Ponašanje pri savijanju toplinski obrađenih aluminijskih pjena

Metalne pjene su porozni, ćelijasti materijali s vrlo nejednolikom strukturom. Upravo ta struktura značajno utječe na njihova mehanička svojstva. Glavni cilj ovog rada bio je ispitivanje savojnih svojstava uzoraka okruglog profila, jednakog olumena i gustoće, napravljenih od aluminijske pjene legure AlMgSi0, 6 s zatvorenim ćelijama, a koji su toplinski obrađeni. Zbog toga su provedena ispitivanja mehaničke otpornosti pri savijanju na kidalici uzoraka od kojih je polovica hlađena u vodi, a polovica na zraku. Dio uzoraka ohlađenih na zraku podvrgnuti homogenizaciji i umjetnom dozrijevanju, a dio ohlađenih u vodi umjetnom dozrijevanju

Quality by Design approach in the development of hydrophilic interaction liquid chromatographic method for the analysis of iohexol and its impurities

This study presents the development of hydrophilic interaction liquid chromatographic method for the analysis of iohexol, its endo-isomer and three impurities following Quality by Design (QbD) approach. The main objective of the method was to identify the conditions where adequate separation quality in minimal analysis duration could be achieved within a robust region that guarantees the stability of method performance. The relationship between critical process parameters (acetonitrile content in the mobile phase, pH of the water phase and ammonium acetate concentration in the water phase) and critical quality attributes is created applying design of experiments methodology. The defined mathematical models and Monte Carlo simulation are used to evaluate the risk of uncertainty in models prediction and incertitude in adjusting the process parameters and to identify the design space. The borders of the design space are experimentally verified and confirmed that the quality of the method is preserved in this region. Moreover, Plackett-Burman design is applied for experimental robustness testing and method is fully validated to verify the adequacy of selected optimal conditions: the analytical column ZIC HILIC (100 mm x 4.6 mm, 5 mu m particle size); mobile phase consisted of acetonitrile-water phase (72 mM ammonium acetate, pH adjusted to 6.5 with glacial acetic acid) (86.7:13.3) v/v; column temperature 25 degrees C, mobile phase flow rate 1 mL min(-1), wavelength of detection 254 nm.This is peer-reviewed version of the following article: Jovanović, M.; Rakić, T.; Tumpa, A.; Jančić Stojanović, B. Quality by Design Approach in the Development of Hydrophilic Interaction Liquid Chromatographic Method for the Analysis of Iohexol and Its Impurities. J. Pharm. Biomed. Anal. 2015, 110, 42–48. [https://doi.org/10.1016/j.jpba.2015.02.046

Optimizacija HILIC metode za analizu bisoprolola i njegovih nečistoća uz procenu mogućnosti variranja položaja pikova

This paper presents the robust optimization of hydrophilic interaction liquid chromatographic method for the analysis of bisoprolol and its impurities A and C. Chemometric strategy is applied for detailed understanding of system's behavior and establishing the mathematical relationship between investigated factors (acetonitrile content in the mobile phase, pH of the water phase and buffer concentration in the water phase) and chromatographic responses. Grid point search methodology is then performed with the aim to identify the point with satisfactory separation quality for all analyzed substances and to achieve minimal analysis duration. Oversized chromatograms are made creating an extra band broadening for each chromatographic peak corresponding to the value of standard deviation in order to evaluate the incertitude originating from the model uncertainty. On the other hand, the uncertainty originating from the variation of experimental parameters is assessed by simulated experimental design robustness testing. Finally, the obtained robust optimal conditions were: chromatographic column Kinetex HILIC 100Å (100 mm x 4.5 mm, 2.6 mm particle size); mobile phase composed of acetonitrile - water phase (35 mM ammonium acetate, pH 4.9 adjusted with glacial acetic acid) (85:15 v/v); flow rate 1 mL min-1, column temperature 30°C and UV detection at 254 nm.U ovom radu prikazana je optimizacija metode tečne hromatografije hidrofilnih interakcija za analizu bisoprolola i njegovih nečistoća A i C uz procenu mogućnosti variranja položaja pikova. Primenjena je hemometrijska strategija za detaljno razumevanje ponašanja sistema i uspostavljanje matematičke veze između ispitivanih faktora (sadržaj acetonitrila u mobilnoj fazi, pH vrednost vodene faze i koncentracija pufera u vodenoj fazi) i hromatografskih odgovora. Enumerativna tehnika optimizacije upotrebljena je za identifikaciju tačke koja pokazuje zadovoljavajući kvalitet razdvajanja svih ispitivanih supstanci i minimalno vreme trajanja analize. Kreirani su prošireni hromatogrami širenjem pikova svih ispitivanih supstanci za vrednosti standardne devijacije kako bi se procenila mogućnost greške odgovora koja potiče iz greške matematičkog modela. Mogućnost greške koja potiče iz greške u podešavanju eksperimentalnih parametara procenjena je simuliranim testiranjem robusnosti primenom eksperimentalnog dizajna. Konačno, dobijeni optimalni uslovi bili su: hromatografska kolona Kinetex HILIC 100Å (100 mm x 4,5 mm, 2,6 mm veličina čestica); mobilna faza sastavljena od smeše acetonitril - vodena faza (35 mM amonijum-acetat, pH 4,9 podešen glacijalnom sirćetnom kiselinom) (85:15 v/v); protok 1 mL min-1, temperatura kolone 30°C i UV detekcija na 254 nm

Testiranje robusnosti metode tečne hromatografije za određivanje itrakonazola i njegovih nečistoća primenom frakcionog faktorskog dizajna

Test of robustness is a part of the method validation and it is carried out in the end of the method development or in the beginning of the method validation. The purpose of robustness testing is to avoid problems in interlaboratory studies and to define parameters with the greatest impact on the method. The chosen factors are investigated within the range that slightly exceeds the expected variations when the method is transferred from one instrument/laboratory to another. The application of experimental design is recommended to perform robustness testing and two most often utilized - Plackett-Burman and fractional factorial design - are described. Furthermore, the manners of evaluation of factor significance, the methods for calculation of the range of insignificance for significant factors and the procedure for determination of system suitability test parameters are described. Such an approach of robustness testing was applied to the high performance liquid chromatographic method for determination of itraconazole and its impurities B and F. The robustness is tested by using fractional factorial design and 4 factors in 11 experiments were analyzed. After the application and the analysis of all the suggested steps for robustness, the impact of factors on the system responses was evaluated, insignificance ranges were defined and system suitability test limits for suggested method were determined.Test robusnosti metode predstavlja deo validacije metode, a izvodi se na kraju razvoja metode ili na početku validacije. Testiranje robusnosti je uvedeno da bi se izbegli problemi u međulaboratorijskim ispitivanjima i da bi se definisali faktori koji imaju najveći uticaj na metodu. Izabrani faktori ispituju se u intervalu koji blago prevazilazi varijacije koje se očekuju kada se metoda prenosi sa jednog instrumenta/laboratorije na drugi. Za testiranje robusnosti korisno je primeniti eksperimentalni dizajn. U ovom radu opisana su dva najčešće korišćena, Plakett-Burman-ov i frakcioni faktorski dizajn. Takođe, opisani su i načini procene značajnosti faktora, zatim načini izračunavanja intervala neznačajnosti za značajne faktore, kao i postupak određivanja parametara za procenu pogodnosti sistema. Ovakav pristup procene robusnosti metode primenjen je na metodu tečne hromatografije za određivanje itrakonazola i njegovih nečistoća B i F. Robusnost je testirana primenom frakcionog faktorskog dizajna, a analizirana su četiri faktora kroz 11 eksperimenata. Sprovodeći i analizirajući sve predložene korake za robusnost procenjen je uticaj faktora na faktore rezolucije kao odgovore sistema, definisani su intervali neznačajnosti i određeni limiti za proveru pogodnosti sistema predložene metode

Chromatographic Analysis of Olopatadine in Hydrophilic Interaction Liquid Chromatography

In this paper, chromatographic analysis of active substance olopatadine hydrochloride, which is used in eye drops as antihistaminic agent, and its impurity E isomer by hydrophilic interaction liquid chromatography (HILIC) and application of design of experiments (DoE) methodology are presented. In addition, benzalkonium chloride is very often used as a preservative in eye drops. Therefore, the evaluation of its chromatographic behavior in HILIC was carried out as well. In order to estimate chromatographic behavior and set optimal chromatographic conditions, DoE methodology was applied. After the selection of important chromatographic factors, Box-Behnken design was utilized, and on the basis of the obtained models factor effects were examined. Then, multi-objective robust optimization is performed aiming to obtain chromatographic conditions that comply with several quality criteria simultaneously: adequate and robust separation of critical peak pair and maximum retention of the first eluting peak. The optimal conditions are identified by using grid point search methodology. The experimental verification confirmed the adequacy of the defined optimal conditions. Finally, under optimal chromatographic conditions, the method was validated and applicability of the proposed method was confirmed

Evaluation of Seven Chromatographic Response Functions on Simulated and Experimentally Obtained Chromatograms in Hydrophilic Interaction Liquid Chromatography System

This paper investigates the ability of seven chromatographic response functions to measure the quality of chromatograms obtained in hydrophilic interaction liquid chromatography (HILIC). First, the functions were tested on a set of simulated chromatograms and differences in their mathematical design were discussed. Second, the functions were evaluated on the experimentally obtained chromatograms in HILIC analysis of model mixture consisted of beta agonists and antagonists. The ranking of chromatograms obtained by different functions was significantly different, implying that the accuracy of the optimization procedure is strongly dependent on the function that was selected as an output. Investigation of potential drawbacks of each function was conducted and general recommendations concerning the use of chromatographic response functions in optimization strategies are proposed.This is peer-reviewed version of the following article: Rakić, T.; Stojanović, B. J.; Jovanović, M.; Malenović, A.; Ivanović, D.; Medenica, M. Evaluation of Seven Chromatographic Response Functions on Simulated and Experimentally Obtained Chromatograms in Hydrophilic Interaction Liquid Chromatography System. Anal. Lett. 2013, 46 (8), 1198–1212. [https://doi.org/10.1080/00032719.2012.755689

Five different columns in the analysis of basic drugs in hydrophilic interaction liquid chromatography

Five different columns (two silica, two cyanopropyl and one diol) were investigated in hydrophilic interaction liquid chromatography (HILIC). For the assessment of columns behavior in HILIC mode, six basic drugs (lamotrigine, thioridazine, clozapine, chlorpheniramine, pheniramine and sulpiride) were chosen. The assessment of the influence of the concentration of organic modifier on analytes' retention on each column was provided by fitting the retention data into theoretical models. Utilizing the statistical analysis, the selection of the model that provides better prediction of the retention behavior was enabled. Dual RP-HILIC mechanism was suggested on cyanopropyl and diol columns, therefore the transition points between the two mechanisms on these columns were calculated. Furthermore, in order to investigate the impact of three factors simultaneously on the retention behavior of the analyzed substances on Betasil Silica column, chemometrically-aided empirical models were built. The experiments were conducted according to the matrix of Box-Behnken design and on the basis of the retention data, six quadratic models were obtained and their adequacy was confirmed using ANOVA test. The obtained coefficients of quadratic models enabled the elucidation of both single factor and factor interactions influence. This was also graphically presented in 3D response surface plots

Chemometrically assissted optimization and validation of RP-HPLC method for the analysis of itraconazole and its impurities

This paper presents the chemometrically assisted optimization and validation of the RP-HPLC method intended for the quantitative analysis of itraconazole and its impurities in pharmaceutical dosage forms. To reach the desired chromatographic resolution with a limited number of experiments in a minimum amount of time, Box-Behnken design was used to simultaneously optimize some important chromatographic parameters, such as the acetonitrile content in the mobile phase, pH of the aqueous phase and the column temperature. Separation between itraconazole and impurity F was identified as critical and selected as a response during the optimization. The set optimal mobile phase composition was set as acetonitrile/water pH 2.5 adjusted with o-phosphoric acid (50:50, V/V). Separations were performed on the Zorbax Eclipse XDB-C18 4.6 × 150 mm, 5 m particle size column with the flow rate 1 mL min–1, column temperature set at 30 °C and UV detection at 256 nm. The established method was then subjected to method validation and the required validation parameters were tested. For the robustness evaluation, fractional factorial 24–1 design was utilized and factors that might significantly affect the system performance were defined. As other validation parameters were also found to be suitable, the possibility to apply the proposed method for the determination of itraconazole, its impurities B and F in any laboratory under different circumstances has been proven

Theoretical Models and QSRR in Retention Modeling of Eight Aminopyridines

In this article, retention modeling of eight aminopyridines (synthesized and characterized at the Faculty of Pharmacy) in reversed-phase high performance liquid chromatography (RP-HPLC) was performed. No data related to their retention in the RP-HPLC system were found. Knowing that, it was recognized as very important to describe their retention behavior. The influences of pH of the mobile phase and the organic modifier content on the retention factors were investigated. Two theoretical models for the dependence of retention factor of organic modifier content were tested. Then, the most reliable and accurate prediction of log k was created, testing multiple linear regression model-quantitative structure-retention relationships (MLR-QSRR) and support vector regression machine-quantitative structure-retention relationships (SVM-QSRR). Initially, 400 descriptors were calculated, but four of them (POM, log D, M-SZX/RZX and m-RPCG) were included in the models. SVM-QSRR performed significantly better than the MLR model. Apart from aminopyridines, four structurally similar substances (indapamide, gliclazide, sulfamethoxazole and furosemide) were followed in the same chromatographic system. They were used as external validation set for the QSRR model (it performed well within its applicability domain, which was defined using a bounding box approach). After having described retention of eight aminopyridines with both theoretical and QSRR models, further investigations in this field can be conducted

Comparation of mechanical behaviour of SiC sintered specimen to analysis of surface defects

This research examined SiC sintered specimens with high hardness and strength. This material is used to protect of projectile impact for military purposes. The testing procedure consists of structure examination obtained using XRD analysis, surface examination by SEM analysis and optical microscopy, examination of mechanical properties and density determination. Analysis confirmed surface irregularities characterized using image analysis. The sample is subjected to bending. Finite element modeling was used to simulate the behavior of sample subjected to bending in presence of critical damage on surface. It is confirmed that there is correlation between the largest irregularities determined on surface and measured strength of sample. Simulations show the significance of damage size. The size of damage on surface is considered to be the critical parameter for quality determination.Program and the book of abstracts available at: [https://dais.sanu.ac.rs/handle/123456789/175