Common Active Ingredients Research Articles

VALPARIN XR IN THE TREATMENT OF EPILEPSY (А REVIEW OF LITERATURE AND A DESCRIPTION OF CLINICAL CASES)

Although epileptologists have a lot of antiepileptic drugs (AEDs) at their disposal now and there are more than 10 novel AEDs; until the present time, two groups of drugs (valproic acid and carbamazepine, which were designed in the 1970s) have remained the gold standard for the treatment of epilepsy. These 2 AEDs are called traditional or standard and the European literature on epileptology describes them as first-choice anticonvulsants. Carbamazepine has a narrower spectrum of therapeutic action and may aggravate a few types of seizures. On the contrary, valproates are effective in all forms of epilepsy, both focal and generalized ones. The anticonvulsant properties of valproic acid were discovered in 1962. Now valproates are successfully used in various age groups of patients with different forms of epilepsy and types of seizures during both mono- and polytherapy in more than 100 countries of Europe and the world, by firmly holding the leading position. A lot of cheaper valproic acid generic drugs have emerged in clinical practice in the past decades. By and large, almost 20 valproates that have one common active ingredient (valproic acid) and are commonly used to treat epilepsy are now available on the global pharmaceutical market. The authors give the results of trials and describe their own experience with Valparin XR, an extended-release valproic acid drug. The results of the trials and clinical experience show the efficacy and good tolerability of Valparin XR in the treatment of epilepsy.

FDA Requests More Data on Antiseptics

The Food and Drug Administration has requested more scientific data on the safety and effectiveness of the active ingredients in antiseptic products used in hospitals, physician's offices, and other health care settings in a recently proposed rule. Alcohol and iodine are among the most common active ingredients in these products, which include hand washes and rubs, surgical hand scrubs and rubs, and preoperative skin preparations used on patients. These products are marketed under an over-the-counter drug monograph and are different than antibacterial soaps, hand sanitizers, and other consumer antiseptic products, which are not included in this proposed rule. To continue to market these products under the monograph, manufacturers must provide the FDA with more data on the safety and effectiveness of the active ingredients, including absorption, hormonal effects, and bacterial resistance, according to an FDA statement. “Emerging science” suggests that, for at least some active ingredients used in these products, “systemic exposure … is higher than previously thought, and existing data raise potential concerns about the effects of repeated daily human exposure to some antiseptic active ingredients,” the statement said. The agency “is particularly interested in gathering additional data on the long-term safety of daily, repeated exposure to these ingredients in the health care setting and on the use of these products by certain populations, including pregnant and breastfeeding health care workers, for which topical absorption of the active ingredients may be important.” The proposed rule is available at www.federalregister.gov. Public comments can be submitted until Oct. 27. Elizabeth Mechcatie is a reporter with Frontline Medical News.

Variability in Acetaminophen Labeling Practices: a Missed Opportunity to Enhance Patient Safety.

Confusion regarding a drug's active ingredient may lead to simultaneous use of multiple acetaminophen-containing prescriptions and increase the risk of unintentional overdose. The objective of this study was to examine prescription labeling practices for commonly prescribed acetaminophen-containing analgesics, specifically focusing on how active ingredient information and concomitant use warnings were conveyed. Patients with new acetaminophen-containing prescriptions were recruited upon discharge from an emergency department in Chicago or at an outpatient, hospital-based pharmacy in Atlanta. Label information was transcribed from prescription bottles and patients' knowledge of active ingredient was assessed by in-person interviews. Among the 245 acetaminophen-containing prescriptions, hydrocodone was the most common second active ingredient (n = 208, 84.8 %) followed by oxycodone (n = 28, 11.4 %). Acetaminophen was identified by its full name on 6.9 % (n = 17) of labels; various abbreviations were used in 93.1 % of cases. One hundred forty-seven bottles used auxiliary warning labels with the majority of labels (n = 130, 88.4 %) warning about maximum dose and 11.5 % (n = 17) about concomitant use. Most of the study participants (n = 177, 72.2 %) were not able to identify acetaminophen as an active ingredient in their prescription. There was no significant association between the use of unabbreviated labels including warning information and patients' awareness of acetaminophen as an active ingredient (36.4 vs. 27.3 %, p = 0.50). We noted high variability in labeling practices and warning information conveyed to patients receiving acetaminophen-containing prescriptions. Missed opportunities to adequately convey risk information may contribute to the burden of acetaminophen-related liver injury.

Formulation design for topical drug and nanoparticle treatment of skin disease.

The skin has evolved to resist the penetration of foreign substances and particles. Topical therapeutic and cosmeceutical delivery is a growing field founded on selectively overcoming this barrier. Both the biology of the skin and the nature of the formulation/active ingredient must be aligned for efficient transcutaneous delivery. This review discusses the biological changes in the skin barrier that occur with common dermatological conditions. This context is the foundation for the discussion of formulation strategies to improve penetration profiles of common active ingredients in dermatology. Finally, we compare and contrast those approaches to recent advances described in the research literature with an eye toward the future of topical formulation design.

Removal of polycyclic musks by anaerobic membrane bioreactor: Biodegradation, biosorption, and enantioselectivity

This study aims to investigate the performance of anaerobic membrane bioreactor (AnMBR) for removing five polycyclic musks (PCMs), which are common active ingredients of personal care and household cleaning products. A laboratory scale AnMBR system was used in this investigation. Concentrations of the PCMs in both the liquid and biosolids phase were measured to conduct a mass balance analysis and elucidate their fate during AnMBR treatment. The AnMBR was effective for removing PCMs from the aqueous phase by a combination of biotransformation and sorption onto the biosolids. However, biotransformation was observed to be the dominant removal mechanism for all five PCMs. Enantioselective analysis of the PCMs in influent, effluent and biomass samples indicated that there was negligible enantioselectivity in the removal of these PCMs. Accordingly, all enantiomers of these PCMs can be expected to be removed by AnMBR with similar efficiency.

Influence of Time of Assay on Behavioral Responses of Laboratory and Field Populations Aedes aegypti and Culex quinquefasciatus (Diptera: Culicidae) to DEET.

Knowledge on test conditions that may influence behavioral responses of mosquitoes is critical when excito-repellency tests are conducted. The objective of this study was to investigate the effect of test time differences on normal circadian activity and behavioral responses of field and colonized Aedes aegypti (L.) (=Stegomyia aegypti) and Culex quinquefasciatus Say to DEET, one of the most common synthetic repellent active ingredients available. Two field populations of Ae. aegypti and Cx. quinquefasciatus from Kanchanaburi and Nonthaburi provinces, respectively, and two long-standing laboratory populations, Ae. aegypti obtained from the U.S. Department of Agriculture, and Cx. quinquefasciatus from the Ministry of Public Health, Thailand, were used. Each population was exposed to DEET during two different periods of time (0900-1500 hours) and (2100-0300 hours). Both field and laboratory Cx. quinquefasciatus showed marked differences in spatial repellent escape responses between day and nighttime periods but none in direct contact tests. No significant differences between day and nighttime testing periods were observed with field or laboratory Ae. aegypti, except a higher daytime escape response from noncontact DEET treatment. This study indicates that test time may influence the behavioral avoidance responses and is a potential confounder of excito-repellency evaluations.

Potential neural mechanisms underlying the effectiveness of early intervention for children with autism spectrum disorder.

Although evidence supports the efficacy of early intervention for improving outcomes for children with autism spectrum disorder (ASD), the mechanisms underlying their effectiveness remain poorly understood. This paper reviews the research literature on the neural bases of the early core deficits in ASD and proposes three key features of early intervention related to the neural mechanisms that may contribute to its effectiveness in improving deficit areas. These features include (1) the early onset of intensive intervention which capitalizes on the experience-expectant plasticity of the immature brain, (2) the use of treatment strategies that address core deficits in social motivation through an emphasis on positive social engagement and arousal modulation, and (3) promotion of complex neural networks and connectivity through thematic, multi-sensory and multi-domain teaching approaches. Understanding the mechanisms of effective early intervention will enable us to identify common or foundational active ingredients for promoting optimal outcomes in children with ASD.

Evaluation of a Virucidal Quantitative Carrier Test for Surface Disinfectants

Surface disinfectants are part of broader preventive strategies preventing the transmission of bacteria, fungi and viruses in medical institutions. To evaluate their virucidal efficacy, these products must be tested with appropriate model viruses with different physico-chemical properties under conditions representing practical application in hospitals.The aim of this study was to evaluate a quantitative carrier assay. Furthermore, different putative model viruses like adenovirus type 5 (AdV-5) and different animal parvoviruses were evaluated with respect to their tenacity and practicability in laboratory handling. To evaluate the robustness of the method, some of the viruses were tested in parallel in different laboratories in a multi-center study. Different biocides, which are common active ingredients of surface disinfectants, were used in the test. After drying on stainless steel discs as the carrier, model viruses were exposed to different concentrations of three alcohols, peracetic acid (PAA) or glutaraldehyde (GDA), with a fixed exposure time of 5 minutes. Residual virus was determined after treatment by endpoint titration.All parvoviruses exhibited a similar stability with respect to GDA, while AdV-5 was more susceptible. For PAA, the porcine parvovirus was more sensitive than the other parvoviruses, and again, AdV-5 presented a higher susceptibility than the parvoviruses. All parvoviruses were resistant to alcohols, while AdV-5 was only stable when treated with 2-propanol. The analysis of the results of the multi-center study showed a high reproducibility of this test system.In conclusion, two viruses with different physico-chemical properties can be recommended as appropriate model viruses for the evaluation of the virucidal efficacy of surface disinfectants: AdV-5, which has a high clinical impact, and murine parvovirus (MVM) with the highest practicability among the parvoviruses tested.

Effects of subchronic exposure to N,N-diethyl-m-toluamide on selected biomarkers in common carp (Cyprinus carpio L.).

DEET (N,N-diethyl-m-toluamide) is the most common active ingredient in the insect repellents commonly detected in European groundwater. The aim of this study was to investigate the effect of subchronic DEET exposure on biochemical and haematological parameters, antioxidant enzymes, including catalase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase, and the amount of thiobarbituric acid reactive substances (TBARS) in common carp (Cyprinus carpio L.). Two specific proinflammatory and anti-inflammatory cytokine genes were selected to assess an immunological status of the fish. Fish were exposed for 28 days to three concentrations of DEET (1.0 µg/L, 0.1 mg/L, and 1.0 mg/L) where 1 µg/L is corresponding to the concentration found in the environment. DEET had a significant (P < 0.05) effect on increased RBC, decreased mean corpuscular volume (MCV), and mean corpuscular haemoglobin value (MCH) compared to control groups in the concentration of 1 mg/L. A significant decline (P < 0.05) in triacylglycerols (TAG) in plasma was found in the concentration of 1 mg/L compared to the control groups. The parameters of oxidative stress in tissues of common carp were weekly affected and immunological parameters were not affected.

Antimicrobial activity of commercial "antibacterial" handwashes and soaps.

Antimicrobial activity of commercial "antibacterial" handwashes and soaps.

Household organophosphorus pesticide use and Parkinson’s disease

Household pesticide use is widespread in the USA. Since the 1970s, organophosphorus chemicals (OPs) have been common active ingredients in these products. Parkinson's disease (PD) has been linked to pesticide exposures but little is known about the contributions of chronic exposures to household pesticides. Here we investigate whether long-term use of household pesticides, especially those containing OPs, increases the odds of PD. In a population-based case-control study, we assessed frequency of household pesticide use for 357 cases and 807 controls, relying on the California Department of Pesticide Regulation product label database to identify ingredients in reported household pesticide products and the Pesticide Action Network pesticide database of chemical ingredients. Using logistic regression we estimated the effects of household pesticide use. Frequent use of any household pesticide increased the odds of PD by 47% [odds ratio (OR)=1.47, (95% confidence interval (CI): 1.13, 1.92)]; frequent use of products containing OPs increased the odds of PD more strongly by 71% [OR=1.71, (95% CI: 1.21, 2.41)] and frequent organothiophosphate use almost doubled the odds of PD. Sensitivity analyses showed that estimated effects were independent of other pesticide exposures (ambient and occupational) and the largest odds ratios were estimated for frequent OP users who were carriers of the 192QQ paraoxonase genetic variant related to slower detoxification of OPs. We provide evidence that household use of OP pesticides is associated with an increased risk of developing PD.

Household Organophosphorus Pesticide Use and Parkinson's Disease

Background: Household pesticide use is widespread in the United States. Since the 1970s, organophosphorus chemicals (OPs) have been common active ingredients in these products. Parkinson’s disease (PD) has been linked to pesticide exposures but little is known about the contributions of chronic exposures to household pesticides. Aims: Investigate whether long-term use of household pesticides, especially those containing OPs, increases the odds of PD. Methods: In a population based case-control study, we assessed frequency of household pesticide use between ages 16-&lt;45 years for 357 cases and 807 controls relying on the California Department of Pesticide Regulation product label database to identify ingredients in reported household pesticide products and the Pesticide Action Network pesticide database of chemical ingredients. Using logistic regression we estimated the effects of household pesticide use. Results: Frequent use of any household pesticide increased the odds of PD by 39% [odds ratio (OR) =1.39 (95% confidence interval (CI): 1.06, 1.83)]; frequent use of products containing OPs increased the odds of PD more strongly by 82% [OR=1.82 (95% CI: 1.26, 2.63)] and frequent organothiophosphate use more than doubled the odds of PD. Sensitivity analyses showed that estimated effects were independent of other pesticide exposures (ambient and occupational) and the largest odds ratios were estimated for frequent OP users who were carriers of the 192QQ paraoxonase genetic variant related to slower detoxification of OPs. Conclusions: We provide evidence that household use of OP pesticides is associated with an increased risk of developing PD.

Efficacy of Commonly Used Disinfectants for Inactivation of Human Noroviruses and Their Surrogates

Human noroviruses (HuNoVs) are the most common cause of acute viral gastroenteritis worldwide and are a leading cause of foodborne disease. Their environmental persistence and purported resistance to disinfection undoubtedly contribute to their success as foodborne disease agents. The purpose of this study was to compare the efficacy of three commonly used disinfectant active ingredients against representative HuNoV strains and cultivable surrogates. Ethanol (50, 70, and 90%), sodium hypochlorite (5, 75, 250, 500, and 1,000 ppm), and a quaternary ammonium compound blend (at 0.1×, 1.0×, and 10× concentrations) were evaluated against two norovirus (NoV) genogroup II strains (GII.2 and GII.4) and two surrogates (feline calicivirus [FCV] and murine norovirus [MNV-1]). Virucidal suspension assays (30-s exposure) were conducted in accordance with ASTM International standard E-1052. Virus inactivation was quantified using reverse transcription quantitative PCR targeting the ORFI-ORFII junction (HuNoV), the RNA polymerase region (MNV-1), or the ORFI region (FCV); infectivity assays were also performed for MNV-1 and FCV. The two HuNoV strains and FCV were relatively resistant to ethanol (<0.5 log inactivation) irrespective of concentration, but MNV-1 was much more susceptible (log inactivation, ∼2.0 log at higher ethanol concentrations). Both HuNoV strains were more resistant to hypochlorite than were either of the animal surrogates, with the human strains requiring ≥500 ppm of hypochlorite to achieve statistically significant reduction (≥3.0 log) in virus concentration. All four viruses were resistant to inactivation (<0.5-log reduction) using the quaternary ammonium compound formulation at all concentrations tested. This study is novel in that it clearly demonstrates the relative ineffectiveness of common active disinfectant ingredients against HuNoV and highlights the fact that the cultivable surrogates do not always mimic HuNoV strains.

Forensic profiling of sassafras oils based on comprehensive two-dimensional gas chromatography

Safrole, the main compound in the essential oil of several plants of the Laurel family (Lauraceae), and its secondary product piperonylmethylketone are the predominantly used precursors for the illicit synthesis of 3,4-methylenedioxymethamphetamine (MDMA) which is, in turn, the most common active ingredient in Ecstasy tablets. Analytical methods with adequate capacity to identify links and origin of precursors, such as safrole, provide valuable information for drug-related police intelligence. Authentic sassafras oil samples from police seizures were subjected to comparative analysis based on their chemical profiles obtained by comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC–TOFMS). The enhanced separation power and increased sensitivity of GC×GC allowed for the detection of minor compounds present in the essential oils which were of particular interest in case of very pure samples whose impurity profiles were not very pronounced. Discrimination of such samples was still possible even in the absence of characteristic main compounds.

CONTRACEPTIVE VAGINAL SUPPOSITORY CONTAINING nONOXYNOL-9 AND ZINC ACETATE SALT IN A CLINICAL TRIAL

Nonoxynol-9 (N-9) is the most common active ingredient of spermicides. Spermicides containing N-9 are available in many forms, such as jelly, films, suppositories and foams. The two major problems reported on using N-9 spermicide were high failure and high irritation rates which were the main causes of its withdrawing from markets and as we know local methods of contraception (condoms and vaginal suppositories) have high acceptability especial in short term use. We tried to modify N-9 products in a new formula which is safe, and effective. The new preparation based on the addition of low concentrations of zinc acetate salt (Zn (OAC)2) to N-9 that reduce the irritation of mucous membranes on frequent use and increase the efficacy of N-9. The new preparation made in the form of vaginal foaming suppository. It was tested in-vitro and in-vivo. The in-vitro results show a significant increase in efficacy of the combination (Zn (OAC)2 &amp; N-9) than N-9 alone. Additionally, the in-vivo results indicated a significant decrease in failure and irritation rates in the combination than (N-9 alone) market suppository. Key words: Contraceptive, Nonoxynol-9, Zinc acetate, irritation and efficacy

“Bath Salts”–Induced Psychosis and Serotonin Toxicity

Article AbstractBecause this piece does not have an abstract, we have provided for your benefit the first 3 sentences of the full text."Bath salts" are a group of synthetic derivatives of cathinone, a naturally occurring psychostimulant found in khat plants. The most common active ingredients, mephedrone, methylenedioxypyrovalerone, and methylone, are found to have strong amphetamine-like psychoactive properties. Smoked, inhaled, injected, or ingested, they have a rapid onset of action of 30 to 60 minutes.

Healthcare Facility Effluents as Point Sources of Select Pharmaceuticals to Municipal Wastewater

Effluents from four healthcare facilities were characterized for the concentration of 16 common active pharmaceutical ingredients. The sampled facilities included a hospital, nursing care, assisted living, and independent living facility located within a single municipal wastewater system in Texas. Eleven of the 16 monitored pharmaceuticals were detected in at least 1 healthcare facility effluent and 2 measured antibiotics (sulfamethoxazole and trimethoprim) were detected in all 4 facility effluents. Active pharmaceutical ingredient concentrations ranged from non-detectable levels for several corticosteroids in all facility effluents to 180 microg/L sulfamethoxazole in the nursing care wastewater effluent. The mass of active pharmaceutical ingredients discharged to the municipality's wastewater conveyance system was determined by combining individual facility concentration data and daily wastewater flow. The estimated daily mass loading of all 16 pharmaceuticals ranged from 0.16 g/day to 23 g/day in the assisted living facility and nursing wastewater effluents, respectively. The combined active pharmaceutical ingredient mass loading for all four facilities was 42.6 g/day. These findings provide source characterization data for 16 common pharmaceuticals in healthcare facility wastewater and provide a basis for risk assessment of pharmaceuticals present in healthcare facility wastewaters.

High throughput quantitation of artesunate and its degradation products by flow injection gradient ratio standard addition mass spectrometry (FI-GRSA-MS)

There is a pressing need to equip post-marketing drug quality surveillance systems with higher throughput and robust analytical tools that can reinforce pharmaceutical quality control to ensure safety of patients and integrity of treatment practices. This manuscript reports the development of a flow injection analysis mass spectrometry-based gradient ratio standard addition (FI-GRSA-MS) method for quantification of artesunate, a common antimalarial active pharmaceutical ingredient in a simple, efficient, accurate, and high throughput manner. Dodecylamine (DDA) was evaluated as an electrospray modifier for improving the sensitivity of the GRSA quantitation method. The linear dynamic range and precision for artesunate quantification were found to be 7 ng to 86 pg artesunate and 2.1%, respectively. When compared to high performance liquid chromatography, results were found to be equivalent at the 95% confidence level. To identify chemical markers of improper drug storage and artesunate degradation, tablets were artificially exposed to heat for time periods ranging between 1 and 12 hours and the degradation products detected were identified via accurate mass and isotopic cluster abundance measurements. Moreover, degradation behavior of artesunate tablets from two different manufacturers under identical degradation conditions was investigated, indicating that tablet formulation plays a significant role in the shelf life of these valuable medicines.

Combining formulation and process aspects for optimizing the high-shear wet granulation of common drugs

The purpose of this research was to determine the effects of some important drug properties (such as particle size distribution, hygroscopicity and solubility) and process variables on the granule growth behaviour and final drug distribution in high shear wet granulation. Results have been analyzed in the light of widely accepted theories and some recently developed approaches. A mixture composed of drug, some excipients and a dry binder was processed using a lab-scale high-shear mixer. Three common active pharmaceutical ingredients (paracetamol, caffeine and acetylsalicylic acid) were used within the initial formulation. Drug load was 50% (on weight basis). Influences of drug particle properties (e.g. particle size and shape, hygroscopicity) on the granule growth behaviour were evaluated. Particle size distribution (PSD) and granule morphology were monitored during the entire process through sieve analysis and scanning electron microscope (SEM) image analysis. Resistance of the wet mass to mixing was furthermore measured using the impeller torque monitoring technique. The observed differences in the granule growth behaviour as well as the discrepancies between the actual and the ideal drug content in the final granules have been interpreted in terms of dimensionless quantity (spray flux number, bed penetration time) and related to torque measurements. Analysis highlighted the role of liquid distribution on the process. It was demonstrated that where the liquid penetration time was higher (e.g. paracetamol-based formulations), the liquid distribution was poorer leading to retarded granule growth and selective agglomeration. On the other hand where penetration time was lower (e.g. acetylsalicylic acid-based formulations), the growth was much faster but uniformity content problem arose because of the onset of crushing and layering phenomena.

Antimicrobial activity of medicated soaps commonly used by Dar es Salaam residents in Tanzania

An in vitro evaluation of the anti-microbial activity of medicated soaps was conducted using ditch-plate and hand washing techniques. Strains of reference microbes namely Candida albicans (ATCC90028), Staphylococcus aureus (ATCC25923), Pseudomonas aureginosa (ATCC27853) and Escherichia coli (ATCC25922) were tested at three different soaps’ concentrations (1.0, 4.0 and 8.0 mg/ml). A total of 16 medicated soaps were assayed for their antimicrobial efficacy. Of these, 13 were medicated and 3 non-medicated soaps, which served as control. Ciprofloxacin and ketaconazole were employed as positive controls. Label disclosure for the soaps’ ingredients and other relevant information were absorbed. The most common antimicrobial active ingredients were triclosan, trichloroxylenol and trichlorocarbanilide. ANOVA for means of zones of inhibition revealed variability of antimicrobial activity among the medicated soaps. Positive correlation (r=0.318; P<0.01) between zones of inhibition and soaps’ concentrations was evidenced. Hand washing frequencies positively correlated with microbial counts. Roberts® soap exhibited the largest zone of inhibition (34 mm) on S. aureus. Candida albicans was the least susceptible microbe. Regency® and Dalan® exhibited the least zone of inhibition on the tested bacteria. Protex®, Roberts®, Family® and Protector® were equally effective (P<0.01) against S. aureus. In conclusion, majority of the assayed medicated soaps have satisfactory antibacterial activity; though lack antifungal effect with exception of Linda® liquid soap. The hand washing technique has proved to be inappropriate for evaluation of soaps’ antimicrobial efficacy due to presence of the skin microflora.