M{\o}ller's Energy in the Kantowski-Sachs Space-time

We present a counter example to paper \cite{P71} and show that the result obtained is correct for a class of metric but not general. We calculate the total energy of the Kantowski-Sachs space-time by using the energy-momentum definitions of M{\o}ller in the theory of general relativity and the tetrad theory of gravity.Comment: 7 pages and no figure

Revisiting the Light Cone of the Goedel Universe

The structure of a light cone in the Goedel universe is studied. We derive the intrinsic cone metric, calculate the rotation coefficients of the ray congruence forming the cone, determine local differential invariants up to second order, describe the crossover (keel) singularities and give a first discussion of its focal points. Contrary to many rotation coefficients, some inner differential invariants attain simple finite standard values at focal singularities.Comment: 23 pages, 3 figures, iopar

On the Singularities of Reissner-Nordstr\"{o}m Space-Time

It is shown that if two Reissner-Nordstr\"{o}m space-times, both with the same mass m and charge e, glued together in the singularities, then the light ray in black hole of the first space-time can go continuously through the singularity into black hole of the second. The behavior of tidal forces near the Reissner-Nordstr\"{o}m space-time singularity is examined by considering what happens between two particles falling freely towards the singularity.Comment: Latex, 4 figures, 11 page

DEVELOPMENT AND VALIDATION OF HPLC METHOD FOR THE SIMULTANEOUS DETERMINATION OF ENALAPRIL MALEATE IN PRESENT OF THEIR IMPURITIES: APPLICATION TO TABLET ANALYSIS

Objective: A simple, rapid, economical, and highly sensitive stability-indicating HPLC method was developed and fully validated for determination of enalapril maleate in presence of its related substances namely enalaprilat dihydrate and diketopiperazine.Methods: Chromatographic separation was achieved on Grace Platinumр C8 EPS column (4.6 mm i.d. X 250 mm, 5 μm) at room temperature. The mobile phase consisted of acetonitrile: 20 mmol phosphate buffer adjusted to pH 2.2 (25:75 v/v) isocratically pumped at a flow rate 2 ml/min and UV-detection was monitored at 215 nm.Results: The proposed method was validated according to ICH guidelines with total run time less than 9 min. The correlation coefficient (r2) was noted as 0.99981 which states that the method was good linear to the concentration versus peak area responses. The developed method found to be high sensitivity with LOD and LOQ of 0.021 and 0.062 %; respectively. The developed, validated method was successfully applied for the determination of enalapril maleate in presence of their impurities in tablet dosage form.Conclusion: A rapid, economical, simple and sensitive HPLC method was developed and validated for the determination of enalapril maleate in tablet dosage form in presence of their impurities. The developed method can help research studies, quality control and routine analysis with lesser resources available. Therefore, the proposed validated method is fast and reliable and can be used for routine quantitative analysis as well as quality control of enalapril maleate in pharmaceutical formulation

ASSOCIATION OF OBESITY WITH RS1421085 AND RS9939609 POLYMORPHISMS OF FTO GENE WITH T2DM IN EGYPTIAN FEMALES

Objective: Obesity has been described as a worldwide increasing health problem and risk factor of various disorders including type 2 diabetes mellitus (T2DM). So, our study aim to determine of common variants of fat mass and obesity associated gene polymorphisms rs1421085 and rs 9939609; confers risk of obesity and type 2 diabetic mellitus in Egyptian females.Methods: In this population rs1421085 and rs9939609 polymorphisms of fat mass and obesity (FTO) gene were genotyped in 105 obese patients and 100 healthy controls with ages 14-60 y were collected from Medicine Specialized Hospital, Mansoura University, Egypt during the period between Jul.-Oct. 2016, genotyping of SNPs was performed by restriction fragment length polymorphism (RFLP) assay, fasting blood glucose, homeostasis model assessment of insulin resistance (HOMA IR), body mass index (BMI), waist-to-hip ratio (WHR) lipid profile was determined.Results: There was the significantly higher frequency of the AA compared to controls p=0.0001) of genotypers9939609. Also, cases have shown a significantly higher frequency of the C allele, p<0.00001) of rs1421085 genotype polymorphisms increased the risks of obesity. On the other hand, there were no significant correlations between genotypes and obesity-related (anthropometric body composition) parameters. Only the fasting blood glucose was significantly higher in the TA p=0.004).Conclusion: The FTO rs9939609 and rs1421085 single nucleotide polymorphisms (SNPs) was associated with increased risk of obesity in type 2 diabetic populations on Egyptian females

Enhancement Reinforcing Concrete Beams Using Polypropylene Cord-Knitted Bars

Currently, technical fabrics play a major role in many industries due to their multiple characteristics. The aim of this research was to utilize composite knitted bars to reinforce concrete beams. Six cord-knitted samples with two different polypropylene yarn counts (outer layer) and three different core materials were manufactured and immersed in a local epoxy material (Kemapoxy 150). Composite knitted bars were prepared in this way. Several tests were conducted for fabrics and knitted bar samples. All data were collected and analysed using two different tools: ANOVA test and radar chart area. Finally, three concrete beams with a varying number of cord-knitted bars (one bar, two bars and three bars) were produced. The results indicated that the differences in outer and core yarns for cord-knitted samples have a significant effect on several fabric and bar characteristics. The knitted bars with PP core yarn can be more beneficial for concrete that do does not require high stress, while the knitted bars using glass fibres and polypropylene (50% and 50% PE) as core materials are not appropriate for applications that require more flexibility and extensibility. Reinforced concrete beams were improved significantly with cord-knitted bars, taking into account the number of bars per area, which may cause the minimizing of flexure force through an increase in that number of bars per area

HPLC METHOD DEVELOPMENT FOR THE ANALYSIS OF BISOPROLOL IN COMBINED DOSAGE FORM CONTAINING BISOPROLOL AND ENALAPRIL AND IN VITRO DISSOLUTION STUDIED

Objective: A simple, rapid and reproducible HPLC method was developed for the determination of bisoprolol in experimental combined dosage forms containing bisoprolol and enalapril and for drug dissolution studies. Methods: A C18 column (Hi Qsil C18, 5 μm, 4.6х250 mm) and a mobile phase methanol: phosphate buffer solution (65:35, v/v) mixture were used for separation and quantification. Analyses were run at a flow rate of 1.0 ml/min and at ambient temperature. The injection volume was 300 μL and the ultraviolet detector was set at 225 nm. The method was validated as per ICH guidelines. Results: Under these conditions, bisoprolol was eluted at 4.75 min. Total run time was shorter than 6 min. A linear relationship between the concentration and the area of ​​chromatographic peaks of bisoprolol in the range of 0.625 mg/ml-5.000 mg/ml (3.750 mg/ml at pH 1.2) has been established. In the medium with pH 1.2 release of bisoprolol from tablets in 5 min is 38.42%, and after 15 min-85.51%, in medium with pH 4.5 the release of bisoprolol from tablets in 5 min makes 59.78%, and after 15 min-103.71%; in a medium with pH 6.8, the release of bisoprolol from tablets in 5 min is 61.29%, and after 15 min-85.90%. Conclusion: The developed method was applied successfully for quality control assay of bisoprolol in experimental tablets and in vitro dissolution studies

Biosimilars: Review of regulatory, manufacturing, analytical aspects and beyond

Biologics have more complex production processes compared to small-molecule drugs. They may even prove labile when drifting from batch-to-batch or in different production locations. The development of new similar biological product was regulated early to face the relevant challenges of this industry. As a result, since 2006 biosimilars were introduced to biotechnology arena with a massive competition in pharmaceutical industry. In this review, the aspects related to similarity testing of biosimilars to the original biological products are discussed involving manufacturing challenges to ensure the quality, safety, and efficacy of these products to the patient health. Immunogenicity studies are highlighted as an important part of the safety assessments. Additionally, several analytical methods that are usually used to evaluate biosimilars in comparison to their reference biologic are summarized and categorized in terms of the intended physicochemical and biological characterization. On the other hand, the international efforts of several regulatory agencies including the European Medicines Agency, World Health Organization and United States Food and Drug Administration for biosimilar development are discussed according to updated revised guidelines