Changes in micro- and central hemodynamic parameters in rats under the action of acetylsalicylic acid and its coordination compounds with metals

Introduction. The cutaneous blood circulation is a representative model both for studying the mechanisms of vascular diseases and for assessing the current state of the central hemodynamics in preclinical researches of various chemical compounds. Aim. The changes in the parameters of cutaneous microcirculation and central hemodynamics (heart rate and blood pressure) were studied in the animals under the action of acetylsalicylic acid and its coordination compounds with cations of cobalt, zinc, nickel and manganese at a dose of 20 mg/kg. Materials and methods. The research was conducted using the laser Doppler flowmetry method on the Lazma-MC device (manufactured by RPE Lazma, Russia) and the NIBP200A system (Biopac Systems, Inc., USA). Results. The study shows that animals develop bradycardia, and microcirculation and central hemodynamics change in two ways after the introduction of acetylsalicylic acid and the tested metal salicylates. These ways are hypotension-related hyperemia (acetylsalicylic acid and cobalt salicylate) and ischemia (zinc, nickel and manganese salicylates) associated with hypertension. Conclusion. The obtained data confirm the cardiotropic activity of new coordination compounds. The data also prove that the generation of the acetylsalicylic acid derivatives allows enhancing it physiological effects, as well as obtaining completely new molecules. The molecules are different from the precursor one and are necessary for the production of effective drugs.

Management of validation of HPLC method for determination of acetylsalicylic acid impurities in a new pharmaceutical product

The work mainly focused on a validation of the method for determining the content of salicylic acid and individual unknown impurities in new pharmaceutical product—tablets containing: 75, 100 or 150 mg of acetylsalicylic acid and glycine in the amount of 40 mg for each dosage. The separation of the components was carried out by means of HPLC, using a Waters Symmetry C18 column (4.6 × 250 mm, 5 μm) as the stationary phase. The mobile phase consisted of a mixture of 85% orthophosphoric acid, acetonitrile and purified water (2:400:600 V/V/V). Detection was carried out at a wavelength of 237 nm, with a constant flow rate of 1.0 ml min−1. In order to verify the method, linearity, precision (repeatability and reproducibility), accuracy, specificity, range, robustness, system precision, stability of the test and standard solution, limit of quantification and forced degradation were determined. Validation tests were performed in accordance with ICH (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use) guidelines. The method was validated successfully. It was confirmed that the method in a tested range of 0.005–0.40% salicylic acid with respect to acetylsalicylic acid content is linear, precise and accurate.

General Explanation of Aspirin: Recent and Future Advancement

Salicylates have been derived from the willow tree bark. Acetylsalicylic acid has analgesic, antipyretic and anti-inflammatory actions. Salicylate elimination happens throughout dual pathways via the invention of salicyluric acid and salicyl phenolic glucuronide. Salicylic acid is renally cleared, which can be escalated by ascending the urinary pH. Medicines like antacids can accelerate renal clearance as they ascend urinary pH. Aspirin should be used with chariness in children taking some distinctive medications. Levels of methotrexate, valproic acid, phenytoin, and disparate non-steroidal anti-inflammatory drugs (tolmetin, diclofenac) perhaps escalated in children who are also taking aspirin.

Acetylsalicylic Acid Reduces Passive Aortic Wall Stiffness and Cardiovascular Remodelling in a Mouse Model of Advanced Atherosclerosis

Acetylsalicylic acid (ASA) is widely used in secondary prevention of cardiovascular (CV) disease, mainly because of its antithrombotic effects. Here, we investigated whether ASA can prevent the progression of vessel wall remodelling, atherosclerosis, and CV complications in apolipoprotein E deficient (ApoE−/−) mice, a model of stable atherosclerosis, and in ApoE−/− mice with a mutation in the fibrillin-1 gene (Fbn1C1039G+/−), which is a model of elastic fibre fragmentation, accompanied by exacerbated unstable atherosclerosis. Female ApoE−/− and ApoE−/−Fbn1C1039G+/− mice were fed a Western diet (WD). At 10 weeks of WD, the mice were randomly divided into four groups, receiving either ASA 5 mg/kg/day in the drinking water (ApoE−/− (n = 14), ApoE−/−Fbn1C1039G+/− (n = 19)) or plain drinking water (ApoE−/− (n = 15), ApoE−/−Fbn1C1039G+/− (n = 21)) for 15 weeks. ApoE−/−Fbn1C1039G+/− mice showed an increased neutrophil–lymphocyte ratio (NLR) compared to ApoE−/− mice, and this effect was normalised by ASA. In the proximal ascending aorta wall, ASA-treated ApoE−/−Fbn1C1039G+/− mice showed less p-SMAD2/3 positive nuclei, a lower collagen percentage and an increased elastin/collagen ratio, consistent with the values measured in ApoE−/− mice. ASA did not affect plaque progression, incidence of myocardial infarction and survival of ApoE−/−Fbn1C1039G+/− mice, but systolic blood pressure, cardiac fibrosis and hypertrophy were reduced. In conclusion, ASA normalises the NLR, passive wall stiffness and cardiac remodelling in ApoE−/−Fbn1C1039G+/− mice to levels observed in ApoE−/− mice, indicating additional therapeutic benefits of ASA beyond its classical use.

Study of compatibility of components of a new combined drug for treatment of alcoholic intoxication and its hepatoprotective effect on a model of alcoholic liver injury

The aim of the work is the development of a combined drug for use in alcohol intoxication based on the physicochemical properties and chemical compatibility of active pharmaceutical ingredients and excipients, and the study of the hepatoprotective effect in alcoholic hepatitis in rats. Materials and methods. During the studies, physical and physicochemical methods were used, a Specord 200 spectrophotometer (Germany), analytical scales Sartorius (SARTORIUS, Germany), class A volumetric glassware and reagents that meet the requirements of the State Pharmacopoeia of Ukraine (SPhU). Alcoholic hepatitis in rats was reproduced by intragastric administration of an aqueous 40% ethanol solution at a dose of 7 ml/kg for 1 week. Results. A new combined agent is proposed for use in alcohol intoxication in the form of an effervescent powder for the preparation of an oral solution, which contains glycine, L-glutamic acid, acetylsalicylic acid, ascorbic acid, fructose / sorbitol and sodium bicarbonate and citric acid to accelerate the dissolution of medicinal substances. To study the compatibility of the components, experimental studies of hygroscopicity, chemical interaction / chemical stability and an assessment of the redox potential of the proposed active pharmaceutical ingredients were carried out. To study the stability of the API, studies were carried out on sugaramine condensation due to the choice of amino acids and ascorbic acid in the composition of drugs. Based on the research results, it was decided to divide the API into 2 packages, separating sodium bicarbonate and glycine, which can interact with ascorbic acid / acetylsalicylic acid and ascorbic acid, respectively. In an in vivo experiment, it was found that the use of the new drug is accompanied by the normalization of the antioxidant-prooxidant status of the liver due to a likely decrease in the TBA-AP level and an increase in the RG index in the liver homogenate relative to the control group. Conclusions. Evaluation of the physicochemical properties of API allowed us to propose a new combined drug (TS-PP) for use in alcohol intoxication in the form of an effervescent powder for the preparation of oral solution. In alcoholic hepatitis in rats, it was found that the use of the studied drug largely prevents the formation of the effects of the toxic effects of ethanol on the rat organism, which is manifested by inhibition of destruction of hepatocyte membranes, a decrease in the level of LPO products, restoration of the RG index and improvement of the protein synthesizing function of the liver due to the complex effect of amino acids and ascorbic acid contained in the product

Solubility Study of Acetylsalicylic Acid in Ethanol + Water Mixtures: Measurement, Mathematical Modeling, and Stability Discussion

Solubility determination of poorly water-soluble drugs is pivotal for formulation scientists when they want to develop a liquid formulation. Performing such a test with different ratios of cosolvents with water is time-consuming and costly. The scarcity of solubility data for poorly water-soluble drugs increases the importance of developing correlation and prediction equations for these mixtures. Therefore, the aim of the current research is to determine the solubility of acetylsalicylic acid in binary mixtures of ethanol+water at 25 and 37°C. Acetylsalicylic acid is non-stable in aqueous solutions and readily hydrolyze to salicylic acid. So, the solubility of acetylsalicylic acid is measured in ethanolic mixtures by HPLC to follow the concentration of produced salicylic acid as well. Moreover, the solubility of acetylsalicylic acid is modeled using different cosolvency equations. The measured solubility data were also predicted using PC-SAFT EOS model. DSC results ruled out any changes in the polymorphic form of acetylsalicylic acid after the solubility test, whereas XRPD results showed some changes in crystallinity of the precipitated acetylsalicylic acid after the solubility test. Fitting the solubility data to the different cosolvency models showed that the mean relative deviation percentage for the Jouyban-Acree model was less than 10.0% showing that this equation is able to obtain accurate solubility data for acetylsalicylic acid in mixtures of ethanol and water. Also, the predicted data with an average mean relative deviation percentage (MRD%) of less than 29.65% show the capability of the PC-SAFT model for predicting solubility data. A brief comparison of the solubilities of structurally related solutes to acetylsalicylic acid was also provided.

Effect of soft beverages on the in vitro dissolution of gastro-resistant tablets containing low dose Acetylsalicylic acid

The need for additional fluids for easy absorption is typical for elderly patients and those with dysphagia. Most often, these patients take their medication with a glass of orange juice or another liquid instead of a glass of water. We conducted a dissolution test with gastro-resistant tablets acetylsalicylic acid where different kind of orange juice or soft drink wеre added to the release medium. As a control, release medium - buffers 1.2, 4.5 and 6.8 were used. The released aspirin was determined after HPLC analysis. The obtained data were fitted to different kinetic models. The results of the dissolution test in medium buffers with added different beverage showed results similar to those obtained in pure buffer, where it is used an artificial sweetener and different, when sugar or glucose-fructose syrup was used to sweeten the beverage. The most significant change was observed in the release kinetics of the active substance.To exclude the possibility that the other beverage ingredients or excipients used to make the tablets affect the release profile of acetylsalicylic acid, we conducted a beverage-like dissolution test. Instead of a original beverage, we used water and sugar syrup, in a concentration that is declared on the label of the original beverages. The results obtained confirm that different sugar concentrations alter the release profile of acetylsalicylic acid from gastro resistant tablets when they are taken with a glass of sugar-containing beverage instead of a glass of water.