РЕФЛЕКТОМЕТРИЧЕСКОЕ И ВИЗУАЛЬНО-ТЕСТОВОЕ ОПРЕДЕЛЕНИЕ PD(II) В ОБЪЕКТАХ СЛОЖНОГО СОСТАВА С ИСПОЛЬЗОВАНИЕМ ИНДИКАТОРНОЙ БУМАГИ

RIP-Pd-Test reagent indicator paper based on 1-phenyl-5-(3,4-dihydro-6-methyl-4-oxo-3H-pyrimidin-2-yl)-formazan-6-cellulose has been proposed for determining the palladium content using the sorption-reflectometry and visual-test methods in objects of complex composition. The RIP synthesis technique was described. The estimated composition of the metal complex formed as a result of the heterogeneous indicator reaction at pH 1.5–2.5 was indicated, and the forced coordination of palladium : reagent = 1:1 was ensured. When the RIP interacted with palladium (II) ions, the yellow indicator strip became green with different intensities. Under the selected conditions, the high selectivity for the detection and determination of Pd(II) was shown. With the help of the «Ecotest-2040» portable reflectometer, the reflectometry measurements were carried out using the red LED with the radiation wavelength of 660 nm. For the visual testing, the color scales were used. The indicator reaction was proposed to be carried out in three modes: without concentration and with concentration of the test solution in 100 and 1000 times on the reaction indicator zone of the paper strip (using the pocket pumping device). By the statistical method, the limit of Pd(II) determination for the visual test method (40, 0.47, 0.042 mg/l) was estimated. The palladium detection limit using the reflectometer (19, 0.22, 0.018 mg/l) for the three modes, respectively, was calculated by 3s criterion. The found values of the limiting concentrations were comparable with the metrological characteristics of the known analysis methods in which solid-phase reagents were used. The trueness of the palladium determinations in technological objects of complex composition and drugs has been proven by the independent methods - atomic emission, spectrophotometric and gravimetric methods of analysis. The value of the relative standard deviation of the determined Pd(II) concentration using the portable reflectometer did not exceed 7%.Keywords: palladium(II), formazan, reagent indicator paper, sorption, reflectometry, visual test analysisDOI: http://dx.doi.org/10.15826/analitika.2020.24.2.007  V.M. Ostrovskaya1, E.A. Reshetnyak2, O.S. Chernyshova3, E.Yu. Bryleva3 1 25 State research institute of the Ministry of Defence of Russian Federation", 10 Molodogvardeyskaya Str., Moscow, 121467, Russian Federation2 V.N. Karazin National University, 4 Svoboda Sq., Kharkiv, 61022, Ukraine3 SSI "Institute for Single Crystals" NAS of Ukraine, 60 Nauky Ave, Kharkiv, 61072, UkraineРеагентная индикаторная бумага РИБ-Pd-Тест на основе 1-фенил-5-(3,4-дигидро-6-метил-4-оксо-3Н-пиримидин-2-ил)-формазан-6-целлюлозы предложена для определения содержания палладия сорбционно-рефлектометрическим и визуально-тестовым методами в объектах сложного состава. Изложена методика синтеза РИБ, указан предполагаемый состав металлокомплекса, образующегося в результате гетерогенной индикаторной реакции при рН = 1.5-2.5, с принудительной координацией палладий : реагент = 1 : 1. При взаимодействии РИБ с ионами палладия(II) желтая индикаторная полоса становилась зеленого цвета разной интенсивности. В выбранных условиях показана высокая селективность обнаружения и определения Pd(II). Рефлектометрические измерения проводили с помощью портативного рефлектометра «Экотест-2040», используя красный светодиод с длиной волны излучения 660 нм; для визуального тестирования применяли цветовые шкалы. Индикаторную реакцию предложено проводить в трех режимах: без концентрирования и с концентрированием исследуемого раствора в 100 и 1000 раз на реакционной индикаторной зоне бумажной полосы (применяя карманное прокачивающее устройство). Статистическим методом оценены значения предела определения Pd(II) для визуально-тестовой методики (40, 0.47, 0.042 мг/л) и по 3s-критерию вычислены значения предела обнаружения палладия с использованием рефлектометра (19, 0.22, 0.018 мг/л) для трех режимов, соответственно. Найденные значения предельных концентраций сопоставимы с метрологическими характеристиками известных методик анализа, в которых применяли твердофазные реагенты. Правильность определений палладия в технологических объектах сложного состава и лекарственных препаратах доказана независимыми методами – атомно-эмиссионным, спектрофотометрическим и гравиметрическим методами анализа. Величина относительного стандартного отклонения определяемой концентрации Pd(II) с использованием портативного рефлектометра не превысила 7 %.Ключевые слова: палладий(II), формазан, реагентная индикаторная бумага, сорбция, рефлектометрия, визуальный тестовый анализDOI: http://dx.doi.org/10.15826/analitika.2020.24.2.00

Reflectometric and visual test determination of Pd(II) in objects of complex composition using the indicator paper

Реагентная индикаторная бумага РИБ-Pd-Тест на основе 1-фенил-5-(3,4-дигидро-6-метил-4-оксо-3Н-пиримидин-2-ил)-формазан-6-целлюлозы предложена для определения содержания палладия сорбционно-рефлектометрическим и визуально-тестовым методами в объектах сложного состава. Изложена методика синтеза РИБ, указан предполагаемый состав металлокомплекса, образующегося в результате гетерогенной индикаторной реакции при рН = 1.5-2.5, с принудительной координацией палладий : реагент = 1 : 1. При взаимодействии РИБ с ионами палладия(II) желтая индикаторная полоса становилась зеленого цвета разной интенсивности. В выбранных условиях показана высокая селективность обнаружения и определения Pd(II). Рефлектометрические измерения проводили с помощью портативного рефлектометра «Экотест-2040», используя красный светодиод с длиной волны излучения 660 нм; для визуального тестирования применяли цветовые шкалы. Индикаторную реакцию предложено проводить в трех режимах: без концентрирования и с концентрированием исследуемого раствора в 100 и 1000 раз на реакционной индикаторной зоне бумажной полосы (применяя карманное прокачивающее устройство). Статистическим методом оценены значения предела определения Pd(II) для визуально-тестовой методики (40, 0.47, 0.042 мг/л) и по 3s-критерию вычислены значения предела обнаружения палладия с использованием рефлектометра (19, 0.22, 0.018 мг/л) для трех режимов, соответственно. Найденные значения предельных концентраций сопоставимы с метрологическими характеристиками известных методик анализа, в которых применяли твердофазные реагенты. Правильность определений палладия в технологических объектах сложного состава и лекарственных препаратах доказана независимыми методами – атомно-эмиссионным, спектрофотометрическим и гравиметрическим методами анализа. Величина относительного стандартного отклонения определяемой концентрации Pd(II) с использованием портативного рефлектометра не превысила 7 %.RIP-Pd-Test reagent indicator paper based on 1-phenyl-5-(3,4-dihydro-6-methyl-4-oxo-3H-pyrimidin-2-yl)-formazan-6-cellulose has been proposed for determining the palladium content using the sorption-reflectometry and visual-test methods in objects of complex composition. The RIP synthesis technique was described. The estimated composition of the metal complex formed as a result of the heterogeneous indicator reaction at pH 1.5–2.5 was indicated, and the forced coordination of palladium : reagent = 1:1 was ensured. When the RIP interacted with palladium (II) ions, the yellow indicator strip became green with different intensities. Under the selected conditions, the high selectivity for the detection and determination of Pd(II) was shown. With the help of the «Ecotest-2040» portable reflectometer, the reflectometry measurements were carried out using the red LED with the radiation wavelength of 660 nm. For the visual testing, the color scales were used. The indicator reaction was proposed to be carried out in three modes: without concentration and with concentration of the test solution in 100 and 1000 times on the reaction indicator zone of the paper strip (using the pocket pumping device). By the statistical method, the limit of Pd(II) determination for the visual test method (40, 0.47, 0.042 mg/l) was estimated. The palladium detection limit using the reflectometer (19, 0.22, 0.018 mg/l) for the three modes, respectively, was calculated by 3s criterion. The found values of the limiting concentrations were comparable with the metrological characteristics of the known analysis methods in which solid-phase reagents were used. The trueness of the palladium determinations in technological objects of complex composition and drugs has been proven by the independent methods - atomic emission, spectrophotometric and gravimetric methods of analysis. The value of the relative standard deviation of the determined Pd(II) concentration using the portable reflectometer did not exceed 7%

QUALITY RISK MANAGEMENT FOR SALBUTAMOL PRESSURIZED METERED DOSE INHALERS

The risks for the functional characteristics of Salbutamol pressurized metered dose inhaler (pMDI), such as the uniformity of delivered dose, the distribution of salbutamol particles at the stages of the Andersen impactor (apparatus D), and the respirable fraction, were studied and identified. It is shown that these risks can be associated with the solubility of salbutamol sulfate (SS), the formulation of pMDI, the water content in the SS and ethanol, as well as the particle size distribution of SS. A relationship is shown between the particle size distribution of the SS, the rate of their sedimentation and the performance characteristics of the preparation. The properties of SS crystals are investigated and the possibility of enantiomers presence is shown. The risks associated with the production process, the materials of the primary packaging and the correctness of the quality control procedures are discussed. It is shown that the use of containers made of aluminum alloy EN AW-5052-0 without internal coating does not pose the risk of the release of elemental impurities into the preparation. Unjustified replacement of actuators may pose a risk to the performance characteristics of Salbutamol pMDI and in vitro equivalence as compared with the reference medicinal product

LABORATORY EQUIPMENT DURING PHARMACEUTICAL DEVELOPMENT OF SEMI-SOLID PREPARATIONS

Introduction. When developing drugs it is necessary to use laboratory equipment that simulates pilot and industrial equipment. For the production of semi-solid preparations the key equipment are rotor-stator dispersers and vacuum reactors-homogenizers.Aim. Investigation of the functional characteristics of laboratory equipment: Megatron® MT 1-50 dispersant SHS F/2 (Kinematica AG, Switzerland) and the RP-5 vacuum homogenizer reactor (Promvit, Ukraine).Materials and methods. During development a generic product Penciclovir cream 1% the initial particle size in suspension of penciclovir and particle size after grinding were studied by optical microscopy and laser diffraction methods. In a cream made in the reactor, the particle size of the dispersed phase of the o/w emulsion and suspension, as well as the absence of air bubbles, were determined by optical microscopy. The assay of penciclovir in 9 samples of the cream taken from the reactor-homogenizer was performed by liquid chromatography. By the of rotational viscometry method the rheological properties of the cream were studied. By the inductively coupled plasma atomic emission spectroscopy the getting of metal impurities from the disperser and the reactor-homogenizer into the suspension and cream were investigated.Results and discussion. With an increase in the rotor speed, the particle size of penciclovir in suspension decreases. The disperser effectively performs its function at a rotor speed of 25,000 rpm. In a cream made in the reactor, the deviations in the quantitative content of penciclovir from the average value in each sample are within the uncertainty of the analytical procedure, which indicates its uniform distribution. The reactor provides effective dispersion and uniform distribution of the oil phase, prevents the formation of a gas emulsion and allows getting a cream that, according to its rheological properties, corresponds to the reference preparation Fenistil® Pencivir cream 1%. In the production process metal impurities were not emitted into the suspension and the cream from the equipment.Conclusion. The disperser and the reactor during the production of cream with penciclovir are suitable for their intended use. It is rational to combine these two types of equipment at the sites for the production of semi-solid preparations. The disperser can also be used to produce emulsions with a very small particle size of the dispersed phase