Removal of Pharmaceutically Active Compounds in Sequencing Batch Reactor

Biological treatment efficiency of six pharmaceutical compounds （acetazolamide, metronidazole, opipramol, piracetam, salicylamide and tinidazole） was evaluated using lab-scale Sequencing Batch Reactor （SBR）. Comparative biological degradation processes of two types of activated sludge from municipal and pharmaceutical industry sewage treatment plants were examined. Three different organic loadings （0.05 g COD/g MLSS.d, 0.1 g COD/g MLSS.d and 0.2 g COD/g MLSS-d） and reaction time on the efficiency of Active Pharmaceutical Ingredient （API） decomposition were examined. Chemical oxygen demand, non-purgeable organic carbon as well as ammonium nitrogen contents were monitored by standard methods. Percentage of API decomposition was analysed by High Performance Liquid Chromatography （HPLC）. The overall API removal efficiency was strictly dependent on the type of activated sludge origin. The main biodegradation products were identified using HPLC-MS,1H NMR and 13C NMR methods as e.g. （{4-[3-（5H-dibenzo[b,f]azepin-5-yl]piperazin-l-yl}methanamine） and （2-amino-1,3,4-thiadiazol-5-sulfonamide） for opipramol and acetazolamide respectively.

Multiple Emulsions Able to Be Used for Oral Administration of Active Pharmaceutical Ingredients: Physico-Chemical Parameters Study of Different Phases

Multiple emulsions are of great therapeutic interest especially in the administration of medicines which can be inactivated by digestive enzymes;moreover the researches of formulation not being often easy, a control of the different phases physicochemical parameters would be of great interest in rapid formulations and at low cost. When formulating emulsions, the preliminary tests, also known as formulation tests, constitute a step which can be long and expensive because of the quantity of reagents that can be used. A rigorous methodology could thus be of great interest, which is at the aim of our study which consists of evaluating the physico-chemical parameters of different phases used to make thus multiple emulsions. In our study, physico-chemical parameters such as conductivity, pH, density, viscosity, and surface tension have been studied by direct measurement using equipment and also by means of suitable mounting. The results showed that the pH and the surface tension have an important role in the prediction of the stability of emulsions, these latter must be of the same order of magnitude. For all phases conductivity does not have too much interest apart from helping to determine the type of the emulsion.

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

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

Proposal and evaluation of a new norm index-based QSAR model to predict pEC50 and pCC50 activities of HEPT derivatives

The search and development of anti-HIV drugs is currently one of the most urgent tasks of pharmacological studies. In this work, a quantitative structure-activity relationship （QSAR） model based on some new norm indexes, was obtained to a series of more than 150 HEPT derivatives （1-[（2-hydroxyethoxy）methyl]-6-（phenylthio）thymine） to find their pEC50 （the required effective concentration to achieve 50% protection of MT-4 cells against the cytopathic effect of virus） and pCC50 （the required cytotoxic concentration to reduce visibility of 50% mock infected cell） activities. The model efficiencies were then validated using the leave-one-out cross validation （LOO-CV） and y- randomization test. Results indicated that this new model was efficient and could provide satisfactory results for prediction of pECso and pCC50 with the higher R2 train and the higher Rt2est. By using the leverage approach, the applicability domain of this model was further investigated and no response outlier was detected for HEFT derivatives involved in this work. Comparison results with reference methods demonstrated that this new method could result in significant improvements for predicting pEC50 and pCC50 of anti-HIV HEPT derivatives. Moreover, results shown in this present study suggested that these two absolutely different activities pECso and pCC50 of anti-HIV HEPT derivatives could be predicted well with a totally similar QSAR model, which indicated that this model mizht have the potential to be further utilized for other biological activities of HEFT derivatives.

Safe Disposal of Medicines in Palestine

The disposal of unwanted and expired medications has been a concern to public health practitioners, and patients alike. The objective of the current investigation was to look closely at the practice of patients and carers in Nablus-Palestine with regard to disposal of unused or expired medicines. The study was a cross-sectional survey administered via face-to-face structured interviews with randomly selected patients, community pharmacists and physicians from Nablus-Palestine. Two hundred and fifty patients/carers completed a questionnaire regarding medicines disposal current practice, effects on environment, and their views to overcome this problem. Most of the people completing the questionnaire （67%） stated that they throw unwanted medicines in the normal household bins, and about 75% think that this can impose illegal and environmental hazards. Nearly half of the questionnaire showed that main reason for need to dispose medicines was possessing expired ones with almost believe there should be more appropriate way to dispose medicines. About 95% said they have not been directed for safe disposal of medicines with 46% thinking that a national campaign can be very educative in this issue mainly through Ministry of Health （54%） followed by .73% of the sampled patients were in favor of national campaign to direct people to safe disposal of medicines. This pilot study in Nablus clearly highlights the need for appropriate method for safe disposal of medicines in Palestine through guidelines in pharmacies and hospitals. A well organized method for collecting unwanted medicines from people should be encouraged through appropriate teaching of patients and caters about effects of waste medicines on environment as well as being domestic hazard. The data and information is valuable for furthering discussions regarding patients behaviour and also provides a basis for future research into determining what quantities of active pharmaceutical ingredients （APIs） are disposed, enter the environment and what effects it can impose.

Role of the aquatic environment in enhancing and inhibiting phototransformation of pharmaceutically active compounds

Pharmaceutically active compounds(PhACs)are widely used in medical treatments but pose risks to ecosystems and human health when present in the environment.Understanding their fate in nature is complex and influenced by various factors.Phototransformation,where PhACs change chemically upon light exposure,offers the potential for reducing their environmental levels.Studying this process is crucial for understanding risks,developing safe disposal strategies,and innovating removal methods to mitigate adverse effects.This review delves into the major factors influencing the transformation of PhACs under natural conditions.It provides a comprehensive analysis of the mechanisms involved in the photochemical activity of PhACs,shedding light on their behavior upon exposure to sunlight.Special attention is given to delineating the differences in the phototransformation processes among 13 major pharmaceutical classes.By examining the various factors influencing PhAC transformation and eluci-dating their mechanisms,this review aims to contribute to a deeper understanding of the fate of pharmaceuticals in the environment.Such insights are invaluable for developing effective strategies to mitigate the risks posed by PhAC contamination and safeguarding environmental and human health.

Evaluation of pharmaceutical activities of G-protein coupled receptor targeted pharmaceuticals in Chinese wastewater effluent

The occurre nce of biologically active pharmaceuticals in aquatic enviro nments raised the potential risks to aquatic species.Among these marketed biological active pharmaceuticals,it has been estimated that40%of them target G-protein-coupled receptors(GPCRs).We have illustrated pharmaceutical activities of GPCR targeted pharmaceuticals in English and Japanese wastewater by the in vitro transforming growth factor-α(TGFα)shedding assay.However,as the most important producer and consumer of pharmaceuticals,the occurrence of GPCR targeted pharmaceuticals in China had remained unclear.In this study,we investigated the pharmaceutical activities of GPCR targeted pharmaceuticals in secondary effluents of Chinese wastewater treatment plants.We discovered antagonistic activities against angiotensin(AT1)receptor at up to 7.2×102 ng-valsartan-equivalent quantity/L in Chinese wastewater for the first time as well as agonistic activities against dopamine(D2)receptor.Furthermore,in parallel with the assay,we determined concentrations of GPCR targeted pharmaceuticals in target wastewater by liquid chromatography coupled with tandem mass spectrometry(LC-MS/MS).Through the comparison of predicted antagonistic activities calculated by concentrations and potency values from the assay,we found that the measured antagonistic activities against AT1 receptor from the assay were higher than the predicted AT1 activities from valsartan,irbesartan,and losartan,indicating the potential existence of other unknown AT1 antagonists in wastewater.

Occurrence,spatial and seasonal variation,and environmental risk of pharmaceutically active compounds in the Pearl River basin,South China

The occurrence,fate,and environmental risk of 40 pharmaceutically active compounds(PhACs)from surface waters and sediments were comprehensively investigated in the Beijiang River,Xijiang River,and Maozhou River of the Pearl River basin,South China.Salicylic acid and diclofenac(antiinflammatory drugs),gemfibrozil(a lipid regulator),carbamazepine(an antiepileptic drug),diazepam(a psychoactive drug),and 2-methyl-4-chloro-phenoxyacetic acid(MCPA,a pesticide)were the most ubiquitous compounds in the studied region.The average concentrations of detected PhACs in surface waters and sediments ranged from 0.17 to 19.1 ng/L and 0.10 to 10.4 ng/g,respectively.Meanwhile,PhACs concentration in surface waters and sediments varied greatly among and within the Beijiang River,Xijiang River,and Maozhou River.The largest annual flux of PhACs of the Xijiang River and Beijiang River was more than 11000 kg per annum,whereas only 25.7 kg/a in the Maozhou River.In addition,the estimated emissions of PhACs in the Beijiang River,Xijiang River,and Maozhou River ranged respectively from 0.28 to 4.22 kg/a,0.12 to 6.72 kg/a,and 6.66 to 91.0 kg/a,and the backestimated usage varied with a range from 12.0 to 293 kg/a,6.79 to 944 kg/a,368 to 17459 kg/a.Moreover,the emissions of PhACs showed a close relationship with the gross domestic product(GDP)of each city along the Pearl River.The environmental risk assessment suggested that diazepam and ibuprofen had a moderate risk in this region.

Synthesis, Characterization and Antibacterial Activities Study of a Pharmaceutical Cocrystal of Artesunate and 4,4’-Bipyridine

We report here a cocrystal with artesunate as the active pharmaceutical ingredient(API)and a pharmaceutical intermediate 4,4?-bipyridine as the cocrystal former(CCF).The analysis of single-crystal X-ray diffraction demonstrates that the eutectic structural unit consists of two artesunate molecules and one 4,4?-bipyridine molecule with their ratio to be 2:1.The carboxyl group on artesunate acts as a donor,and the acceptor is N on 4,4?-bipyridine,forming an O–H···N hydrogen bond.The appearance of new diffraction peaks in the X-ray powder diffraction pattern also indicates the formation of new phases.The PXRD results indicated a pure phase for the synthesized sample.The cocrystal is slightly soluble in water.Antimicrobial activities showed that the cocrystal displayed effective inhibition of different bacteria.

Recent advances in the synthesis and applications of furocoumarin derivatives

Furocoumarins are an important class of heterocyclic compounds with a fused tricyclic structure of coumarin and furan rings.They are commonly found in bioactive natural products and have a diverse range of biological and pharmaceutical properties,including cytotoxicity,photosensitivity,insecticidal,antibacterial,and antifungal activity,among others.The elegant linear/angular tricyclic skeleton and superior pharmacological properties,make them ideal for building and developing advanced biological scaffolds for biomedical applications.As a result,the family of furocoumarins has been the focus of intensive research,and lots of encouraging progress have been achieved in recent years.This review summarizes the most recent methods reported for the synthesis of the furocoumarin derivative family,along with their applications in medicinal chemistry covering from 2018 to 2022.

Natural ingredients from Chinese materia medica for pulmonary hypertension

Pulmonary hypertension(PH)is a severe pathophysiological condition characterized by pulmonary artery remodeling and continuous increases in pulmonary artery pressure,which may eventually develop to right heart failure and death.Although newly discovered and incredible treatment strategies in recent years have improved the prognosis of PH,limited types of effective and economical drugs for PH still makes it as a life-threatening disease.Some drugs from Chinese materia medica(CMM)have been traditionally applied in the treatment of lung diseases.Accumulating evidence suggests active pharmaceutical ingredients(APIs)derived from those medicines brings promising future for the prevention and treatment of PH.In this review,we summarized the pharmacological effects of APIs derived from CMM which are potent in treating PH,so as to provide new thoughts for initial drug discovery and identification of potential therapeutic strategies in alternative medicine for PH.

Removal of sulfamethoxazole by nanofiltration membrane

The retention of sulfamethoxazole (SMZ) by nanofiltration (NF) membranes is strongly influenced by the pH value of the solution. The retention of SMZ reaches its peak value when the solution pH rises above its pKa2 value as the compound transforms into a negatively charged species. Charge repulsion is the main mechanism involved in SMZ removal by NF membranes. In this study, the removal of SMZ by NF membranes, as a function of solution chemistry, was examined at pH 8.9 to investigate the effect of solution conditions on charge repulsion. The results show that the retention of negatively charged SMZ is relatively independent of SMZ concentration, and an increase in the ionic strength of the solution causes a relatively small reduction in retention. A small effect of humic acid (HA) on SMZ retention was noticed at pH 8.9, which can be explained by a small but insignificant improvement in the zeta potential of the membrane caused by HA at high pH values. However, it was found that SMZ concentration in the feed decreased significantly in solutions containing tannic acid (TA). The Adams-Bohart model was applied to our experimental data and was found to be suitable for describing the initial part of the breakthrough curves. The adsorptive parameters of the membrane were determined.