Direct Assembly of Bioactive Nanoparticles Constructed from Polyphenol-Nanoengineered Albumin.

Albumin nanoparticles are widely used in biomedicine due to their safety, low immunogenicity, and prolonged circulation. However, incorporating therapeutic molecules into these carriers faces challenges due to limited binding sites, restricting drug conjugation efficiency. We introduce a universal nanocarrier platform (X-UNP) using polyphenol-based engineering to incorporate phenolic moieties into albumin nanoparticles. Integration of catechol or galloyl groups significantly enhances drug binding and broadens the drug conjugation possibilities. Our study presents a library of X-UNP nanoparticles with improved drug-loading efficiency, achieving up to 96% across 10 clinically used drugs, surpassing conventional methods. Notably, ibuprofen-UNP nanoparticles exhibit a 5-fold increase in half-life compared with free ibuprofen, enhancing in vivo analgesic and anti-inflammatory effectiveness. This research establishes a versatile platform for protein-based nanosized materials accommodating various therapeutic agents in biotechnological applications.

Exploring the impact of polyvinylidenefluoride membrane physical properties on the enrichment efficacy of microfluidic electro-membrane extraction of acidic drugs.

Membrane technology has revolutionized various fields with its energy efficiency, versatility, user-friendliness, and adaptability. This study introduces a microfluidic chip, comprised of silicone rubber and polymethylmethacrylate (PMMA) sheets to explore the impacts of polymeric support morphology on electro-membrane extraction efficiency, representing a pioneering exploration in this field. In this research, three polyvinylidenefluoride (PVDF) membranes with distinct pore sizes were fabricated and their characteristics were assessed through field-emission scanning electron microscopy (FESEM), and atomic force microscopy (AFM). This investigation centers on the extraction of three widely prescribed non-steroidal anti-inflammatory drugs: aspirin (ASA), naproxen (NAP), and ibuprofen (IBU). Quantitative parameters in the extraction process including voltage, donor phase flow rate, and acceptor phase composition were optimized, considering the type of membrane as a qualitative factor. To assess the performance of the fabricated PVDF membranes, a comparative analysis with a commercially available Polypropylene (PP) membrane was conducted. Efficient enrichment factors of 30.86, 23.15, and 21.06 were attained for ASA, NAP, and IBU, respectively, from urine samples under optimal conditions using the optimum PVDF membrane. Significantly, the choice of the ideal membrane amplified the purification levels of ASA, NAP, and IBU by factors of 1.6, 7.5, and 40, respectively.

Role for Carboxylic Acid Moiety in NSAIDs: Favoring the Binding at Site II of Bovine Serum Albumin.

The molecular structures of nonsteroidal anti-inflammatory drugs (NSAIDs) vary, but most contain a carboxylic acid functional group (RCOOH). This functional group is known to be related to the mechanism of cyclooxygenase inhibition and also causes side effects, such as gastrointestinal bleeding. This study proposes a new role for RCOOH in NSAIDs: facilitating the interaction at the binding site II of serum albumins. We used bovine serum albumin (BSA) as a model to investigate the interactions with ligands at site II. Using dansyl-proline (DP) as a fluorescent site II marker, we demonstrated that only negatively charged NSAIDs such as ibuprofen (IBP), naproxen (NPX), diflunisal (DFS), and ketoprofen (KTP) can efficiently displace DP from the albumin binding site. We confirmed the importance of RCOO by neutralizing IBP and NPX through esterification, which reduced the displacement of DP. The competition was also monitored by stopped-flow experiments. While IBP and NPX displaced DP in less than 1 s, the ester derivatives were ineffective. We also observed a higher affinity of negatively charged NSAIDs using DFS as a probe and ultrafiltration experiments. Molecular docking simulations showed an essential salt bridge between the positively charged residues Arg409 and Lys413 with RCOO-, consistent with the experimental findings. We performed a ligand dissociation pathway and corresponding energy analysis by applying molecular dynamics. The dissociation of NPX showed a higher free energy barrier than its ester. Apart from BSA, we conducted some experimental studies with human serum albumin, and similar results were obtained, suggesting a general effect for other mammalian serum albumins. Our findings support that the RCOOH moiety affects not only the mechanism of action and side effects but also the pharmacokinetics of NSAIDs.

Quantifying the Lymphatic Transport of Model Therapeutics from the Brain in Rats.

In recent years, the drainage of fluids, immune cells, antigens, fluorescent tracers, and other solutes from the brain has been demonstrated to occur along lymphatic outflow pathways to the deep cervical lymph nodes in the neck. To the best of our knowledge, no studies have evaluated the lymphatic transport of therapeutics from the brain. The objective of this study was to determine the lymphatic transport of model therapeutics of different molecular weights and lipophilicity from the brain using cervical lymph cannulation and ligation models in rats. To do this, anesthetized Sprague-Dawley rats were cannulated at the carotid artery and cannulated, ligated, or left intact at the cervical lymph duct. Rats were administered 14C-ibuprofen (206.29 g/mol, logP 3.84), 3H-halofantrine HCl (536.89 g/mol, logP 8.06), or 3H-albumin (∼65,000 g/mol) via direct injection into the brain striatum at a rate of 0.5 µL/min over 16 min. Plasma or cervical lymph samples were collected for up to 6-8 h following dosing, and brain and lymph nodes were collected at 6 or 8 h. Samples were subsequently analyzed for radioactivity levels via scintillation counting. For 14C-ibuprofen, plasma concentrations over time (plasma AUC0-6h) were >2 fold higher in lymph-ligated rats than in lymph-intact rats, suggesting that ibuprofen is cleared from the brain primarily via nonlymphatic routes (e.g., across the blood-brain barrier) but that this clearance is influenced by changes in lymphatic flow. For 3H-halofantrine, >73% of the dose was retained at the brain dosing site in lymph-intact and lymph-ligated groups, and plasma AUC0-8h values were low in both groups (<0.3% dose.h/mL), consistent with the high retention in the brain. It was therefore not possible to determine whether halofantrine undergoes lymphatic transport from the brain within the duration of the study. For 3H-albumin, plasma AUC0-8h values were not significantly different between lymph-intact, lymph-ligated, and lymph-cannulated rats. However, >4% of the dose was recovered in cervical lymph over 8 h. Lymph/plasma concentration ratios of 3H-albumin were also very high (up to 53:1). Together, these results indicate that 3H-albumin is transported from the brain not only via lymphatic routes but also via the blood. Similar to other tissues, the lymphatics may thus play a significant role in the transport of macromolecules, including therapeutic proteins, from the brain but are unlikely to be a major transport pathway from the brain for small molecule drugs that are not lipophilic. Our rat cervical lymph cannulation model can be used to quantify the lymphatic drainage of different molecules and factors from the brain.

Compatibilizing of cotton fabric with hydrophobic drug cover layer for anti-inflammatory performance with the implementation of ibuprofen.

This paper presents active analgesic and anti-inflammatory dressings based on cotton woven material with surface functionalization enabling drug implementation. For this purpose, lactide was polymerized on the surface of cotton textiles to achieve better compatibility with hydrophobic drug and polylactide (PLA)-based macromolecules. Subsequently, ibuprofen-loaded PLA and PLA-PEG were implemented through the exhausting method. Such material was tested for cytotoxicity (toward L929 mouse fibroblasts) and anti-inflammatory activity (towards human Hs68 fibroblasts) based on the secretion of pro-inflammatory cytokines IL-1ß and TNF-α. The results showed that the drug attachment and its performance are influenced by a combination of mercerization, bleaching and polylactide grafting, and the release of ibuprofen depends on the drug-loaded layer structure. Moreover, we show that cotton woven fabric with ibuprofen-loaded PLA and PLA-PEG cover layers had anti-inflammatory properties. These new dressings may open possibilities for developing prolonged analgesic and anti-inflammatory materials for wound healing or transdermal drug delivery.

Design, Synthesis, Anti-Inflammatory Activity, DFT Modeling and Docking Study of New Ibuprofen Derivatives.

A new ibuprofen derivative, (E)-2-(4-isobutylphenyl)-N'-(4-oxopentan-2-ylidene) propane hydrazide (IA), was synthesized, along with its metal complexes with Co, Cu, Ni, Gd, and Sm, to investigate their anti-inflammatory efficacy and COX-2 inhibition potential. Comprehensive characterization, including 1H NMR, MS, FTIR, UV-vis spectroscopy, and DFT analysis, were employed to determine the structural configurations, revealing unique motifs for Gd/Sm (capped square antiprismatic/tricapped trigonal prismatic) and Cu/Ni/Co (octahedral) complexes. Molecular docking with the COX-2 enzyme (PDB code: 5IKT) and pharmacokinetic assessments through SwissADME indicated that these compounds have superior binding energies and pharmacokinetic profiles, including BBB permeability and gastrointestinal absorption, compared to the traditional ibuprofen standalone. Their significantly lower IC50 values further suggest a higher efficacy as anti-inflammatory agents and COX-2 inhibitors. These research findings not only introduce promising ibuprofen derivatives for therapeutic applications but also set the stage for future validation and exploration of this new generation of ibuprofen compounds.

Ultrasonic-assisted synthesis of CaCu3Ti4O12/reduced graphene oxide composites for enhanced photocatalytic degradation of pharmaceutical products: Ibuprofen and Ciprofloxacin.

The objective of this research is to create a highly effective approach for eliminating pollutants from the environment through the process of photocatalytic degradation. The study centers around the production of composites consisting of CaCu3Ti4O12 (CCTO) and reduced graphene oxide (rGO) using an ultrasonic-assisted method, with a focus on their capacity to degrade ibuprofen (IBF) and ciprofloxacin (CIP) via photodegradation. The impact of rGO on the structure, morphology, and optical properties of CCTO was inspected using XRD, FTIR, Raman, FESEM, XPS, BET, and UV-Vis. Morphology characterization showed that rGO particles were dispersed within the CCTO matrix without any specific chemical interaction between CCTO and C in the rGO. The BET analysis revealed that with increasing the amount of rGO in the composite, the specific surface area significantly increased compared to the CCTO standalone. Besides, increasing rGO resulted in a reduction in the optical bandgap energy to around 2.09 eV, makes it highly promising photocatalyst for environmental applications. The photodegradation of IBF and CIP was monitored using visible light irradiation. The results revealed that both components were degraded above 97% after 60 min. The photocatalyst showed an excellent reusability performance with a slight decrease after five runs to 93% photodegradation efficiency.

Multifunctional Deep Eutectic Solvent-Based Microemulsion for Transdermal Delivery of Artemisinin.

As a serious public health issue, malaria threatens the health of millions of people. Artemisinin, a gift from traditional Chinese medicine, has been used in the treatment of malaria and has shown good therapeutic efficiency. However, due to its low solubility, poor bioavailability, and short half-life time, some smart delivery strategies are still required. Herein, a multifunctional DES prepared from ibuprofen and menthol was prepared. This DES was shown to efficiently promote the solubility of artemisinin up to 400-fold. Then, it was further applied as the oil phase to construct an O/W microemulsion with the help of Tween-80 + Span-20 mixed surfactants. The prepared microemulsion displayed high efficiency in improving the permeability of artemisinin, which can be ascribed to the presence of the permeation enhancer menthol in DES and the microstructure of the O/W microemulsion. Moreover, the simultaneous permeation of artemisinin and ibuprofen further indicated the potential benefits of the presented formulation in the treatment of malaria. To sum up, the microemulsion based on multifunctional DES presented herein provided an effective method for transdermal delivery of artemisinin.

Enantioselective separation and determination of ibuprofen: Stereoselective pharmacokinetics, pharmacodynamics and analytical methods.

Ibuprofen (IBP), the 29th most prescribed drug in the United States in 2019, is a widely used nonsteroidal anti-inflammatory drug (NSAID) comprising two enantiomers, (R)-IBP and (S)-IBP, collectively known as (RS)-IBP. This critical review examines analytical techniques for the enantioselective separation and determination of IBP enantiomers, crucial for pharmaceutical and clinical applications. The review focuses on state-of-the-art methods, including chromatographic techniques including high-performance liquid chromatography, gas chromatography, liquid chromatography-tandem mass spectrometry, and some other techniques. This review addresses pharmacokinetics, pharmacology, and side effects of each enantiomer, ensuring safe drug usage. By consolidating diverse analytical methods and their applicability in different matrices, this review serves as a valuable resource for researchers, analysts, and practitioners in pharmaceutical analysis, pharmacology, and clinical studies.

Effect of graphene oxide on sodium alginate hydrogel as a carrier triggering release of ibuprofen.

The design and preparation of safe wound dressings with antibacterial and controlled drug release abilities is valuable in medicine. This research focuses on the fabrication of a hydrogel carrier with graphene oxide (GO)-triggered ibuprofen (IBU) release to control inflammation. The hydrogel was prepared by cross-linking the base polymer sodium alginate (SA) and functionalized GO. The morphology of the gel was observed by a scanning electron microscope (SEM), and its structure was analyzed through X-ray diffraction (XRD) and Fourier transform infrared reflection (FTIR) spectroscopy. The effects of GO on swelling capacity, IBU release behavior and antibacterial activity were investigated by using the prepared GO/SA hydrogel as a drug carrier and IBU as a drug model. In vitro studies confirmed that the GO/SA hydrogel had good antimicrobial activity and excellent cytotoxicity. The analysis of cumulative IBU release rates revealed that the addition of GO could promote the release of IBU, and the change in GO content did not have a prominent effect on IBU release. At the same time, the rate of IBU release from the GO/SA hydrogel was affected by near-infrared light. Under a light source, the release rate of IBU increased, and the release amount of IBU showed a clear stepwise increase under light on-off conditions. These results suggest that the GO/SA hydrogel could be a potential antibacterial and anti-inflammatory wound dressing.

Silver and Copper Complexes with Ibuprofen and Caffeine-Preparation and Evaluation of Their Selected Biological Effects.

Several organometallic complexes based on more than twenty different metals have already been approved for medical applications. The aim of the presented research was to obtain complexes of silver and copper with the non-steroidal anti-inflammatory drugs ibuprofen and xanthine alkaloid caffeine and evaluate selected aspects of their bioactivity and biosafety in terms of their future possible applications. The obtained complexes were characterized by Fourier-transform infrared spectroscopy, thermogravimetry, UV-VIS spectroscopy, conductometry, elemental analysis, and bioassays. Cytotoxicity for normal human cells of the CCD-Co18 cell line was evaluated by determining the IC50 value, with metabolic and morphology assessments. It was observed that complexes containing ibuprofen and caffeine exhibited lower toxicity than those with ibuprofen only. Complexes with copper showed lower toxicity towards healthy human fibroblasts compared to silver-based compounds, with an IC50 above 140 µg mL-1. However, in the silver complexes, the presence of caffeine increased the potency of COX-2 inhibition. Antimicrobial effects against different Gram-positive and Gram-negative bacterial strains were evaluated by MIC determination with values less than 20 µg mL-1.

Cleaning of direct compression continuous manufacturing equipment through displacement of API residues by excipients.

This feasibility study evaluates a cleaning process designed to avoid the use of detergents and reduce operator exposure to the active pharmaceutical ingredient (API). The continuous manufacturing equipment was cleaned using excipients to displace ibuprofen residues from the system. The cleaning process was performed using 3.0 kg of Prosolv® and 3.0 kg of Tablettose® 70. The impact of different volumetric feed rates of the cleaning excipient was assessed. The displacement of API and blend residues was evaluated with in-line near infrared (NIR) spectroscopy. Principal component analysis (PCA) was performed to evaluate the cleaning progress as the Prosolv® flowed through the feeder, mixer and stream sampler. In-place Raman spectra were acquired from the material sticking to detect the ibuprofen residues. The study showed that Prosolv® and Tablettose® can remove ibuprofen residues effectively from the hopper, feeder screw, mixer paddles, shaft and stream sampler. The Process Analytical Technology (PAT) system can be utilized to detect API displacement during the cleaning process. However, dismantling and manual cleaning was required to remove material sticking at the surfaces adjacent to the rotating feeder screws and mixer paddles.

Molecular Characterization of Mesoporous Silica (Un)loading by Gemcitabine and Ibuprofen - An Interplay of Salt-Bridges and Hydrogen Bonds.

The molecular mechanisms of mesoporous silica nanomaterial (MSN) loading by gemcitabine and ibuprofen molecules, respectively, are elucidated as functions of pore geometry. Based on a small series of MSN archetypes, we use molecular dynamics simulations to systematically explore molecule-by-molecule loading of the carrier material. Apart from predicting the maximum active pharmaceutical ingredient (API) loading capacity, more detailed statistical analysis of the incorporation energy reveals dedicated profiles stemming from the interplay of guest-MSN salt-bridges/hydrogen bonding in concave and convex domains of the silica surfaces - which outcompete interactions among the drug molecules. Only after full coverage of the silica surface, we find secondary layer growth stabilized by guest-guest interactions exclusively. Based on molecular models, we thus outline a two-step type profile for drug release from MSN networks. Subject to the MSN structure, we find 50-75 % of the API within amorphous domains in the inner regions of the pores - from which drug release is provided at constant dissociation energy. In turn, the remaining 50-25 % of drug molecules are drastically hindered from dissociation.

Analysis of stabilization mechanisms in ß-lactoglobulin-based amorphous solid dispersions by experimental and computational approaches.

Our previous work shows that ß-lactoglobulin-stabilized amorphous solid dispersion (ASD) loaded with 70 % indomethacin remains stable for more than 12 months. The stability is probably due to hydrogen bond networks spread throughout the ASD, facilitated by the indomethacin which has both hydrogen donors and acceptors. To investigate the stabilization mechanisms further, here we tested five other drug molecules, including two without any hydrogen bond donors. A combination of experimental techniques (differential scanning calorimetry, X-ray power diffraction) and molecular dynamics simulations was used to find the maximum drug loadings for ASDs with furosemide, griseofulvin, ibuprofen, ketoconazole and rifaximin. This approach revealed the underlying stabilization factors and the capacity of computer simulations to predict ASD stability. We searched the ASD models for crystalline patterns, and analyzed diffusivity of the drug molecules and hydrogen bond formation. ASDs loaded with rifaximin and ketoconazole remained stable for at least 12 months, even at 90 % drug loading, whereas stable drug loadings for furosemide, griseofulvin and ibuprofen were at a maximum of 70, 50 and 40 %, respectively. Steric confinement and hydrogen bonding to the proteins were the most important stabilization mechanisms at low drug loadings (≤ 40 %). Inter-drug hydrogen bond networks (including those with induced donors), ionic interactions, and a high Tg of the drug molecule were additional factors stabilizing the ASDs at drug loading greater than 40 %.

Scalability of Pharmaceutical Co-Crystal Formation by Mechanochemistry in Batch.

The development of mechanochemistry is considerably growing. Benign by design, this technology complies with several principles of green chemistry, contributing to the achievement of the United Nations Sustainable Development Goals (UN SDGs) and the European Green Deal objectives. Herein, we report the use of mechanochemical processes in batch to prepare kilogram-scale of the Active Pharmaceutical Ingredient (API): Ibuprofen-Nicotinamide (rac-IBP:NCT) co-crystal in an industrial eccentric vibration mill. This scenario shows a sustainable approach to the industrial up-scaling of pharmaceutical co-crystals by a solvent-free mechanochemical process in batch. The quantitative assessment of the greenness of the mechanochemical process against the Twelve Principles of Green Chemistry was performed using the DOZN 2.0 Green Chemistry Evaluator.

A comparison of USP 2 and µDISS Profiler™ apparatus for studying dissolution phenomena of ibuprofen and its salts.

BACKGROUND: Pharmaceutical salts of poorly soluble drugs typically dissolve faster than their corresponding free acid or base, resulting in supersaturation under some circumstances. The key questions relevant to drug bioavailability "does the salt invoke the supersaturated state?" and, if so, "does precipitation occur?" remain. To answer these questions, different types of dissolution equipment are often used at different stages of the development process. AIM: To compare the dissolution behaviour of ibuprofen and its sodium and lysine salts in the USP 2 apparatus and the µDISS Profiler™ apparatus. The dissolution, supersaturation of the salt forms and precipitation to the free acid of ibuprofen were characterized along with the dissolution of the free acid form. METHODS: Media containing different concentrations of the salt-forming counterions - sodium and lysine - were used to investigate the influence of the type of dissolution apparatus used for the study on dissolution, supersaturation and precipitation behaviour. KEY RESULTS: Supersaturation was observed for both the sodium and lysinate salts of ibuprofen in all USP 2 apparatus and µDISS Profiler™ experiments. However, precipitation tended to be far greater in the µDISS Profiler™ than in the USP 2 apparatus. The difference was most pronounced in pH 4.5 acetate buffer, in which precipitation was observed exclusively in experiments with the µDISS Profiler™. CONCLUSION: Choice of dissolution apparatus can affect the dissolution/supersaturation/precipitation characteristics of pharmaceutical salts. This has to be carefully taken into account when investigating salts over different stages of pharmaceutical research and development.

Use of In silico Methodologies to Predict the Bioavailability of Oral Suspensions: A Regulatory Approach.

BACKGROUND: Oral suspensions are heterogeneous disperse systems, and the particle size distribution, crystalline form of the dispersed solid, and composition of the formulation can be listed as parameters that control the drug dissolution rate and its bioavailability. OBJECTIVE: The aim of this work was to develop a discriminative dissolution test, which, in association with in silico methodologies, can make it possible to safely anticipate bioavailability problems. METHODS: Nimesulide and ibuprofen (BCS class II) and cephalexin (BCS class I) oral suspensions were studied. Previously, solid-state structure and particle size in active pharmaceutical ingredients were characterized and the impact of differences on solubility was evaluated for the choice of discriminative medium. Afterwards, particle size distribution (0.1 to 360 µm), dissolution profile, and in vitro permeability in Caco-2 cell of commercial suspensions, were determined. These parameters were used as input for the establishment of the in vitro-in vivo correlation (IVIVC) for the suspensions using the GastroPlus™ with Wagner-Nelson and Loo- Riegelmann deconvolution approach. RESULTS: The predicted/observed pharmacokinetic model showed good correlation coefficients (r) of 0.960, 0.950, and 0.901, respectively. The IVIVC was established for one nimesulide and two ibuprofen suspensions with r between 0.956 and 0.932, and the percent prediction error (%PE) did not exceed 15%. CONCLUSION: In this work, we have performed a complete study combining in vitro/in silico approaches with the aim of anticipating the safety and efficacy of oral pharmaceutical suspensions in order to provide a regulatory tool for this category of products in a faster and more economical way.

Exploring Alkyl Ester Salts of L-Amino Acid Derivatives of Ibuprofen: Physicochemical Characterization and Transdermal Potential.

This research presents novel ibuprofen derivatives in the form of alkyl ester salts of L-amino acids with potential analgesic, anti-inflammatory, and antipyretic properties for potential use in transdermal therapeutic systems. New derivatives of (RS)-2-[4-(2-methylpropyl)phenyl]propionic acid were synthesized using hydrochlorides of alkyl esters (ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, and pentyl) of L-glutamine. These were further transformed into alkyl esters of L-amino acid ibuprofenates through neutralization and protonation reactions. Characterization involved spectroscopic methods, including nuclear magnetic resonance and Fourier-transform infrared spectroscopy. Various physicochemical properties were investigated, such as UV-Vis spectroscopy, polarimetric analysis, thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction, water solubility, octanol/water partition coefficient, and permeability through pig skin using Franz diffusion cells. The research confirmed the ionic structure of the obtained hydrochlorides of alkyl esters of L-amino acids and ibuprofenates of alkyl esters of L-glutamic acid. It revealed significant correlations between ester chain length and thermal stability, crystallinity, phase transition temperatures, lipophilicity, water solubility, skin permeability, and skin accumulation of these compounds. Compared to the parent ibuprofen, the synthesized derivatives exhibited higher water solubility, lower lipophilicity, and enhanced skin permeability. This study introduces promising ibuprofen derivatives with improved physicochemical properties, highlighting their potential for transdermal therapeutic applications. The findings shed light on the structure-activity relationships of these derivatives, offering insights into their enhanced solubility and skin permeation, which could lead to more effective topical treatments for pain and inflammation.

Sticking Detection by Repeated Compactions on a Single Tablet.

"Sticking" during tablet manufacture is the term used to describe the accumulation of adhered tablet material on the punch over the course of several compaction cycles. The occurrence of sticking can affect tablet weight, image, and structural integrity and halt manufacturing operations. The earlier the risk of sticking is detected during R&D, the more options are available for mitigation and the less potential there is for significant delays and costs. The detection osf sticking, however, during the early stages of drug development is challenging due to the limitations of available material quantity. In this work, single tablet multi-compaction (STMC) and a highly sensitive laser reflection sensor are used to detect the propensity of sticking with ibuprofen powder blends. STMC can differentiate the various formulations and replicates the trends of sticking at different punch speeds. The results demonstrate the potential for STMC to be used as an extremely material sparing (requiring very few tablets) methodology for the assessment of sticking during early-stage development.

New insights into the degradation mechanism of ibuprofen in the UV/H2O2 process: role of natural dissolved matter in hydrogen transfer reactions.

Ibuprofen (IBU), a widely used antipyretic and analgesic, has been frequently detected in various natural water systems. Advanced oxidation processes (AOPs) are effective ways to remove pollutants from water. The degradation of IBU under UV/H2O2 conditions in the presence of various kinds of natural dissolved matter was investigated using density functional theory (DFT). The eco-toxicological properties were predicted based on a quantitative structure-activity relationship (QSAR) model. The calculated results showed that two H-abstraction reactions occurring at the side chain are predominant pathways in the initial reaction. H2O, NH3, CH3OH, C2H5OH, HCOOH and CH3COOH can catalyze the H transfer in the degradation process through decreasing the energy barriers and the catalysis effects follow the order of NH3 > alcohols > acids > H2O. The catalysis effects differ under acid or alkaline conditions. The overall rate coefficient of the reaction of IBU with ˙OH is calculated to be 5.04 × 109 M-1 s-1 at 298 K. IBU has harmful effects on aquatic organisms and human beings and the degradation process cannot significantly reduce its toxicity. Among all products, 2-(4-formylphenyl)propanoic acid, which is more toxic than IBU, is the most toxic with acute and chronic toxicity, developmental toxicity, mutagenicity, genotoxic carcinogenicity and irritation/corrosivity to skin. The findings in this work provide new insights into the degradation of IBU and can help to assess its environmental risks.