Compatibility of Drotaverine Hydrochloride with Ibuprofen and Ketoprofen Nonsteroidal Anti-Inflammatory Drugs Mixtures

Formulations with two or more active pharmaceutical ingredients (APIs) are a researched trend due to their convenient use compared with multiple medications. Moreover, drug-drug combinations may have a synergistic effect. Drotaverine hydrochloride (D-HCl) is commonly used for its antispasmodic action. The combination of a spasmolytic and an analgesic drug such as ibuprofen (Ibu) or ketoprofen (Ket) could become the answer for the treatment of localized pain. D-HCl:Ibu and D-HCl:Ket drug-drug interactions leading to the formation of eutectic compositions with increased bioavailability, obtained by mechanosynthesis, a green, solvent-free method was explored for the first time. The compatibility of Ibuprofen, Ketoprofen, and Drotaverine Hydrochloride was investigated using differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier-Transform Infrared spectroscopy (FTIR). Solid-liquid equilibrium (SLE) phase diagrams for the binary systems of active pharmaceutical ingredients were developed and the Tammann diagrams were designed to determine the eutectic compositions. The excess thermodynamic functions G^E for the pre-, post-, and eutectic compositions were obtained using the computed activity coefficients data. Results show that drotaverine-based pharmaceutical forms for pain treatment may be obtained at 0.9 respectively 0.8 molar fractions of ibuprofen and ketoprofen which is advantageous because the maximum allowed daily dose of Ibu is about 6 times higher than those of D-HCl and Ket. The obtained eutectics may be a viable option for the treatment of pain associated with cancer therapy.     

The Difficult Task of Diagnosing Depression in Elderly People with Cancer: A Systematic Review

Background:Depression is a common psychiatric problem in the elderly and oncology patients. In elderly people with cancer, depression has a peculiar phenomenology. It has a significant impact on the quality of life. Moreover, it is associated with poor adherence to treatments, increased risk of suicide, and mortality. Nevertheless, the topic of depression in elderly people with cancer remains unexplored.Objective:The main goal of this article is to review the literature from the past 20 years on the relationships between depression, cancer, and aging.Methods:The methods followed the Prisma model for eligibility of studies. The articles in which the keywords “depression”, “cancer”, “ elderly, aging, or geriatric” were present, either in the text or in the abstract, were selected. 8.056 articles, by matching the keywords “depression and elderly and cancer,” were identified. Only 532 papers met the eligibility criteria of search limits and selection process. Out of 532 papers, 467 were considered irrelevant, leaving 65 relevant studies. Out of 65 suitable studies, 39 (60.0%) met our quality criteria and were included.Results:The risk factors associated with depression in elderly people with cancer can be divided into 4 groups: 1) tumor-related; 2) anticancer treatment-related; 3) patients-related; 4) number and type of comorbidity. The main obstacles in diagnosing depression in elderly patients with cancer are the overlap of the symptoms of cancer and side effects of treatment with the symptoms of depression but also the different ways of reporting depressive symptoms of elderly people and the different clinical types of depression. There is a lack of data regarding validated scales to assess depression in geriatric patients with cancer. Any mental illness, specifically co-occurring anxiety and depression, increases the risk of diagnosis delay and anticancer treatment adherence. Cancer and the diagnosis of mental disorders prior to cancer diagnosis correlate with an increased risk for suicide. A non-pharmacological therapeutic approach, pharmacological treatment and/or a combination of both can be used to treat elderly patients with cancer, but a detailed analysis of comorbidities and the assessment of polypharmacy is mandatory in order to avoid potential side-effects and interactions between antidepressants and the other drugs taken by the patients.Conclusion:Future research should be conducted with the aim of developing a modified and adapted assessment method for the diagnosis and treatment of depression in elderly people with cancer in order to improve their clinical outcomes and quality of life.     

Micro flow injection analysis of leucomalachite green in fish muscle using modified henequen fibers as microfluidic channels

In this work a simple and novel procedure for leucomalachite green determination based on micro flow injection analysis (μFIA) with amperometric detection is presented. The method involves the use of henequen modified fibers as microfluidic channels. The μFIA system proposed offers a simple, rapid, and low-cost alternative for the determination. Capillary and gravitational forces across the modified henequen fibers control the flow rate, eliminating the need for external pumps. This technique requires low reagent consumption and allows portability for in situ measurements. The flow system is described, and the operational variables were studied and optimized using a Taguchi parameters design to increase analytical sensitivity. Under optimal conditions a limit of detection of 1.16 μg kg⁻¹ was achieved with adequate repeatability and reproducibility (expressed as %RSD <5.0%, n = 3, n = 9 respectively) in all cases. The effect of interfering species and the accuracy of the method were also investigated. The proposed methodology was validated and applied to determine LMG in tilapia muscle samples.

In this work a simple and novel procedure for leucomalachite green determination based on micro flow injection analysis (μFIA) with amperometric detection is presented.     

A highly chlorinated xylene promoter for ethylene–propylene copolymerisation over a vanadium catalyst

The regularities of ethylene–propylene copolymerisation over a vanadium oxytrichloride (VOCl₃)–ethylaluminium sesquichloride (EASC) catalytic system in the presence of hexachloro-p-xylene (HCPX), tert-butyl chloride, trichlorotoluene, hexachlorocyclopentadiene, and trichloroacetate were studied. The main kinetic regularities of ethylene–propylene copolymerisation when using HCPX were determined and the kinetic parameters of the process were obtained. It was shown that hexachloro-p-xylene is the most efficient promoter of polymerisation that increases activity of the “vanadium” catalyst severalfold and enhances propylene reactivity in its copolymerisation with ethylene. A number of molecular characteristics and physicochemical parameters were determined for the synthesised samples of ethylene–propylene copolymers. The resulting copolymers have a higher molecular weight and a broad molecular weight distribution and are richer in propylene monomers compared to the copolymers synthesised in the catalytic system without HCPX. Modification of the “vanadium” catalyst yields the copolymer with a more homogeneous structure. Assumptions were made about the mechanism of action of the promoter under study in the VOCl₃–EASC catalytic system.

Hexachloro-p-xylene was found to be an effective promoter of olefin copolymerisation in the presence of vanadium catalyst, which increases the activity severalfold, enhances propylene incorporation in the copolymer, and results in a more homogeneous polymer.     

Supramolecular D⋯A-layered structures based on germanium complexes with 2,3-dihydroxynaphthalene and N,N′-bidentate ligands

The concept of using redox-active ligands, which has become extremely widespread in organometallic chemistry, is often considered from ‘their effect on the metal center properties’ point of view and ‘how to modify the ligands’. In this paper, we present the reverse side of this effective approach – a dramatic change of redox properties of ligands under the influence of a redox-inert metal. Germanium derivatives based on 2,3-dihydroxynaphthalene (1) and N,N′-bidentate ligands, namely 2,2′-bipyridine (2) and 1,10-phenanthroline (3), were obtained and characterized by CV, UV-vis spectroscopy, DFT calculations and in the case of 3 X-ray diffraction. It was shown that the HOMO of the complexes is almost completely located on the naphthalene fragment while the LUMO is on the N,N-ligands. At the same time, there are no boundary molecular orbitals on the germanium atom, but it forms the axial part of the molecule holding two opposite motifs together. Moreover, it sharply affects the level of HOMO and LUMO. Derivatives 2 and 3 are more easily oxidized compared to 2,3-dihydroxynaphthalene by 0.31–0.34 V (7–8 kcal mol⁻¹) and are more easily reduced compared to N,N-donors by 1.08–1.15 V (25–26.5 kcal mol⁻¹). All this together makes it possible to form a system with a narrow HOMO/LUMO gap (∼2 eV). The crystal structure of 3 consists of alternating monomolecular easily oxidizing and easily reducing layers formed due to intermolecular interactions, in particular π-stacking. In addition, in contrast to 1 that starts to decompose noticeably at the temperatures from 200 °C, 2 and 3 have an extremely high thermal stability. They remain stable with no signs of decomposition and melting up to 400 °С. We believe that this approach to the formation of the supramolecular structure may present prospects for obtaining new functional materials.

The concept of using redox-active ligands is often considered from ‘their effect on the metal center properties’ point of view. We present the reverse side of this approach – change of redox properties of ligands under the influence of metal.     

Morphological changes of the dorsal contour of the corpus callosum during the first two years of life

Background

In the medicolegal literature, focal concavities or notching of the corpus callosum has been thought to be associated with fetal alcohol spectrum disorders. Recent work suggests corpus callosum notching is a dynamic and normal anatomical feature, although it has not yet been defined in early life or infancy.

Objective

Our purpose was to characterize the dorsal contour of the corpus callosum during the first 2 years of life by defining the prevalence, onset and trajectory of notching on midsagittal T1-weighted images.

Materials and methods

We reviewed retrospectively 1,157 consecutive patients between birth and 2 years of age. Corpus callosum morphology was evaluated and described. A notch was defined as a dorsal concavity of at least 1 mm in depth along the dorsal surface of the corpus callosum. Patient age as well as notch depth, location, number and presence of the pericallosal artery in the notch were noted.

Results

Two hundred thirty-three notches were identified in 549 patients: 36 anterior, 194 posterior and 3 patients with undulations. A statistically significant (R²=0.53, Beta=0.021, P=0.002) positive correlation between posterior notch prevalence and age in months was noted. A positive correlation between age and depth of the posterior notch was also statistically significant (r=0.32, n=179, P≤0.001). A trend for increased anterior notch prevalence with age was identified with significant correlation between visualized pericallosal artery indentation and anterior notching (r=0.20, n=138, P=0.016). Sub-analysis of the first month of life showed corpus callosum notching was not present.

Conclusion

The presence of posterior notching increased significantly with age and was more frequent than that of anterior notching. Corpus callosum notching was absent in the first week of life, building on prior studies suggesting corpus callosum notching is acquired. This study provides baseline data on normative corpus callosum notching trajectories by age group during early life, a helpful correlate when associating corpus callosum morphology with disease.