulate dispersion, which is particularly relevant in non-sterile pharmaceutical production, while larger particles (>5 μm) are more critical in aseptic processes. The influence of personnel and air exchange rates on cleanliness was also assessed during the final years of the study. Results demonstrate that continuous, systematic validation ensures the controlled environmental conditions required for pharmaceutical production and supports the sustained quality and safety of the finished products. This study provides a technical reference for engineers, pharmacists, and quality professionals involved in cleanroom design, qualification, and regulatory compliance. Full article

A series of silver-polygalacturonate complexes with improved structure and activity against bacterial infections was developed. Pure sodium polygalacturonate was obtained by saponification of a pectin precursor and identified by NMR as predominantly homogalacturonan (uronide content 95%). Polygalacturonate complexes with ionic and borohydride-reduced silver with a controllable metallic component were synthesized; the role of spontaneous Ag⁺ reduction was revealed. The presence of uniform 5 nm nanoparticles and negligible particulate by-products in the reduced complexes was verified. The complexes showed similar silver-normalized activity against non-resistant bacteria, irrespective of complex stoichiometry/silver state. Pharmaceutical silver proteinate with a similar nanoparticle profile exhibited the same silver-normalized activity, indicating the lack of a ligand effect. The Ag⁺ complex was more effective against some hospital drug-resistant strains. The cytotoxicity of the complexes depended on fibroblast type, silver state, ligand type, exposure time, presumably in association with cellular availability and glutathione depletion. The complexes were administered to rats with excisional wounds persistently infected with S. aureus. Swab/histological analyses of the treated wounds revealed decreased bacterial burden/tissue damage, along with promotion of wound contraction/closure and matrix formation. The nanoparticle complexes that were compared had similar antibacterial/regenerative effects, while the Ag⁺ complex demonstrated higher efficacy in vivo. These results encourage the use of the developed silver-polygalacturonate complexes as antibacterial substances. Full article

Indoor air pollution has become a significant concern, contributing to the decline in air quality through the presence of gaseous pollutants and particulate matter, especially under poor ventilation. Hospitals, functioning as non-industrial microenvironments, particularly in Thailand, face challenges due to insufficient and incomplete databases for effective air quality management. Within these environments, patients with heightened sensitivity, along with hospital staff who are predominantly exposed indoors, face increased risk of exposure to indoor air pollutants. This study aimed to review current evidence on VOCs in hospital settings in Thailand, identifying their sources, concentrations, and health impacts. It also aimed to provide recommendations for improved air quality monitoring and management. The review included studies published between 2008 and 2023 in English or Thai. Studies were selected based on relevance to VOCs in hospital environments, while excluding those lacking sufficient data or methodological rigor. Literature searches were conducted using Google Scholar, ScienceDirect, Scopus, and PubMed. Results from international studies were also considered to address gaps. Data extraction focused on VOC sources, concentrations, measurement methods, and associated health impacts. Results were synthesized into six thematic categories: characterization, health effects, control measures, etiological studies, monitoring systems, and comparative studies. The review identified 87 relevant studies. VOC exposure was associated with several adverse health impacts resulting from short- and long-term exposures, leading to an increased risk of cancer. Identified sources of VOC emissions within hospitals encompass anesthetic gases, sterilization processes, pharmaceuticals, laboratory chemicals, patient care, and household products, as well as building materials and furnishings. Commonly encountered VOCs include alcohols (e.g., ethanol, 2-methyl-2-propanol, isopropanol), ether, isoflurane, nitrous oxide, sevoflurane, chlorine, formaldehyde, aromatic hydrocarbons, limonene, and glutaraldehyde, among those commonly detected in hospital environments. Yet, limited knowledge exists regarding their source contributions, emissions, and concentrations associated with health impacts in Thai hospitals. Full article

Antimicrobial resistance (AMR) has emerged as a planetary health emergency, driven not only by the clinical misuse of antibiotics but also by diverse environmental dissemination pathways. This review critically examines the role of environmental compartments—water, soil, and air—as dynamic reservoirs and transmission routes for antibiotic-resistant bacteria (ARB) and resistance genes (ARGs). Recent metagenomic, epidemiological, and mechanistic evidence demonstrates that anthropogenic pressures—including pharmaceutical effluents, agricultural runoff, untreated sewage, and airborne emissions—amplify resistance evolution and interspecies gene transfer via horizontal gene transfer mechanisms, biofilms, and mobile genetic elements. Importantly, it is not only highly polluted rivers such as the Ganges that contribute to the spread of AMR; even low concentrations of antibiotics and their metabolites, formed during or after treatment, can significantly promote the selection and dissemination of resistance. Environmental hotspots such as European agricultural soils and airborne particulate zones near wastewater treatment plants further illustrate the complexity and global scope of pollution-driven AMR. The synergistic roles of co-selective agents, including heavy metals, disinfectants, and microplastics, are highlighted for their impact in exacerbating resistance gene propagation across ecological and geographical boundaries. The efficacy and limitations of current mitigation strategies, including advanced wastewater treatments, thermophilic composting, biosensor-based surveillance, and emerging regulatory frameworks, are evaluated. By integrating a One Health perspective, this review underscores the imperative of including environmental considerations in global AMR containment policies and proposes a multidisciplinary roadmap to mitigate resistance spread across interconnected human, animal, and environmental domains. Full article

The advancement of high-tech industries, notably in semiconductor manufacturing, pharmaceuticals, and precision instrumentation, has imposed stringent requirements on cleanroom environments, where strict control of airborne particulates, microbial presence, temperature, and humidity is essential. However, these controlled environments incur significant energy consumption, with air conditioning systems accounting for 40–60% of total usage due to high air circulation rates, intensive treatment demands, and system resistance. In light of global carbon reduction goals and escalating energy costs, improving the energy efficiency of cleanroom heating, ventilation, and air conditioning (HVAC) systems has become a critical research priority. Recent efforts have focused on optimizing airflow distribution, integrating heat recovery technologies, and adopting low-resistance filtration to reduce energy demand while maintaining stringent environmental standards. Concurrently, artificial intelligence (AI) methods, such as machine learning, deep learning, and adaptive control, are being employed to enable intelligent, energy-efficient system operations. This review systematically examines current energy-saving technologies and strategies in cleanroom HVAC systems, assesses their real-world performance, and highlights emerging trends. The objective is to provide a scientific basis for the green design, operation, and retrofit of cleanrooms, thereby supporting the industry’s transition toward low-carbon, sustainable development. Full article

Objective: Current good manufacturing practice (cGMP) guidance for positron emission tomography (PET) drugs has been established in Europe and the United States. In Japan, the Pharmaceuticals and Medical Devices Agency (PMDA) approved the use of radiosynthesizers as medical devices for the in-house manufacturing of PET drugs in hospitals and clinics, regardless of the cGMP environment. Without adequate facilities, equipment, and personnel required by cGMP regulations, the quality assurance (QA) and clinical effectiveness of PET drugs largely depend on the radiosynthesizers themselves. To bridge the gap between radiochemistry standardization and site qualification, the Japanese Society of Nuclear Medicine (JSNM) has issued guidance for the in-house manufacturing of small-scale PET drugs under academic GMP (a-GMP) environments. The goals of cGMP and a-GMP are different: cGMP focuses on process optimization, certification, and commercialization, while a-GMP facilitates the small-scale, in-house production of PET drugs for clinical trials and patient-specific standard of care. Among PET isotopes, N-13 has a short half-life (10 min) and must be synthesized on site. [¹³N]Ammonia ([¹³N]NH₃) is used for myocardial perfusion imaging under the Japan Health Insurance System (JHIS) and was thus selected as a working example for the manufacturing of PET drugs in an a-GMP environment. Methods: A [¹³N]NH₃-radiosynthesizer was installed in a hot cell within an a-GMP-compliant radiopharmacy unit. To comply with a-GMP regulations, the air flow was adjusted through HEPA filters. All cabinets and cells were disinfected to ensure sterility once a month. Standard operating procedures (SOPs) were applied, including analytical methods. Batch records, QA data, and radiation exposure to staff in the synthesis of [¹³N]NH₃ were measured and documented. Results: 2.52 GBq of [¹³N]NH₃ end-of-synthesis (EOS) was obtained in an average of 13.5 min in 15 production runs. The radiochemical purity was more than 99%. Exposure doses were 11 µSv for one production run and 22 µSv for two production runs. The pre-irradiation background dose rate was 0.12 µSv/h. After irradiation, the exposed dosage in the front of the hot cell was 0.15 µSv/h. The leakage dosage measured at the bench was 0.16 µSv/h. The exposure and leakage dosages in the manufacturing of [¹³N]NH₃ were similar to the background level as measured by radiation monitoring systems in an a-GMP environments. All QAs, environmental data, bacteria assays, and particulates met a-GMP compliance standards. Conclusions: In-house a-GMP environments require dedicated radiosynthesizers, documentation for batch records, validation schedules, radiation protection monitoring, air and particulate systems, and accountable personnel. In this study, the in-house manufacturing of [¹³N]NH₃ under a-GMP conditions was successfully demonstrated. These findings support the international harmonization of small-scale PET drug manufacturing in hospitals and clinics for future multi-center clinical trials and the development of a standard of care. Full article

Volatile organic compounds (VOCs), the precursors of ozone and fine particulate matter, are one of the atmospheric pollutants harmful to human health. The emission characteristics of VOCs in Anyang, a typical industrial city in the Central Plains of China, are unclear. To determine the emission level and composition of local VOCs, this study conducted on-site sampling of 20 factories in eight key industries. A total of 105 VOC species in seven categories were observed. The concentration of total VOCs emitted from the eight industries in order from large to small was as follows: packaging and printing > pharmaceutical > paint manufacturing > industrial coating > chemical industry > metal smelting > furniture manufacturing > textile printing and dyeing. In addition to industrial coating, the total VOCs and their corresponding ozone formation potential of organized emissions in seven industries (1.44–87.64, 1.52–181.61 mg/m³) were higher than those of unorganized emissions (0.38–24.17, 0.38–125.55 mg/m³). The VOC emissions were concentrated in the central, south-central, and south-eastern parts of the city, mainly from the factories in the packaging and printing, pharmaceutical, paint, and coating industries. The furniture manufacturing (4.55 × 10⁻³) and pharmaceutical (1.66 × 10⁻³) industries in organized emissions were at high risk of carcinogenesis, while the pharmaceutical industry in unorganized emissions (3.61 × 10⁻⁴) was at moderate risk of carcinogenesis. Naphthalene was the main high-risk compound. In terms of non-carcinogenic risk, the packaging and printing industry in organized emissions (228.51) and the metal smelting industry in unorganized emissions (16.16) had the highest risk, and the main high-risk compound was ethyl acetate. Full article

Objectives: Parenteral drug products manufactured under GMP conditions should be visually inspected for defects and particulate contamination by trained and qualified personnel. Although personnel qualification is required, no practical protocols or formal guidelines are available for the development of qualification test sets (QTSs) used for qualification procedures. The current practice is to either procure a standardized QTS from a commercial supplier or amass sufficient manufacturing rejects during visual inspection procedures to compile in-house QTSs. However, both strategies inherently possess disadvantages and limitations. The objective of this study was to develop a manufacturing protocol for an optimal and adaptable QTS for training and qualification procedures. Methods: We combined the results of a literature search, survey of five Dutch hospital pharmacy compounding facilities, semi-structured personnel interviews, and extensive pre-GMP formulation studies to develop an optimal and adaptable QTS manufacturing protocol. Results: The literature search did not identify a manufacturing protocol for an optimal and adaptable QTS, but did identify specifications and requirements for optimal QTSs. The survey among hospital pharmacy compounding facilities revealed considerable variability in the qualification procedures and used QTSs. Semi-structured personnel interviews and pre-GMP formulation studies demonstrated that defects encountered during routine productions could be realistically simulated with pharmaceutical-grade excipients. As a proof-of-concept, we manufactured two different QTSs under GMP conditions and assessed these for formal GMP training and qualification purposes, which were considered a significant improvement compared to using manufacturing rejects. Conclusions: To the best of our knowledge, this is the first study presenting these data and our adaptable protocol, which is provided in the Supplemental Materials, may aid compounding facilities in the standardization, training, and qualification of personnel involved in visual inspection procedures. Full article

Background: Extracellular vesicles (EVs), including exosomes, are promising pharmaceutical modalities. They are purified from cell culture supernatant; however, the preparation may contain EVs with the desired therapeutic effects and different types of EVs, lipoproteins, and soluble proteins. Evaluating the composition of particulate impurities and the levels of protein impurities in final preparations is critical for quality control. However, few analytical methods can detect these impurities. Methods: We established and evaluated an analytical method using size-exclusion chromatography–multi-angle light scattering (SEC-MALS) for particle and protein impurity analyses of EV samples. Results: In the particle size distribution analysis of EV samples, SEC-MALS showed higher resolution compared with nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS). MALS showed comparable accuracy and precision to that of other methods for particle size evaluation using polystyrene standard beads with 60, 100, or 200 nm diameter. Coupling SEC-MALS with UV detection quantitatively evaluated soluble protein impurities. Proteomic analysis on the SEC-MALS-fractionated samples identified different EV and lipoprotein marker proteins in different fractions. Conclusions: SEC-MALS can characterize EV preparations obtained from human adipose-derived mesenchymal stem cells, suggesting that it can evaluate the particle component composition in various EV samples and therapeutic exosome preparations. Full article

The present study investigated the effect of different polymers and manufacturing methods (hot melt extrusion, HME, and spray drying, SD) on the solid state, stability and pharmaceutical performance of amorphous solid dispersions. In the present manuscript, a combination of different binary amorphous solid dispersions containing 20% and 30% of drug loadings were prepared using SD and HME. The developed solid-state properties of the dispersions were evaluated using small- and wide-angle X-ray scattering (WAXS) and modulated differential scanning calorimetry (mDSC). The molecular interaction between the active pharmaceutical ingredients (APIs) and polymers were investigated via infrared (IR) and Raman spectroscopy. The in vitro release profile of the solid dispersions was also evaluated to compare the rate and extend of drug dissolution as a function of method of preparation. Thereafter, the effect of accelerated stability conditions on the physicochemical properties of the solid dispersions were also evaluated. The results demonstrated higher stability of Soluplus^® (SOL) polymer-based solid dispersions as compared to hydroxypropyl methylcellulose (HPMC)-based solid dispersions. Moreover, the stability of the solid dispersions was found to be higher in the case of API having high glass transition temperature (Tg) and demonstrated higher interaction with the polymeric groups. Interestingly, the stability of the melt-extruded dispersions was found to be slightly higher as compared to the SD formulations. However, the down-processing of melt-extruded strands plays critical role in inducing the API crystal nuclei formation. In summary, the findings strongly indicate that the particulate properties significantly influence the performance of the product. Full article

The production of nanoparticles has recently surged due to their varied applications in the biomedical, pharmaceutical, textile, and electronic sectors. However, this rapid increase in nanoparticle manufacturing has raised concerns about environmental pollution, particularly its potential adverse effects on human health. Among the various concerns, inhalation exposure to nanoparticles poses significant risks, especially affecting the respiratory system. Airway epithelial cells play a crucial role as the primary defense against inhaled particulate matter and pathogens. Studies have shown that nanoparticles can disrupt the airway epithelial barrier, triggering inflammatory responses, generating reactive oxygen species, and compromising cell viability. However, our understanding of how different types of nanoparticles specifically impact the airway epithelial barrier remains limited. Both in vitro cell culture and in vivo murine models are commonly utilized to investigate nanoparticle-induced cellular responses and barrier dysfunction. This review discusses the methodologies frequently employed to assess nanoparticle toxicity and barrier disruption. Furthermore, we analyze and compare the distinct effects of various nanoparticle types on the airway epithelial barrier. By elucidating the diverse responses elicited by different nanoparticles, we aim to provide insights that can guide future research endeavors in assessing and mitigating the potential risks associated with nanoparticle exposure. Full article

Particle aggregation is essential in many industrial processes, spanning the pharmaceutical and food industries, polymer production, and the environment, among others. However, aggregation can also occur, in some processes, as a non-desired side effect. Thus, to be able to monitor aggregation in industrial processes is of high importance to guarantee that the final, required product characteristics are obtained. In this paper, we present an extensive review of the different techniques available for monitoring particle characteristics in industrial processes involving particulate materials, with special emphasis on aggregation processes. These methods include both off-line and on-line techniques, based either on image acquisition techniques or different radiation scattering techniques (light-scattering and ultrasound spectroscopy). The principles behind each technique are addressed, together with their relevant applications, advantages, and disadvantages. Full article

The increasing demand for innovative approaches in wound healing and skin regeneration has prompted extensive research into advanced biomaterials. This review focuses on showcasing the unique properties of sustainable silk-based particulate systems in promoting the controlled release of pharmaceuticals and bioactive agents in the context of wound healing and skin regeneration. Silk fibroin and sericin are derived from well-established silkworm production and constitute a unique biocompatible and biodegradable protein platform for the development of drug delivery systems. The controlled release of therapeutic compounds from silk-based particulate systems not only ensures optimal bioavailability but also addresses the challenges associated with conventional delivery methods. The multifaceted benefits of silk proteins, including their inherent biocompatibility, versatility, and sustainability, are explored in this review. Furthermore, the intricate mechanisms by which controlled drug release takes place from silk-based carriers are discussed. Full article

The increasing interest in protein- and peptide-based oral pharmaceuticals has culminated in the first protein-based products for oral delivery becoming commercially available. This study investigates the compaction properties of proteins in binary mixtures with common excipients up to 30% (w/w) of particulate protein. Two model proteins, lysozyme and bovine serum albumin, were compacted with either microcrystalline cellulose, spray-dried lactose monohydrate, or calcium hydrogen phosphate dihydrate at two different compaction pressures. Compared to the compacted pure materials, a significant increase in the tensile strength of the compacts was observed for the binary blends containing lysozyme together with the brittle excipients. This could be attributed to the increased bonding forces between the particles in the blend compared to the pure materials. The use of bovine serum albumin with a larger particle size resulted in a decrease in tensile strength for all the compacts. The change in the tensile strength with an increasing protein content was non-linear for both proteins. This work highlights the importance of considering the particulate properties of protein powders and that protein-based compacts can be designed with similar principles as small-molecules in terms of their mechanical tablet properties. Full article

Air pollution causes various airway diseases. However, many commonly used treatments can have high risks of side effects or are costly. To examine the anti-inflammatory properties of Inula japonica Thunb. and Potentilla chinensis Ser., a mouse model was generated via inhalation of both particulate matter 10 and diesel particulate matter, and 30% ethanol extracts of either I. japonica (IJ) or P. chinensis (PC) and a mixture of both ethanol extracts (IP) were orally administered to BALB/c mice for 12 days. IJ, PC, and IP inhibited immune cell numbers and their regulation in both the bronchoalveolar lavage fluid (BALF) and lungs. These agents suppressed the levels of interleukin (IL)-1α, IL-17, tumor necrosis factor (TNF)-α, C-X-C motif chemokine ligand (CXCL)-1, and CXCL-2 in BALF, and also inhibited F4/80 and IL-1 receptor-associated kinase (IRAK)-1 in lungs. They reduced the gene expression of TNF-α, CXCL-1, inducible NOS, COX-2, Mucin 5AC, and transient receptor potential cation channel subfamily V member 1 in lungs. These extracts also reduced histopathological changes and inflammatory progression, manifested as decreased cell infiltration, collagen deposition, and respiratory epithelial cell thickness. I. japonica and P. chinensis show potential for development as pharmaceuticals that suppress inflammatory progression and alleviate airway inflammation diseases caused by air pollutants. Full article