Development and validation of the method for simultaneous determination of benzydamine hydrochloride and methylparaben in benzydamine dosage form by GC

Introduction: Modern analytical chemistry is heading to the side of the “Green Chemistry” approach. The implementation of the current approach is in the development of fast analytical methods that combine the determination of several compounds with the utilization of methods that do not generate wastes of organic solvents.  Aim: The aim of the current work was to develop a method for the simultaneous determination of benzydamine hydrochloride (API) and methyl parahydroxybenzoate (preservative) in the dosage form.Materials and Methods: The development and validation of the proposed methodology were carried out.Results and Discussion: The validation parameters were determined; it was shown that the technique is robust, specific to determinable analytes.Conclusion: The developed technique can be used in control laboratories for the simultaneous determination of benzydamine hydrochloride and methyl parahydroxybenzoate in the finished dosage form of benzydamine

Risk assessment of manufacturing and usage of test systems for quality control of compounded preparations

Introduction: The development and implementation of test systems in pharmacy practice could be one of the ways of optimization of the quality control of compounded preparations. Test kits, which have been manufactured in a pharmacy, are simple, cheap and effective for the quality control of a wide range of pharmaceutical preparations. Guidelines for quality must be taken into account during the production of such test kits to enable a pharmacist-analyst to fully perform his tasks using these analytical tools.The aim of the work is to analyze the risks that may occur during the lifecycle of test systems; to establish the risks that have the biggest impact on quality control of compounded preparations with these analytical tools and to determine the major ways to minimize the impact of risks at all stages of work with test systems.Materials and Methods: Ishikawa diagrams and Failure Mode, Effects and Criticality Analysis (FMECA) were used to analyze the risks during the lifecycle of test systems. Data were received through `brainstorming session` and questioning respondents that were related to the development and practical use of these analytical tools.Results: According to the results Risk Priority Number (RPN) for each of the stages of the lifecycle of the test systems has been calculated. The highest values of RPN are observed at the stages of manufacturing of the test systems (54.95%), the quality control (21.93%) and the use of the test systems (18.66 %). Each of the stages of the lifecycle of the test system consists of a number of phases; the most important among them are: preparation of the reagent solution - 20.24%; chemical analysis - 17.93%; visual fixation of results - 9.21% and training of the personnel - 8.89%.Conclusions: The recommendations concerning minimization of risk throughout the lifecycle of test kits were developed relying on the results. Optimization in accordance with these guideline procedures of manufacturing, quality control, storage and using these test systems allows to ultimately get high-quality analytical tools for the quality control of compounded preparations

CENTRAL HEMODYNAMICS AND OXYGEN TRANSPORT IN PATIENTS WITH ACUTE RESPIRATORY DISTRESS SYNDROME CAUSED BY COVID-19 AND THEIR IMPACT ON THE COURSE AND OUTCOMES OF THE DISEASE

The aim. Determine hemodynamic status and its impact on oxygen transport, frequency of adverse events and outcomes in patients with severe SARS-CoV-2 associated with acute respiratory distress syndrome (ARDS). Materials and methods. A single-center prospective comparative study was conducted with 29 patients enrolled over the period of July—October 2020 who suffered a severe course of coronavirus disease and bilateral pneumonia associated with ARDS. Based on the estimated cardiac index (CI), patients were allocated to two groups: Group 1 included 14 patients with severe ARDS and CI 1.9 [1.5–2.5] L/min/m2, whereas Group 2 included 15 patients with CI 4.2 [3.2–8.1] L/min/m2 (p=0.001). Patient`s intensive care was regulated by the relevant orders of the Ministry of Health of Ukraine. Statistical analysis of the results was carried out using Statistica 10 software. Statistical significance of parameters was assessed using the non-parametric Wilcoxon criterion. Results were considered significant at p values <0.05. Data are presented as M [25–75]. Relative risk (RR) and odds ratio (OR) of adverse events were calculated. Results. The severe course of coronavirus disease is associated with significant oxygen transport disorders that increase with hypovolemia. Despite the increase in oxygen delivery in the group with normal CI its high tissue extraction remained, which may be a sign of development mitochondrial distress. Conclusions. Patients admitted to the ICU with severe COVID-19 may be in a state of hypovolemia and require individual assessment of hemodynamic status and the appointment of infusion therapy. Increased oxygen delivery in patients with normal cardiac index was associated with decreased adverse events rate and statistically significant decrease of mortality rat

The influence excipients on the dissolution profiles of nifedipine tablets

PURPOSE: Study of dissolution profiles of nifedipine tablets from different manufacturers to further assess of their equivalence in vitro, as well as study of the dependence of the dissolution profile on the adjuvants composition.MATERIAL AND METHODS: 3 buffer media with pH 1.2 (hydrochloric acid buffer); 4.5 (acetate buffer); 6.8 (phosphate buffer) was used. The absorptions were observed at 343.RESULTS: The dissolution profiles of nifedipine tablets from different manufacturers have been studied and have been founded that the percentage of nifedipine release from the sample B is higher than from `Corinfar`, and the percentage of nifedipine release from `Corinfar` is higher than from the sample A. Adjuvants composition of nifedipine tablets have been studied. It is founded that the inclusion of surfactants, solubilizers and emulsifiers into tablets contribute to increasing of active substance release from the dosage form.CONCLUSIONS: Found that the introduction of surfactants into tablets, solubilizers and emulsifiers help to increase the release of active substance from the dosage form

Research of interaction between metronidazole tablets and metal salts `in vitro`

Introduction: Along with the efficacy and safety of drugs, the interaction of drugs with each other and with other accompanying substances is important, too. There are no data about the interaction or influence of antacids and other drugs with polyvalent cations on the metronidazole bioavailability. The purpose of this research was the studying of the metronidazole release kinetics from the tablets in an environment that simulates stomach conditions with the addition of metal salts, which are part of the widespread drugs. The research was conducted to assess the impact of possible interactions between the active substance and polyvalent metal cations on their bioavailability and efficacy.Material and Methods: Metronidazole tablets were chosen as research object. 0.1 N HCl solution with addition of metal salts was chosen as medium dissolution. The `PharmaTest-DT70` Device with basket, the `Evolution 60S` Spectrophotometer as well as the `AB 204 S/A METTLER TOLEDO` analytical balances were used in the study.Results: Research of chemical interaction between metronidazole and metal salts, which are part of the widespread drugs, in the experiment `in vitro` was carried out. Metal salts don`t influence the metronidazole release from the tablets, as evidenced by dissolution profiles and similarity factors for each of the cases.Conclusions: The chemical interactions between the chosen medicines were not observed in the `in vitro` experiment. Thus, separate intake of metronidazole with other drugs, containing metal cations, is important for further research in the `in vivo` experiment

EVALUATION OF PAIN SYNDROME AND EFFICIENCY OF PAIN MANAGEMENT IN LUMBAR SPINE SURGERY

Multimodal analgesia for lumbar spine surgery is still a controversial problem, because of possible fusion problems, significant neuropathic component of pain, and influence of anesthesia type. Aim of the study was to assess the efficacy of pain management after lumbar spine surgery considering characteristics of pain, type of anesthesia and analgesic regimen. Material and methods. 254 ASA I-II patients with degenerative lumbar spine disease were enrolled into prospective study. Patients were operated either under spinal anesthesia (SA) or total intravenous anesthesia (TIVA). In postoperative period patients got either standard pain management (SPM – paracetamol±morphine) or multimodal analgesia (MMA – paracetamol+parecoxib+pregabalin±morphine). Results. We revealed neuropathic pain in 53.9 % of patients, who were elected for lumbar spine surgery. VAS pain score in patients with neuropathic pain was higher, than in patients with nociceptive pain. Total intravenous anesthesia was associated with greater opioid consumption during the first postoperative day. Multimodal analgesia based on paracetamol, parecoxib and pregabalin allowed to decrease requirements for opioids, postoperative nausea and dizziness. Pregabalin used for evening premedication had equipotential anxiolytic effect as phenazepam without postoperative cognitive disturbances. Conclusions. Multimodal analgesia is opioid-sparing technique that allows to decrease complications. Spinal anesthesia is associated to a decreased opioid consumption in the 1st postoperative day

EVALUATION OF PAIN SYNDROME AND EFFICIENCY OF PAIN MANAGEMENT IN LUMBAR SPINE SURGERY

Multimodal analgesia for lumbar spine surgery is still a controversial problem, because of possible fusion problems, significant neuropathic component of pain, and influence of anesthesia type. Aim of the study was to assess the efficacy of pain management after lumbar spine surgery considering characteristics of pain, type of anesthesia and analgesic regimen.Material and methods. 254 ASA I-II patients with degenerative lumbar spine disease were enrolled into prospective study. Patients were operated either under spinal anesthesia (SA) or total intravenous anesthesia (TIVA). In postoperative period patients got either standard pain management (SPM – paracetamol±morphine) or multimodal analgesia (MMA – paracetamol+parecoxib+pregabalin±morphine).Results. We revealed neuropathic pain in 53.9 % of patients, who were elected for lumbar spine surgery. VAS pain score in patients with neuropathic pain was higher, than in patients with nociceptive pain. Total intravenous anesthesia was associated with greater opioid consumption during the first postoperative day. Multimodal analgesia based on paracetamol, parecoxib and pregabalin allowed to decrease requirements for opioids, postoperative nausea and dizziness. Pregabalin used for evening premedication had equipotential anxiolytic effect as phenazepam without postoperative cognitive disturbances.Conclusions. Multimodal analgesia is opioid-sparing technique that allows to decrease complications. Spinal anesthesia is associated to a decreased opioid consumption in the 1st postoperative day

Development of methods for identification and quantitative determination of Analben in tablets

PURPOSE: Analben has been created by the researchers of the National University of Pharmacy and recommended in the solid dosage form as a promising non-narcotic analgesic and anti-inflammatory drug. The aim of the work is to develop physico-chemical and chemical methods of identification and quantitative determination of the active pharmaceutical ingredient in Analben tablets.MATERIALS AND METHODS: As the object of research a pilot batch of tablets `Analben, 1 mg` produced by the pharmaceutical firm `Neopharm` together with the company `Zdorovie` was selected. Analytical studies were performed by the methods of spectrophotometry, thin-layer chromatography and chemical reactions.RESULTS AND CONCLUSIONS: As the result of the work performed, the spectral characteristics of the analben substance in various solvents have been studied, the optimal conditions for determining related impurities have been selected using the method of thin-layer chromatography. The pectrophotometric method for quantitative determination of Analben in the tablets under study has been developed; the solvent, concentration and wavelength have been chosen. The validation characteristics of the quantitative determination method have been studied and it has been determined that linearity is observed in the range of concentrations from 0.16 μg/ml to 0.24 μg/ml (±20%), the systematic error of the method (0.33%) is practically insignificant, the relative confidence interval for the value Z (0.62%) is less than the critical value for convergence of results (1.66%)

Synthesis of novel substituted 4-phenyl-5-phenoxymethyl-3-mercapto-1,2,4-triazole (4 H) derivatives as potential anti-ulcer agents

In this work, the series of new 4-phenyl-5-4-(R)-phenoxymethyl-1,2,4-triazole-3-ylthio-1-(R1)-acetophenones have been synthesized by alkylation of correspondent 4-phenyl-5-phenoxymethyl-3-mercapto-1,2,4-triazoles (4H) with the α-chloroacetophenones. The structure of the synthesized substances has been proven by NMR spectra. High possibility of anti-ulcer and anti-helicobacter activity was determined by the PASS program. Molecular docking and anti-ulcer screening of new 1,2,4-triazole(4H) derivatives on the acute alcohol-prednisolone model NSAID-induced ulcers in rats has been performed