Search Results (1,032)

Immobilizing enzymes onto nanomaterials is a promising approach for increasing the efficiency of industrial biotransformation processes. Nanomaterials have large surface areas and unique physicochemical characteristics, they increase enzyme stability and catalytic efficiency, and they can be reused multiple times, making them favorable over free enzymes. Various nanomaterials, including carbon-based materials, metal and metal oxide nanoparticles, and polymeric nanoparticles, have been explored for immobilizing enzymes. Immobilized enzymes are more reusable than free enzymes, which are suitable for industrial applications such as in pharmaceuticals, as drug intermediates, and for synthesizing fine chemicals. Using immobilized enzymes multiple times enables numerous catalytic reactions, substantially increasing product yield and minimizing enzyme consumption, thus optimizing process efficiency and cost-effectiveness of manufacturing processes. This review explores recent developments in nanomaterials for immobilizing enzymes and biotransformation. Full article

Background/Objectives: Copovidone (polyvinylpyrrolidone-vinyl acetate copolymer, PVP/VA) is a widely used pharmaceutical excipient with various applications in drug formulation. In hot melt extrusion (HME), PVP/VA is an approved carrier material for the production of amorphous solid dispersions (ASDs) by embedding drugs on a molecular level. This study investigates the properties and processability of two copovidone grades—Plasdone™ S-630 (PS-630) and the novel Plasdone™ S-630 Ultra (PS-630U)—to assess their suitability as ASD carrier materials. Methods: The thermal and physicochemical characteristics of both polymers were evaluated, focusing on glass transition temperature and polymer melt rheology. The process performance in HME was investigated on small-scale as well as in production-scale extrusion. The two model drugs itraconazole and griseofulvin were used to examine drug dissolution and degradation during HME via in-line UV-vis spectroscopy. Results: When comparing both polymers, PS-630U offers various advantages due to the improved powder feeding behavior and reduced yellowing of extruded products while maintaining similar melt properties and drug compatibility compared to PS-630. Conclusions: These findings support the use of PS-630U as an optimized copovidone grade for ASD manufacturing, facilitating improved processing characteristics and best product qualities without the requirement of significant formulation adjustments. Full article

Background/Objectives: Visual inspection of parenteral drug products is a mandatory and critical unit operation, typically followed by an Acceptable Quality Level (AQL) check, as required by current Good Manufacturing Practices (cGMP) and regulatory authorities worldwide. Visual inspection and AQL checks need to ensure—probabilistically and statistically—that sterile product units with critical, major, or minor defects are excluded from the acceptable portion of a batch, thereby preventing such defective units from reaching distribution and eventually patients. Despite clearly defined batch defect categories, classifying individual defects and assigning them to the correct category remains challenging and has historically lacked standardization and scientific rationale. This paper presents a science-based risk assessment methodology for categorizing defects in sterile dosage forms, incorporating considerations of severity (with emphasis on patient safety), probability of occurrence, and probability of detection. Methods: The methodology is based on a modified Failure Mode and Effects Analysis (FMEA), tailored specifically for visual inspection defect classification. Results: Three examples demonstrate the practical application of this risk-based approach across different container formats: vials, pre-filled syringes, and cartridges. Conclusions: This standardized methodology offers a clear, consistent, and scientifically justified framework for defect classification. Its use enables pharmaceutical manufacturers to establish robust, risk-based defect categorization for the visual inspection of clinical and commercial sterile products. Full article

Background/Objectives: Drug products on the pharmaceutical market must meet a number of requirements that guarantee their quality, safety, and efficacy. Accordingly, periodic inspection of the content of active pharmaceutical ingredients (APIs) in marketed drug products is carried out, confirming that they meet all quality and quantity requirements for a given drug formulation before the expiration date. Therefore, the purpose of this study was to evaluate the suitability of the most commonly used thermal analysis methods, differential thermal analysis (DTA), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA), in the control of the composition of commercially available drug products. Results: Based on a review of the literature, it was shown that thermal methods can be useful in distinguishing drug products from different manufacturers, which guarantees their usefulness in quality control of finished drug products and detecting drug products from illegal manufacturers. They are also useful as tools for confirming the presence of APIs in dosage forms under investigation. The cited literature also indicates that DSC and TGA methods can be used in the quantification of APIs in marketed drug products and to detect non-compliant drug products. The use of chemometric techniques to interpret thermal data can eliminate the adverse effects of excipients on quantification results. Conclusions: Thermal methods are a good complement to chromatographic and spectroscopic methods, with the particular advantages of not needing any sample pretreatment, low sample weight, and short analysis time. Full article

Vanillin is the compound of great interest to the industry. It is used to augment and enhance the aroma and taste of food preparations and also as a fragrance compound in perfumes and detergents. Currently, majority of the world’s supply consists of chemically synthesized or lignin-derived vanillin. The application of biocatalysis for sustainable manufacturing of food ingredients, pharmaceutical intermediates, and fine chemicals is the key concept of modern industrial biotechnology. The main goal of this research was to conduct optimization procedures aimed at intensifying the microbial hydrolysis process of the lignin-rich plant raw materials and further bioconversion of the released ferulic acid to vanillin. The tests were performed in the solid-state fermentation system with strains selected during the screening stage on agri-food by-products such as brewer’s spent grain. A specially designed single-use bag bioreactor was used to carry out the process on a preparative scale with the most effective strain. The experiment was designed using the RSM, which allowed for an increase in biosynthesis efficiency from 363 mg/kg to 1413 mg/kg (an increase of 389%). The progress of the process was controlled by the use of chromatographic techniques (HPLC) by quantitative determination of vanillin content in the obtained extracts. Full article

Background/Objectives: This study aimed to develop a nanostructured lipid carrier (NLC) system incorporating a catechin-rich Vanda coerulea extract for topical cosmetic applications and to evaluate its physicochemical properties, release behavior, and skin retention performance. Methods: Blank NLCs were prepared using hot emulsification followed by sonication, with glyceryl monostearate, caprylic triglyceride, Poloxamer^® 188, and Tween^® 80 as the formulation components. NLCs with varying solid-to-liquid lipid ratios were developed while maintaining a constant total lipid content of 5% w/w. The formulations were characterized based on their particle size, polydispersity index (PDI), zeta potential, and physical stability, including stability after a heating–cooling cycle test. The effect of ultrasonication duration was also evaluated. The optimized NLC was then loaded with a V. coerulea extract and evaluated for in vitro release and skin retention using catechin as a marker. Results: The NLC with a particle size of 235.5 ± 29.8 nm, a narrow PDI range of 0.382 ± 0.090, and a strong zeta potential of −29.8 ± 0.3 mV was selected for the incorporation of the V. coerulea extract. The extract-loaded NLC exhibited a sustained release over 24 h, significantly different from the V. coerulea extract solution (p < 0.05). Skin retention studies revealed that the NLC achieved approximately twice the catechin retention compared to the solution at the 1 h time point (1.30 ± 0.01% vs. 0.68 ± 0.03% w/w). Conclusions: The V. coerulea-extract-loaded NLC demonstrated favorable physicochemical properties, sustained release behavior, and enhanced skin retention. These findings support its potential as a promising topical delivery system for antioxidant-rich botanical extracts in cosmetic applications. Full article

Nitrosamine impurities have provoked numerous global medicine recalls due to their possible presence during drug manufacturing or storage. Regarding formulation of nitrosamine impurities, a key risk involves reactions between nitrosating agents (nitrite) in excipients and vulnerable amines as impurities or degradants. Rapid detection across various sample types is essential to support pharmaceutical manufacturing. In this study, two methods were developed to detect nitrite in excipients and crucial secondary amines in active ingredient metformin hydrochloride at trace levels, respectively. The former method was developed based on the reaction of nitrite ions with 2,3-diaminonaphthalene to form 1-[H]-naphthotriazole (NAT), whereas the latter was based on amine tosylation. Mass spectrometric conditions were optimized using electrospray ionization in the positive mode. Multiple reaction monitoring transitions were determined at m/z 170 → 115 for NAT, and m/z 200.1 → 91 for dimethylamine (DMA) and 228.1 → 91 for diethylamine (DEA). These methods were validated using selected eight excipients or metformin hydrochloride in terms of specificity, linearity, accuracy, precision, robustness, limit of quantification (LOQ), and limit of determination according to the ICH guidelines. The results of the validation were within the acceptable criteria. Applicability of the methods was evaluated using 170 pharmaceutical samples donated by industries. The nitrite content in the excipients ranged from <LOQ to 4.74 ppm, with observed levels 1.3 to 6 times higher than the average (0.8 ppm) in the samples. The DMA levels in the metformin hydrochloride were within the limit (500 ppm) but varied significantly (0.2–209.2 ppm) among manufacturers. DEA was detected at lower levels (0.7–0.9 ppm). To mitigate the nitrosamine content in the metformin products, the excipient compositions were investigated by selecting those with low nitrite levels. As the types of impurities detected have become increasingly diverse and detection cycles have become more frequent, the requirement for preemptive safety management to relieve public anxiety is essential for regulatory aspects. Nitrite and secondary amines are crucial precursors to N-nitrosamine, and the suggesting approach could be a means to mitigate N-nitrosamine contamination. Full article

Background: Silkworm cocoons are rich in bioactive compounds beneficial for cosmetic applications. This study presented a novel approach by comparing microwave and ultrasonic pretreatments to enhance silk protein extraction efficiency. The aim was to evaluate the effects of pretreatment methods and extraction solvents on the bioactive components, physicochemical properties, and biological activities of silkworm cocoon extracts for cosmetic applications. Methods: Cocoons of Bombyx mori (Nang Lai) were pretreated using conventional soaking (12 h), microwave (3 min), or ultrasonication (30 min), and then subjected to aqueous or enzymatic extraction. The extracts were analyzed for protein, phenolic, and flavonoid content. Structural and thermal properties were characterized using infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. Antioxidant and anti-aging properties were assessed by measuring the inhibition of nitric oxide, 2,2-diphenyl-1-picrylhydrazyl (DPPH^•), and collagenase. Skin moisturizing effects and irritation potential were tested. Results: Silkworm cocoons pretreated with microwave (ALM) and ultrasonication (ALS), followed by enzymatic extraction, had the highest yields (21.6 ± 0.5% and 21.7 ± 0.4%, respectively). Despite their slightly lower protein contents, these extracts showed elevated phenolic and flavonoid content. ALM and ALS demonstrated strong antioxidant activities, with DPPH^• scavenging of 65.9 ± 0.2% and 65.2 ± 0.3%, collagenase inhibition of 60.3 ± 0.8% and 59.7 ± 1.7%, and nitric oxide inhibition of 13.5 ± 0.4% and 12.9 ± 0.2%, respectively. Skin moisturizing effects increased by 63.6 ± 2.1% for ALM and 61.2 ± 1.5% for ALS, compared to 1.3 ± 0.6% in the control. All extracts were found to be non-irritating for topical application, indicating their safety for skincare formulations. Conclusions: Microwave and ultrasonication pretreatments, in combination with enzymatic extraction, provide an effective, time-efficient, and sustainable method for producing silkworm cocoon extracts with promising cosmetic applications. Full article

Background. Physicomechanical properties and clinical service of bulk-fill composites depend on their adequate polymerization and depth of cure. Some manufacturers claim that these composites can be adequately cured when used in bulks exceeding 4 mm. Objective. The aim of this study was to compare Vickers microhardness (VMH) and depth of cure (DOC) of six contemporary bulk-fill resin composites at depths of 4 mm and 6 mm. Material and methods. Six bulk-fill composites were evaluated in this study: 1. Tetric EvoCeram Bulk (Ivoclar Vivadent, Schaan, Liechtenstein), (TEC); 2. Filtek Bulk Fill Posterior (3M ESPE Dental Products Division, St. Paul, MN, USA), (FBF); 3. Filtek One Bulk Fill (3M ESPE Dental Products Division, St. Paul, MN, USA, (FOB); 4. SonicFill 2 (Kerr, Orange, CA, USA), (SF2); 5. Admira Fusion X-tra (Voco, GmbH, Cuxhaven, Germany), (AFX); 6. GrandioSO X-tra (Voco, GmbH, Cuxhaven, Germany), (GSX). The 18 specimens (3 of each composite) were prepared in split Teflon moulds of 4 mm diameter and 6 mm thickness. All composites were cured in standard mode for 20 s using LED LCU (D-Light Duo, RF-Pharmaceuticals Sarl, Geneva, Switzerland; 1200–1300 mW/cm). The VMH was measured using a digital Micro Hardness Tester Shimadzu (HMV-2T E, Shimadzu Corporation, Kyoto, Japan). A 50 g (0.5 N) load force was applied for 30 s. Each specimen was measured at five places selected by chance at each level (N = 15). The hardness ratio or DOC was calculated for all samples as the ratio of bottom and surface microhardness at levels of 4 and 6 mm. Data were analysed using one-way ANOVA and Tukey’s post hoc test. Results. Significant reduction in VMH was observed for all tested materials when comparing top surface and bottom (p < 0.01). The highest VMH was obtained for GSX and AFX, and the lowest for TEC. The results show that the degree of polymerization was adequate for all tested materials at a depth of 6 mm, since the hardness ratio exceeded 0.80 in all cases. The hardness ratio at 4 mm was high for all tested composites ranging from 0.91 for TEC to 0.98 for GSX. All composites showed adequate DOC at the bottom of the 6 mm bulk samples. However, the hardness ratio was the highest for Admira Fusion X-tra (0.96) and GrandioSO X-tra (0.97). Conclusions. All tested materials showed a significant decrease in microhardness from the top surface to the bottom. The DOC was adequate for all bulk-fill composites at a depth of 6 mm cured under standard mode for 20 s. All bulk-fill resin composites evaluated in this study can be used in bulk, up to 6 mm. Full article

Background: Precision medicine refers to the formulation of personalized drug regimens according to the individual characteristics of patients to achieve optimal efficacy and minimize adverse reactions. Additive manufacturing (AM), also known as three-dimensional (3D) printing, has emerged as an optimal solution for precision drug delivery, enabling customizable and the fabrication of multifunctional structures with precise control over morphology and release behavior in pharmaceutics. However, the influence of 3D printing parameters on the printed tablets, especially regarding in vitro and in vivo performance, remains poorly understood, limiting the optimization of manufacturing processes for controlled-release profiles. Objective: To establish the fabrication process of 3D-printed controlled-release tablets via comprehensively understanding the printing parameters using fused deposition modeling (FDM) combined with hot-melt extrusion (HME) technologies. HPMC-AS/HPC-EF was used as the drug delivery matrix and carbamazepine (CBZ) was used as a model drug to investigate the in vitro drug delivery performance of the printed tablets. Methodology: Thermogravimetric analysis (TGA) was employed to assess the thermal compatibility of CBZ with HPMC-AS/HPC-EF excipients up to 230 °C, surpassing typical processing temperatures (160–200 °C). The formation of stable amorphous solid dispersions (ASDs) was validated using differential scanning calorimetry (DSC), hot-stage polarized light microscopy (PLM), and powder X-ray diffraction (PXRD). A 15-group full factorial design was then used to evaluate the effects of the fan speed (20–100%), platform temperature (40–80 °C), and printing speed (20–100 mm/s) on the tablet properties. Response surface modeling (RSM) with inverse square-root transformation was applied to analyze the dissolution kinetics, specifically t_50% (time for 50% drug release) and Q_4h (drug released at 4 h). Results: TGA confirmed the thermal compatibility of CBZ with HPMC-AS/HPC-EF, enabling stable ASD formation validated by DSC, PLM, and PXRD. The full factorial design revealed that printing speed was the dominant parameter governing dissolution behavior, with high speeds accelerating release and low speeds prolonging release through porosity-modulated diffusion control. RSM quadratic models showed optimal fits for t_50% (R² = 0.9936) and Q_4h (R² = 0.9019), highlighting the predictability of release kinetics via process parameter tuning. This work demonstrates the adaptability of polymer composite AM for tailoring drug release profiles, balancing mechanical integrity, release kinetics, and manufacturing scalability to advance multifunctional 3D-printed drug delivery devices in pharmaceutics. Full article

Ozonation and ozone-based advanced oxidation processes, including ozone/hydrogen peroxide and ozone/ultraviolet irradiation, have been extensively studied for their efficacy in treating wastewater across various industries. While sectors such as pulp and paper, textile, food and beverage, microelectronics, and municipal wastewater have successfully implemented ozone at full scale, others have yet to fully embrace these technologies’ effectiveness. This review article examines recent publications from the past two decades, exploring novel applications of ozone-based technologies in treating wastewater from diverse sectors, including food and beverage, agriculture, aquaculture, textile, pulp and paper, oil and gas, medical and pharmaceutical manufacturing, pesticides, cosmetics, cigarettes, latex, cork manufacturing, semiconductors, and electroplating industries. The review underscores ozone’s broad applicability in degrading recalcitrant synthetic and natural organics, thereby reducing toxicity and enhancing biodegradability in industrial effluents. Additionally, ozone-based treatments prove highly effective in disinfecting pathogenic microorganisms present in these effluents. Continued research and application of these ozonation and ozone-based advanced oxidation processes hold promise for addressing environmental challenges and advancing sustainable wastewater management practices globally. Full article

Background/Objectives: Hot-melt extrusion (HME) has become a key technology in pharmaceutical formulation, particularly for enhancing the solubility of poorly soluble Active Pharmaceutical Ingredients (APIs). While horizontal HME is widely adopted, vertical HME remains underexplored despite its potential benefits in footprint reduction, feeding efficiency, temperature control, and integration into continuous manufacturing. This study investigates vertical HME as an innovative approach in order to optimize drug polymer interactions and generate stable amorphous dispersions with controlled release behavior. Methods: Extrusion trials were conducted using a vertical hot-melt extruder developed by Rondol Industrie (Nancy, France). Acetylsalicylic acid (ASA) supplied by Seqens (Écully, France) was used as a model API and processed with Soluplus^® and Kollidon^® 12 PF (BASF, Ludwigshafen, Germany). Various process parameters (temperature, screw speed, screw profile) were explored. The extrudates were characterized by powder X-ray diffraction (PXRD) and small-angle X-ray scattering (SAXS) to evaluate crystallinity and microstructure. In vitro dissolution tests were performed under sink conditions using USP Apparatus II to assess drug release profiles. Results: Vertical HME enabled the formation of homogeneous amorphous solid dispersions. PXRD confirmed the absence of residual crystallinity, and SAXS revealed nanostructural changes in the polymer matrix influenced by drug loading and thermal input. In vitro dissolution demonstrated enhanced drug release rates compared to crystalline ASA, with good reproducibility. Conclusions: Vertical HME provides a compact, cleanable, and modular platform that supports the development of stable amorphous dispersions with controlled release. It represents a robust and versatile solution for pharmaceutical innovation, with strong potential for cost-efficient continuous manufacturing and industrial-scale adoption. Full article

Pharmaceutical packaging materials play a crucial role in ensuring the safety and efficacy of medications. This mini-review examines the properties of common packaging materials (glass, plastics, metals, and rubber) and their implications for drug safety. By analyzing 127 research articles from PubMed, Web of Science, and CNKI databases (2000–2025), we also discuss recent regulatory updates in China and highlight emerging technologies, including nanomaterials, sustainable packaging solutions, and intelligent packaging systems that present new opportunities for the pharmaceutical industry. Key findings include the following: (1) The physicochemical properties of packaging materials and potential microbial contamination risks during production significantly impact drug quality and safety, underscoring the need for enhanced research and regulatory oversight. (2) Each material exhibits distinct advantages and limitations: glass demonstrates superior chemical stability but may leach ions; plastics offer versatility but risk plasticizer migration; metals provide exceptional strength yet have limited applications; rubber ensures effective sealing but may release additives compromising drug quality. (3) The pharmaceutical packaging sector is evolving toward intelligent systems and sustainable solutions to address contemporary healthcare challenges. This review can aid pharmaceutical companies in selecting drug packaging and guide manufacturers in developing innovative packaging solutions. Full article

Background/Objectives: The integration of machine learning (ML) and artificial intelligence (AI) has revolutionized the pharmaceutical industry by improving drug discovery, development and manufacturing processes. Based on literature data, an ML model was developed by our group to predict the formation of binary co-amorphous systems (COAMSs) for inhalation therapy. The model’s ability to develop a dry powder formulation with the necessary properties for a predicted co-amorphous combination was evaluated. Methods: An extended experimental validation of the ML model by co-milling and X-ray diffraction analysis for 18 API-API (active pharmaceutical ingredient) combinations is presented. Additionally, one COAMS of rifampicin (RIF) and ethambutol (ETH), two first-line tuberculosis (TB) drugs are developed further for inhalation therapy. Results: The ML model has shown an accuracy of 79% in predicting suitable combinations for 35 APIs used in inhalation therapy; experimental accuracy was demonstrated to be 72%. The study confirmed the successful development of stable COAMSs of RIF-ETH either via spray-drying or co-milling. In particular, the milled COAMSs showed better aerosolization properties (higher ED and FPF with lower standard deviation). Further, RIF-ETH COAMSs show much more reproducible results in terms of drug quantity dissolved over time. Conclusions: ML has been shown to be a suitable tool to predict COAMSs that can be developed for TB treatment by inhalation to save time and cost during the experimental screening phase. Full article

This comprehensive review of the synergistic use of Quality by Design (QbD) and the Pi–Buckingham theorem explores an innovative approach to enhancing product development and process optimization within the pharmaceutical industry. QbD is a systematic, proactive methodology that integrates quality considerations throughout the product lifecycle to ensure that pharmaceutical products meet regulatory standards for safety and efficacy from the outset of development. The Pi–Buckingham theorem serves as a foundational principle in dimensional analysis, facilitating the simplification of complex models by transforming physical variables into dimensionless parameters. This synergy enables researchers to better understand and control the factors affecting critical quality attributes (CQAs), thereby improving manufacturing outcomes and minimizing variability. Full article