Enalapril Maleate Research Articles

Losartan and enalapril maleate differently influence SARS-CoV-2-infected vero cells

Background: The COVID-19 pandemic has posed significant challenges to global healthcare systems, particularly impacting individuals with pre-existing conditions like hypertension. This study sought to assess the impact of the antihypertensive medications, losartan and enalapril maleate on SARS-CoV-2 infected cells. Vero E6 cells were infected and treated in vitro, evaluating cell viability via the MTT colorimetric assay. Additionally, the study measured relative levels of viral RNA and selected gene messenger RNAs using reverse transcriptase followed by quantitative real-time polymerase chain reaction. Results: The findings revealed that losartan substantially reduced nucleocapsid RNA levels of SARS-CoV-2 to nearly undetectable levels, while enalapril maleate did not demonstrate a significant effect. In response to viral infection, the expression of il-18, p53, p21, and p62 increased compared to uninfected-untreated cells. Notably, il-6 expression was upregulated by both infection and treatments. A comparison between infected cells treated with losartan or enalapril maleate highlighted the presence of distinct profiles in the expression of il-6, p53, p21, and p62. Conclusions: The data from our study suggest that these medications could interfere with certain effects triggered by SARS-CoV-2 infection in Vero E6 cells. However, their influence appears to vary both quantitatively and qualitatively in the modulation of metabolic and signal transduction pathways.

A Case Report: Myxomatous Mitral Valve Disease in a Shih Tzu

Myxomatous Mitral Valve Disease (MMVD) is a degenerative condition of the mitral valve where it weakens and causes regurgitation, eventually leading to cardiac remodeling. Jason, a seven-year-old male Shih Tzu weighing 7.5 kg, was presented with a persistent cough and exercise intolerance lasting over a month. A physical examination revealed a Grade II/VI heart murmur. Radiography and echocardiography were performed as part of the laboratory examinations. Radiography demonstrated cardiac remodeling, with a VHS of 10.3 viscerocranial, an intercostal space of 3, and a VLAS of 2.3. Echocardiography unveiled left atrial enlargement, mitral valve regurgitation, and a reduction in heart function. The dog was treated with Pimobendan (Cardisure® 10mg, Dechra, England) as an inodilatator at 0.25mg, Enalapril Maleate 0.5mg/kg (Tenace® 5mg, Combiphar, Indonesia), and furosemide (Farsix® 40mg, Fahrenheit, Indonesia) at 2 mg/kg via oral route twice a day over the course of seven days. Thereafter, the dose was reduced to 1.5 mg/kg PO twice a day for seven days, and eventually once a day for the remainder of the seven days. Following the three-week treatment, there was a significant reduction in the frequency and intensity of coughing.

The first description of mucous membrane pemphigoid induced by enalapril maleate: a case report

BackgroundMucous membrane pemphigoid (MMP) is an autoimmune blistering disease (AIBD). Some reports suggest that it has a drug-related pathogenesis especially anti-hypertensive drug.Case presentationA 67-year-old man with a 7-year history of essential hypertension was prescribed enalapril maleate for 5 months. He presented at our department with pain, ulcers, and blisters on the oral mucosa. We performed clinical, histopathology, and direct immunofluorescence examinations, and findings were consistent with the diagnostic criteria for MMP. Consequently, we consulted with the cardiovascular physician and agreed to discontinue the enalapril maleate replacing it with irbesartan/hydrochlorothiazide tablets and topical corticosteroid therapies instead. The lesions healed without recurrence.ConclusionsABID induced by antihypertensive drugs have been reported, and enalapril maleate has been implicated as an antihypertensive agent that may trigger AIBDs, such as MMP. This case highlights the potential relationship between antihypertensive drugs and MMP, of which clinicians should be aware to accurately diagnose and promptly relieve patients’ pain.

Characterization of Liquid Dosage Forms of Atenolol and Enalapril Maleate for Oral and Enteral Feeding Administration.

The limited availability of pharmaceutical formulations tailored for cardiovascular diseases in both pediatric and geriatric populations generates the need for compounded dosage forms to guarantee precise dosing and medication adherence. This study aimed to analyze the physicochemical properties and stability of formulations of atenolol and enalapril maleate prepared with a proprietary oral vehicle, SuspendIt®. To this end, palatability, injectability, pH, rheological behavior, and physical, microbiological, and chemical stability over a 180-day storage period at 25 °C and 5 °C were evaluated. Injectability tests confirmed the suitable use of both formulations for administration through enteral feeding tubes. By using a potentiometric electronic tongue, it was confirmed that the SuspendIt® vehicle effectively served as a bitter-blocking strategy for atenolol and enalapril maleate. Adequate stability throughout the storage period was confirmed in terms of the mechanical properties, pH, and effectiveness of the preservative system. The atenolol concentration remained above 90% of the initial amount, while the concentration of enalapril maleate decreased to 88% after 90 days of storage at 25 °C. In summary, the atenolol formulation maintained suitable chemical, physical, and microbiological stability after 180 days at both storage temperatures, while the enalapril maleate formulation remained stable up to 60 days at 25 °C and for 180 days at 5 °C.

Quality of medicines for Cardio-Vascular Diseases (CVDs) in the Ethiopian border with Kenya: The case of enalapril maleate and furosemide tablet quality in Borena and Gedeo zones.

Hypertension (HTN), a cardiovascular disease (CV), is a major public health challenge. Therefore, the quality of drugs used to treat it has become a major concern. Enalapril and furosemide are among the drugs prescribed to manage hypertension. Hence, this study is aimed at evaluating the quality of different brands of enalapril and furosemide tablets available in the Gedeo and Borena zones, southern Ethiopia. Thirteen generic brands of enalapril maleate (5 mg) and furosemide (40 mg) tablets were evaluated for visual defects, in vitro dissolution test, weight variations, friability, hardness, and disintegration tests. The analysis of active pharmaceutical ingredient (API) content was performed by high performance liquid chromatography (HPLC). Out of 55 samples, 7 (12.73%) failed to comply with the criteria for visual inspection; otherwise, all samples passed the identification test. Except for one brand of each of enalapril maleate and furosemide, all passed the dissolution test. The assay value showed that all enalapril maleate samples were within the limits of United States Pharmacopoeia (USP), 2020. Additionally, except for two batches, all furosemide samples were within the USP and British Pharmacopoeia (BP), 2020 standards. Out of 55 samples, 8% (2/25) and 6.67% (2/30) of enalapril maleate and furosemide tablets failed the uniformity of dosage units test per the USP-2020, respectively. All samples passed the disintegration test, and selected furosemide samples passed the microbial limit tests. However, 36% (9/25) and 20% (6/30) of enalapril maleate and furosemide samples failed to pass hardness test. Generally, from the total samples, 50.91% (28/55) were substandard (did not meet the specifications failing any one or more parameters assessed). The studied drugs circulating in the market did not meet some of the needed quality specifications. This could have brought a risk of reduced efficacy due to the distribution of poor quality medicines in the area.

Preparation of graphene oxide and multi-walled carbon nanotubes, and they are used to modify the glassy carbon electrode for sensing Enalapril Maleate

In this study, the graphene oxide and multi-walled carbon nanotubes fabrication was evaluated using (SEM), (FTIR), Raman spectroscopy and (XRD). The results showed promising accuracy for the graphene oxide and multi-walled carbon nanotubes voltammetric sensor. The direct voltammetric determination of Enalapril Maleate in pharmaceutical samples, urine, and serum is detailed using a straightforward and extremely sensitive technique. Graphene oxide-multiwall carbon nanotubes are added to glassy carbon electrodes in an efficient manner to activate the GO-MWNT structures, which then electrocatalyzes the reduction of Enalapril Maleate. The results of the cyclic voltammetric (CV) experiment showed that the electrocatalytic activity of GO-MWNTs to reduce Enalapril Maleate was significantly improved, leading to a much higher cathodic peak current for EM. This finding opens the door to the possibility of creating a very sensitive voltammetric sensor to detect EM in biological and pharmaceutical fluid samples. A linear calibration curve in the 2.5–12.5 ppm concentration range, a detection limit of 0.2 ppm, and a relative standard deviation (R.S.D.%) lower than 1.0 % (n = 5) were all indicative of ideal conditions. Lastly, EM is a diffusion-controlled process that proceeds through a two-electron-two-proton change, which provides a mechanism for the reduction of EM.. The GO-MWCNTs/GCE sensor had a good repeatability and excellent reproducibility, R.S.D.% =1.77 and 1.82.

Optimal folic acid dosage in lowering homocysteine: Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy)

BackgroundWhile folic acid (FA) is widely used to treat elevated total homocysteine (tHcy), promoting vascular health by reducing vascular oxidative stress and modulating endothelial nitric oxide synthase, the optimal daily dose and individual variation by MTHFR C677T genotypes have not been well studied. Therefore, this study aimed to explore the efficacy of eight different FA dosages on tHcy lowering in the overall sample and by MTHFR C677T genotypes.MethodsThis multicentered, randomized, double-blind, controlled clinical trial included 2697 eligible hypertensive adults with elevated tHcy (≥ 10 mmol/L) and without history of stroke and cardiovascular disease. Participants were randomized into eight dose groups of FA combined with 10 mg enalapril maleate, taken daily for 8 weeks of treatment.ResultsThe intent to treat analysis included 2163 participants. In the overall sample, increasing FA dosage led to steady tHcy reduction within the FA dosing range of 0–1.2 mg. However, a plateau in tHcy lowering was observed in FA dose range of 1.2–1.6 mg, indicating a ceiling effect. In contrast, FA doses were positively and linearly associated with serum folate levels without signs of plateau. Among MTHFR genotype subgroups, participants with the TT genotype showed greater efficacy of FA in tHcy lowering.ConclusionsThis randomized trial lent further support to the efficacy of FA in lowering tHcy; more importantly, it provided critically needed evidence to inform optimal FA dosage. We found that the efficacy of FA in lowering tHcy reaches a plateau if the daily dosage exceeds 1.2 mg, and only has a small gain by increasing the dosage from 0.8 to 1.2 mg.ClinicalTrials.gov IdentifierNCT03472508 (Registration Date: March 21, 2018).

Concurrent exercise training potentiates the effects of angiotensin-converting enzyme inhibitor on regulatory systems of blood pressure control in ovariectomized hypertensive rats.

Enalapril has shown satisfactory potential in controlling increased and sustained blood pressure (BP). However, multiple dysregulated mechanisms that interact with each other and are involved in the pathophysiology of arterial hypertension may not be affected, contributing to the remaining cardiovascular risk. Using an exercise training protocol, we investigated whether adding both approaches to arterial hypertension management could promote higher modulation of regulatory mechanisms of BP in postmenopausal rats. Spontaneously hypertensive rats were allocated into sedentary (S) and ovariectomized groups: sedentary (OS), sedentary treated with enalapril maleate (OSE) and trained treated with enalapril maleate (OTE). Both the pharmacological and exercise training protocols lasted for 8 weeks. The BP was directly recorded. Inflammation and oxidative stress were evaluated in the cardiac tissue. Although BP reduction was similar between OSE and OTE, trained group showed lower vasopressor systems outflow after sympathetic ganglion blocking by hexamethonium (mean BP) (OTE: -53.7 ± 9.86 vs. OS: -75.7 ± 19.2 mmHg). Bradycardic and tachycardic response were increased in OTE group (-1.4 ± 0.4 and -2.6 ± 0.4 vs. OS: -0.6 ± 0.3 and -1.3 ± 0.4 bpm/mmHg, respectively), as well as BP variability. In addition, the combination of approaches induced an increase in interleukin 10, antioxidant defense (catalase and glutathione peroxidase) and nitrite levels compared with the OS group. Despite similar BP, the inclusion of exercise training in antihypertensive drug treatment exacerbates the positive adaptations induced by enalapril alone on autonomic, inflammatory and oxidative stress profiles, probably affecting end-organ damage and remaining risk.

Impact of exercise training associated with enalapril treatment on blood pressure variability and renal dysfunctions in an experimental model of arterial hypertension and postmenopause.

In this study, we aimed to investigate the effects of the concurrent exercise training (CET) associated with the enalapril maleate on blood pressure variability (BPV) and renal profile in an experimental model of arterial hypertension (AH) and postmenopause. Female ovariectomized spontaneously hypertensive rats (SHR) were distributed into 4 groups (n = 8/group): sedentary (SO), sedentary + enalapril (SOE), trained (TO) and trained + enalapril (TOE). Both enalapril (3mg/kg) and CET (3 days/week) were conducted during 8 weeks. Blood pressure (BP) was directly recorded for BPV analyses. Renal function, morphology, inflammation and oxidative stress were assessed. The SOE, TO e TOE groups presented decreased systolic BP compared with SO. Both trained groups (TO and TOE) presented lower BPV and increased baroreflex sensitivity (TO: 0.76 ± 0.20 and TOE: 1.02 ± 0.40 vs. SO: 0.40 ± 0.07 ms/mmHg) compared with SO group, with additional improvements in TOE group. Creatinine and IL-6 levels were reduced in SOE, TO and TOE compared with SO group, while IL-10 was increased only in TOE group (vs. SO). Enalapril combined with CET promote reduction in lipoperoxidation (TOE: 1.37 ± 0.26 vs. SO: 2.08 ± 0.48 and SOE: 1.84 ± 0.35 μmol/mg protein) and hydrogen peroxide (TOE: 1.89 ± 0.40 vs. SO: 3.70 ± 0.19 and SOE: 2.73 ± 0.70 μM), as well as increase in catalase activity (vs. sedentary groups). The tubulointerstitial injury was lower in interventions groups (SOE, TO and TOE vs. SO), with potentialized benefits in the trained groups. Enalapril combined with CET attenuated BPV and baroreflex dysfunctions, probably impacting on end-organ damage, as demonstrated by attenuation in the AH-induced renal inflammations, oxidative stress and morphofunctional impairments in postmenopausal rats.

Effect of Formulation Parameters on Enalapril Maleate Mucoadhesive Buccal Tablet Using Quality by Design (QbD) Approach.

The buccal route has great prospects and possible benefits for the administration of drugs systemically. The present study involves designing, developing and optimising the buccal tablet formulation of Enalapril Maleate (EM) by using the QbD approach. We prepared the EM buccal tablets using the dry granulation method. In the QTPP profile, the CQAs for EM buccal tablets are Mucoadhesive strength, swelling index and drug release (dependent variables); the CMAs identified for EM buccal tablets were Carbopol 934P, HPMC-K100M and chitosan (independent variables). Diluent quantity, blending time and compression force were selected as CPPs; the Box-Behnkentdesign was used to evaluate the relationship between the CMAs and CPPs. Based on the DoE, the composition of the optimised formulation of EM BT-18 consists of 20mg of EM, 15 mg of carbopol 934p, 17 mg of HPMC-K100M, 10mg of chitosan, 30 mg of PVP K-30, 1 mg of magnesium stearate, 16 mg of Mannitol, 1 mg of aspartame, and 50 mg of Ethyl cellulose. The optimised formulation of EM BT 18 was found to have a Mucoadhesive strength of 24.32±0.30g. The swelling index was 90.74±0.25% and drug release was sustained up to 10 hours 98.4±3.62% compared to the marketed product, whose release was up to 8 hours. We attempted to design a buccal tablet of Enalapril Maleate for sustained drug release in the treatment of hypertension. Patients who cannot take oral medication due to trauma or unconscious conditions could receive the formulation. Development of a newly P.ceutical product is very time-consuming, extremely costly and high-risk, with very little chance of a successful outcome. Hence, this study showed EM tablets are already available on the market but we have chosen a buccal drug delivery system using a novel approach using QbD tools to target the quality of the product accurately.

Characterization of enalapril maleate: An approach using thermoanalytical, thermokinetic and spectroscopic techniques

Enalapril maleate is a widely used drug for the treatment of cardiovascular diseases. Its mechanism of action is to inhibit the angiotensin-converting enzyme selectively. Therefore, it is metabolized to enalaprilat by liver cells. The thermal behavior of enalapril maleate was investigated by simultaneous thermogravimetry and differential scanning calorimetry (TG-DSC), and evolved gas analysis by simultaneous thermogravimetry and differential scanning calorimetry coupled infrared spectroscopy (TG-DSC-FTIR). The results provided information on thermal stability, purity, thermal decomposition steps, and the main products formed in the heating. The enalapril maleate was found to be stable up to 148 ?C. Above this temperature causes thermal degradation of the substance, which occurs in two stages in an inert atmosphere (N2) and three stages in an oxidizing atmosphere (air). Through the TG-DSC-FTIR the released gases were identified as maleic anhydride as a thermal decomposition intermediate. DSC analysis showed that the material obtained 99.5% purity, which indicates high purity. Employing both the Kissinger and Friedman equations, alongside Model Fitting methods, the study reveals key insights. The Kissinger method unveils an apparent activation energy of 47.07?15.45 kJ mol?? for the complete thermal breakdown, a finding corroborated by the Friedman method. Model Fitting methods, the article applies them, yielding an apparent activation energy of 55.70?3.4 kJ mol?? with a three-dimensional diffusion thermal degradation model.

Quality Control Parameters of Antihypertensive Medications Marketed in Eastern Ethiopia: Amlodipine Besylate and Enalapril Maleate Tablets

Quality Control Parameters of Antihypertensive Medications Marketed in Eastern Ethiopia: Amlodipine Besylate and Enalapril Maleate Tablets

Therapeutic Effect of Amlodipine Besylate in Conjunction with Enalapril Maleate Tablets in Diabetic Nephropathy and Hypertension

Therapeutic Effect of Amlodipine Besylate in Conjunction with Enalapril Maleate Tablets in Diabetic Nephropathy and Hypertension

Enhancing ventricular remodeling and cardiac function in post-acute myocardial infarction with sacubitril/valsartan.

To evaluate the therapeutic effect of sacubitril/valsartan compared to enalapril in managing heart failure (HF) after percutaneous coronary intervention (PCI). From January 2018 to December 2021, 63 hospitalized patients diagnosed with HF following acute myocardial infarction (AMI) were enrolled in this prospective clinical trial. The observation group was comprised of 31 patients treated with sacubitril/valsartan (LCZ696) sodium tablets, while the control group, including 32 patients, received enalapril maleate tablets. All patients received standard HF therapy, including water-soluble aspirin, hydroclopidogrel sulfate, once-daily bivalirudin calcium, twice-daily metoprolol tartrate (dose titrated based on heart rate), once-daily spironolactone (dose adjusted for electrolytes), and once-daily dehydroimidazole (dose adjusted for electrolytes). HF symptom control, N-terminal B-type natriuretic peptide precursor (NT-proBNP) levels, cardiac anatomical parameters, heart rate, blood pressure, and 6-minute walking distance over a 90-day follow-up were assessed. The study is registered under ClinicalTrials.gov [ChiCTR2100042944]. On the 30th day post-discharge, the observation group exhibited a marked decrease in NT-proBNP levels and an improvement in left ventricular end-diastolic diameter, in contrast to the control group (both P<0.05). By the 90th day, the observation group showed significant improvements in left ventricular ejection fraction and left ventricular end-systolic diameter index, along with reduced blood pressure and serum creatinine levels (all P<0.05). Furthermore, the observation group displayed a more favorable New York Heart Association class distribution and enhanced performance in the 6-minute walk test (both P<0.05). No significant difference in the incidence of major adverse cardiovascular events was observed between the two groups during the 90-day follow-up period (P>0.05). Our findings indicate that sacubitril/valsartan (LCZ696) Sodium Tablets effectively enhance ventricular remodeling and cardiac function in patients with HF post-AMI, following a short-term treatment regimen. This therapeutic approach holds promise for improving clinical outcomes in this patient population.

Simultaneous Estimation of Amlodipine and Enalapril Maleate by Stability Indicating UHPLC Method

Simultaneous Estimation of Amlodipine and Enalapril Maleate by Stability Indicating UHPLC Method

Substantiation of creation of transdermal forms of drug delivery with antihypertensive action

The article presents the theoretical justification for the choice of active pharmaceutical ingredients of antihypertensive action for the creation of new forms of delivery - transdermal therapeutic systems.&#x0D; Purpose: monitoring of studies on the use of angiotensin-converting enzyme (ACE) inhibitors in the development of transdermal drugs for the treatment of hypertension.&#x0D; Materials: open access electronic resources of scientific periodicals from around the world: Google Scholar (https://scholar.google.com/); PubMed (https://pubmed.ncbi.nlm.nih.gov/); Sciencedirect (https://www.sciencedirect.com/); Pubchem (https://pubchem.ncbi.nlm.nih.gov/); National Library of Ukraine named after V. I. Vernadskyi (http://www.nbuv.gov.ua/); Ukrainian Institute of Intellectual Property (Ukrpatent) (https://sis.ukrpatent.org/uk/); Industrial Property (https://base.uipv.org/searchBul/); USPTO. The United States Patent and Trademark Office (https://www.uspto.gov/patents/search); European Patent Office (EPO) (https://www.epo.org/).&#x0D; Methods of the research: information search, theoretical analysis and systematization of data from scientific sources, logical analysis.&#x0D; Results: a review of scientific sources was carried out, and an analysis of ACE inhibitors as candidates for the creation of transdermal forms for the treatment of arterial hypertension was carried out. The pharmacological and physicochemical aspects of the possibility of their use for introduction through the skin are defined. It has been established that the search and development of the latest means of treatment of arterial hypertension, which would significantly increase the duration and quality of life of patients, are extremely relevant. Transdermal drug delivery systems are one of the pharmaceutical products being developed on the world market, and their use allows overcoming the associated disadvantages of other delivery routes.&#x0D; Conclusions: the review of domestic and foreign literature confirmed the relevance of biopharmaceutical research in the field of development of innovative dosage forms - transdermal therapeutic systems for the treatment of hypertension.&#x0D; The choice of promising antihypertensive active pharmaceutical ingredients of the ACE group (enalapril maleate, lisinopril dihydrate, and captopril) is substantiated, taking into account their specific physicochemical properties that are suitable for penetration through the skin.&#x0D; The market for transdermal drug delivery is increasing, and there is a prospect of higher growth rates in this market in the coming years

Clinical Efficacy of Dapagliflozin in the Treatment of Patients with Diabetic Nephropathy and Its Effect on Proteinuria Level.

This study aimed to analyze the clinical efficacy of dapagliflozin in the treatment of diabetic kidney disease and its impact on proteinuria levels in patients. Retrospective analysis of medical records of 176 patients with diabetic kidney disease treated at our hospital from January 2020 to January 2022. According to the different treatment methods, the patients were divided into a control group (n=88) receiving enalapril maleate treatment and an observation group (n=88) receiving dapagliflozin treatment. The clinical treatment effects, blood glucose levels, renal function indicators, inflammation factor indicators, and adverse reactions were compared between the two groups. The total effective rate of treatment (97.73%) in the observation group was significantly higher than that (79.55%) in the control group (P<0.05). After treatment, the FPG, 2hPG, and HbAlc levels in the observation group were significantly lower than those in the control group (P<0.05). After treatment, the Scr, BUN, UmAlb, UAER, UACR, and 24-hour urine protein quantitative levels in the observation group were significantly lower than those in the control group (P<0.05). After treatment, the hs-CRP, IL-1β, and TNF-α levels in the observation group were significantly lower than those in the control group (P<0.05). The incidence of adverse reactions in the observation group significantly lower than the control group (P<0.05). Compared with enalapril maleate alone, the combined application of dapagliflozin in the treatment of diabetic kidney disease has more significant clinical efficacy. It can further control patients' blood sugar, reduce their body's inflammatory response, alleviate or eliminate their proteinuria symptoms, promote the recovery of their renal function, and enhance the safety of their treatment to a certain extent, which helps to further improve the clinical treatment effect of patients.

Removal of enalapril maleate drug from industry waters using activated biochar prepared from Butia capitata seed. Kinetics, equilibrium, thermodynamic, and DFT calculations

Porous biochar was fabricated from Butia capitata (Bc) seed, which was used to uptake enalapril maleate from synthetic wastewater. Activated biochars were fabricated by blending Bc and ZnCl2 at 1:1 (BcB-1.0) or 1:1.5 (BcB-1.5) proportions and furtherly pyrolyzed at 600 °C. The elemental analysis, Boehm titration, hydrophobic balance ratio, FTIR, TGA, and N2 isotherm characterized the carbon-based materials. They presented a hydrophilic behavior with diverse polar groups on their surface. BcB-1 and BcB-1.5 biochars have a total pore volume of 0.392 and 0.492 cm3 g−1 and a surface area of 1267 and 1520 m2/g, respectively. The kinetics and isothermal data were adequately adjusted to the fractal-like pseudo-second-order and Liu models. The employment of BcB-1.0 and BcB-1.5 for treating synthetic wastewater containing high levels of pollutants had elevated efficiency in their removals (up to 99.06%). We also conducted a DFT computational study, density functional theory (DFT), to examine the interactions between enalapril and a graphitic domain of biochar by using these calculations, the most stable configuration presented interaction energy of −88.7 kJ mol−1 implies a face-to-face π–π stacking interaction involving the enalapril phenyl segment and an aromatic ring of the graphitic domain, as well as London dispersion arising from the proximity of ethoxy/pyrrolidine to biochar carbon atoms, with interatomic distances of 3.31 Å for the former and 3.60 Å /3.48 Å for the latter. Also, the DFT calculations agreed with the thermodynamic data calculated from the isotherms (283–318 K).

Studies on charge transfer of enalapril maleate: from solid-state to molecular dynamics.

Enalapril maleate is an antihypertensive ethyl ester pro-drug with two crystalline forms. A network of hydrogenbonds in both polymorphs plays an important role on solid-state stability, charge transfer process and degradationreactions (when exposed to high humidity, temperature and/or pH changes). Supramolecular arrangement was proposed by Hirshfeld surface using the CrystalExplorer17 software and quantum theory of atoms in molecules. The electronic structure properties were calculated using the functional hybrid M06-2X with 6-311++G** base function employing diffuse and polarization functions to improve the description of hydrogen atoms on intermolecular interactions. Also, the H+ charge transfer between enalapril and maleate molecules was performed using Car-Parrinello molecular dynamics with the Verlet algorithm. In both simulations, the temperature of the ionic system was maintained around 300 K using the Nosé-Hoover thermostat and the electronic system evolved without the use of the thermostat. This work evaluates the effect of maleate on the structural stability of enalapril maleate solid state. The electronic structural analysis points out a partially covalent character for N1-H∙∙∙O7 interaction; and the molecular dynamic showed a decentralized hydrogen on maleate driving a decomposition by charge transfer process while a centered hydrogen driving the stabilization. The charge transfer process and the mobility of the proton (H+) between enalapril and maleate molecules was demonstrated using supramolecular modeling analyses and molecular dynamics calculations.

КОЛИЧЕСТВЕННОЕ ОПРЕДЕЛЕНИЕ ЭНАЛАПРИЛА МАЛЕАТА В СУБСТАНЦИИ И ТАБЛЕТКАХ МЕТОДОМ ГАЛЬВАНОСТАТИЧЕСКОЙ КУЛОНОМЕТРИИ

Enalapril, belonging to the class of ACE inhibitors, is one of the leading drugs in the treatment of cardiovascular diseases and is used to treat essential hypertension of any severity, renovascular hypertension, heart failure and its prevention, as well as the prevention of coronary ischemia in patients with left ventricular dysfunction. Increasing requirements for the quality of pharmaceutical substances and pharmaceutical dosage forms create conditions for improving existing and creating new analytical developments performed using modern instrumentation. A promising method for quality control of pharmaceutical substances is the method of galvanostatic coulometry, in particular, coulometric titration with electrogenerated hydroxide ions, in which the main controlled parameters are time and current flowing through the electrochemical cell. Electrogenerated hydroxide ions are formed during the electrolysis of water. As an electron carrier, sodium sulfate, potassium sulfate, and other salts are usually used. Currently, devices are being produced that allow you to measure these parameters automatically with high accuracy. Galvanostatic coulometry is distinguished by the simplicity of the experiment, rapidity, and accuracy. Does not require expensive equipment, preliminary standardization of the titrant, the use of standard samples (except for the determination of water by the Karl Fischer method). Electrogenerated hydroxide ions interact with enalapril maleate quickly and quantitatively in a ratio of 3:1. Unified methods have been developed for the quantitative determination of enalapril maleate in the substance and tablets by coulometric titration with electrogenerated hydroxide ions. The auxiliary components of the tablet mass do not interfere with the determination of the active ingredient. The relative standard deviation does not exceed 0.6%, the relative error of the mean does not exceed 0.8%. Methods can be used in the practice of control and analytical laboratories to assess the parameter "Assay" in the substance and tablets.