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

Kinetics of the Synthesis of Aluminum Boride by the Self-Propagating High-Temperature Synthesis Method

The influence of certain factors on the kinetics of the process of obtaining aluminum borides (burning rate, ingot formation, and phase separation) was investigated. In this study, we report the registration of diboride using the SHS protocol. The synthesis of aluminum diboride from boric anhydride occurred by the aluminothermic method. The initial components were boron trioxide and aluminum in the form of powders. Researchers paid special attention to the degree of grinding of the charge fluxing substances. The influence this had on the rate of development of the degree of charge concentration was studied. To calculate the degree of charge, a composition was chosen according to the speed obtained from a number of experiments where melting was carried out with the following charge densities in g/cm(3): 0.80; 1.08; 1.18; 1.74. The method of melting was ignition from above. The experimental results allowed us to conclude that the nature of the change in the combustion rate of the system, where there was an excess of the reducing agent in the charge, is the same. An increase in the combustion rate, where there was an excess of aluminum of up to 20%, was likely due to the fact that the reaction area of the charge components increased. In addition, an increase in speed can be explained by a decrease in heat losses due to a reduction in the melting time. With an increase in excess aluminum above 20% of the stoichiometry, the observed decrease in the combustion rate can be explained by a decrease in the specific heat of the process due to the melting of the excess aluminum, which played the role of a ballast

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of bodysurface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2 ), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of endstage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years. (Funded by Janssen Research and Development; CREDENCE ClinicalTrials.gov number, NCT02065791.

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Верифікація тесту «розчинення» для капсул доксицикліну хіклату для впровадження до фармакопейної монографії

The study of dissolution profiles is important as a cheap and easy supplement to bioequivalence research, and as a variation to such studies. This method is not outlined in the State Pharmacopoeia of Ukraine for the doxycycline capsules. Therefore, according to the current requirements, it was necessary to verify the procedure recommended by the US Pharmacopeia to confirm that this laboratory test will be reproduced correctly, and to use it in our further studies.The aim of our research was to verify the "Dissolution" test analytical procedure for doxycycline hyclate capsules, recommended by the US Pharmacopoeia.Methods. Capsules of doxycycline hyclate 100 mg and set of mineral waters were taken as study objects. A standard sample of doxycycline was used for preparation the comparison solutions. All reagents and test specimens meet the requirements of the SPhU. The experimental data were obtained at the same time in a standardized procedure. For this purpose, 9 points were studied within the range 55-135 % with a step of 10 %. The obtained results were processed statistically in accordance with the requirements of the SPhU.Results. The conducted prediction showed that the total uncertainty of the results of the methodic is 1.04 %, which does not exceed the critical value (3.0 %). To determine the specificity, the effect of placebo was investigated. The calculation showed that the overall effect of placebo on the total absorption of the drug is non-significant (0.51 % ≤ 0.96 %). Also, the method is linear in the range of concentrations from 55 % to 135 %. The systematic error of the results meets the recommended criteria.Conclusions. The analysis of model mixtures of doxycycline hyclate showed the correctness of the investigated methodВивчення профілів розчинення є важливими в якості доповнення до дослідження біоеквівалентності, і як різновид таких досліджень, як простий і недорогий метод. Тест «Розчинення» для капсул доксицикліну не описаний у ДФУ. Отже, відповідно до поточних вимог, було необхідно верифікувати методику, рекомендовану Американською Фармакопеєю та підтвердити те, що вона буде відтворена правильно в конкретній лабораторії для використання в наших подальших дослідженнях.Метою нашого дослідження було перевірити аналітичну методику тест "Розчинення" для капсул доксіцикліну хіклату, рекомендований Американською Фармакопеєю.Методи. Капсули доксицикліну хіклату 100 мг та ряд мінеральних вод були взяті в якості об'єктів дослідження. Для приготування порівняльних розчинів використовували стандартний зразок доксицикліну. Всі реактиви та пробні зразки відповідають вимогам ДФУ. Експериментальні дані одержували одночасно за стандартною процедурою. З цією метою було вивчено 9 точок у межах 55-135 % з кроком 10 %. Отримані результати оброблялися статистично відповідно до вимог ДФУ.Результати. Проведений прогноз показав, що повна невизначеність результатів методики становить 1,04 %, що не перевищує критичного значення (3,0 %). Для визначення специфічності досліджували вплив плацебо. Розрахунок показав, що загальний вплив плацебо на сумарне поглинання препарату є незначним (0,51 % ≤ 0,96 %). Крім того, метод лінійний у діапазоні концентрацій від 55 % до 135 %. Систематична похибка результатів задовольняє рекомендованим критеріям.Висновки. Аналіз модельних сумішей доксицикліну хіклату показав правильність досліджуваного метод

Modelling and investigation of amoxicillin chemical interaction with mineral waters containing a significant amount of calcium and magnesium salts

In recent years, the interaction of drugs with the components of food and drinks has been actively researched to ensure rational therapy. It is particularly important for amoxicillin as an antibiotic group of drugs, considering the issue of resistance. A study of the interaction of amoxicillin with mineral waters, which in significant quantities may contain cations and anions and enter complexation reactions, has not been conducted before. For the study, various chemical and physicochemical methods were used. Also in vitro dissolution test with conditions of simultaneous administration of amoxicillin with mineral waters in a 0.1M HCl was modelled. Results showed that amoxicillin could form multiple complex compounds with magnesium cations in the 0.1 M HCl with different stoichiometry. The study showed that from several investigated mineral waters, presented on the Ukrainian market, the “Karpatska dzherelna” could interact with amoxicillin in the medium of a 0.1 M HCl

Simultaneous assaying of famotidine, calcium carbonate and magnesium hydroxide in the extemporaneously prepared suspension

INTRODUCTION: The share of extemporaneously prepared drugs on the pharmaceutical  market  has been on the increase lately. The suspension of famotidine with calcium carbonate and magnesium hydrox- ide is one of such drugs.AIM: The aim of our study is to develop the assay methods for each component in the simultaneous sample of the suspension in order to decrease the volume of the medical form and the time for  analysis.MATERIALS AND METHODS: The object of study is the extemporaneously prepared suspension with the content of active substances per 5 ml: famotidine 10 mg; calcium carbonate 400 mg; magnesium hydrox- ide 120 mg. Tablets with famotidine content (20 mg) were used for suspension   preparation.The substance of famotidine was used as the working standard sample (WSS). The `Evolution 60S` spectro- photometer, the AB 204 S/A Mettler Toledo analytical balances, class A measuring vessels as well as reagents that meet the requirements of the State Pharmacopeia of Ukraine were used in the   study.RESULTS: Complexometric titration for calcium carbonate and magnesium hydroxide using murexide and Eriochrome Black T as indicators and UV-spectrophotometric determination of  famotidine at  λmax=265 nm wavelength were carried out in the simultaneous sample of the suspension. The metrological character- istics confirm the correctness of the proposed  methods.CONCLUSIONS: The developed methods can be used to determine the active compounds in the simultane- ous sample of the suspension. The uncertainty of the average results for calcium carbonate quantitative de- termination was 0.94%, for magnesium hydroxide - 1.14%, and for famotidine -   0.75%

Kinetics of the Synthesis of Aluminum Boride by the Self-Propagating High-Temperature Synthesis Method

The influence of certain factors on the kinetics of the process of obtaining aluminum borides (burning rate, ingot formation, and phase separation) was investigated. In this study, we report the registration of diboride using the SHS protocol. The synthesis of aluminum diboride from boric anhydride occurred by the aluminothermic method. The initial components were boron trioxide and aluminum in the form of powders. Researchers paid special attention to the degree of grinding of the charge fluxing substances. The influence this had on the rate of development of the degree of charge concentration was studied. To calculate the degree of charge, a composition was chosen according to the speed obtained from a number of experiments where melting was carried out with the following charge densities in g/cm3: 0.80; 1.08; 1.18; 1.74. The method of melting was ignition from above. The experimental results allowed us to conclude that the nature of the change in the combustion rate of the system, where there was an excess of the reducing agent in the charge, is the same. An increase in the combustion rate, where there was an excess of aluminum of up to 20%, was likely due to the fact that the reaction area of the charge components increased. In addition, an increase in speed can be explained by a decrease in heat losses due to a reduction in the melting time. With an increase in excess aluminum above 20% of the stoichiometry, the observed decrease in the combustion rate can be explained by a decrease in the specific heat of the process due to the melting of the excess aluminum, which played the role of a ballast

Optimization of Aluminum Boride Synthesis in the Self-Propagating High-Temperature Synthesis Mode to Create Waste-Free Technology

This paper is the continuation of our previous paper. In this work, we optimized the synthesis of aluminum borides by the SHS method. The purpose of the research was to develop the foundations of waste-free technology. The initial components were powders of boric anhydride (B2O3), aluminum (Al), the oxide-heating additive (KNO3), various fluxing additives, including mixed ones. The optimal ratios of the initial components for increasing the yield of aluminum boride with a high boron content and obtaining slag suitable for the production of high-alumina clinkers were determined. Studies have shown that the development of a waste-free technology for producing aluminum borides by the method of self-propagating high-temperature synthesis (SHS) is possible and yields target (alloy) and by-product (slag) products that meet the requirements for chemical and phase composition

Optimization of Aluminum Boride Synthesis in the Self-Propagating High-Temperature Synthesis Mode to Create Waste-Free Technology

This paper is the continuation of our previous paper. In this work, we optimized the synthesis of aluminum borides by the SHS method. The purpose of the research was to develop the foundations of waste-free technology. The initial components were powders of boric anhydride (B2O3), aluminum (Al), the oxide-heating additive (KNO3), various fluxing additives, including mixed ones. The optimal ratios of the initial components for increasing the yield of aluminum boride with a high boron content and obtaining slag suitable for the production of high-alumina clinkers were determined. Studies have shown that the development of a waste-free technology for producing aluminum borides by the method of self-propagating high-temperature synthesis (SHS) is possible and yields target (alloy) and by-product (slag) products that meet the requirements for chemical and phase composition