Dr Milan Antonijevic


Associate Professor in Pharmaceutical Sciences
PhD, FHEA, FRSC, MAPS

About

My qualifications

1997
BSc in Chemistry
Faculty of Chemistry, University of Belgrade, Serbia
2005
PhD
Queen's University Belfast
2007
PGCert in Higher Education
University of Greenwich

Research

Research interests

Publications

Dunja Šilić, Biserka Cetina-Čižmek, Steven A. Ross, Andrew Hurt, Milan Antonijevic, Dennis Douroumis (2023)Optimization of Hot-Melt Extrusion Processing for the Synthesis of Ionic Cocrystals, In: Crystal growth & design
Dunja Šilić, Biserka Cetina-Čižmek, Steven A. Ross, Andrew Hurt, Milan Antonijevic, Dennis Douroumis (2023)Optimization of Hot-Melt Extrusion Processing for the Synthesis of Ionic Cocrystals, In: Crystal growth & design23(10)pp. 7355-7364 American Chemical Society

Cocrystals are multicomponent crystalline forms that are an appealing alternative to modify undesirable properties of drug substances, such as poor solubility and stability. Hot-melt extrusion (HME), a solvent-free, robust, and scalable technology, has been proven to be a suitable approach for cocrystallization of several drug-coformer pairs. However, HME has been mainly implemented for the synthesis of molecular cocrystals when most of the marketed products are manufactured in the form of ionic cocrystals. In this study, the synthesis of extruded fluoxetine HCl-succinic acid cocrystals was investigated using different screw configurations. Ionic cocrystals manufactured by HME showed complete transformation of the drug-coformer pair with high purity, improved intrinsic dissolution rates, and long-term storage stability when compared to their counterparts produced by solvent evaporation.

M. D. Antonijevic, S. Owusu-Ware, B. Sanchon-Lopez (2018)Emollient product design: objective measurements of formulation structure, texture and performance, and subjective assessments of user acceptability, In: Clinical and experimental dermatology43(4)pp. 423-429 Wiley

Background. The choice of prescribed emollients is usually based on cost and patient preference. Differences in formulations can affect user acceptability. Aim. To compare the physical performance, user acceptability and various product design features of two emollient gels that are prescribed in the UK and alleged to be therapeutically interchangeable because their formulations are described as having the same contents of oily ingredients. Results. We found that here are in fact significant measurable differences between the structure and performance of the two formulations, which materially affect their user acceptability. These differences are attributed to the use of different types of gelling agents and other ingredients of differing grades/quality and concentrations, and probably due to the formulations being made by different manufacturing processes. We also identified other product design features that are important to user appeal, including the type of container in which the formulations are presented, the type of dispensing devices provided, and the nature and form of the supplied user instructions. Conclusion. Patients and prescribers should be aware that there can be important differences in performance and user appeal between emollients, even between products that, superficially, may appear to be very similar. These important performance aspects should be characterized for new emollient introductions to encourage better informed product selection.

Steven A. Ross, Andrew P. Hurt, Milan Antonijevic, Nicolaos Bouropoulos, Adam Ward, Pat Basford, Mark McAllister, Dennis Douroumis (2021)Continuous Manufacture and Scale-Up of Theophylline-Nicotinamide Cocrystals, In: Pharmaceutics13(3) Mdpi

The aim of the study was the manufacturing and scale-up of theophylline-nicotinamide (THL-NIC) pharmaceutical cocrystals processed by hot-melt extrusion (HME). The barrel temperature profile, feed rate and screw speed were found to be the critical processing parameters with a residence time of approximately 47 s for the scaled-up batches. Physicochemical characterization using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction of bulk and extruded materials revealed the formation of high purity cocrystals (98.6%). The quality of THL-NIC remained unchanged under accelerated stability conditions.

Katarina S. Postolovic, Milan D. Antonijevic, Biljana Ljujic, Marina Miletic Kovacevic, Marina Gazdic Jankovic, Zorka D. Stanic (2022)pH-Responsive Hydrogel Beads Based on Alginate, kappa-Carrageenan and Poloxamer for Enhanced Curcumin, Natural Bioactive Compound, Encapsulation and Controlled Release Efficiency, In: Molecules (Basel, Switzerland)27(13) Mdpi

Polyphenolic compounds are used for treating various diseases due to their antioxidant and anticancer properties. However, utilization of hydrophobic compounds is limited due to their low bioavailability. In order to achieve a greater application of hydrophobic bioactive compounds, hydrogel beads based on biopolymers can be used as carriers for their enhanced incorporation and controlled delivery. In this study, beads based on the biopolymers-K-carrageenan, sodium alginate and poloxamer 407 were prepared for encapsulation of curcumin. The prepared beads were characterized using IR, SEM, TGA and DSC. The curcumin encapsulation efficiency in the developed beads was 95.74 +/- 2.24%. The release kinetics of the curcumin was monitored in systems that simulate the oral delivery (pH 1.2 and 7.4) of curcumin. The drug release profiles of the prepared beads with curcumin indicated that the curcumin release was significantly increased compared with the dissolution of curcumin itself. The cumulative release of curcumin from the beads was achieved within 24 h, with a final release rate of 12.07% (gastric fluid) as well as 81.93% (intestinal fluid). Both the in vitro and in vivo studies showed that new hydrogel beads based on carbohydrates and poloxamer improved curcumin's bioavailability, and they can be used as powerful carriers for the oral delivery of different hydrophobic nutraceuticals.

Slobodan M. Najdanovic, Milica M. Petrovic, Milos M. Kostic, Jelena Z. Mitrovic, Danijela Bojic, Milan D. Antonijevic, Aleksandar L. J. Bojic (2020)Electrochemical synthesis and characterization of basic bismuth nitrate [Bi6O5(OH)(3)](NO3)(5)center dot 2H(2)O: a potential highly efficient sorbent for textile reactive dye removal, In: Research on chemical intermediates46(1)pp. 661-680 Springer Nature

A new method of synthesis was developed for the preparation of basic bismuth nitrate [Bi6O5(OH)(3)](NO3)(5)center dot 2H(2)O (ECBBN). Electrochemical synthesis of the material was carried out by galvanostatic electrodeposition from an acidic Bi(III) solution on a Ti substrate and further thermal treatment in air at 200 degrees C. Characterization of ECBBN was conducted by employing SEM-EDX, N-2 adsorption, XRD and FTIR, and its pI was also determined. The analyses showed that the material obtained was pure [Bi6O5(OH)(3)](NO3)(5)center dot 2H(2)O. Morphologically, ECBBN aggregates were composed of crystals, some smaller than 50 nm. Electrochemically synthesized sorbent (ECBBN) was used for the removal of the textile dye Reactive Blue 19 (RB19) from deionized water and model solutions of polluted river water, and it showed considerably superior sorption performance compared to other inorganic sorbents synthesized by conventional methods reported in the literature. A kinetic study suggests that the sorption process is both under reaction and diffusion control. Equilibration of the sorption process was attained in several minutes, i.e. the sorption process is very fast. The sorption equilibrium data were well interpreted by the Langmuir, Redlich-Peterson and Brouers-Sotolongo isotherm. Using Langmuir isotherm, the maximum sorption capacity of ECBBN was reached at pH 2 and was 1049.19 mg g(-1).

Milan D. Antonijevic, Ovidiu Novac, Barry M. G. O'Hagan (2018)Can emollients of similar composition be assumed to be therapeutically equivalent: a comparison of skin occlusivity and emulsion microstructure, In: Clinical, cosmetic and investigational dermatology11pp. 461-465 Dove Medical Press Ltd

Introduction: Emollient therapy is the mainstay for treating skin conditions such as atopic dermatitis and psoriasis. New emollients have been introduced recently and are assumed to be therapeutically interchangeable with the innovator products because, superficially, they appear to have similar compositions. This study compares a) the ex vivo human skin occlusion performance and b) the visual and microscopic properties of Isomol gel (IMG) and Doublebase gel (DBG). Materials and Methods: Occlusion was measured gravimetrically by reduction in cumulative 48-hour evaporative weight loss from ex vivo human skin samples following single applications of the two test emollients and Vaseline. Skin samples from a single donor were mounted in Franz diffusion cells and then the emollients were spread over the skin surface with an applied dose of approximately 2 mg/cm(2) . The assemblies (four replicates per treatment) were then accurately weighed at baseline (T-0) and again after 5-, 24-, and 48-hour postapplication. The quality of the two emollient gel formulations was compared by visual examination of their film-forming characteristics and by microstructural examination using environmental scanning electron microscopy (ESEM). Results: Occlusivity of the DBG emollient gel formulation was comparable with Vaseline and substantially better than IMG, with the DBG-treated skin samples losing less than half as much weight as the IMG-treated skin samples over 48 hours and at a much slower rate during the first 5 hours. The film-forming characteristics and microstructure of the gels were also very different. Whereas DBG maintained a smooth, uniform film over 24 hours, the IMG formulation phase-separated. ESEM results showed that the DBG emulsion has a stable structural matrix with uniform oil droplets, whereas for IMG the emulsion system is inhomogeneous with the oil phase coalescing into larger irregular shaped rafts. Conclusions: We have demonstrated substantial performance differences between two prescribed emollient gels.

Alessandra D'Angelo, Mike Reading, Milan Antonijevic (2019)A novel micro-photogrammetric instrument for visualizing in 3D small objects applied to the quantitative study of the dissolution behavior of a pharmaceutical dosage form, In: Review of scientific instruments90(12)pp. 124101-124101 Amer Inst Physics

The work presented here proposes an innovative approach to 3D chemical mapping of solid formulations by microphotogrammetry. We present details of a novel microphotogrammetry apparatus and the first results for the application of photogrammetry to the dissolution analysis of solid pharmaceutical dosage forms. Unlike other forms of optical imaging, microphotogrammetry allows a true 3D model to be constructed that includes direct observation of the sides of the sample rather than only top-down topographic imaging. Volume and structural changes are assessed quantitatively and related to chemical analysis by high performance liquid chromatography. The recently introduced method of chemical identification by dissolution analysis, or chemical imaging by dissolution analysis, is employed for the first time to obtain tomographic images of the dissolution process. Published under license by AIP Publishing.

Katarina S. Postolović, Milan D. Antonijević, Biljana Ljujić, Slavko Radenković, Marina Miletić Kovačević, Zoltan Hiezl, Svetlana Pavlović, Ivana Radojević, Zorka Stanić (2022)Curcumin and Diclofenac Therapeutic Efficacy Enhancement Applying Transdermal Hydrogel Polymer Films, Based on Carrageenan, Alginate and Poloxamer, In: Polymers14(19) MDPI

Films based on carrageenan, alginate and poloxamer 407 have been formulated with the main aim to apply prepared formulations in wound healing process. The formulated films were loaded with diclofenac, an anti-inflammatory drug, as well as diclofenac and curcumin, as multipurpose drug, in order to enhance encapsulation and achieve controlled release of these low-bioavailability compounds. The obtained data demonstrated improved drug bioavailability (encapsulation efficiency higher than 90%), with high, cumulative in vitro release percentages (90.10% for diclofenac, 89.85% for curcumin and 95.61% for diclofenac in mixture-incorporated films). The results obtained using theoretical models suggested that curcumin establishes stronger, primarily dispersion interactions with carrier, in comparison with diclofenac. Curcumin and diclofenac-loaded films showed great antibacterial activity against Gram-positive bacteria strains ( Bacillus subtilis and Staphylococcus aureus , inhibition zone 16.67 and 13.67 mm, respectively), and in vitro and in vivo studies indicated that curcumin- and diclofenac-incorporated polymer films have great potential, as a new transdermal dressing, to heal wounds, because diclofenac can target the inflammatory phase and reduce pain, whereas curcumin can enhance and promote the wound healing process.

A. D'Angelo, B. Edgar, A. P. Hurt, M. D. Antonijevic (2018)Physico-chemical characterisation of three-component co-amorphous systems generated by a melt-quench method, In: Journal of thermal analysis and calorimetry134(1)pp. 381-390 Springer Nature

The purpose of this work was to evaluate the possibility of creating a ternary co-amorphous system and to determine how the properties of a co-amorphous material are altered by the addition of a selected third component. Piroxicam and indomethacin form a stable co-amorphous with the T-g above room temperature. The third component added was selected based on tendency to crystallise (benzamide, caffeine) or form amorphous (acetaminophen, clotrimazole) on cooling. Generated co-amorphous systems were characterised with TGA, HSM, DSC, FTIR and XRD. Stable ternary co-amorphous systems were successfully generated, which were confirmed using XRD, DSC and FTIR analysis. In all cases, T-g of the ternary system was lower than the T-g of the binary system, although higher than that of the individual third component. Upon storage for 4 weeks, all created ternary systems showed significantly smaller variation in T-g compared to the binary system. Stable three-component co-amorphous systems can be generated via melt-quench method using either a crystalline or an amorphous third component. Addition of third component can alter the T-g of co-amorphous system and in all cases created more stable co-amorphous system upon storage. Physical parameters may not be sufficient in predicting the resulting T-g; therefore, knowledge of chemical interaction must be brought into equation as well.

Milica Petrović, Saša Rančev, Nena Velinov, Miljana Radović Vučić, Milan Antonijević, Goran Nikolić, Aleksandar Bojić (2021)Triclinic ZnMoO4 catalyst for atmospheric pressure non-thermal pulsating corona plasma degradation of reactive dye; role of the catalyst in plasma degradation process, In: Separation and purification technology269 Elsevier B.V

[Display omitted] •α-ZnMoO4 catalyst was synthesized electrochemically, followed by thermal treatment.•Catalyst was used in atmospheric pressure corona plasma degradation of reactive dye.•Catalyst enhanced plasma-generated H2O2 decomositon into dye-degrading ·OH radicals.•Dye degradation followed pseudo-first order kinetics.•TOC removal was 85.4% after 180 min of the treatment. Microcrystalline α-ZnMoO4 catalyst for degradation of Reactive Black 5 by self-made open air atmospheric pressure pulsating corona plasma reactor was synthesized by electrodeposition, followed by thermal treatment. The effect of electrodeposition current density on the catalyst’ characteristics was examined by SEM, EDX, FTIR XRD and TG. The catalyst enhanced plasma decolourization rate by 7.5 times. The role of the catalyst in the consumption of plasma generated H2O2 and in dye degradation was examined in details for the first time to the best of our knowledge; the catalyst enhanced the generation of ⋅OH radical, a principle dye degradation reagent, by enhancing decomposition of plasma–generated H2O2. The catalyst’ excitation mostly proceeded by the strikes of plasma–generated active species accelerated by electric field, which transferred their energy to the catalyst, causing the creation of electron – holes pairs which attacked H2O2. Decolourization followed pseudo – first order kinetics. Decolourization rate increases with the increase of discharge current density and reactor input voltage. The ratio between cylindrical reactor cell’s diameter and the liquid level in it didn’t affect the decolourization rate. Relatively high energy yield of 1.86 gkWh−1 was achieved for 50% decolourization. TOC removal was 85.4% after 180 min of the treatment.

Snezana Maletic, Ivana Ivancev-Tumbas, Annie Brossas, Milan Antonijevic, Josef Caslavsky, Branimir Jovancicevic, Zoran Matovic, Renata Kongoli, Vasjari Majlinda, Maja Petrovic, Nenad Andrejic, Sasa Popov, Natasa Ljubojevic Vesovic, Jean-Claude Tabet, Anna Warnet, Darko Andelkovic, Gordana Gajica, Tatjana Andelkovic (2021)Overview of Erasmus plus NETCHEM project: ICT networking for overcoming technical and social barriers in instrumental analytical chemistry education, In: Environmental science and pollution research international28(2)pp. 2479-2483 Springer Nature

The paper briefly presents goals, activities, challenges, and outcomes of the NETCHEM project () that was co-funded by the Erasmus+ Program of European Union (573885-EPP-1-2016-1-RS-EPPKA2- CBHE-JP). The project has been started in October 2016 and with extension lasted until April 2020. Western Balkan region has been targeted by upgrading capacities for education and research in environmental and food analysis in cooperation with partners from France, the UK, and Czech Republic. NETCHEM platform providing Web Accessed Remote Instrumental Analytical Laboratories (WARIAL) network, Database service and Open education system was created in order to improve the cooperation, educational, and research capacities of Higher Education Institutions involved, but also targeting whether audience not only from academic domain but from industry as well. The NETCHEM platform is free for access to public; thus, the external users to NETCHEM consortium can not only see its content but also actively participate, enter Database and WARIAL network, and upload their own educational/research material.

Deeb Abu Fara, Suha M. Dadou, Iyad Rashid, Riman Al-Obeidi, Milan D. Antonijevic, Babur Z. Chowdhry, Adnan Badwan (2019)A Direct Compression Matrix Made from Xanthan Gum and Low Molecular Weight Chitosan Designed to Improve Compressibility in Controlled Release Tablets, In: Pharmaceutics11(11) Mdpi

The subject of our research is the optimization of direct compression (DC), controlled release drug matrices comprising chitosan/xanthan gum. The foregoing is considered from two main perspectives; the use of low molecular weight chitosan (LCS) with xanthan gum (XG) and the determination of important attributes for direct compression of the mixtures of the two polymers. Powder flow, deformation behaviour, and work of compression parameters were used to characterize powder and tableting properties. Compression pressure and LCS content within the matrix were investigated for their influence on the crushing strength of the tablets produced. Response surface methodology (RSM) was applied to determine the optimum parameters required for DC of the matrices investigated. Results confirm the positive contribution of LCS in enhancing powder compressibility and crushing strength of the resultant compacts. Compactibility of the XG/LCS mixtures was found to be more sensitive to applied compression pressure than LCS content. LCS can be added at concentrations as low as 15% w/w to achieve hard compacts, as indicated by the RSM results. The introduction of the plasticity factor, using LCS, to the fragmenting material XG was the main reason for the high volume reduction and reduced porosity of the polymer mixture. Combinations of XG with other commonly utilized polymers in controlled release studies such as glucosamine, hydroxypropyl methylcellulose (HPMC), Na alginate (ALG), guar gum, lactose and high molecular weight (HMW) chitosan were also used; all the foregoing polymers failed to reduce the matrix porosity beyond a certain compression pressure. Application of the LCS/XG mixture, at its optimum composition, for the controlled release of two model drugs (metoprolol succinate and dyphylline) was examined. The XG/LCS matrix at 15% w/w LCS content was found to control the release of metoprolol succinate and dyphylline. The former preparation confirmed the strong influence of compression pressure on changing the drug release profile. The latter preparation showed the ability of XG/LCS to extend the drug release at a fixed rate for 12 h of dissolution time after which the release became slightly slower.

Samuel K. Owusu-Ware, Joshua S. Boateng, Babur Z. Chowdhry, Milan D. Antonijevic (2019)Glassy state molecular mobility and its relationship to the physico-mechanical properties of plasticized hydroxypropyl methylcellulose (HPMC) films, In: International journal of pharmaceutics: X1pp. 100033-100033 Elsevier

Changes in tensile properties and the glass transition temperature (T-g) of plasticized polymer films are typically attributed to molecular mobility, often with no empirical data to support such an assertion. Herein solvent cast HPMC films containing varying amounts of PEG, as the plasticizer, were used to assess the dependence of tensile properties and the T-g on glassy state molecular mobility. Molecular mobility (molecular relaxation time and temperature) parameters were determined by Thermally Stimulated Current Spectroscopy (TSC). The tensile properties and T-g of the HPMC films were determined by texture analysis and DSC, respectively. Molecular mobilities detected by TSC were cooperative and occurred at temperatures (T-g') well below (113 to 127 degrees C) the bulk T-g. The relaxation times (tau) were 71 +/- 1, 46 +/- 1, 42 +/- 1, 36 +/- 1 and 29 +/- 1 s for HPMC films containing 0, 6, 8, 11 and 17% (w/w) PEG, respectively. The T-g and glassy state molecular mobility were found to be intimately linked and demonstrated a linear dependence. While tensile strength was found to be linearly related to molecular relaxation time, tensile elongation and elastic modulus exhibited a non-linear dependence on molecular mobility. The data presented in this work demonstrates the complex nature of the relationship between plasticizer content, molecular mobility, T-g and tensile properties for plasticized polymeric films. It highlights the fact that the dependence of the bulk physico-mechanical properties on glassy state molecular mobility, differ greatly. Therefore, empirical characterization of molecular mobility is important to fully understand and predict the thermo-mechanical behavior of plasticized polymer films. This work demonstrates the unique capability of TSC to provide key information relating to molecular mobility and its influence on the bulk properties of materials. Data generated using TSC could prove useful for stability and performance ranking, in addition to the ability to predict materials behavior using data generated at or below typical storage conditions in the pharmaceutical, food, and polymer industries.

Suha M Dadou, Musa I El-Barghouthi, Milan D Antonijevic, Babur Z Chowdhry, Adnan A Badwan (2020)Elucidation of the Controlled-Release Behavior of Metoprolol Succinate from Directly Compressed Xanthan Gum/Chitosan Polymers: Computational and Experimental Studies, In: ACS biomaterials science & engineering6(1)pp. 21-37

The development and evaluation of a controlled-release (CR) pharmaceutical solid dosage form comprising xanthan gum (XG), low molecular weight chitosan (LCS), and metoprolol succinate (MS) are reported. The research is, partly, based upon the utilization of computational tools: in this case, molecular dynamics simulations (MDs) and the response surface method (RSM) in order to underpin the design/prediction and to minimize the experimental work required to achieve the desired pharmaceutical outcomes. The capability of the system to control the release of MS was studied as a function of LCS (% w/w) and total polymer (LCS and xanthan gum (XG)) to drug ratio (P/D) at different tablet tensile strengths. MDs trajectories, obtained by using different ratios of XG/LCS as well as XG and high molecular weight chitosan (HCS), showed that the driving force for the interaction between XG and LCS is electrostatic in nature, the most favorable complex is formed when LCS is used at 15% (w/w) and, importantly, the interaction between XG and LCS is more favorable than that between XG and HCS. RSM outputs revealed that the release of the drug from the LCS/XG matrix is highly dependent on both the % LCS and the P/D ratio and that the required CR effect can be achieved when using weight fractions of LCS ≤ 20% and P/D ratios ≥2.6:1. Results obtained from in vitro drug release and swelling studies on the prepared tablets showed that using LCS at the weight fractions suggested by MDs and RSM data plays a major role in overcoming the high sensitivity of the controlled drug release effect of XG on ionic strength and pH changes of the dissolution media. In addition, it was found that polymer relaxation is the major contributor to the release of MS from LCS/XG tablets. Using Raman spectroscopy, MS was shown to be localized more in the core of the tablets at the initial stages of dissolution due to film formation between LCS and XG on the tablet surface, which prevents excess water penetration into the matrix. In the later stages of the dissolution process, the film starts to dissolve/erode, allowing full tablet hydration and a uniform drug distribution in the swollen tablet.

Atabak Ghanizadeh Tabriz, Md Sadeque Mithu, Lilian Vilain, Youri Derrar, C Grau, Anaïs Morales, Orestis L. Katsamenis, Dennis Douroumis, Milan Antonijevic (2023)3D printing of LEGO® like designs with tailored release profiles for treatment of sleep disorder, In: International journal of pharmaceutics632 Elsevier B.V

3D printed LEGO®-like designs are an attractive approach for the development of compartmental delivery systems due to their potential for dose personalisation through the customisation of drug release profiles. Additive manufacturing technologies such as Fused Deposition Modelling (FDM) are ideal for the printing of structures with complex geometries and various sizes. This study is a paradigm for the fabrication of 3D printed LEGO® -like tablets by altering the design of the modular units and the filament composition for the delivery of different drug substances. By using a combination of placebo and drug loaded compartments comprising of immediate release (hydroxypropyl cellulose) and pH dependant polymers (hypromellose acetate succinate) we were able to customise the release kinetics of melatonin and caffeine that can potentially be used for the treatment of sleep disorders. The LEGO® -like compartments were designed to achieve immediate release of melatonin followed by variable lag times and controlled release of caffeine.

Samuel K. Owusu-Ware, Babur Z. Chowdhry, Stephen A. Leharne, Milan D. Antonijevic (2017)Phase behaviour of dehydrated phosphatidylcholines, In: Journal of thermal analysis and calorimetry127(1)pp. 415-421 Springer Nature

Dehydrated DLPC, DMPC, DPPC and DSPC have been characterised at temperatures below the diacyl carbon chain-melting transition (T (m)), using DSC. For the first time, the existence of pre-Tm transition processes, which are, usually, only observed in the colloidal/liposomal state of saturated phospholipids, has been detected for the dehydrated phosphatidylcholines. Temperature-modulated differential scanning calorimetry was used to characterise the several complexes, overlapping pre-T (m) transition processes. Kinetic studies of the chain-melting (T (m)) transition show the activation energy dependence on alpha (conversion rate), i.e. activation energy decreases as the transition progresses, pointing to the importance of initial cooperative (intra- and inter-molecular) mobility. Furthermore, the activation energy increases with increase in diacyl chain length of the phosphatidylcholines which supports the finding that greater molecular interactions of the polymer chain and its head groups in the dehydrated solid state lead to enhanced stability of dehydrated phosphatidylcholines.

Farnoosh Kianfar, Babur Z. Chowdhry, Milan D. Antonijevic, Joshua S. Boateng (2012)Novel films for drug delivery via the buccal mucosa using model soluble and insoluble drugs, In: Drug development and industrial pharmacy38(10)pp. 1207-1220 Taylor & Francis

Bioadhesive buccal films are innovative dosage forms with the ability to adhere to the mucosal surface and subsequently hydrate to release and deliver drugs across the buccal membrane. This study aims to formulate and characterize stable carrageenan (CAR) based buccal films with desirable drug loading capacity. The films were prepared using CAR, poloxamer (POL) 407, various grades of PEG (plasticizer) and loaded with paracetamol (PM) and indomethacin (IND) as model soluble and insoluble drugs, respectively. The films were characterized by texture analysis, thermogravimetric analysis (TGA), DSC, scanning electron microscopy, X-ray powder diffraction (XRPD), and in vitro drug release studies. Optimized films were obtained from aqueous gels comprising 2.5% w/w.-CAR 911, 4% w/w POL 407 and 6% w/w (PM) and 6.5% w/w (IND) of PEG 600 with maximum drug loading of 1.6% w/w and 0.8 % w/w for PM and IND, respectively. TGA showed residual water content of approximately 5% of films dry weight. DSC revealed a T-g at 22.25 and 30.77 degrees C for PM and IND, respectively, implying the presence of amorphous forms of both drugs which was confirmed by XRPD. Drug dissolution profiles in simulated saliva showed cumulative percent release of up to 45 and 57% of PM and IND, respectively, within 40 min of contact with dissolution medium simulating saliva.

Suha M. Dadou, Musa I. El-Barghouthi, Samer K. Alabdallah, Adnan A. Badwan, Milan D. Antonijevic, Babur Z. Chowdhry (2017)Effect of Protonation State and N-Acetylation of Chitosan on Its Interaction with Xanthan Gum: A Molecular Dynamics Simulation Study, In: Marine drugs15(10) Mdpi

Hydrophilic matrices composed of chitosan (CS) and xanthan gum (XG) complexes are of pharmaceutical interest in relation to drug delivery due to their ability to control the release of active ingredients. Molecular dynamics simulations (MDs) have been performed in order to obtain information pertaining to the effect of the state of protonation and degree of N-acetylation (DA) on the molecular conformation of chitosan and its ability to interact with xanthan gum in aqueous solutions. The conformational flexibility of CS was found to be highly dependent on its state of protonation. Upon complexation with XG, a substantial restriction in free rotation around the glycosidic bond was noticed in protonated CS dimers regardless of their DA, whereas deprotonated molecules preserved their free mobility. Calculated values for the free energy of binding between CS and XG revealed the dominant contribution of electrostatic forces on the formation of complexes and that the most stable complexes were formed when CS was at least half-protonated and the DA was 50%. The results obtained provide an insight into the main factors governing the interaction between CS and XG, such that they can be manipulated accordingly to produce complexes with the desired controlled-release effect.

Samuel K. Owusu-Ware, Babur Z. Chowdhry, Stephen A. Leharne, Milan D. Antonijevic (2013)Quantitative analysis of overlapping processes in the non-isothermal decomposition of chlorogenic acid by peak fitting, In: Thermochimica acta565pp. 27-33 Elsevier

The decomposition behaviour of chlorogenic acid (CGA) was studied under inert (nitrogen) and oxidative (air) atmospheres by themogravimetric analysis (TGA). Thermal decomposition was found to be faster under an air atmosphere with a total weight change of 97 +/- 1% compared to 61 +/- 1% under a nitrogen atmosphere. At least 3 or 4 processes were observed for decomposition under air and nitrogen atmospheres, respectively. Furthermore, the 1st process, which follows a melt-crystallisation, was found not to be influenced by the different atmospheric conditions. Peak fitting of the CGA decomposition profile, in the form of a derivative thermogram (DTG), under a nitrogen atmosphere, revealed the presence of five complete decomposition processes and the first half of a sixth process between 160 and 500 degrees C. A comparison is made between the peak fitting and dynamic High-Res (TM) TGA experiments to demonstrate the reliability of the peak fitting approach. The predictions were then converted into discrete thermogravimetric (TG) curves with a single-step weight change. Since this approach provides baseline separation between overlapping processes, it has been possible to reliably determine the fractional weight change and the activation energy dependence on the reaction progression for the discrete TGA decomposition processes. The fractional weight change associated with processes 1-5 is: 5.3 +/- 10.7, 2.0 +/- 0.4, 16.4 +/- 0.9, 30.9 +/- 1.6 and 5.5 +/- 0.5%. Catechol was found to be the major decomposition product. The average activation energies of the 5 processes were calculated to be 176 +/- 34, 185 +/- 4,223 +/- 19,245 +/- 47, 295 +/- 80 kJ/mol when an integral method (Kissinger-Akahiro-Sunose) is used and 120 +/- 25, 169 +/- 18, 191 +/- 12, 284 +/- 64, 245 +/- 46 kJ/mol when a differential method (Friedman) is used for processes 1-5, respectively (c) 2013 Elsevier B.V. All rights reserved.

Milan D. Antonijevic, Marija Arsovic, Josef Caslavsky, Vesna Cvetkovic, Predrag Dabic, Mladen Franko, Gordana Ilic, Milena Ivanovic, Nevena Ivanovic, Milica Kosovac, Dragana Medic, Slobodan Najdanovic, Milica Nikolic, Jovana Novakovic, Tatjana Radovanovic, Durdina Ranic, Bojan Sajatovic, Gorica Spijunovic, Ivana Stankov, Jelena Tosovic, Polonca Trebse, Olivera Vasiljevic, Jan Schwarzbauer (2014)Actual contamination of the Danube and Sava Rivers at Belgrade (2013), In: Journal of the Serbian Chemical Society79(9)pp. 1169-1184 Serbian Chemical Soc

This study was focussed on a comprehensive investigation on the state of pollution of the Danube and Sava Rivers in the region of Belgrade. Different complementary analytical approaches were employed covering both i) organic contaminants in the river water by target analyses of hormones and neonicotinoids as well as non-target screening analyses and ii) heavy metals in the sediments. Finally, some common water quality parameters were analysed. The overall state of pollution is on a moderate level. Bulk parameters did not reveal any unusual observations. Moreover, quantification of preselected organic contaminants did not indicate to elevated pollution. More significant contaminations were registered for chromium, nickel, zinc and partially copper in sediments with values above the target values according to Serbian regulations. Lastly, non-target screening analysis revealed a wider spectrum of organic contaminants comprising pharmaceuticals, technical additives, personal care products and pesticides. The study presented a comprehensive view on the state of pollution of the Sava and Danube Rivers and is the base for setting up further monitoring programs. As a superior outcome, it was illustrated how different chemical analyses can result in different assessments of the river quality. A comparison of target and non-target analyses pointed to potential misinterpretation of the real state of pollution.

Miljana D. Radovic, Jelena Z. Mitrovic, Danijela V. Bojic, Milan D. Antonijevic, Milos M. Kostic, Rada M. Baosic, Aleksandar Lj Bojic (2014)Effects of system parameters and inorganic salts on the photodecolourisation of textile dye Reactive Blue 19 by UV/H2O2 process, In: WATER SA40(3)pp. 571-577 Water Research Commission

The photodecolourisation of textile dye Reactive Blue 19 (RB 19), an anionic anthraquinone dye of the reactive class, was investigated using UV radiation in the presence of H2O2 in a batch photo-reactor with low-pressure mercury lamps. The effects of the system parameters: initial pH, initial dye concentration, concentration of peroxide and radiation intensity, as well as the presence of salts, (NaCl, Na2SO4, NaNO3, NaH2PO4) on dye decolourisation was examined. Increasing the initial pH resulted in an increase in decolourisation efficiency. Results showed that with an increase of dye concentration from 10 to 100 mg.l(-1), the efficiency of the process decreases. The highest decolourisation rates were noted at H2O2 concentrations of approximately 30 mmol.l(-1). The increase of radiation intensity from 730 to 1 950 mu W.cm(-2), linearly increases decolourisation efficiency. The inorganic ions investigated have inhibiting effects on RB 19 decolourisation by the UV/H2O2 process with inhibition intensities in the following order: H2PO4-> NO3-> SO42-> Cl-. This study has shown that the UV/H2O2 process is a promising technology for degradation of RB 19 in water and wastewater.

Michael Reading, Muhammad U. Ghori, D. Robert Brown, Leigh T. Fleming, Milan D. Antonijevic, David B. Grandy, Douglas J. Hourston, Mo Song, Barbara R. Conway (2017)Chemical Imaging by Dissolution Analysis: Localized Kinetics of Dissolution Behavior to Provide Two-Dimensional Chemical Mapping and Tomographic Imaging on a Nanoscale, In: Analytical chemistry (Washington)89(11)pp. 5883-5891 Amer Chemical Soc

A new approach to achieving chemical mapping on a nanoscale is described that can provide 2D and tomographic images of surface and near-surface structure. The method comprises dissolving material from the surface of the sample by applying a series of aliquots of solvent, then analyzing their contents after removing them; in between exposures, the surface is imaged with atomic force microscopy. This technique relies on being able to compensate for any drift between images by use of software. It was applied to a blend of two polymers, PMMA and PS. The analytical data identified the material that was dissolved, and the topography images enabled the location of the various materials to be determined by analyzing local dissolution kinetics. The prospects for generalizing the approach are discussed.

Christine B. Baltus, Neil J. Press, Milan D. Antonijevic, Graham J. Tizzard, Simon J. Coles, John Spencer (2012)Synthesis of a biphenyl library for studies of hydrogen bonding in the solid state, In: Tetrahedron68(45)pp. 9272-9277 Elsevier

A biphenyl library incorporating amide and sulfonamide groups has been synthesised via microwave-mediated Suzuki-Miyaura couplings. Many derivatives were crystallised from dichloromethane/methanol and analysed by single crystal X-ray diffraction. An interesting structure was obtained for N-(4'-methylbiphenyl-4-yl)acetamide with Z'=6 and hydrogen-bonding networks of the type N-H center dot center dot center dot O in the unit cell. (C) 2012 Elsevier Ltd. All rights reserved.

Samuel K. Owusu-Ware, Joshua Boateng, Daniel Jordan, Sara Portefaix, Renata Tasseto, Camila D. Ramano, Milan D. Antonijevic (2016)Molecular mobility of hydroxyethyl cellulose (HEC) films characterised by thermally stimulated currents (TSC) spectroscopy, In: International journal of pharmaceutics497(1-2)pp. 222-227 Elsevier

Molecular mobility has long been established to relate to textural properties and stability of polymer films and is therefore an important property to characterise to better understand pharmaceutical film formulations. The molecular mobility of solvent cast hydroxyethyl cellulose (HEC) films has been investigated by means of thermally stimulated current (TSC) below the temperature at which the film was formed. Preliminary physical characterisation of the films was performed using XRPD, TGA, DSC and texture analysis (tensile properties). XRPD results showed the films to be completely amorphous with T-g determined by DSC to be 127 +/- 1 degrees C. TGA analysis showed the films to contain 8 +/- 1% water and film was dried to only 0.06 +/- 0.01% water content when heated to 160 degrees C. Application of TSC detected molecular mobility in HEC films at sub-zero temperatures. Two motional transitions with average relaxation time of 50 +/- 3 s were identified; a beta-relaxation at -57 +/- 2 degrees C, attributed to localised non-cooperative orientation of HEC polymer chain ends and the hydroxyethyl side groups and an a-relaxation, originating from cooperative segmental mobility, at -20 +/- 2 degrees C. The tensile properties i.e., elongation, tensile strength and elastic modulus of the HEC film have been related to the molecular relaxation processes detected by TSC. (C) 2015 Elsevier B.V. All rights reserved.

Ali Nokhodchi, Hiba Al-Hamidi, Milan D. Antonijevic, Samuel Owusu-Ware, Waseem Kaialy (2015)Dissolution and solid state behaviours of carbamazepine-gluconolactone solid dispersion powders: The potential use of gluconolactone as dissolution enhancer, In: Chemical engineering research & design100pp. 452-466 Elsevier

Solid dispersions are one of the most effective methods for improving the dissolution rate of poorly water-soluble drugs; however, this is reliant on the selection of a suitable carrier and solvent. The present study is the mechanistic evaluation of the changes in polymorphic form of carbamazepine when the type of solvent and the concentration of D-gluconolactone (D-GL) change. The studies reported herein also explore the use of D-GL as a potential hydrophilic carrier to improve the dissolution rate of a poorly water-soluble drug, carbamazepine (CBZ), from physical mixtures and solid dispersion formulations. The effect of using different solvents in the preparation of solid dispersion formulations was also investigated. Different ratios of solid dispersions of the drug and D-GL were prepared using a conventional solvent evaporation method. Different solvents (ethanol, acetone and water) were used as a second experimental variable in the preparation of solid dispersions. Physical mixtures of CBZ and D-GL were also prepared for comparison. The results showed that the presence of D-GL can increase the dissolution rate of CBZ compared to pure CBZ. This study showed that D-GL could be used as a new carrier in solid dispersion formulations and physical mixtures. The interesting solid state behaviour of CBZ in all solid dispersions in the presence of D-GL was fully analyzed using Fourier-transform infrared (FT-IR), X-ray powder diffraction (XRPD), scanning electron microscope (SEM), hot stage microscopy (HSM) and differential scanning calorimetry (DSC). The results showed that depending on the type of solvent and concentration of D-GL used in the preparation of solid dispersions different forms of CBZ (Form I, Form III and dihydrate) can be existed in the formulations. (C) 2015 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.

Milan D. Antonijevic, Duncan Q. M. Craig, Susan A. Barker (2008)The role of space charge formation in the generation of thermally stimulated current (TSC) spectroscopy data for a model amorphous drug system, In: International journal of pharmaceutics353(1-2)pp. 8-14 Elsevier

Thermally stimulated current (TSC) spectroscopy is attracting increasing attention as a means of materials characterization, particularly in terms of measuring slow relaxation processes in solid samples. However, wider use of the technique within the pharmaceutical field has been inhibited by difficulties associated with the interpretation of TSC data, particularly in terms of deconvoluting dipolar relaxation processes froth charge distribution phenomena. Here, we present evidence that space charge and electrode contact effects may play a significant role in the generation of peaks that have thus far proved difficult to interpret. We also introduce the use of a stabilization temperature in order to control the space charge magnitude. We have studied amorphous indometacin as a model drug compound and have varied the measurement parameters (stabilization and polarization temperatures), interpreting the changes in spectral composition in terms of charge redistribution processes. More specifically, we suggested that charge drift and diffusion processes, charge injection from the electrodes and high activation energy charge redistribution processes may all contribute to the appearance of shoulders and 'spurious' peaks. We present recommendations for eliminating or reducing these effects that may allow more confident interpretation of TSC data. (c) 2007 Elsevier B.V. All rights reserved.

Jelena Janicijevic, Danina Krajisnik, Bojan Calija, Bojana Nedic Vasiljevic, Vladimir Dobricic, Aleksandra Dakovic, Milan D. Antonijevic, Jela Milic (2015)Modified local diatomite as potential functional drug carrier-A model study for diclofenac sodium, In: International journal of pharmaceutics496(2)pp. 466-474 Elsevier

Diatomite makes a promising candidate for a drug carrier because of its high porosity, large surface area, modifiable surface chemistry and biocompatibility. Herein, refined diatomite from Kolubara coal basin, which complied with the pharmacopoeial requirements for heavy metals content and microbiological quality, was used as a starting material. Inorganic modification of the starting material was performed through a simple, one-step procedure. Significant increase in adsorbent loading with diclofenac sodium (DS) was achieved after the modification process (similar to 373 mg/g) which enabled the preparation of comprimates containing therapeutic dose of the adsorbed drug. Adsorption of DS onto modified diatomite resulted in the alteration of the drug's XRD pattern and FTIR spectrum. In vitro drug release studies in phosphate buffer pH 7.5 demonstrated prolonged DS release over 8 h from comprimates containing DS adsorbed on modified diatomite (up to 37% after 8 h) and those containing physical mixture of the same composition (up to 45% after 8 h). The results of in vivo toxicity testing on mice pointed on potential safety of both unmodified (starting) and modified diatomite. All these findings favor the application of diatomite as a potential functional drug carrier. (C) 2015 Elsevier B.V. All rights reserved.

Richard E. J. Forster, Sharon A. Small, Yiqing Tang, Clare L. Heaysman, Andrew W. Lloyd, Wendy Macfarlane, Gary J. Phillips, Milan D. Antonijevic, Andrew L. Lewis (2010)Comparison of DC Bead-irinotecan and DC Bead-topotecan drug eluting beads for use in locoregional drug delivery to treat pancreatic cancer, In: Journal of materials science. Materials in medicine21(9)pp. 2683-2690 Springer Nature

DC Bead(A (R)) is a drug delivery embolisation system that can be loaded with doxorubicin or irinotecan for the treatment of a variety of liver cancers. In this study we demonstrate that the topoisomerase I inhibitor topotecan hydrochloride can be successfully loaded into the DC Bead sulfonate-modified polyvinyl alcohol hydrogel matrix, resulting in a sustained-release drug eluting bead (DEBTOP) useful for therapeutic purposes. The in vitro drug loading capacity, elution characteristics and the effects on mechanical properties of the beads are described with reference to our previous work with irinotecan hydrochloride (DEBIRI). Results showed that drug loading was faster when the solution was agitated compared to static loading and a maximum loading of ca. 40-45 mg topotecan in 1 ml hydrated beads was achievable. Loading the drug into the beads altered the size, compressibility moduli and colour of the bead. Elution was shown to be reliant on the presence of ions to perform the necessary exchange with the electrostatically bound topotecan molecules. Topotecan was shown by MTS assay to have an IC(50) for human pancreatic adenocarcinoma cells (PSN-1) of 0.22 and 0.27 mu M compared to 28.1 and 19.2 mu M for irinotecan at 48 and 72 h, respectively. The cytotoxic efficacy of DEBTOP on PSN-1 was compared to DEBIRI. DEPTOP loaded at 6 & 30 mg ml(-1), like its free drug form, was shown to be more potent than DEBIRI of comparable doses at 24, 48 & 72 h using a slightly modified MTS assay. Using a PSN-1 mouse xenograft model, DEBIRI doses of 3.3-6.6 mg were shown to be well-tolerated (even with repeat administration) and effective in reducing the tumour size. DEBTOP however, was lethal after 6 days at doses of 0.83-1.2 mg but demonstrated reasonable efficacy and tolerability (again with repeat injection possible) at 0.2-0.4 mg doses. Care must therefore be taken when selecting the dose of topotecan to be loaded into DC Bead given its greater potency and potential toxicity.

Dimitrios G. Fatouros, Kieron Power, Omar Kadir, Imre Dekany, Spyros N. Yannopoulos, Nikolaos Bouropoulos, Aristides Bakandritsos, Milan D. Antonijevic, George D. Zouganelis, Marta Roldo (2011)Stabilisation of SWNTs by alkyl-sulfate chitosan derivatives of different molecular weight: towards the preparation of hybrids with anticoagulant properties, In: Nanoscale3(3)pp. 1218-1224 Royal Soc Chemistry

We have previously demonstrated that chitosan derivative N-octyl-O-sulfate chitosan (NOSC), which presents important pharmacological properties, can suspend single walled carbon nanotubes (SWNTs) up to 20 times more effectively than other chitosan derivatives in an aqueous environment. In an attempt to further investigate the impact of different molecular weights of chitosan to the solubilization and anticoagulant properties of these hybrids an array of NOSC derivatives varying their molecular weight (low, medium and high respectively) was synthesised and characterised by means of FT-IR spectroscopy, NMR spectroscopy and thermal gravimetric analysis (TGA). Microwave and nitric acid purified SWNTs, characterised by FT-IR spectroscopy, transmission electron microscopy (TEM) and Raman spectroscopy, were colloidally stabilised by these polymers and their anticoagulant activity was assessed. The results revealed that the low molecular weight NOSC coated SWNTs exhibit the highest activity when 0.5 mg mL(-1) NOSC solutions are used, activity which is similar to that of the free polymer. Preliminary studies by exposure of these hybrids to Brine Shrimp (Artemia) cysts revealed no effect on the viability of sub-adult Artemia. Our findings suggest the possibility of tailoring these nanomaterials to bear the required properties for application as biocompatible building blocks for nanodevices including biosensors and biomaterials.

Samuel K. Owusu-Ware, Anthony J. Cherry, Christine B. Baltus, John Spencer, Milan D. Antonijevic (2015)Thermal analysis of novel biphenylamide derivatives, In: Journal of thermal analysis and calorimetry121(1)pp. 437-452 Springer Netherlands

The physicochemical properties of a small library of 4-methyl-biphenylamide derivatives have been investigated by means of differential scanning calorimetry, thermogravimetric analysis and hot-stage microscopy. The obtained results show that positional isomerism has a significant influence on the thermal behaviour of the 4-methyl-biphenylamide derivatives; however, no clear relationship between functional group isomerism and thermal properties could be established. Ortho-substituted derivatives revealed two polymorphic forms, whilst the para-substituted derivatives exhibit three polymorphic forms. The ortho-substituted biphenylamides were more likely to generate metastable forms when cooled from the melt. Furthermore, the self-heating properties were revealed by the para-substituted 4-methyl-biphenylamide derivatives, in which the highly energetic crystallization processes raised the sample temperature by as much as 4 °C during cooling. Such a high-energy exothermic crystallization process suggests crystallization to be highly favourable, from a thermodynamic standpoint. Hence, the para -substituted derivatives are unlikely to generate amorphous forms. Pharmaceutical application of these compounds will depend on the solubility of their crystalline forms, but their manufacture may possess some challenges due to the number of monotropic polymorphic forms that may coexist.

Gordana D. Gajica, Aleksandra M. Sajnovic, Ksenija A. Stojanovic, Milan D. Antonijevic, Nikoleta M. Aleksic, Branimir S. Jovancicevic (2017)The influence of pyrolysis type on shale oil generation and its composition (Upper layer of Aleksinac oil shale, Serbia), In: Journal of the Serbian Chemical Society82(12)pp. 1461-1477 Serbian Chemical Soc

The influence of pyrolysis type on the shale oil generation and its composition was studied. Different methods such as Rock-Eval pyrolysis, thermogravimetric analysis (TGA) and pyrolysis in the open and closed systems were applied. Samples from the Upper layer of Aleksinac oil shale (Serbia) were used as a substrate and first time characterized in detail. The impact of kerogen content and type on the shale oil generation in different pyrolysis systems was also estimated. Majority of the analysed samples have total organic carbon content >5 wt. % and contain oil prone kerogen types I and/or II. Therefore, they can be of particular interest for the pyrolytic processing. The thermal behaviour of analysed samples obtained by TGA is in agreement with Rock-Eval parameters. The pyrolysis of oil shale in the open system gives higher yield of shale oil than the pyrolysis in the closed system. The yield of hydrocarbons (HCs) in shale oil produced by the open pyrolysis system corresponds to an excellent source rock potential, while HCs yield from the closed system indicates a very good source rock potential. The kerogen content has a greater impact on the shale oil generation than kerogen type in the open pyrolysis system, while kerogen type plays a more important role on the generation of shale oil than the kerogen content in the closed system. The composition of the obtained shale oil showed certain undesirable features, due to the relatively high contents of olefinic HCs (open system) and polar compounds (closed system), which may require further treatment to be used.

Milica M. Petrović, Jelena Z. Mitrović, Milan D. Antonijević, Branko Matović, Danijela V. Bojić, Aleksandar Lj Bojić (2015)Synthesis and characterization of new Ti–Bi2O3 anode and its use for reactive dye degradation, In: Materials chemistry and physics158pp. 31-37 Elsevier B.V

This paper reports the synthesis, characterization and application of a Ti–Bi2O3 anode for the electrochemical decolorization of the textile dye Reactive Red 2. The anode was synthesized by electrodeposition on a Ti substrate immersed in an acidic bismuth (III) solution at constant potential, followed by calcination in air at 600 °C. Thermogravimetric Analysis (TGA), Energy-dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD) analysis revealed that the electrodeposited material was predominantly metallic bismuth, which was oxidized to pure α-Bi2O3 during the calcination in air. SEM micrographs revealed that the Bi2O3 coat at the anode surface was inhomogeneous and porous. Reactive Red 2 was completely electrochemically decolorized at the synthesized anode in the presence of H2O2. The applied current density, H2O2 and Na2SO4 concentration, medium pH and initial dye concentration affected the dye decolorization rate. The optimal process parameters were found to be as follows: an applied current density of 40 mA cm−2 using a mixture of 10 mmol dm−3 H2O2 and 10 mmol dm−3 Na2SO4 at pH 7. The dye decolorization rate was shown to decrease as its initial concentration increased. The decolorization reactions were found to follow pseudo-first order kinetics. •Ti–Bi2O3 anode was synthesized by electrodeposition and calcination.•The anode is prepared fast and easy, using low-cost materials and simple equipment.•The synthesized anode was characterized by EDX, SEM, TG and XRD techniques.•Synthetic dye was completely removed by electrochemical oxidation at Ti–Bi2O3 anode.

Miloš Kostić, Miloš Đorđević, Jelena Mitrović, Nena Velinov, Danijela Bojić, Milan Antonijević, Aleksandar Bojić (2017)Removal of cationic pollutants from water by xanthated corn cob: optimization, kinetics, thermodynamics, and prediction of purification process, In: Environmental science and pollution research international24(21)pp. 17790-17804

The removal of Cr(III) ions and methylene blue (MB) from aqueous solutions by xanthated corn cob (xCC) in batch conditions was investigated. The sorption capacity of xCC strongly depended of the pH, and increase when the pH rises. The kinetics was well fitted by pseudo-second-order and Chrastil's model. Sorption of Cr(III) ions and MB on xCC was rapid during the first 20 min of contact time and, thereafter, the biosorption rate decrease gradually until reaching equilibrium. The maximum sorption capacity of 17.13 and 83.89 mg g for Cr(III) ions and MB, respectively, was obtained at 40 °C, pH 5, and sorbent dose 4 g dm for removal of Cr(III) ions and 1 g dm for removal of MB. The prediction of purification process was successfully carried out, and the verification of theoretically calculated amounts of sorbent was confirmed by using packed-bed column laboratory system with recirculation of the aqueous phase. The wastewater from chrome plating industry was successfully purified, i.e., after 40 min concentration of Cr(III) ions was decreased lower than 0.1 mg dm . Also, removal of MB from the river water was successfully carried out and after 40 min, removal efficiency was about 94%.

Susan Barker, Milan D Antonijevic (2011)Thermal Analysis – Dielectric Techniques, In: Richard A Storey, Ingvar Ymén (eds.), Solid State Characterization of Pharmaceuticalspp. 187-206 John Wiley & Sons, Ltd

This chapter contains sections titled: General Introduction Common Background to the Techniques Dielectric Spectroscopy Thermally Stimulated Current (TSC) Spectroscopy Overall Conclusions References

M. M. Kostic, I. J. Slipper, M. D. Antonijevic, J. Z. Mitrovic, M. D. Radovic, D. V. Bojic, A. L. Bojic (2015)PREPARATION AND CHARACTERISATION OF XANTHATED Lagenaria vulgaris SHELL BIOSORBENT, In: Oxidation communications38(4A)pp. 2173-2188 Scibulcom Ltd

Preparation and characterisation of chemically modified, improved biosorbent, xanthated Lagenaria vulgaris shell (xLVB), and its application for Cu(II) ions removal from aqueous solutions, were investigated in the present study. The chemically modified material was characterised by using FTIR, SEM and EDX analysis. Equilibrium isotherms and kinetics were obtained and the effect of various parameters including contact time, initial pH, biosorbent dosage, particle size, temperature, initial Cu(II) concentration was studied under batch conditions. xLVB was applied to test the sorption of Cu(II) ions in batch column system with recirculation of aqueous phase. The experimental data were best fitted by using pseudo-second order kinetics and the Langmuir isotherm model; equilibrium within less than 40 min and sorption capacity of 25.2 mg g(-1) for Cu(II) ions, at 20 degrees C were achieved. With increasing temperature from 10 to 40 degrees C the free energy change was negative, suggesting that the biosorption was exothermic and spontaneous.

Milica M. Petrović, Ian J. Slipper, Milan D. Antonijević, Goran S. Nikolić, Jelena Z. Mitrović, Danijela V. Bojić, Aleksandar Lj Bojić (2015)Characterization of a Bi2O3 coat based anode prepared by galvanostatic electrodeposition and its use for the electrochemical degradation of Reactive Orange 4, In: Journal of the Taiwan Institute of Chemical Engineers50pp. 282-287 Elsevier B.V

•Bi2O3 thin coat based anodes are prepared by electrodeposition and calcination.•Anodes are calcined at different temperatures and characterized by SEM, XRD and TGA.•Anodes have different surface morphology, XRD patterns and electrochemical stability.•Dye RO4 was completely decolorized at the electrochemically more stable anode.•The optimal electrochemical decolorization parameters and kinetics are determined. Two anodes were prepared by galvanostatic electrodeposition from an acidic Bi(III) solution on a Ti substrate and calcination in air at 350 °C and 600 °C. The surface coat of the anode calcined at 350 °C displayed irregular, predominantly sheet-like and needle-like morphology and it was composed of α-Bi2O3, with minor amounts of rhombohedral Bi and β-Bi2O3, and traces of ω-Bi2O3. The surface coat of the anode calcined at 600 °C predominantly displayed an oval morphology, and it was composed solely of α-Bi2O3. Only this anode was electrochemically stable. TG analysis showed that it was chemically stable in the investigated temperature range from 25 °C to 600 °C, both in oxygen and nitrogen. This anode was used for electrochemical decolorization of a dye, Reactive Orange 4, in the presence of H2O2. The optimal values for the decolorization parameters (applied current density, H2O2 and Na2SO4 concentration and pH), which provided the fastest decolorization, were determined. Decolorization reactions follow pseudo-first order kinetics.

Farnoosh Kianfar, Milan Antonijevic, Babur Chowdhry, Joshua S. Boateng (2013)Lyophilized wafers comprising carrageenan and pluronic acid for buccal drug delivery using model soluble and insoluble drugs, In: Colloids and surfaces, B, Biointerfaces103pp. 99-106 Elsevier

Lyophilized muco-adhesive wafers with optimum drug loading for potential buccal delivery have been developed. A freeze-annealing cycle was used to obtain optimized wafers from aqueous gels containing 2% kappa-carrageenan (CAR 911), 4% pluronic acid (F127), 4.4% (w/w) polyethylene glycol with 1.8% (w/w) paracetamol or 0.8% (w/w) ibuprofen. Thermogravimetric analysis showed acceptable water content between 0.9 and 1.5%. Differential scanning calorimetry and X-ray diffraction showed amorphous conversion for both drugs. Texture analysis showed ideal mechanical and mucoadhesion characteristics whilst both drugs remained stable over 6 months and drug dissolution at a salivary pH showed gradual release within 2 h. The results show the potential of CAR 911 and F127 based wafers for buccal mucosa drug delivery. (c) 2012 Elsevier B.V. All rights reserved.

Ichioma Onyesom, Dimitrios A. Lamprou, Lamprini Sygellou, Samuel K. Owusu-Ware, Milan Antonijevic, Babur Z. Chowdhry, Dennis Douroumis (2013)Sirolimus Encapsulated Liposomes for Cancer Therapy: Physicochemical and Mechanical Characterization of Sirolimus Distribution within Liposome Bilayers, In: Molecular pharmaceutics10(11)pp. 4281-4293 Amer Chemical Soc

Sirolimus has recently been introduced as a therapeutic agent for breast and prostate cancer. In the current study, conventional and Stealth liposomes were used as carriers for the encapsulation of sirolimus. The physicochemical characteristics of the sirolimus liposome nanoparticles were investigated including the particle size, zeta potential, stability and membrane integrity. In addition atomic force microscopy was used to study the morphology, surface roughness and mechanical properties such as elastic modulus deformation and deformation. Sirolimus encapsulation in Stealth liposomes showed a high degree of deformation and lower packing density especially for dipalmitoyl-phosphatidylcholine (DPPC) Stealth liposomes compared to unloaded. Similar results were obtained by differential scanning calorimetry (DSC) studies; sirolimus loaded liposomes were found to result in a distorted state of the bilayer. X-ray photon electron (XPS) analysis revealed a uniform distribution of sirolimus in multilamellar DPPC Stealth liposomes compared to a nonuniform, greater outer layer lamellar distribution in distearoylphosphatidylcholine (DSPC) Stealth liposomes.

Milos Kostic, Miljana Radovic, Jelena Mitrovic, Milan Antonijevic, Danijela Bojic, Milica Petrovic, Aleksandar Bojic (2014)Using xanthated Lagenaria vulgaris shell biosorbent for removal of Pb(II) ions from wastewater, In: Journal of the Iranian Chemical Society11(2)pp. 565-578 Springer Nature

Chemically modified Lagenaria vulgaris shell was applied as a new sorbent for the removal of lead (II) ions from aqueous solution in a batch process mode. The influence of contact time, initial concentration of lead (II) ions, initial pH value, biosorbent dosage, particle size and stirring speed on the removal efficiency was evaluated. Biosorbent characterization was performed by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). Four kinetic models (pseudo-first order, pseudo-second order, Elovich model and Intraparticle diffusion model) were used to determine the kinetic parameters. The experimental results were fitted to the Langmuir, Freundlich, Dubinin-Radushkevich and Temkin models of isotherm. Pseudo-second order kinetic model and Langmuir isotherm model best fitted the experimental data. Sorption process is obtained to be fast and equilibrium was attained within 40 min of contact time. The maximum sorption capacity was 33.21 mg g(-1). Biosorption was highly pH-dependent where optimum pH was found to be 5. The results of FTIR and SEM analysis showed the presence of new sulfur functional groups. This study indicated that xanthated Lagenaria vulgaris shell could be used as an effective and low-cost biosorbent for the removal of lead (II) ions from aqueous solution.

Nataša Djordjević Filijović, Milan D. Antonijević, Aleksandar Pavlović, Ivan Vučković, Katarina Nikolić, Danica Agbaba (2015)The stress stability of olanzapine: studies of interactions with excipients in solid state pharmaceutical formulations, In: Drug development and industrial pharmacy41(3)pp. 502-514 Informa Healthcare

Stress stability testing represents an important part of the drug development process. It is used as an important tool for the identification of degradation products and degradation pathways, as well as for the assessment of changes in physical form of drug molecules. The impact of excipients on the stability of olanzapine confirms that levels of impurities and degradants are limiting parameters and are therefore used for stability evaluation. The major degradation product of olanzapine was identified as 2-methyl-5,10-dihydro-4H-thieno[2,3-b][1,5]benzodiazepine-4-one (III). The structure of III was determined by using LC-MS, IR and NMR. Compatibility and stress stability results demonstrated that tablet formulations of olanzapine are sensitive to temperature and moisture. In samples protected from moisture, the increase in concentration of III was shown to be highly temperature dependent and the degradation followed zero-order kinetics. In addition, studies of olanzapine with excipients and in formulated tablets revealed polymorphic phase changes in some samples, influenced by a combination of stress temperature and humidity conditions. Polymorphic transitions were monitored using x-ray powder diffraction (XRPD) analysis and exhibited no correlation between the phase change (appearance of a new polymorph) and the degradation process.

A. Zarubica, M. Vasic, M. D. Antonijevic, M. Randelovic, M. Momcilovic, J. Krstic, J. Nedeljkovic (2014)Design and photocatalytic ability of ordered mesoporous TiO2 thin films, In: Materials research bulletin57pp. 146-151 Elsevier

Homogeneous and crack-free TiO2 films with templated mesoporosity were prepared by the dip coating technique using an evaporation-induced, self-assembly method. The synthesized mesoporous TiO2 films were characterized using SEM/TEM, BET and XRD techniques. Degradation reactions of methylene blue and crystal violet dyes were used to test the photocatalytic capability of mesoporous TiO2 films. The degradation kinetics of methylene blue and crystal violet were investigated over a broad range of initial concentrations of the organic dyes. The kinetic data were correlated with the specific surface area and thickness of mesoporous TiO2 films, as well as number of reaction cycles. (C) 2014 Elsevier Ltd. All rights reserved.

Samuel K Owusu-Ware, Babur Z Chowdhry, Stephen A Leharne, Milan D Antonijevic (2013)Novel analytical approaches for the study of mobility and relaxation phenomena in positional isomers of GABA, In: Physical chemistry chemical physics : PCCP15(46)pp. 20046-20053

γ-Aminobutyric acid (GABA), and its positional isomers DL-α-aminobutyric acid (AABA) and DL-β-aminobutyric acid (BABA) have been analysed, in the solid state, using thermally stimulated current (TSC) spectroscopy. Secondary relaxations in these molecules have been detected for the first time. GABA displays two secondary relaxations at 77 ± 2 °C and 114 ± 2 °C, whilst AABA and BABA each display a single secondary relaxation at 109 ± 1 °C and 104 ± 1 °C, respectively. Analysis (decoupling of molecular mobilities) of secondary relaxations using thermal windowing (TW) and relaxation map analysis (RMA) show that the dipole relaxation associated with secondary transitions observed for the aminobutyric acids requires activation energies of 189.9 ± 3.2 kJ mol(-1) (GABA), 142.4 ± 1.4 kJ mol(-1) (AABA) and 195.7 ± 0.8 kJ mol(-1) (BABA). However, the ΔH(≠) values observed were found to exhibit negligible deviations from the zero entropy line. This indicates that the relaxation processes are localised, non-cooperative rotational motions that have a negligible influence on entropy changes of detected molecular mobilities. Furthermore, RMA analysis revealed that AABA and BABA display compensation behaviour i.e., entropy and enthalpy are linearly related to each other, whereas GABA did not demonstrate such behaviour. The coordinates of the compensation point (compensation temperature (Tc) and the compensation relaxation time (τc)) were found to be 214 ± 6 °C and 0.051 ± 0.024 s, respectively for AABA and 153 ± 3 °C and 0.025 ± 0.011 s for BABA. For the molecules investigated the compensation points coincide with the starting temperature of the higher temperature thermal events i.e. sublimation, melt/decomposition, and indicate a correlation between secondary relaxation processes and the main thermal transitions, found via TGA and DSC studies.

Gordana Gajica, Aleksandra Sajnovic, Ksenija Stojanovic, Aleksandar Kostic, Ian Slipper, Milan Antonijevic, Hans Peter Nytoft, Branimir Jovancicevic (2017)ORGANIC GEOCHEMICAL STUDY OF THE UPPER LAYER OF ALEKSINAC OIL SHALE IN THE DUBRAVA BLOCK, SERBIA, In: Oil shale (Tallinn, Estonia : 1984)34(3)pp. 197-218 ESTONIAN ACADEMY PUBLISHERS

A detailed evaluation of geochemical properties of oil shale samples,from the outcrops of the Lower Miocene upper layer in the Dubrava area, Aleksinac basin, Serbia, was performed. For that purpose X-ray diffraction (XRD) analysis, Rock Eval pyrolysis, gas chromatography-mass spectrometry (GC-MS) analysis of biomarkers and conventional pyrolysis in an autoclave were used. Most of the samples have similar mineral compositions with predominance of clay and feldspar minerals. Three samples are characterised by an elevated content of carbonates, and among them one sample has a notable prevalence of this mineral group. This sample also demonstrated certain differences in biomarker distribution. In most samples organic matter (OM) consists predominantly of type I and II kerogens, showing high oil generative potential, whereas three samples, which contain type II kerogen with a certain input of type III kerogen, demonstrated potential to produce both, oil and gas. The OM of all samples is immature and corresponds to the vitrinite reflectance of ca. 0.40%. Biomarker patterns along with Rock-Eval data indicated a strong contribution of aquatic organisms such as green and brown algae and bacteria with some influence of higher plants OM. The organic matter was deposited in a reducing lacustrine alkaline brackish to freshwater environment under warm climate conditions. Preservation of OM was governed by stratification of the water column rather than its height. Tectonic movements that caused the regional tilting of an investigated area and supported minor marine ingression and influx of fresh water played an important role in formation of the sediments. Conventional pyrolytic experiments confirmed that these sediments at the catagenetic stage could be a significant source of liquid hydrocarbons.