Criteria Of Purity Research Articles

Evaluation and Standardization of RNA Extractions with Quality for RNA-Seq for Balamuthia mandrillaris

Balamuthia mandrillaris is a free-living amoeba (FLA) that causes granulomatous amebic encephalitis (GAE) and skin lesions. Transcriptomic analysis is a powerful tool used to study B. mandrillaris pathogenic infections. However, preliminary tests of RNA extraction showed poor results, so it has become essential to standardize a protocol for high-quality RNA. The present study evaluated 11 RNA extraction protocols based on three commercial kits by making modifications to the temperature and centrifugation times, and by combining kits. Four protocols, namely Q3 (based on QIAGEN RNeasy Mini Kit, with modifications in temperature and centrifugation times), T1 (Invitrogen TRIzol Reagent), T2 (combination of TRIzol and QIAGEN modified protocols) and T3 (combination of TRIzol and PROMEGA SV Total RNA Isolation protocols), presented RNA with good integrity and purity, except for the T1 protocol, which obtained an A260/230 value below the acceptable threshold. High RNA integrity (RIN) values were obtained with the Q3 (9.8), T2 (9.2), and T3 (8.9) protocols, while the T1 protocol obtained a lower RIN value (7.1). The Q3, T2, and T3 protocols obtained high-quality RNA from B. mandrillaris based on the criteria of integrity, purity, and concentration, where the implemented modifications and combinations raised the quality; thus, their use is recommended to obtain accurate results when performing transcriptomic analysis.

Three-zone simulated moving bed for the separation of chlorogenic acid and caffeine fractions in the liquid extract of spent coffee grounds

Spent Coffee Grounds (SCG) is an agricultural residue obtained in a large quantity from local cafes in Thailand. In order to handle this waste effectively, the valorization of SCG is essential. SCG consists of beneficial phenolic compounds with antioxidative properties and caffeine, which can be recovered through extraction followed by separation and purification processes. In this work, water extraction of SCG was carried out. The volumetric composition of the liquid extract of SCG was then adjusted with an organic solvent, and the obtained mixture was used as the feed for subsequent separation. For the separation method of the SCG extract, a single chromatographic column was employed to separate a group of phenolic compounds (represented by chlorogenic acid) and a group of contaminants (represented by caffeine). The volumetric composition of the mobile phase was varied to determine the condition suitable for the separation of chlorogenic acid and caffeine in a C18 column. Adsorption parameters were determined and used to formulate the mathematical models describing the adsorption dynamics of those two bioactive compounds in the experimental breakthrough curves of standard solutions and the liquid extract of SCG. Furthermore, the three-zone simulated moving bed system (TZ-SMB) was designed to continuously separate fractions of chlorogenic acid and caffeine in the liquid extract of SCG. The adsorption parameters were employed in the optimization of TZ-SMB operating conditions using triangle theory, conducted via computer simulation. The experimental result of water extraction revealed that the yields of chlorogenic acid and caffeine were 0.292 and 0.583 mg/g dried SCG, respectively, using solid-to-liquid ratio of 1 g: 30 mL and temperature of 75 °C. The separation result in a single chromatographic column showed that the mobile phase consisting of acetonitrile, water, and formic acid (10: 90: 1.5 vol%) provided the linear adsorption isotherms for both chlorogenic acid and caffeine, and the chromatographic peaks of all compounds in the liquid extract of SCG were well separated. The simulated results of TZ-SMB at the optimal point revealed that the flow rates of desorbent, feed, extract product, and raffinate product were 0.626, 0.115, 0.081, and 0.593 mL/min, respectively, with the switching time of 20 min. At this point, the relative purities of caffeine in the extract product and chlorogenic acid in the raffinate product were 99.45 % and 98.88 %, respectively, with the maximum productivity of 0.045 mg/mL⋅h. In addition, for demonstration purposes, the lab-scale TZ-SMB experiment was conducted to show the separation of chlorogenic acid and caffeine in the liquid extract of SCG. The operating point from the triangle separation region was chosen based on the sensitivity of flow rate that ensured the criteria of purity. The experimental results showed that the relative purities of caffeine in extract product and chlorogenic acid in raffinate product were both 100 %, verifying the successful separation.

Pharmacognostic and Preliminary Phytochemical Investigation of Clerodendrum thomsoniae Leaves

Clerodendrum thomsoniae (Lamiaceae) is an ornamental plant grown almost worldwide in humid environment. The phytocompounds present in plant protect the body from oxidative stress, brain disorders, skin rashes, sores and depression. Present study deals with to establish pharmacognostic, physiochemical and phytochemical standards of Clerodendrum thomsoniae leaves. Microscopical evaluation of Clerodendrum thomsoniae leaves showed the presence of covering trichomes, epidermis and other characteristics. Results of Clerodendrum thomsoniae leaves yielded 7.5% w/w total ash, alcohol extractive value not more than 23.33% w/w (Hot extraction), 21.66% w/w (Cold maceration) and water extractive value not more than 30.12% w/w (Hot extraction), 36.66% w/w (Cold maceration) and 8% w/w total moisture content by LOD. The Phytochemical investigation of extracts of Clerodendrum thomsoniae leaves shows the presence of sterols, triterpenes, alkaloids, flavonoids, tannins, glycosides, proteins and carbohydrate. Pharmacognostical and phytochemical parameters determined in the present work can serve as major criteria for identity, quality and purity of a crude drug and extracts.

Shor–Laflamme distributions of graph states and noise robustness of entanglement

The Shor–Laflamme distribution (SLD) of a quantum state is a collection of local unitary invariants that quantify k-body correlations. We show that the SLD of graph states can be derived by solving a graph-theoretical problem. In this way, the mean and variance of the SLD are obtained as simple functions of efficiently computable graph properties. Furthermore, this formulation enables us to derive closed expressions of SLDs for some graph state families. For cluster states, we observe that the SLD is very similar to a binomial distribution, and we argue that this property is typical for graph states in general. Finally, we derive an SLD-based entanglement criterion from the purity criterion and apply it to derive meaningful noise thresholds for entanglement. Our new entanglement criterion is easy to use and also applies to the case of higher-dimensional qudits. In the bigger picture, our results foster the understanding both of quantum error-correcting codes, where a closely related notion of SLDs plays an important role, and of the geometry of quantum states, where SLDs are known as sector length distributions.

Prediction of inotropic effect based on calcium transients in human iPSC-derived cardiomyocytes and machine learning

Functional changes to cardiomyocytes are undesirable during drug discovery and identifying the inotropic effects of compounds is hence necessary to decrease the risk of cardiovascular adverse effects in the clinic. Recently, approaches leveraging calcium transients in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been developed to detect contractility changes, induced by a variety of mechanisms early during drug discovery projects. Although these approaches have been able to provide some predictive ability, we hypothesised that using additional waveform parameters could offer improved insights, as well as predictivity. In this study, we derived 25 parameters from each calcium transient waveform and developed a modified Random Forest method to predict the inotropic effects of the compounds. In total annotated data for 48 compounds were available for modelling, out of which 31 were inotropes. The results show that the Random Forest model with a modified purity criterion performed slightly better than an unmodified algorithm in terms of the Area Under the Curve, giving values of 0.84 vs 0.81 in a cross-validation, and outperformed the ToxCast Pipeline model, for which the highest value was 0.76 when using the best-performing parameter, PW10. Our study hence demonstrates that more advanced parameters derived from waveforms, in combination with additional machine learning methods, provide improved predictivity of cardiovascular risk associated with inotropic effects.

MOS2/WS2/FINELPN COMPOSITE LAYERS – A NEW APPROACH TO LOW FRICTIONAL COATINGS FOR PISTON RINGS

In the search for alternative processes of technologically difficult and environmentally dangerous galvanic chromium coatings on cast iron piston rings, composite coatings of low-friction nanoparticles MoS2, WS2 and/or rGO embedded in a hard matrix of iron nitrides have been investigated. Laboratory tribological and operational tests on a real aircraft engine have been carried out to select the optimal technological parameters and microstructures of low frictional layers. A dry friction coefficient of 0.13 has been obtained for the best of the processes, i.e., four times lower than for raw reference samples (0.55). According to that technological option, the low-friction layers were produced for a set of rings for three cylinders of a Boxer aircraft engine and tested comparatively in an operational test with the rings in the other three cylinders. The experimental engine has passed the operational test obtaining the assumed power performance, fuel consumption and admission criteria of exhaust purity and oil purity.

Making Anti-CD19 CAR-T Cell Therapy Accessible and Affordable: First-in-Human Phase I Clinical Trial Experience from India

Background: Chimeric Antigen Receptor (CAR) T cells therapy has shown remarkable success in haematological malignancies. However, complexity of the manufacturing platform and exorbitant costs of the available therapy limits their accessibility in limited resource settings including India. Recently, we developed a novel humanized anti-CD19 CAR-T cell therapy (HCAR19) and showed its efficacy in preclinical models (Dwivedi et al, Mol Cancer Ther. 2021). Here we report our experience of HCAR19 manufacturing in an integrated platform for first-in-human Phase-I clinical trial. Further, we performed the cost analysis of CAR-T delivery from development to clinic. Methods: Lymphocytes were collected from 17 patients of r/r B cell malignancies (DLBCL, transformed follicular lymphoma, PMBCL and B-ALL) through apheresis (Fresenius Fomtek or Spectra Optia) upon receiving the regulatory approvals from central and local agencies. CD3+ T cells were enriched and activated using CTS™Dynabeads™ CD3/CD28 for 36-48 hours followed by consecutive double transduction with CD19 encoding lentivirus vector. Final product was harvested, cryopreserved and stored in ultra-low temperature until further use. All steps were carried out in closed gas permeable bags. Final product quality control (QC) assays were performed by flowcytometry, ELISA, analytical and cell-based assays. The cost of CAR T cell manufacturing was calculated for unit economics on fully scale production model by standard costing methodology. The final unit economics included cost of goods and services (COGS), overhead costs, financing costs of infrastructure, R&D and clinical trials costs. The model was scaled towards a 200 patient per annum in a centralized manufacturing facility. Results: Of the 19 patients enrolled in the study, only 17 patients underwent apheresis procedure for harvest of total 5-10 X 109 mononuclear cells. HCAR19 cells from all 17 patients were manufactured successfully in functionally closed integrated manufacturing platform. The required HCAR19 dose was achieved within 8 days of culture (dosage range: 1.78 x 106 - 17 x 106 viable HCAR19/kg). The transduction efficiency of HCAR19 in r/r DLBCL, r/r PMBCL and r/r B-ALL was 37.7 ± 6.64%, 28.8 ± 8.81% and 34.6 ± 9.72% (Mean ± SEM) respectively . The HCAR19 showed a robust expansion (~20-fold) ex vivo and maintained the presence of potent anti-tumor subsets like naïve and central memory T cells (Figure 1a). Final product from all 17 patients qualified the QC release criteria for safety, identity, purity and potency as per specifications. Finally, the unit economics in fully-scaled production model indicated the estimated cost of CAR-T cell delivery was approximately 30,000 USD (or 25,00,000 INR) per dosage including logistics, lentiviral vector cost and quality control (Figure 1b). The major costs incurred were towards consumables, overhead and financing costs of clinical trials and infrastructure. There was very minor components of logistics and utility costs. More importantly, the major contributors of overall low cost of CAR-T delivery in our settings were frugal R&D costs in an academic setting, scalable integrated manufacturing platform, and highly qualified yet economical manpower. Conclusions: We developed a robust, scalable and highly affordable CAR-T cell therapy platform (product and process development, and first-in-human clinical study), and proven its clinical delivery successfully with our first indigenous HCAR19 product. Given the benefit of affordable platform to broader socio-economic base of patients, the cell and gene therapy will be poised for a transformational change as a mass therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Pharmacognostical Standardization, Phytochemical Characteristics of Stem-bark of Zanthoxylum alatum Roxb

Pharmacognosy Research,2022,14,3,316-320.DOI:10.5530/pres.14.3.46Published:July 2022Type:Original ArticleAuthors:Nishant Kumar, Pooja Puri, Navdeep Kaur, Jasreen Uppal, Apporva Chawla, Monika, and Prince Ahad Mir Author(s) affiliations:Nishant Kumar1, Pooja Puri2, Navdeep Kaur3, Jasreen Uppal1, Apporva Chawla1, Monika3, Prince Ahad Mir1,* 1Khalsa College of Pharmacy, GT Road, Amritsar, Punjab, INDIA. 2Pharmacy Officer, Community Health Center (Punjab Govt.), Kairon, Punjab, INDIA. 3Amritsar College of Pharmacy, Amritsar-Jalandhar GT Road, Manawal, Amritsar, Punjab, INDIA. 4University Institute of Pharmaceutical Sciences and Research, BFUHS, Faridkot, Punjab, INDIA. Abstract:Background: Zanthoxylum alatum Roxb (ZA) also known as ‘Indian Prickly Ash’ is a member of the Rutaceae family. It is native to the Himalayas, Jammu and Kashmir, Andhra Pradesh, and various other parts of India and is an important medicinal plant species. The stem bark of the plant is known to be a particularly rich source of medicinal compounds, and it is frequently utilized as an anti-diabetic, antioxidant, and anti-inflammatory agent. Despite the high therapeutic efficacy of bark, nothing is known about the requirements for its standardization. Since the quality control and standardization qualities of the product must be thoroughly documented, of the stem bark of Zanthoxylum alatum Roxb was produced as a result of the current research, which may be seen here. As part of this research, the stem bark of Z. alatum was harvested, dried in the shade, and then pulverised. The establishment of pharmacognostical standards was accomplished via the use of techniques such as microand macroscopy, physicochemical parameters, extractive values, and fluorescence analysis. Results: There were numerous distinguishing traits in the stem bark of Z. alatum Roxb that were discovered using macroscopic, microscopic, and physical-chemical criteria. Conclusion: This is the first research to provide a comprehensive pharmacognostic profile of the stem bark of Z. alatum Roxb, and it will be a helpful source of information in the development of pharmacognostic criteria for identification, purity, quality, and categorization of Z. alatum Roxb stem bark. Keywords:Indian Prickly Ash, Microscopical features, Phytochemical screening., Standardization, Zanthoxylum alatumView:PDF (235.01 KB)

Selection of recycled waste plastic for incorporation in sustainable asphalt pavements: A novel multi-criteria screening tool based on 31 sources of plastic

This study investigated the suitability of 31 recycled waste plastic samples obtained from 15 major recycling companies across Australia and New Zealand to be used as bitumen/asphalt modifiers. The plastics have been selected to be representative of recycled waste plastic around Australia and New Zealand. The recycled waste plastics belonged to either the post-industrial or post-consumer collection scheme. A new classification scheme was developed to rank each recycled waste plastic based on their chemical and physical properties against those of bitumen/asphalt. Specifically, density, polarity, melting point, solubility and melt flow index of the samples as well as the presence of contaminants, fillers and additives were analyzed for each recycled waste plastic material and their virgin counterpart. These 8 properties were used to rank various sources of recycled low-density poly(ethylene), linear low-density poly(ethylene), high density poly(ethylene) and poly(propylene) in addition to commingled plastics based on their suitability for bitumen modification (wet method). The modification of asphalt via replacement of virgin quarry aggregate with plastic aggregate (dry method) by recycled acrylonitrile butadiene styrene and poly(ethylene terephthalate) was also assessed by considering four criteria of purity, polarity, recycling contamination and hazardous additives. This new multi-criterion ranking approach revealed that low-density and linear low-density poly(ethylene) and acrylonitrile butadiene styrene and poly(ethylene terephthalate) should be preferentially used as bitumen/asphalt modifiers. This tool has been developed for recycling companies and bitumen/asphalt contractors to determine the suitability of recycled waste plastics within asphalt roads by a series of experimental techniques.

Language policy in the Kingdom of Prussia at the junction of the 18th-19th centuries

The present paper examines the principles of the language policy designed in the Kingdom of Prussia at the junction of the 18th-19th centuries. This research aims to identify the main factors affecting the introduction of the Lithuanian language as the official regional language in the Kingdom of Prussia and to evaluate the parameters applied to such language planning. The main research objects in this study are the prefaces to Christian Gottlieb Mielcke’s dictionary Littauisch-deutsches und Deutsch-littauisches Wörter-Buch (1800) and the archival material of the end of the 18th century, which provide information on the preconditions, directions, goals, and objectives of the language policy of the time.The politics favorable to the Lithuanian language was preconditioned by the political changes in the 18th century. After the third partition of the Commonwealth of the Two Nations (1795) and with the annexation of Užnemunė to Prussia, the range of the Lithuanian language use expanded, and the ideas of regional particularism strengthened.Christoph Friedrich Heilsberg, the author of the third preface to Mielcke’s dictionary, a counsellor in the Königsberg Chamber of War and Domains, and an inspector of East Prussian schools, was well aware of the Lithuanian attitudes to the influence of language on identity, motives for language learning, legislation, and the potential of schools and churches. On the grounds of this versatile expertise, he undertook language status planning.With regards to Mielcke’s observation about civil servants who need to learn Lithuanian and the Lithuanian approach to language, Heilsberg took a practical position on language planning. He suggested expanding the Lithuanian language use in the public sphere rather than considering the idea of German as a common state language. At Heilsberg’s initiative, the Lithuanian language had to be used in such important areas as education, church, law, business, and administration. Heilsberg sought to ensure that it did not lose its cultural or administrative functions. Such plans presuppose the status of Lithuanian as an official regional language, equivalent to linguistic autonomy, where the language of a national minority has political autonomy and coexists with the official language of the state.Heilsberg initiated not only the development but also the implementation of language policy. He developed the directions and measures of corpus planning: to help non-Lithuanians to learn Lithuanian, he encouraged Mielcke to prepare a Lithuanian-German and German-Lithuanian dictionary and supervised the publication of a Lithuanian grammar and a collection of sermons. This highlights the priorities of his education policy, which aimed to develop the language skills of teachers and priests, and to create conditions for civil servants working in the province to learn the Lithuanian language.Three statements of Heilsberg as a high-ranking state official were important for increasing the prestige of the Lithuanian language: 1) language is a guarantor of identity; 2) provincial languages must be learned by civil servants and not vice versa; and 3) language must be nurtured.The author of the fourth preface to Mielcke’s dictionary, the German philosopher Immanuel Kant, raised the criterion of language purity. Considering that only pure language is important for the maintenance of the nation’s distinctiveness, for science, and especially history, he emphasized the need to preserve the purity of language and proposed two ways to achieve this: to use pure language in schools and churches, and to expand the domains of its use.This is the earliest attempt in the history of Prussian Lithuanian culture to give the Lithuanian language the status of an official regional language. Such policy ensured its functioning in all spheres of public life, its use in the education system, and created conditions for maintaining identity.

IsabelWilkersonCaste: The Origins of Our DiscontentsRandom House, 2020. 496 p. $32.00

IsabelWilkersonCaste: The Origins of Our DiscontentsRandom House, 2020. 496 p. $32.00

Bacteriophages as Therapeutic Agents: Alternatives to Antibiotics.

Bacteriophages are bacterio-specific viruses that constitute the main portion of the environment. Bacteriophages inject their genome into the targeted bacterial cells and some of them can disrupt the metabolism of bacteria and cause bacterial cell disintegration. The application of bacteriophages to kill bacteria is known as bacteriophage therapy. Since bacteriophages target bacteria and are strain-specific, every bacteriophage/bacterial host pair is unique. They are believed to cause no harm to humans. An additional advantage of the strain-specific nature of bacteriophages is that they do not disrupt the beneficial natural flora in the body. Bacteriophage therapy in the West is not a recognized medicine at this time, and no products are registered. Some clinicians are turning to bacteriophage therapy for the treatment of antibiotic-resistant infections. Lack of adverse effects makes bacteriophage therapy ideal for use. Funding research, media attention, and the increased publication of articles helped in a widespread understanding of its therapeutic potential. The first prerequisite for the use of bacteriophage therapy is simply the availability of bacteriophages for treatment, which is often complicated at this stage of bacteriophage production. This includes providing access to all biologically active bacteriophages against the bacterial isolate of the patient and meeting regulatory criteria of purity, traceability, and characterization. A monophage preparation, which is a single bacteriophage, or a phage cocktail, which consists of a number of combined bacteriophages against one or more bacterial species may be used. Accordingly, the antibiotic resistance crisis brought back bacteriophage therapy as a potential complementary or alternative treatment. Bacteriophages are promising cheap antibacterials.

Innovative methodologies for identification and qualification of Impurities: An overview of the latest trends on impurity profiling

Impurity profiling is known to identify, classify and measure both the identified and non-identified contamination present on the medicinal product. Unwanted chemicals which remain or are created during the formulation of medicinal products are pharmaceutical impurities. Impurity profiling helps in the detection, recognition and quantification in bulk products and pharmaceutical formulations of various types of impurities, as well as residual solvents. It is the simplest way to distinguish consistency and stability of bulk drugs and medication formulations. As analytical methodology has developed rapidly, it is essential to consider with their solutions problems related to impurities of drug substances and drug products. Various regulatory agencies including ICH, USFDA, Canadian Drug and Health Agencies stress the criteria for purity and for detecting impurities in active pharmaceutical materials, even in small quantities, as the presence of impurities, may have an effect on pharmaceutical products ’ efficacy and health. Therefore, the study focuses on various analytical methods for identification and quantification of impurities in pharmaceutical products to clarify the need for impurity profiling on drug products in pharmaceutical research. To drug regulators, the product substance’s impurity profile is a reliable fingerprint to prove that the manufacturing process of bulk drug substances is consistent in quality. The study gives a short summary of recent technical developments in the profiling of pharmaceutical products including pharmaceutical active ingredients as well as pharmaceutical products during 2013-2017. Such recent trends in the profiling of impurities have been addressed in the study. This focuses specifically on a thorough update on various analytical techniques, including hyphenated methods to define and measure thresholds in specific pharmaceutical matrices of impurities and degradants.

Control of the Synthesis and Composition of Semiconductors. Low-Defect Silicon Carbide and Low-Dimensional Cadmium Selenide

The details of the controlled synthesis and basic performances determining the properties of the semiconductor substances—composition, structure, size and morphology of the particles forming them—were discussed. The nontrivial, but important for the functional use of semiconductors, criteria of purity and homogeneity were expressed. The noted details of the materiology of semiconductors were discussed with the example of the synthesis of low-defect wafers of silicon carbide, and also low-dimensional powders of cadmium selenide.

Управление синтезом и составом полупроводников. Малодефектный карбид кремния и низкоразмерный селенид кадмия

Abstract The details of the controlled synthesis and basic performances determining the properties of the semiconductor substances—composition, structure, size and morphology of the particles forming them—were discussed. The nontrivial, but important for the functional use of semiconductors, criteria of purity and homogeneity were expressed. The noted details of the materiology of semiconductors were discussed with the example of the synthesis of low-defect wafers of silicon carbide, and also low-dimensional powders of cadmium selenide.

Trace Arsenic Determination in a TiO2 Pigment Matrix Using Electrothermal Atomic Absorption Spectrometry.

This work describes the use of electrothermal atomic absorption spectrometry in combination with a pyrolytic graphite-coated tube with a platform for trace arsenic (As) determination in titanium dioxide (TiO2) pigment. This type of matrix is challenging, as complete digestion in hydrofluoric acid-containing solution is needed. First, closed-vessel microwave digestion was performed for the full-sample decomposition. Next, a temperature program was optimized for drying, pyrolysis, and atomization temperatures. Furthermore, the use of a chemical modifier mixture was proposed that reduced the background contribution and prevented significant analyte loss and therefore improved the analytical procedure. The optimized method was validated for the detection (LOD) and quantification (LOQ) limits, the linear concentration range, accuracy, and precision. Special attention was devoted to the matrix-matching solutions in the calibration procedure. Linearity was confirmed in the 5.0 to 100.0 µg/L concentration range (R2 = 0.999). The average recovery for 16 different real TiO2 pigment samples was 92.0%, and the relative standard deviation value for six replicate measurements was ≤10.4%. Moreover, the LOD and LOQ in terms of the TiO2 pigment mass was determined to be 0.2 µg/(g TiO2) and 0.7 µg/(g TiO2), respectively. The latter complies with Commission Directive 2008/128/EC, which does not allow more than 3 µg As/(g product) as the specific criteria of purity. Finally, based on scanning electron microscopy analysis of unused and several times used pyrolytic graphite-coated tubes, usage of the tube 250 times before replacement is recommended.

60]Fullerene for Medicinal Purposes, A Purity Criterion towards Regulatory Considerations.

Since the early nineties countless publications have reported promising medicinal applications for [60]fullerene (C60) related to its unparalleled affinity towards free radicals. Yet, until now no officially approved C60-based drug has reached the market, notably because of the alleged dangers of C60. Nevertheless, since the publication of the effects of C60 on the lifespan of rodents, a myriad of companies started selling C60 worldwide for human consumption without any approved clinical trial. Nowadays, several independent teams have confirmed the safety of pure C60 while demonstrating that previously observed toxicity was due to impurities present in the used samples. However, a purity criterion for C60 samples is still lacking and there are no regulatory recommendations on this subject. In order to avoid a public health issue and for regulatory considerations, a quality-testing strategy is urgently needed. Here we have evaluated several analytical tools to verify the purity of commercially available C60 samples. Our data clearly show that differential scanning calorimetry is the best candidate to establish a purity criterion based on the sc-fcc transition of a C60 sample (Tonset ≥ 258 K, ∆sc-fccH ≥ 8 J g−1).

Challenges in the quality of herbal medicinal products with a specific focus on contaminants.

The complex regulatory framework for the quality of herbal medicinal products, in particular with regard to potential contaminants, consists of legal provisions including Pharmacopoeia requirements, relating to limits as well as in most cases to methods for determination. This review intends to provide an overview on the legal requirements for testing potential contaminants in herbal drugs used for the production of herbal medicinal products. The following issues are described and discussed: For the assessment of pesticide residues, Chapter 2.8.13 of the European Pharmacopoeia and Regulation (EC) 396/2005 applies, for heavy metals the general Pharmacopoeia monograph as well as the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q3D guideline on elemental impurities. The Pharmacopoeia also includes limits and acceptance criteria for microbiological purity and aflatoxins, respectively. Polycyclic aromatic hydrocarbons are mentioned in Regulation (EC) 1881/2006 for food as well as in a Reflection Paper on herbal medicinal products. For several years, a potential contamination with pyrrolizidine alkaloids was discussed which led to measures being imposed on industry and health authorities. Various examples demonstrate that the evaluation of data from daily analytical practice is extremely useful to gain an overview on the occurrence of residues and/or contaminants in herbal drugs and herbal preparations. Such evaluations might assist manufacturers in their individual risk assessment and the definition of their testing strategies and contribute to guarantee the quality and safety of the marketed products. Annual data evaluations demonstrate that a remarkable decrease of the pyrrolizidine alkaloid content burden in herbal drugs and extracts used for the production of herbal medicinal products has been achieved over the past few years. However, it has also become clear that this issue cannot be completely solved in the near future.

Analysis and modelling of the regeneration process of chemical solutions after brewing equipment cleaning in a Cleaning in Place system based on changes in turbidity

Abstract The study presents the results of an analysis concerning the impact of temperature on the regeneration of the cleaning solution after cleaning the installations of a brewery in a Cleaning in Place system and based on the obtained results optimize the process of chemical solutions regeneration. The solutions were collected from a production plant after the process of cleaning and subjected to 12-h sedimentation. During the sedimentation process in different temperatures, the changes in turbidity were determined, as this represents a purity criterion for chemical solutions. The results were subjected to statistical analysis. The standard deviations of the dispersion in relation to the obtained averages were determined and Tukey's multiple comparisons test was used to identify the significance of the influence of temperature on the purity of the final solution. Based on the obtained results, a non-linear regression model was developed which constituted a mathematical description of the process of sedimentation of chemical solutions after the process of cleaning brewing installations M = f(t,T). The exponential function was assumed to describe the regeneration process. Numerical calculations were carried out based on the nonlinear least squares method using the Gauss-Newton algorithm. Finally, the surface area of the response of the relationship between the time and temperature of sedimentation and the turbidity of solutions was designated. The research results indicated that an appropriate temperature of chemical solutions during their regeneration can significantly influence their final purity degree and the duration of the regeneration process. In the case of sodium hydroxide after cleaning of mash filter, its regeneration is preferably carried out at a temperature below 40 °C, whereas in the case of sodium hydroxide after cleaning of the vessels a temperature of above 50 °C is desirable. Statistical analysis also showed that an acidic solution is best regenerated at 50 °C.

Development DEVELOPMENT AND VALIDATION OF NOVEL ULTRAVIOLET SPECTROPHOTOMETRIC METHOD FOR QUANTITATIVE ESTIMATION OF DALFAMPRIDINE IN BULK AND IN PHARMACEUTICAL FORMULATION

Objective: The objective of the present study is to develop ultraviolet (UV)-spectroscopic method using pure drug and tablet dosage form that consistently produces a drug with a minimal variation that adheres to quality criteria of purity, identity, and potency.
 Methods: UV-spectrophotometric method has been developed using a solvent composed of methanol:water (30:70) as a diluent to determine the dalfampridine (DFP) content in bulk and pharmaceutical dosage form at predetermined λmax of 262 nm.
 Results: It was proved linear in the range of 02–12 μg/ml and exhibited a good correlation coefficient (r2 = 0.9915) and excellent mean recovery (0.004136347%). This method was successfully applied to the determination of DFP content of marketed tablet Dalstep 10 mg (Sun Pharmaceutical Pvt. Ltd.,) from India; the results were in good agreement with the label claims.
 Conclusion: The method proved to be simple, accurate, precise, specific, robust, and less time consuming and can be applied for the determination of DFP in bulk and marketed formulation.