Unveiling the potential of machine learning in cost-effective degradation of pharmaceutically active compounds: A stirred photo-reactor study.

In this study, neural networks and support vector regression (SVR) were employed to predict the degradation over three pharmaceutically active compounds (PhACs): Ibuprofen (IBP), diclofenac (DCF), and caffeine (CAF) within a stirred reactor featuring a flotation cell with two non-concentric ultraviolet lamps. A total of 438 datapoints were collected from published works and distributed into 70% training and 30% test datasets while cross-validation was utilized to assess the training reliability. The models incorporated 15 input variables concerning reaction kinetics, molecular properties, hydrodynamic information, presence of radiation, and catalytic properties. It was observed that the Support Vector Regression (SVR) presented a poor performance as the ε hyperparameter ignored large error over low concentration levels. Meanwhile, the Artificial Neural Networks (ANN) model was able to provide rough estimations on the expected degradation of the pollutants without requiring information regarding reaction rate constants. The multi-objective optimization analysis suggested a leading role due to ozone kinetic for a rapid degradation of the contaminants and most of the results required intensification with hydrogen peroxide and Fenton process. Although both models were affected by accuracy limitations, this work provided a lightweight model to evaluate different Advanced Oxidation Processes (AOPs) by providing general information regarding the process operational conditions as well as know molecular and catalytic properties.

Environmental risk assessment of pharmaceutical pollutants in the Oro River Sub-basin (Colombia).

Pharmaceuticals and Personal Care Compounds (PPCPs) are contaminants present in wastewater and in the receiving surface waters, which have no regulations and can bring on environmental risks. In this study, we evaluated the presence of six PPCPs in the Oro River Sub-basin (Colombia) and the environmental risk associated with them. We have verified that the monitored rivers show the presence of Ibuprofen, Cephalexin and Carbamazepine; the first ones (Ibuprofen and cephalexin) were those that presented higher concentrations since they are widely prescribed in Colombia. Pharmaceutical compound concentrations in the rivers downstream of the wastewater treatment plants from Floridablanca were higher than in other monitoring sites being a significant point source of contamination. This wastewater treatment plant receives hospital discharges from the city, including internationally recognized clinics accepting patients from different parts of the country. The environmental risk assessment showed that ibuprofen and Cephalexin have a higher impact on aquatic organisms.

Bioequivalence risk assessment of oral formulations containing racemic ibuprofen through a chiral physiologically based pharmacokinetic model of ibuprofen enantiomers.

The characterization of the time course of ibuprofen enantiomers can be useful in the selection of the most sensitive analyte in bioequivalence studies. Physiologically based pharmacokinetic (PBPK) modelling and simulation represents the most efficient methodology to virtually assess bioequivalence outcomes. In this work, we aim to develop and verify a PBPK model for ibuprofen enantiomers administered as a racemic mixture with different immediate release dosage forms to anticipate bioequivalence outcomes based on different particle size distributions. A PBPK model incorporating stereoselectivity and non-linearity in plasma protein binding and metabolism as well as R-to-S unidirectional inversion has been developed in Simcyp®. A dataset composed of 11 Phase I clinical trials with 54 scenarios (27 per enantiomer) and 14,452 observations (7129 for R-ibuprofen and 7323 for S-ibuprofen) was used. Prediction errors for AUC0-t and Cmax for both enantiomers fell within the 0.8-1.25 range in 50/54 (93 %) and 42/54 (78 %) of scenarios, respectively. Outstanding model performance, with 10/10 (100 %) of Cmax and 9/10 (90 %) of AUC0-t within the 0.9-1.1 range, was demonstrated for oral suspensions, which strongly supported its use for bioequivalence risk assessment. The deterministic bioequivalence risk assessment has revealed R-ibuprofen as the most sensitive analyte to detect differences in particle size distribution for oral suspensions containing 400 mg of racemic ibuprofen, suggesting that achiral bioanalytical methods would increase type II error and declare non-bioequivalence for formulations that are bioequivalent for the eutomer.

Use of metamizole and other non-opioid analgesics in Switzerland between 2014 and 2019: an observational study using a large health insurance claims database.

OBJECTIVE: To investigate claims patterns for metamizole and other non-opioid analgesics in Switzerland. To characterise users of these non-opioid analgesics regarding sex, age, comedications and canton of residence. METHODS: We conducted a retrospective descriptive study using administrative claims data of outpatient prescribed non-opioid analgesics of the Swiss health insurance company Helsana between January 2014 and December 2019. First, we evaluated the number of claims and defined daily doses  per year of metamizole, ibuprofen, diclofenac and paracetamol in adults aged 18 years or over. Second, we characterised new users of these non-opioid analgesics in terms of sex, age, claimed comedications and canton of residence. RESULTS: From 2014 to 2019, among the investigated non-opioid analgesics, metamizole showed the highest increase in claims (+9545 claims, +50%) and defined daily doses (+86,869 defined daily doses, +84%) per 100,000 adults. Metamizole users had the highest median age (62 years [IQR: 44-77]) compared to ibuprofen (47 years [IQR: 33-62]), diclofenac (57 years [IQR: 43-71]) and paracetamol (58 years [IQR: 39-75]) users. Metamizole users also more frequently claimed proton pump inhibitors, anticoagulants, platelet aggregation inhibitors and antihypertensive drugs than users of other non-opioid analgesics. While metamizole was most frequently claimed in German-speaking regions of Switzerland, ibuprofen and paracetamol were most frequently claimed in the French-speaking regions and diclofenac in German- and Italian-speaking regions. CONCLUSION: In Switzerland, metamizole was increasingly claimed between 2014 and 2019. Metamizole was most frequently claimed by older adults and patients with comedications suggestive of underlying conditions, which can be worsened or caused by use of nonsteroidal anti-inflammatory drugs. The lack of studies regarding the effectiveness and safety of metamizole in this population warrants further investigation.

Patient information leaflets and package inserts of ibuprofen provided in the UK and Thailand: a comparative assessment.

OBJECTIVES: Written medicine information (WMI) is important for ensuring patients understand and use their medicines optimally, but relatively little research has assessed the quality of available WMI. This study assessed the quality of WMI using a sample of leaflets for ibuprofen in the UK and Thailand. METHODS: Leaflets were obtained by purchasing a product from retail outlets or community pharmacies, 18 from each country. In the UK, these were patient information leaflets (PILs); in Thailand, they were package inserts PIs not specifically designed for patients. Leaflets were assessed for content, layout, and readability using standard methods and compared to relevant guidelines. KEY FINDINGS: The UK PILs were uniform and conformed to EU regulatory requirements for content, whereas Thai PIs varied considerably, many failing to include important information required by Thai regulations. Several forms of Thai PIs were found, including some very short leaflets, containing minimal information. The readability of both was rated as poor, all used small font size and had less than desirable white space. Fewer Thai PIs than UK PILs met the Keystone Criteria for ibuprofen. CONCLUSIONS: The extent of variation in format and content of Thai WMI could potentially cause confusion and reduce willingness to read it. PILs, conforming to Thai regulatory guidelines, should be provided with medicines instead. Leaflets in both countries would benefit from improved readability and layout.

Equivalence assessment of creams with quali-quantitative differences in light of the EMA and FDA regulatory framework.

EMA and FDA are upgrading guidelines on assessing the quality and the equivalence of topically applied drug products for developing copies of originator products and supporting post-marketing variations. For topical products having remarkably similar composition, both EMA and FDA accept the equivalence on the bases of the comparison of rheological properties and in vitro drug release constant (k) and skin permeation flux (J) values, instead of clinical studies. This work aims to evaluate the feasibility to expand this approach to variations of the composition of complex semi-solid preparations. Ibuprofen (IB) creams at two different strengths (i.e., 1 % and 10 %) were used as a model formulation. Two formulative changes were performed: (a) the addition of the humectant to simulate a minor post-marketing variation; (b) the substitution of the emulsifying system to simulate a major one. These variations impacted only in 1 % IB formulations where both the equivalences of rheological data and J-values failed. At the highest concentration, the presence of IB crystals broke down the differences in rheological patterns and lead the IB thermodynamic activity at the maximum figuring out an overlapping of the J-values. Such data suggest the combination of these studies, which are thought mainly for the development of copies, could be also applied to the management of post-marketing variations that involve product composition.

Trial of Selective Early Treatment of Patent Ductus Arteriosus with Ibuprofen.

BACKGROUND: The cyclooxygenase inhibitor ibuprofen may be used to treat patent ductus arteriosus (PDA) in preterm infants. Whether selective early treatment of large PDAs with ibuprofen would improve short-term outcomes is not known. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial evaluating early treatment (≤72 hours after birth) with ibuprofen for a large PDA (diameter of ≥1.5 mm with pulsatile flow) in extremely preterm infants (born between 23 weeks 0 days' and 28 weeks 6 days' gestation). The primary outcome was a composite of death or moderate or severe bronchopulmonary dysplasia evaluated at 36 weeks of postmenstrual age. RESULTS: A total of 326 infants were assigned to receive ibuprofen and 327 to receive placebo; 324 and 322, respectively, had data available for outcome analyses. A primary-outcome event occurred in 220 of 318 infants (69.2%) in the ibuprofen group and 202 of 318 infants (63.5%) in the placebo group (adjusted risk ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P = 0.10). A total of 44 of 323 infants (13.6%) in the ibuprofen group and 33 of 321 infants (10.3%) in the placebo group died (adjusted risk ratio, 1.32; 95% CI, 0.92 to 1.90). Among the infants who survived to 36 weeks of postmenstrual age, moderate or severe bronchopulmonary dysplasia occurred in 176 of 274 (64.2%) in the ibuprofen group and 169 of 285 (59.3%) in the placebo group (adjusted risk ratio, 1.09; 95% CI, 0.96 to 1.23). Two unforeseeable serious adverse events occurred that were possibly related to ibuprofen. CONCLUSIONS: The risk of death or moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age was not significantly lower among infants who received early treatment with ibuprofen than among those who received placebo. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Baby-OSCAR ISRCTN Registry number, ISRCTN84264977.).

Drug-induced immune hemolytic anemia: detection of new signals and risk assessment in a nationwide cohort study.

ABSTRACT: More than 130 drugs have been suspected to induce immune hemolytic anemia. Comparative studies measuring the risk of drug-induced immune hemolytic anemia (DIIHA) are lacking. We aimed (1) to detect new signals of DIIHA, excluding vaccines, and (2) to assess the association between all suspected drugs and the occurrence of immune hemolytic anemia in a nationwide comparative study. The new signals were identified using a disproportionality study (case/noncase design) in the World Pharmacovigilance Database, Vigibase, among the cases of adverse drug reactions reported up to February 2020 (>20 million). We then conducted a comparative study in the French National health database that links sociodemographic, out-of-hospital, and hospital data for the entire population (67 million individuals). Associations between exposure to drugs (those already reported as DIIHA, plus new signals identified in Vigibase) and incident cases of immune hemolytic anemia (D59.0 and D59.1 diagnosis codes of the International Classification of Diseases, version 10) from 2012 to 2018 were assessed with case-control and case-crossover designs. In Vigibase, 3371 cases of DIIHA were recorded. Fifty-nine new signals were identified resulting in a final list of 112 drugs marketed in France and measurable in the nationwide cohort (n = 4746 patients with incident immune hemolytic anemia included in the case-control analysis matched with 22 447 controls from the general population). We identified an association between immune hemolytic anemia occurrence and some antibiotics, antifungal drugs, ibuprofen, acetaminophen, furosemide, azathioprine, and iomeprol.

A Comparative Assessment of Cocrystal and Amorphous Solid Dispersion Printlets Developed by Hot Melt Extrusion Paired Fused Deposition Modeling for Dissolution Enhancement and Stability of Ibuprofen.

The primary focus of the research is to study the role of cocrystal and amorphous solid dispersion approaches for enhancing solubility and preserving the stability of a poorly soluble drug, i.e., ibuprofen (IBP). First, the solvent-assisted grinding approach determined the optimum molar ratio of the drug and the coformer (nicotinamide (NIC)). Later, the polymeric filaments of cocrystals and amorphous solid dispersions were developed using the hot melt extrusion (HME) process, and the printlets were fabricated using the fused deposition modeling (FDM) additive manufacturing process. In addition, the obtained filaments were also milled and compressed into tablets as reference samples. The formation of cocrystals and amorphous solid dispersions was evaluated and confirmed using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and powder X-ray diffraction (PXRD) analysis. The drug release profiles of 3D printlets with 50% infill were found to be faster and are in line with the release profiles of compressed tablets. In addition, the 3D-printed cocrystal formulation was stable for 6 months at accelerated conditions. However, the 3D printlets of amorphous solid dispersions and compressed tablets failed to retain stability attributed to the recrystallization of the drug and loss in tablet mechanical properties. This shows the suitability of a cocrystal platform as a novel approach for developing stable formulations of poorly soluble drug substances over amorphous solid dispersions.

Occurrence and risk assessment of pharmaceuticals in hospital wastewater in Costa Rica.

This work aims to determine the occurrence, hazard and prioritization of pharmaceuticals from hospital wastewater in Costa Rica through the monitoring of 70 compounds and assessing their environmental risk through a hazard quotient approach (HQ). Moreover, the quantification of selected antibiotic resistance genes (ARGs) was conducted for the first time in this matrix in this geographical location. Thirty-four pharmaceuticals were detected, being caffeine, 1,7-dimethylxanthine, acetaminophen, ibuprofen, naproxen, ciprofloxacin and ketoprofen the most frequent (>50% of the samples). Eighteen pharmaceuticals exhibited high hazard (HQ ≥ 1), while five more showed medium hazard (1 > HQ ≥ 0.1). Prioritization, which also included frequency parameters, revealed caffeine, lovastatin, diphenhydramine, acetaminophen, ibuprofen, ciprofloxacin, and sildenafil as the compounds of major concern. Similarly, cumulative hazard per sample (ΣHQ) estimated high hazard towards aquatic organisms in every sample. All selected ARGs, except mcr-1 (polymyxin resistance), were detected. Among genes conferring resistance to beta-lactams, blaCTX-M and blaKPC were the most abundant, related to resistance to cephalosporins and carbapenems. Ecotoxicological evaluation showed mostly low toxicity towards Daphnia magna and Vibrio fischeri, contrary to the marked effect observed towards Lactuca sativa. These findings provide relevant and novel information on the risk posed by hospital wastewater and their pharmaceutical content in the Latin American environmental context.

Health risk assessment for uptake and accumulation of pharmaceuticals in jute mallow (Corchorus olitorius) irrigated with treated hospital wastewater.

The use of reclaimed water for crop irrigation presents a route through which pharmaceuticals enter the agro-environment, raising concerns about their potential inclusion into the food chain and associated health risks. The main objective of this study was to determine the accumulation of six pharmaceuticals (paracetamol, diclofenac and ibuprofen, ciprofloxacin, tetracycline, and sulfamethoxazole) in edible part of jute mallow (JM) (Corchorus olitorius) irrigated with treated hospital wastewater (THWW) and potential health risks associated with the consumption of the contaminated JM. In a greenhouse experiment, JM vegetable was grown in soils irrigated with groundwater and THWW. After 4 weeks of cultivation, the pharmaceutical concentrations in the soil and JM tissues were determined. The uptake and accumulation of the pharmaceuticals in the irrigated JM and the human health risks associated with their consumption were evaluated. Results showed that the THWW-irrigated and groundwater-irrigated soils accumulated all the studied pharmaceuticals except paracetamol and sulfamethoxazole, with the concentrations in the soil before and after irrigation ranging from 0.01 to 0.14 µg g-1 and 0.03 to 1.35 µg g-1, respectively. In JM leaves, the accumulation was in the order of tetracycline > ciprofloxacin > ibuprofen > diclofenac and tetracycline > ciprofloxacin > diclofenac > ibuprofen under THWW-irrigated and groundwater-irrigated treatments, respectively. Under both treatments, the uptake and accumulation of the studied pharmaceuticals were in the order of roots > stem > leaves. The health risk assessment indicated that the consumption of the studied pharmaceuticals through JM implies some risks to human health and the risks were in the order of tetracycline > diclofenac > ciprofloxacin > ibuprofen > paracetamol > sulfamethoxazole. This study has demonstrated that irrigation with reclaimed water is a major route of pharmaceuticals into the food chain and a key determinant of associated health risks.

A novel approach for the assessment of invertebrate behavior and its use in behavioral ecotoxicology.

Sublethal effects are becoming more relevant in ecotoxicological test methods due to their higher sensitivity compared to lethal endpoints and their preventive nature. Such a promising sublethal endpoint is the movement behavior of invertebrates which is associated with the direct maintenance of various ecosystem processes, hence being of special interest for ecotoxicology. Disturbed movement behavior is often related to neurotoxicity and can affect drift, mate-finding, predator avoidance, and therefore population dynamics. We show the practical implementation of the ToxmateLab, a new device that allows monitoring the movement behavior of up to 48 organisms simultaneously, for behavioral ecotoxicology. We quantified behavioral reactions of Gammarus pulex (Amphipoda, Crustacea) after exposure to two pesticides (dichlorvos and methiocarb) and two pharmaceuticals (diazepam and ibuprofen) at sublethal, environmentally relevant concentrations. We simulated a short-term pulse contamination event that lasted 90 min. Within this short test period, we successfully identified behavioral patterns that were most pronounced upon exposure to the two pesticides: Methiocarb initially triggered hyperactivity, after which baseline behavior was restored. On the other hand, dichlorvos induced hypoactivity starting at a moderate concentration of 5 µg/L - a pattern we also found at the highest concentration of ibuprofen (10 µg/L). An additional acetylcholine esterase inhibition assay revealed no significant impact of the enzyme activity that would explain the altered movement behavior. This suggests that in environmentally realistic scenarios chemicals can induce stress - apart from mode-of-action - that affects non-target organisms' behavior. Overall, our study proves the practical applicability of empirical behavioral ecotoxicological approaches and thus represents a next step towards routine practical use.

Cost-Effectiveness Analysis of Ibuprofen Versus Indomethacin or Paracetamol for the Treatment of Patent Ductus Arteriosus in Preterm Neonates.

This was a first-time evaluation that sought to analyze the cost-effectiveness of oral paracetamol and intravenous (IV) indomethacin as alternatives to ibuprofen for PDA in neonates. Decision-analytic, literature-based, economic simulation models were constructed, to follow up the use and consequences of oral/IV ibuprofen versus IV indomethacin, and oral/IV ibuprofen versus oral paracetamol, as first-line therapies for PDA closure. Model outcomes of interest were "success", defined as PDA closure with/without adverse events, or "failure" due to no response to the first course of treatment, death or premature discontinuation of therapy due to adverse events. Oral ibuprofen is dominant/cost-effective over IV indomethacin in 97.9% of simulated cases, but oral paracetamol was 75.2% dominant/cost-effective over oral ibuprofen. Against IV ibuprofen, IV indomethacin was 55.3% dominant/cost-effective, whereas oral paracetamol was dominant/cost-effective in 98.5% of the cases. Sensitivity analyses confirmed the robustness of the study results. For PDA closure, while IV indomethacin was cost-effective against IV ibuprofen, oral paracetamol was cost-effective against both oral and IV ibuprofen.

Hydroxyl radical dominated ibuprofen degradation by UV/percarbonate process: Response surface methodology optimization, toxicity, and cost evaluation.

Ibuprofen (IBP) is a typical nonsteroidal anti-inflammatory drug with a wide range of applications, large dosages, and environmental durability. Therefore, ultraviolet-activated sodium percarbonate (UV/SPC) technology was developed for IBP degradation. The results showed that IBP could be efficiently removed using UV/SPC. The IBP degradation was enhanced with prolonged UV irradiation time, with the decreasing IBP concentration and the increasing SPC dosage. The UV/SPC degradation of IBP was highly adaptable to pH ranging from 4.05 to 8.03. The degradation rate of IBP reached 100% within 30 min. The optimal experimental conditions for IBP degradation were further optimized using response surface methodology. IBP degradation rate reached 97.3% under the optimal experimental conditions: 5 µM of IBP, 40 µM of SPC, 7.60 pH, and UV irradiation for 20 min. Humic acid, fulvic acid, inorganic anions, and natural water matrix inhibited the IBP degradation to varying degrees. Scavenging experiments of reactive oxygen species indicated that hydroxyl radical played a major role in the UV/SPC degradation of IBP, while carbonate radical played a minor role. Six IBP degradation intermediates were detected, and hydroxylation and decarboxylation were proposed as the primary degradation pathways. An acute toxicity test, based on the inhibition of luminescence in Vibrio fischeri, indicated that the toxicity of IBP during UV/SPC degradation decreased by 11%. An electrical energy per order value of 3.57 kWh m-3 indicated that the UV/SPC process was cost-effective in IBP decomposition. These results provide new insights into the degradation performance and mechanisms of the UV/SPC process, which can potentially be used for practical water treatment in the future.

Designing coordination polymers as multi-drug-self-delivery systems for tuberculosis and cancer therapy: in vitro viability and in vivo toxicity assessment.

A proof of concept for designing multi-drug-delivery systems suitable for self-drug-delivery is disclosed. Simple coordination chemistry was employed to anchor two kinds of drugs namely isoniazid (IZ - anti-tuberculosis), various non-steroidal-anti-inflammatory-drugs (NSAIDs) namely ibuprofen-IBU, fenoprofen-FEN, naproxen-NAP, diclofenac-DIC and mefenamic acid-MEF and Zn(NO3)2 to synthesize a series of 1D coordination polymers namely IZIBU, IZFEN, IZNAP, IZDIC and IZMEF which were structurally characterized by single crystal X-ray diffraction (SXRD). The coordination polymers wherein both types of drugs were anchored to Zn(II) metal centers could easily be ground to nano-sized particles suitable for biological studies by hand grinding in a mortar and pestle. Zone inhibition studies revealed that all the coordination polymers possessed antibacterial properties against Gram positive, Gram negative and mycobacteria namely Mycobacterium tuberculosis (M.tb). Detailed studies carried out on IZDIC employing flow cytometry and confocal microscopy under various staining conditions established that such antibacterial activity was due to the generation of reactive oxygen species (ROS) such as nitric oxide (NO) and also inhibition of mycolic acid leading to incomplete cell wall formation. It was also established that IZDIC could indeed inhibit the growth of M.tb within a mouse macrophage host cell namely RAW 264.7 thereby simulating the treatment of Tuberculosis (TB) under in vitro conditions. Scratch assay and cell cycle analysis on a human lung cancer cell line (A549) revealed its anti-cancer property, thereby indicating its potential as a multi-drug-delivery system. In vivo toxicity assessment (serum parameters, histopathology, and haemolysis) carried out on BALB/c mice showed that IZDIC was safe up to a concentration of 100 mg kg-1. Finally, a reasonably high yield in bulk synthesis, stability under high temperature and humid conditions, tabletability and, slow and sustained release of the drug component of IZDIC suggested its suitability in real-life applications as multi-drug-delivery systems.

Sequestration and toxicological assessment of emerging contaminants with polypyrrole modified carboxymethyl cellulose (CMC/PPY): Case of ibuprofen pharmaceutical drug.

Ibuprofen (IBU) is a non-steroidal anti-inflammatory drug released into water bodies causing toxic biological effects on living organisms. The current study aims to eliminate IBU from aqueous solutions by a novel carboxymethylcellulose/polypyrrole (CMC/PPY) composite with high removal efficiency. Pyrrole was polymerized to polypyrrole whose average size was about 20 nm on the CMC surface. The maximum removal percentage of IBU by CMC/PPY composite was optimized at initial concentration 10 mg/L, dosage 0.02 g, and pH 7 with adsorption capacity of 72.30 (mg/g) and removal of 83.17 %. IBU adsorption onto CMC/PPY theoretically fits into the Langmuir isotherm and Elovich-kinetic models. Fish and Phytotoxicity assessment were performed with zebrafish and seeds of Vigna mungo (VM) and Vigna radiata (VR). The toxicity study reveals that before adsorption, IBU shows high toxicity towards the zebrafish mortality (33 %), growth inhibition (58.52 % for VM, 60.84 % for VR), and germination (86.66 % for VM and 90 % for VR). As CMC/PPY adsorbs IBU, toxicity drastically decreases. Before adsorption, LC50 was 233.02 mg/L. After adsorption, the LC50 increases to 2325.07 mg/L as IBU molecules get adsorbed by CMC/PPY. These findings show the feasibility of preparing CMC/PPY composite to effectively remove pharmaceutical pollutant IBU from aqueous solutions with their toxicological assessment.

Effective removal of pharmaceutical contaminants ibuprofen and sulfamethoxazole from water by Corn starch nanoparticles: An ecotoxicological assessment.

Pharmaceutical pollutants, a vital type of emerging contaminants, have attracted researchers to study their removal from water. In this research, Corn starch nanoparticles (CSNP) have been synthesized and characterized using various analytical techniques. The synthesized CSNP was used for the biosorption of two pharmaceutical drugs, ibuprofen (IBU) and sulfamethoxazole (SUL). The influence of various experimental conditions was optimized through batch study with the removal efficiency of 86.33 % (IBU) and 85.80 % (SUL) at pH 2 and 3, initial concentration of 10 mg/L, 0.01 g of CSNP dosage. The biosorption of IBU follows Temkin, and SUL follows Langmuir isotherm models. The toxicological assessment was performed using the seeds of Vigna mungo (VM) and Vigna radiata (VR) and zebrafish to evaluate the toxic effects of pollutants on these organisms. The LC50 of IBU and SUL on zebrafish before the biosorption process was 209.50 mg/L and 338.84 mg/L. After biosorption, the LC50 values increase to 1435.82 mg/L for IBU and 1317.04 mg/L for SUL. Thus, CSNP is an efficient biosorbent for removing the pharmaceutical pollutants to protect ecological systems.

Efficacy and Costs of Three Pharmacotherapies for Patent Ductus Arteriosus Closure in Premature Infants.

BACKGROUND: The hemodynamic impact of persistent patent ductus arteriosus (PDA) is associated with neonatal morbidities and mortality in preterm newborns. While there has been considerable debate about optimal management of PDA and its impact on clinical outcomes, there is widespread variation in practice, such as using different pharmacotherapies to achieve closure of hemodynamically significant PDA during the first week of life in very low birth weight infants. AIMS: The objective was to estimate the efficacy of acetaminophen, ibuprofen, and indomethacin with regard to ductal closure and to compare the costs of these three commonly used medications to treat PDA in preterm infants. METHODS: PubMed, Embase, and Cochrane Registry were searched for trials from the years 2010-2020. We identified 17 randomized clinical trials (RCTs) and 14 case series that enrolled preterm infants < 37 weeks gestational age for inclusion. Pooled estimates of closure rates for acetaminophen (n = 630), ibuprofen (n = 694), and indomethacin (n = 312) were analyzed using the weighted proportion ratio using a Mantel­Haenszel random effects model. The chi-squared test of proportions was used to determine significance between groups. We accessed cost estimates of pharmacotherapy from the Lexi-Comp average wholesale price database and utilized a decision tree model to appraise cost benefits for the outcome measure of successful PDA closure. RESULTS: The pooled proportional point estimates of closure rates from RCTs for acetaminophen, ibuprofen, and indomethacin were 70.1% (95% confidence interval [CI] 60-80), 63.4% (95% CI 52.8-74.1), and 71.5% (95% CI 62.3-80.7), respectively. There was no significant statistical difference in closure rates when RCTs and uncontrolled case series were combined. Pairwise comparisons showed both acetaminophen and indomethacin were each more effective in closing PDA than ibuprofen (acetaminophen vs indomethacin: p = 0.01; ibuprofen vs indomethacin: p = 0.02; acetaminophen vs indomethacin: p = 0.93). Comparing costs for successful closure of PDA, at the average wholesale price of different medications, suggested that treatment with acetaminophen costs significantly less, with a mean of $1487 (95% CI 1300-1737), compared to ibuprofen, with a mean of $2585 (95% CI 2214-3104), and indomethacin, with a mean of $2661 (95% CI 2358-3052), per course of treatment. CONCLUSIONS: Our meta-analysis suggests acetaminophen is non-inferior to both indomethacin and ibuprofen, and costs relatively less for successful PDA constriction in premature infants. Further clinical trials are warranted to compare acetaminophen's safety, along with short- and long-term effects, to help resolve the clinical conundrum of the necessity of early treatment in the management of PDA, and the optimal pharmacological course, if indicated.

Evaluating the IVIVC by Combining Tiny-tim Outputs and Compartmental PK Model to Predict Oral Exposure for Different Formulations of Ibuprofen.

Nowadays, the ever-increasing costs of research and development in the pharmaceutical industry have created a big demand for predicting the performances of drug candidates. Of those, the desire to establish an in vitro-in vivo correlation (IVIVC) to better predict the oral drug exposure for different drug products is a growing need. Once a robust IVIVC is established, the performance of different drug products can be predicted and selected for testing in clinical trials with greater confidence. This tool will significantly reduce the cost and speed of drug development and provide new therapy to the patient faster. In this study, we explore combining the outputs of Triskelion's Gastro-Intestinal Model (Tiny-TIM) and multi-compartment pharmacokinetic model for a 200 mg ibuprofen product. The Loo-Riegelman method was used to calculate the amount of ibuprofen absorbed and was combined with the Tiny-TIM data to establish the IVIVC. The IVIVC was used to predict the exposures of both fast release and liquid gel formulations in humans. In general, the predicted exposure using Tiny-TIM-based IVIVC has good agreement with the clinical findings.