Presence Of Active Pharmaceutical Ingredients Research Articles

Ecotoxicological risk assessment of active pharmaceutical ingredients (APIs) against different aquatic species leveraging intelligent consensus prediction and i-QSTTR modeling

The increasing presence of active pharmaceutical ingredients (APIs) in aquatic ecosystems, driven by widespread human use, poses significant risks, including acute and chronic toxicity to aquatic species. However, the scarcity of experimental toxicity data on APIs and related compounds due to the high costs, time requirements, and ethical concerns associated with animal testing hinders comprehensive risk assessment. In response, we developed quantitative structure-toxicity relationship (QSTR) and interspecies quantitative structure toxicity-toxicity relationship (i-QSTTR) models for three key aquatic species: zebrafish, water fleas, and green algae, using NOEC as an endpoint, following OECD guidelines. Algae, daphnia, and fish, recognized as standard organisms in toxicity testing, are crucial bio-indicators due to their size, transparency, adaptability, and regulatory acceptance. We used partial least squares (PLS) and multiple linear regression (MLR) methods for model development alongside machine learning techniques such as Random Forest (RF), Support Vector Machines (SVM), K-nearest Neighbor (kNN), and Neural Networks (NN) to enhance the predictivity. Lipophilicity, electronegativity, unsaturation, a molecular cyclized degree in molecular structure, large fragments, aliphatic secondary C(sp2), and R–CR–R groups were identified as critical biomarkers for API toxicity. Screening of the PPDB (pesticide properties databases) and DrugBank validated the practical application of these models, offering valuable tools for regulatory decisions, safer API design, and the preservation of aquatic biodiversity.

Active pharmaceutical contaminants in drinking water: myth or fact?

Global water availability has been affected by a variety of factors, including climate change, water pollution, urbanization, and population growth. These issues have been particularly acute in many parts of the world, where access to clean water remains a significant challenge. In this context, preserving existing water bodies is a critical priority. Numerous studies have demonstrated the inadequacy of conventional water treatment processes in removing active pharmaceutical ingredients (APIs) from the water. These pharmaceutical active compounds have been detected in treated wastewater, groundwater, and even drinking water sources. The presence of APIs in water resources poses a significant threat not only to aquatic organisms but also to human health. These emerging contaminants have the potential to disrupt endocrine systems, promote the development of antibiotic-resistant bacteria, and bioaccumulate in the food chain, ultimately leading to unacceptable risks to public health. The inability of current conventional treatment methods to effectively remove APIs from water has raised serious concerns about the safety and reliability of water supplies. This issue requires immediate attention and the development of more effective treatment technologies to safeguard the quality of water resources and protect both aquatic ecosystems and human health. Other treatment methods, such as nanotechnology, microalgal treatment, and reverse osmosis, are promising in addressing the issue of API contamination in water resources. These innovative approaches have demonstrated higher removal efficiencies for a wide range of APIs compared to conventional methods, such as activated sludge and chlorination, which have been found to be inadequate in the removal of these emerging contaminants. The potential of these alternative treatment technologies to serve as effective tertiary treatment. To address this critical challenge, governments and policymakers should prioritize investment in research and development to establish effective and scalable solutions for eliminating APIs from various water sources. This should include comprehensive studies to assess the performance, cost-effectiveness, and environmental sustainability of emerging treatment technologies. The emerging contaminants should be included in robust water quality monitoring programs (Aus der Beek et al. in Environ Toxicol Chem 2016;35(4):823-835), with strict regulatory limits enforced to protect public health and the environment. By doing so, the scientific community and regulatory authorities can work together to develop a multi-barrier approach to safeguarding the water resources and ensuring access to safe, clean water for all. This review explores the potential of alternative treatment technologies to serve as viable solutions in the fight against API contamination. Innovative approaches, including nanotechnology, microalgal treatment, and reverse osmosis, have demonstrated remarkable success in addressing this challenge, exhibiting higher removal efficiencies compared to traditional methods.

A robust self-regenerating graphene-based adsorbent for pharmaceutical removal in various water environments

The presence of active pharmaceutical ingredients (APIs) in wastewater effluents and natural aquatic systems threatens ecological and human health. While activated carbon-based adsorbents, such as GAC and PAC, are widely used for API removal, they exhibit certain deficiencies, including reduced performance due to the presence of natural organic macromolecules (NOMs) and high regeneration costs. There is growing demand for a robust, stable, and self-regenerative adsorbent designed for API removal in various environments. In this study, we synthesized a self-generating metal oxide nano-composite (S-MGC) containing titanium dioxide (TiO2) and silicon dioxide (SiO2) combined with 3D graphene oxide (GO) to adsorb APIs and undergo regeneration via light illumination. We determined optimal TiO2:SiO2:GO compositions for the S-MGCs through experiments using a model contaminant, methylene blue. The physical and chemical properties of S-MGCs were characterized, and their adsorption and photodegradation capabilities were studied using five model APIs, including sulfamethoxazole, carbamazepine, ketoprofen, valsartan, and diclofenac, both in single-component and multi-component mixtures. In the absence of TiO2/SiO2, 3D graphene oxide (CGB) displayed better adsorption performance compared to GAC, and S-MGCs further improve CGB's adsorption capacity. This performance remained consistent in two complex water environments: aqueous solutions at varying NOM levels and artificial urine. TiO2 supported on the GO surface exhibits similar photocatalytic activity to suspended TiO2. In a continuous fixed-bed column test, S-MGCs demonstrated robust API adsorption performance that is maintained in the presence of NOM or urine, and can be regenerated through multiple cycles of adsorption and light illumination.

Analysis of unknown (unlabeled/mislabeled) drug products for active pharmaceutical ingredients and related substances by an international mail facility satellite laboratory equipped with rapid screening devices.

Two chemists employed a three-device rapid screening "toolkit" consisting of a handheld Raman spectrometer, transportable mass spectrometer, and portable Fourier transform infrared (FT-IR) spectrometer at an international mail facility (IMF) satellite laboratory to examine unknown (unlabeled/mislabeled) products for the presence of active pharmaceutical ingredients (APIs). Phase I of this project previously demonstrated that this toolkit was the most effective collection of instruments for identifying APIs in product types collected at IMFs during a nationwide mail blitz and Phase II of this project previously demonstrated that results generated using the toolkit during a satellite laboratory pilot program were as reliable as those generated by a full-service library when two or more of these instruments identify an API. This study (Phase III) described the results of the satellite laboratory toolkit during production mode and encompassed the period ranging from June 2021 through December 2022. During this study, a total of 858 products were examined on-site at the IMF. The satellite laboratory yielded conclusive results for 726 (84.6%) products, which were used to support regulatory action, and identified 132 (15.4%) products that required additional full-service laboratory analyses due to inconclusive results. The satellite and full-service laboratory verified/confirmed at least one API/related substance in 617 (71.9%) products. A total of 709 APIs/related substances were found in the 617 products, and 202 of these 709 compounds were unique/different. Overall, during Phases I through III of this program, 350 different substances have been identified in products collected at IMFs.

Active pharmaceutical contaminants in dietary supplements: A tier-based risk assessment approach

The presence of active pharmaceutical ingredients (APIs) in adulterated or contaminated dietary supplements is a current product safety concern. Since there are limited guidelines, and no published consensus methods, we developed a tier-based framework incorporating typical lines of evidence for determining the human health risk associated with APIs in dietary supplements. Specifically, the tiered approach outlines hazard identification and decision to test for APIs in products based on criteria for likelihood of contamination or adulteration, and evaluation of manufacturer production standards. For products with detectable levels of APIs, a variety of default approaches, including the use of fraction of the therapeutic dose and the threshold of toxicological concern (TTC), as well as health-based exposure limits (HBELs) are applied. In order to demonstrate its practical use, as well as any limitations and/or special considerations, this framework was applied to five dietary supplements (currently available to the public). We found that the detected levels of APIs in some dietary supplements were above the recommended dose of the drugs, and thus, pose a significant health risk to consumers and potentially workers involved in manufacturing of these supplements. The results support the value of increased product quality surveillance and perhaps regulatory activity.

Susceptibility of phytoplankton to the increasing presence of active pharmaceutical ingredients (APIs) in the aquatic environment: A review.

Human and veterinary pharmaceuticals either in the form of un-metabolized, incompletely metabolized, and metabolized drugs are increasingly present in aquatic ecosystems. These active pharmaceutical ingredients from pharmaceutical industries, hospitals, agricultural, and domestic discharges find their way into water systems - where they adversely affect non-target organisms like phytoplankton. Different aspects of phytoplankton life; ranging from growth, reproduction, morphology, physiology, biochemical composition, oxidative response, proteomics, and transcriptomics are altered by pharmaceuticals. This review discusses the currently available information on the susceptibility of phytoplankton to the ever-increasing presence of pharmaceutical products in the aquatic environment by focusing on the effect of APIs on the physiology, metabolome, and proteome profiles of phytoplankton. We also highlight gaps in literature concerning the salient underlining biochemical interactions between phytoplankton communities and pharmaceuticals that require an in-depth investigation. This is all in a bid to understand the imminent dangers of the contamination of water bodies with pharmaceutical products and how this process unfavorably affects aquatic food webs.

Structural Polymorphism of Sorafenib Tosylate as a Key Factor in Its Solubility Differentiation

The presence of active pharmaceutical ingredients (APIs) in the forms of different polymorphic states can induce differences in their physicochemical properties. In the case of poorly soluble APIs, like the oncological drug sorafenib tosylate, small variations in solubility may result in large bioavailability differences. The control of its therapeutic dose is crucial from the effective pharmacotherapy point of view and the reduction of side effects. Therefore, this study aimed to assess the influence of sorafenib tosylate polymorphic forms on its solubility and, consequently, permeability, based on passive diffusion through membranes simulating the gastrointestinal tract (GIT) conditions. In the first part of the work, two crystalline forms of sorafenib tosylate were identified using the X-ray powder diffraction, FT-IR, and Raman spectroscopy. Subsequently, solubility studies were carried out. Both forms of sorafenib tosylate were insoluble in 0.1 N hydrochloric acid (HCl), in acetate buffer (pH 4.5), and in phosphate buffer (pH 6.8). Solubility (mg/mL) of form I and III of sorafenib tosylate in 0.1 N HCl + 1.0% SDS was 0.314 ± 0.006 and 1.103 ± 0.014, respectively, in acetate buffer pH 4.5 + 1.0% SDS it was 2.404 ± 0.012 and 2.355 ± 0.009, respectively, and in phosphate buffer pH 6.8 + 1.0% SDS it was 0.051 ± 0.005 and 1.805 ± 0.023, respectively. The permeability study was assessed using the parallel artificial membrane permeability assay (PAMPA) model. The apparent permeability coefficient (Papp—cm s−1) of form I and III in pH 1.2 was 3.01 × 10−5 ± 4.14 × 10−7 and 3.15 × 10−5 ± 1.89 × 10−6, respectively, while in pH 6.8 it was 2.72 × 10−5 ± 1.56 × 10−6 and 2.81 × 10−5 ± 9.0 × 10−7, respectively. Changes in sorafenib tosylate concentrations were determined by chromatography using the high-performance liquid chromatography (HPLC)–DAD technique. As a result of the research on the structural polymorphism of sorafenib tosylate, its full spectral characteristics and the possibility of using FT-IR and Raman spectroscopy for the study of polymorphic varieties were determined for the first time, and the HPLC method was developed, which is appropriate for the assessment of sorafenib solubility in various media. The consequences of various physicochemical properties resulting from differences in the solubility of sorafenib tosylate polymorphs are important for pre-formulation and formulation studies conducted with its participation and for the safety of oncological sorafenib therapy.

Antimicrobial preservation efficacy of liquid glucose and liquid maltitol syrups with and without 0.1% sorbic acid

Abstract Objectives Amongst paediatric pharmaceutical forms, syrups offer advantages such as ease of administration and good palatability. They also exhibited microbial self-preservation properties that may be useful to enhance shelf life of liquid formulation. The objective of our works is to test the self-preservation efficacy of maltitol and glucose syrup without or with sorbic acid as described in the European pharmacopoeia. Methods The European Pharmacopoeia test of antimicrobial preservation efficacy was performed on liquid glucose syrup and liquid maltitol syrup with and without 0.1% sorbic acid. Results Unpreserved glucose and maltitol syrups did not meet the European Pharmacopoeia acceptance criteria for antimicrobial preservative efficacy due to the regrowth of Aspergillus brasiliensis on day 28 whereas glucose and maltitol syrups with 0.1% sorbic acid pass the test. Conclusions The addition of a preservative (sorbic acid) in glucose and maltitol syrups allows the validation of the antimicrobial preservative efficacy test of the European Pharmacopoeia. Further tests are needed to see if preservative efficacy is maintained despite dilutions or in the presence of active pharmaceutical ingredients.

Development of a rapid GC-FID method to simultaneously determine triethylamine, diisopropylamine, and 1,1,3,3-tetramethylguanidine residues in an active pharmaceutical ingredient

A rapid GC-FID method was developed to simultaneously determine residual levels of triethylamine (TEA), 1,1,3,3-tetramethylguanidine (TMG), and diisopropylamine (DIPA) in the synthetic route of an active pharmaceutical ingredient (API). Due to the severe absorption of amines on GC stationary phases, GC columns with various stationary phases were evaluated for optimal peak shape and reproducibility. The final conditions used the Agilent CP-Volamine column to resolve the three amines in 12 min. Various inlet liners were also screened to further improve the sensitivity of the analysis. The Restek Siltek® liner was selected to achieve the desired detectability for the method. The quantitation limits were 4, 3, and 4 μg/mL for TEA, DIPA, and TMG in the presence of API, respectively. All three amines showed good linearity (r > 0.999) and recoveries (> 90%) over the concentration range of 3 to 16 μg/mL. The testing of residual amines was initially performed at the penultimate stage of the synthesis. However, this work demonstrates that TMG can act as a proton sponge to react with salicylic acid, the counter ion of the penultimate, to form a volatile component that elutes at a different retention time. Consequently, in the final method, these three amines were monitored in the final API to circumvent the matrix interference. Key parameters of the method were qualified per method validation requirements in ICH guidelines. The method was successfully applied for batch testing during development and implemented as an in-process control procedure at manufacturing sites.

The removal of pharmaceuticals during wastewater treatment: Can it be predicted accurately?

The presence of active pharmaceutical ingredients (APIs) in the environment is of growing concern and effluents from wastewater treatment works (WwTWs) are one of the major sources. This research combines the outputs of a multimillion pound UK program of work to evaluate the fate of APIs in the wastewater treatment process. A combination of analysis of measured data and modelling has been applied to 18 APIs, representing a wide range of medicinal application and physico-chemical characteristics. Some isomers (for atorvastatin) and metabolites (for sertraline, carbamazepine and erythromycin) were also included. High variability was observed between removal rates for individual APIs between WwTW, which after statistical analysis could not be explained by the nominal WwTW process (e.g. activated sludge or trickling filter). Nor was there a clear relationship between API removal and physico-chemical parameters such as pKa, charge or log Kow. A publically available sewage process model, SimpleTreat 4.0 which has been rigorously validated and is now being used for exposure assessment with REACH legislation for organic chemicals and within the Biocidal Products Regulation by the European Medicines Agency for APIs, was used to estimate removal rates with which to compare with measured data. SimpleTreat provided estimates of removal rates within ±30% of observed values for the majority of the APIs measured, with the use of readily available WwTW specific parameters such as flow, total suspended solids and BOD data. The data and correlations provided in this study provide support for any future considerations regarding the management of API discharge to the aquatic environment.

Identification and quantification of 19 pharmaceutical active compounds and metabolites in hospital wastewater in Cameroon using LC/QQQ and LC/Q-TOF.

Human pharmaceutical residues are a serious environmental concern. They have been reported to have eco, geno, and human toxic effects, and thus their importance as micropollutants cannot be ignored. These have been studied extensively in Europe and North America. However, African countries are still lagging behind in research on these micropollutants. In this study, the wastewaters of the University Teaching Hospital of Yaoundé (UTHY) were screened for the presence of active pharmaceutical ingredients and their metabolites. The screening was carried out using two methods: high-performance liquid chromatography coupled to a triple quadrupole analyzer (LC/QQQ) and high-performance coupled to a mass spectrometer with a time of flight analyzer (LC/Q-TOF). A total of 19 active pharmaceutical ingredients and metabolites were identified and quantified. The compounds identified include paracetamol (211.93μg/L), ibuprofen (141μg/L), tramadol (76μg/L), O-demethyltramadol (141μg/L), erythromycinanhydrate (7μg/L), ciprofloxacin (24μg/L), clarinthromycine (0.088μg/L), azitromycine (0.39μg/L), sulfamethoxazole 0.16μg/L), trimetoprime (0.27μg/L), caffeine (5.8μg/L), carnamaeepine (0.94μg/L), atenolol (0.43μg/L), propranolol (0.3μg/L), cimetidine (34μg/L), hydroxy omeprazole (5μg/L), diphenhydramine (0.38μg/L), metformine (154μg/L), and sucralose (13.07μg/L).

Green pharmacy - a narrative review.

IntroductionActive pharmaceutical ingredients are present in various sections of the environment, because of both the human and veterinary use of medicinal products. Ways of minimizing the risk of environmental contamination should be observed during all pharmaceutical activities (research, manufacturing, prescribing, dispensing and disposal of medicinal products).MethodsFor the present study we searched specific literature on this subject, using the main international databases (Thomson Reuters – Web of Science, SCOPUS and Science Direct).ResultsThis narrative review focuses on the main aspects concerning environmental contamination with medicinal products. Consequently, the present study is structured on four different topics: environmental research on medicinal products, minimizing environmental contamination, waste disposal management and towards a greener community pharmacy.ConclusionWaste management activities are important for reducing the presence of active pharmaceutical ingredients in the environment. Pharmacists should inform patients on proper pharmaceutical waste disposal and organize collection programs for unused and expired medicines, in order to develop a greener pharmacy for the future.

Presence of active pharmaceutical ingredients in the continuum of surface and ground water used in drinking water production

Anthropogenic chemicals in surface water and groundwater cause concern especially when the water is used in drinking water production. Due to their continuous release or spill-over at waste water treatment plants, active pharmaceutical ingredients (APIs) are constantly present in aquatic environment and despite their low concentrations, APIs can still cause effects on the organisms. In the present study, Chemcatcher passive sampling was applied in surface water, surface water intake site, and groundwater observation wells to estimate whether the selected APIs are able to end up in drinking water supply through an artificial groundwater recharge system. The API concentrations measured in conventional wastewater, surface water, and groundwater grab samples were assessed with the results obtained with passive samplers. Out of the 25 APIs studied with passive sampling, four were observed in groundwater and 21 in surface water. This suggests that many anthropogenic APIs released to waste water proceed downstream and can be detectable in groundwater recharge. Chemcatcher passive samplers have previously been used in monitoring several harmful chemicals in surface and wastewaters, but the path of chemicals to groundwater has not been studied. This study provides novel information on the suitability of the Chemcatcher passive samplers for detecting APIs in groundwater wells.

Environmental pollution with antimicrobial agents from bulk drug manufacturing industries in Hyderabad, South India, is associated with dissemination of extended-spectrum beta-lactamase and carbapenemase-producing pathogens.

High antibiotic and antifungal concentrations in wastewater from anti-infective drug production may exert selection pressure for multidrug-resistant (MDR) pathogens. We investigated the environmental presence of active pharmaceutical ingredients and their association with MDR Gram-negative bacteria in Hyderabad, South India, a major production area for the global bulk drug market. From Nov 19 to 28, 2016, water samples were collected from the direct environment of bulk drug manufacturing facilities, the vicinity of two sewage treatment plants, the Musi River, and habitats in Hyderabad and nearby villages. Samples were analyzed for 25 anti-infective pharmaceuticals with liquid chromatography-tandem mass spectrometry and for MDR Gram-negative bacteria using chromogenic culture media. In addition, specimens were screened with PCR for bla VIM, bla KPC, bla NDM, bla IMP-1, and bla OXA-48 resistance genes. All environmental specimens from 28 different sampling sites were contaminated with antimicrobials. High concentrations of moxifloxacin, voriconazole, and fluconazole (up to 694.1, 2500, and 236,950µg/L, respectively) as well as increased concentrations of eight other antibiotics were found in sewers in the Patancheru-Bollaram industrial area. Corresponding microbiological analyses revealed an extensive presence of extended-spectrum beta-lactamase and carbapenemase-producing Enterobacteriaceae and non-fermenters (carrying mainly bla OXA-48, bla NDM, and bla KPC) in more than 95% of the samples. Insufficient wastewater management by bulk drug manufacturing facilities leads to unprecedented contamination of water resources with antimicrobial pharmaceuticals, which seems to be associated with the selection and dissemination of carbapenemase-producing pathogens. The development and global spread of antimicrobial resistance present a major challenge for pharmaceutical producers and regulatory agencies.

Development of the method for quantitative determination of phenylephrine hydrochloride in the combined drops

The work is devoted to development of the method for quantitative determination of phenylephrine hydrochloride in the combined nasal drops Gripocitron Rinis. Combination of phenylephrine hydrochloride possessing the vasoconstrictor action with dimetindene maleate having the antihistaminic action formulated into drops decreases nasal discharge and helps to clear the nasal passages without disturbing physiological functions of the ciliated epithelium and mucous membrane. It has been found that the quantitative content of phenylephrine hydrochloride in the combined nasal drops can be determined by spectrophotometry in the ultraviolet spectrum at the wavelength of 296 nm. The method proposed demonstrates the possibility of phenylephrine hydrochloride determination in combined drops in the presence of another active pharmaceutical ingredient – dimetindene maleate, which has the absorption minimum in sodium hydroxide solution at this wavelength. The influence of the additional ingredient – benzalkonium chloride drops on the nature of the absorption spectrum of phenylephrine hydrochloride is recommended to eliminate by the action of potassium dichromate solution. The optimal amount and concentration of solutions of sodium hydroxide and potassium dichromate, the analytical band have been determined. Validation of the given method has been carried out according to the following validation characteristics: linearity (a = 4.34 ≤ maxa 5.10%, b = 1.04), accuracy (0.52 ≤ maxδ 1.02%), convergence (1.07% ≤ max Δas 3.20%) and the correlation coefficient r, which is 0.9997. It has been found that the method suggested for determination of phenylephrine hydrochloride in nasal drops is precise, accurate, reproducible and linear, and it allows recommending it for using in pharmaceutical analysis. Phenylephrine hydrochloride is a known sympathomimetic providing a selective stimulating effect mainly on postsynaptic α-adrenergic receptors [4, 5]. Being a decongestant with a moderate vasoconstrictor action phenylephrine contains in a number of nasal drugs for local application, such as Nasol Baby (phenylephrine hydrochloride), Nasol Kids (phenylephrine hydrochloride with eucalyptol and benzalkonium chloride), Vibrocil and Gripocitron Rinis (phenylephrine hydrochloride with dimetindene maleate and benzalkonium chloride), which are used for symptomatic treatment of nasal congestion, acute and chronic rhinitis, allergic rhinitis, sinusitis, acute otitis. The search of safe and effective monocomponent and combined decongestant nasal drops for local application with phenylephrine hydrochloride actualizes development and standardization of methods for quality control of this substance in the presence of other active pharmaceutical ingredients (API) [3, 6, 7, 9]. Materials and Methods The object of the research was Gripocitron Rinis, nasal drops, 15 ml. The active substances were phenylephrine hydrochloride equivalent to 2.5 mg of phenylephrine, dimetindene maleate 0.25 mg; excipients were citric acid, monohydrate; anhydrous sodium hydrogen phosphate; sorbitol (Е 420); benzalkonium chloride; peppermint oil; purified water as needed. The reference standard (RS) of the substance of phenylephrine hy

Selective Detection of Hydrazine in the Presence of Excess Electrochemically Active Pharmaceutical Ingredients Using Boron Doped Diamond Metal Nanoparticle Functionalised Electrodes

AbstractDetection of the genotoxic impurity hydrazine (HZ) in the presence of active pharmaceutical ingredients (APIs) represents a significant challenge to the pharmaceutical industry. Here we show how the use of electrochemical strategies in conjunction with metal nanoparticle (NP) functionalised polycrystalline boron‐doped diamond (BDD) electrodes enables detection of HZ in the presence of two different electrochemically active APIs. By simply changing the chemical identity of the metal NP, which shifts the detection potential for HZ, it is possible to selectively screen out the API signature from the HZ current – voltage response. HZ detection limits of 11.1 µM (Au NP BDD) and 3.3 µM (Pt NP BDD) in the presence of excess acetaminophen and promazine respectively, were determined using differential pulse voltammetry in quiescent solution.

Ecopharmacology: Therapeutic Drugs as Environmental Hazards

There is an increasing concern in the medical fraternity regarding the impact of presence of active pharmaceutical ingredients (API) on the environment. In recent years, scientists have detected trace amounts of more than 150 different human and veterinary medicines in environments as far as the Arctic. High level of pollution is seen in the vicinity of large pharmaceutical manufacturing units and effluent river waters from cities. They are known to affect ecosystem in a negative way. Non-targeted population is at the receiving end of the effects of these pollutants, with direct onslaught for years together. Chronic effects are known with continuous inflow of more data, with even acute effects increasingly being reported. A research model has been suggested to bring forth a more realistic and true picture of the effects of these environment pollutants on the flora and the fauna in their natural habitats.

Treatment options for wastewater effluents from pharmaceutical companies

In recent years, concerns about the occurrence and fate of active pharmaceutical ingredients, solvents, intermediates and raw materials that could be present in water and wastewater including pharmaceutical industry wastewater has gained increasing attention. Traditional wastewater treatment methods, such as activated sludge, are not sufficient for the complete removal of active pharmaceutical ingredients and other wastewater constituents from these waters. As a result, complementary treatment methods such as membrane filtration, reverse osmosis and activated carbon are often used in conjunction with the traditional methods for treatment of industrial wastewater. Most of the literature published to date has been on the treatment of municipal wastewater. However, there is a growing body of research that looks at the presence of active pharmaceutical ingredients in industrial wastewater, the treatment of these wastewaters and the removal rates. This article, reviews these treatment methods and includes both traditional methods and advanced oxidation processes. The paper concludes by showing that the problem of pharmaceuticals in wastewaters cannot be solved merely by adopting end of pipe measures. At source measures, such as replacement of critical chemicals, reduction in raw material consumption should continue to be pursued as the top priority.

In-vitro permeability screening of melt extrudate formulations containing poorly water-soluble drug compounds using the phospholipid vesicle-based barrier

The phospholipid vesicle-based barrier has recently been introduced as an in-vitro permeation model mimicking gastro-epithelial barriers in terms of passive diffusion of drugs. The aim of this study was to investigate whether the phospholipid vesicle-based barrier was suitable for permeability screening of complex formulations such as solid dispersions. Solid dispersions containing the poorly water-soluble drugs HIV-PI 1 (log P=6.2, molar mass=628.80g/mol) and HIV-PI 2 (log P=5.3, molar mass=720.95g/mol), a hydrophilic polymer and different surfactants were tested with respect to their influence on integrity of the barrier in terms of electrical resistance and permeability for calcein. Furthermore, utilisation of a more biologically relevant medium, Hank's balanced salt solution supplemented with Mg(2+) - and Ca(2+) -ions (HBSS (Mg(2+) , Ca(2+) )), has been tested. Except for the polyoxyl 40 hydrogenated castor oil-containing solid dispersion, no influence on the phospholipid vesicle-based barrier could be observed from the tested samples. Presence of active pharmaceutical ingredients (APIs) in the solid dispersions led to the same results as the corresponding placebo results. First experiments analysing the passive diffusion of both APIs in HBSS (Mg(2+) , Ca(2+) ), evaluated as suitable transport medium, have shown promising results regarding the suitability of the phospholipid vesicle-based barrier for investigation of solid dispersions. The study indicated that the phospholipid vesicle-based barrier was compatible with selected melt extrudate formulations. The model seemed capable to reveal different transport routes in comparison with Caco-2 cell permeability tests.

Medications for Sexual Health Available from Non-Medical Sources: A Need for Increased Access to Healthcare and Education Among Immigrant Latinos in the Rural Southeastern USA

This study documented the types and quality of sexual health medications obtained by immigrant Latinos from non-medical sources. Samples of the medications were purchased from non-medical sources in the rural Southeast by trained native Spanish-speaking "buyers". Medications were screened the presence of active pharmaceutical ingredients using mass spectrometry. Eleven medications were purchased from tiendas and community members. Six were suggested to treat sexually transmitted diseases, one was to treat sexual dysfunction, one was to prevent pregnancy, and two were to assist in male-to-female transgender transition or maintenance. All medications contained the stated active ingredients. Findings suggest that medications are available from non-medical sources and may not be used as indicated. Interventions that target immigrant Latinos within their communities and rely on existing structures may be effective in reducing barriers to medical and healthcare services and increasing the proper use of medications to reduce potential harm.