15^th Annual European Pharma Congress May 07-09, 2018 Frankfurt, Germany

Irena Žuntar is working as a Full Professor and Specialist of Toxicology at University of Zagreb, Faculty of Pharmacy and Biochemistry, Croatia. She is Course and Unit Leader of Toxicology. Also, she considerably designed postgraduate specialist university program of Toxicology for health professionals and others interested or working in the field. She participated as Expert in scientific and professional opinions for Ministry of Health and Croatian Food Agency, and now she is in mandate Member of the Evaluation Panel of Croatian Science Foundation for scientific field of Biomedicine and Health, Public Health and Health Protection, and Pharmacy. She was Principal Investigator of a scientific grant and researcher on many scientific projects and gained two scientific awards. She was Supervisor of more than 50 student’s diploma thesis, and received 4 Rector Awards and two Dean Awards.

Sulfonamides, macrolides, torasemide, fumagillin and chloramphenicol were simultaneously analyzed in surface water samples by using solid-phase extraction (SPE) and reversed-phase (RP) liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS). In the pre-concentration and clean-up process, the pH value of samples and volume of the solvent for extraction of analytes from cartridge were optimized. Extraction recoveries were high with values in the range from 62 to 115%. Limits of quantification (LoQ) were in the range from 0.02 g L–1–0.2 g L–1. Repeatability of the method was evaluated at LoQ and expressed as relative standard deviation (RSD). Calculated RSDs were low with values in the range from 2.4 to 14.5%. The method was successfully applied for analysis of the real samples of surface waters. Samples were collected along the rivers in Croatia on 19 sampling sites in Danube and Adriatic catchment areas in 2013, and another 20 places in 2014. Altogether, 20 target compounds were analyzed in 362 water samples and detected in 24 samples in the range, 0.02–5.3 g L–1 or in 6.6% of samples. The most frequent and highest concentrations were detected for macrolide antibiotics. This is the first attempt of monitoring of antibiotics in surface waters in Croatia.

Mónika Bakonyi completed her Master’s degree in Pharmaceutical Sciences in 2015 at University of Szeged. Since 2015, she is a PhD student at the Institute of Pharmaceutical Technology and Regulatory Affairs of the University of Szeged. Her research focuses on transdermal delivery of active agents, active and passive penetration enhancement techniques and electroporation. Her studies include experiments with Franz cell diffusion method, tape stripping method, Corneometer and Tewameter, ATR–FTIR and Raman spectroscopy. She has done a three month internship at the University of Freiburg, learning liposomes preparing and evaluating methods.

Topically applied anaesthetics are employed in order to eliminate pain caused by needle insertion and injection, thus ameliorating patient compliance. Furthermore, they are devoid of symptoms of superficial trauma and local reaction. Therefore, the aim of this work was to develop a new formulation of lidocaine, proposed to improve its clinical effectiveness in topical anaesthesia in terms of both enhanced anaesthesia and a prolonged duration of action. For this purpose, we incorporated lidocaine in nanostructured lipid carriers (NLC). Particle size and zeta potential measurements, Fourier transform infrared spectroscopy and Raman spectroscopy were performed to characterize the NLC system. Furthermore, DSC and XRD measurements were conducted to investigate lipid crystallization which plays a very important role in the performance of NLC carriers. Additionally, membrane diffusion and penetration studies were completed in vitro and ex vivo, followed by measurements on skin hydration and transepidermal water loss in vivo. Our results lead us to the conclusion that the developed nanostructured lipid carrier is a promising vehicle for the topical delivery of lidocaine. The penetration of the NLC formulation was remarkable through heat separated epidermis after 24 hours, and the observed skin hydrating and occlusive effect also makes this formulation a favourable dermal carrier system.

Rania Hamed received her PhD in Pharmaceutical Sciences and Experimental Therapeutics at The University of Iowa in 2011, where she worked under the supervision of Professor Jennifer Fiegel. Her research was focused on developing a more physiologically relevant in vitro model mimetic of native, non-diseased tracheal mucus to understand the surface rheology of the airway-lining fluid and to elucidate bioaerosol formation from the trachea. She is currently an Associate Professor in the Faculty of Pharmacy at Al-Zaytoonah University of Jordan. Her current research focuses on developing controlled-release drug delivery systems based on hydrophilic/hydrophobic polymeric matrices and nanoemulsion-based gel and oleogel formulations for transdermal delivery. In addition, she is interested in determining the key parameters of the physiologically-relevant dissolution media that control the rate of dissolution of BCS class II drugs along the gastrointestinal tract to better predict its in vivo performance.

Weakly acidic biopharmaceutics classification system (BCS) class II drugs may exhibit gastric supersaturation and precipitation. The objective of this study was to investigate the transfer behavior of the weakly acidic BCS class II model drug valsartan from the stomach to the small intestine during fasted and fed states. An in vitro transfer method, previously introduced by Kostewicz et al., based on a syringe pump and a USP paddle apparatus was used to obtain the concentration profiles of valsartan in the small intestine. Donor phases of fasted and fed states simulated gastric fluids (FaSSGF of pH 1.2 and FeSSGF of pH 5.0, respectively) were used to pre-dissolve Diovan®, immediate release tablets containing 160 mg valsartan. The initial concentrations of valsartan in FaSSGF and FeSSGF were determined before the transfer experiments. The pre-dissolved valsartan dispersions were transferred to acceptor media that simulate intestinal fluid at a flow rate of 2 mL/min. pH measurements were reported at time intervals corresponding to those of the transfer experiments to investigate the effect of % dissolved valsartan in the donor phase on lowering the pH of the acceptor media. The similarity f2 test was used to compare the concentration profiles in the acceptor media. Results showed that the initial concentration of valsartan in FaSSGF was very low of 6.2±0.6%, whereas in FeSSGF, the initial concentration was high of 91.8±4.2% after 30 mins. The concentration profiles for valsartan pre-dissolved in FaSSGF ranged between 13.1–86.5% after 60 mins, based on the physicochemical properties (buffer capacity and ionic strength) of the acceptor media. Whereas, valsartan pre-dissolved in FeSSGF was fully dissolved in the acceptor media after 60 mins. Therefore, the transfer model provides a useful screen for the concentrations of valsartan in the small intestine after oral administration during fasted and fed conditions.

H J Cho obtained her Bachelor of Pharmacy Degree from Chung-Ang University and a Pharmacist License in 2004. She currently serves as a Pharmacist of Seoul Veterans Health Service Medical Center. She was a Member of Adverse Drug Reaction Evaluation Team of Seoul Veterans Health Service Medical Center from 2016 to 2017. She serves as the Preceptor for the Hospital Pharmacy Practice Learning Experience since 2016 and she is an active Member of the Nutrition Support Team of Seoul Veterans Health Service Medical Center since 2017.

Monitoring the ADR (adverse drug reaction) is very important because of the characteristics of VHSMC where the proportion of elderly patients who are most likely to have ADR is large. Since 2015, we have developed a monitoring system for ADR in the hospital and have been monitoring the ADRs. This study attempts to analyze the report case. A retrospective study was conducted; the ADR was reported and evaluated through the hospital monitoring system in the EMR for 32 months from January 1, 2015 to August 31, 2017. This study analyzed the following: (1) by numbers of reporting case; (2) by reporter; (3) by drug classes (coding into the drug classification number of KFDA [Ministry of Food and Drug Safety of Korea]/possible multiple suspicious drugs in one report); (4) by symptoms (WHO-ART preferred term is used for coding/possible multiple symptoms in one report). A total of 757 evaluations were completed and the average number of reports per month was 22 in 2015, 23 in 2016, and 27 in 2017. According to reporter analysis, pharmacists were 78.7% (596 cases), followed by 11.4% (86) of nurses, 9.6% (73) of physicians and 0.3% (2) of radiation engineers. By drug classes, No. 114 antipyretic/analgesic/anti-inflammatory drug was 15.5% (136 cases), followed by 6.6% (58) of No.618 antibiotics for Gram positive and negative and 5.9% (52) of No.119 other central nervous system drugs, 5.7% (50) of No.117 psychotropic drug and 4.6% (40) of No. 219 other circulatory drugs. By symptoms, dizziness was 10.2% (120 cases), followed by 7.5% (88) of nausea, 7.4% (87) of vomiting, 5.3% (62) of pruritus, 4.2% (50) of dyspepsia. In this study, it is significant that the adverse drug reaction terminology is unified with the WHO-ART preferred term. We aim to improve the adverse drug reaction monitoring system using the WHO-ART preferred term, which can give ease of referral and accuracy of the evaluation. This is expected to contribute to manage the patient’s safe use of medicines and adverse drug reactions.

A Zaid Alkilani is an Assistant Professor, Dean of the Faculty of Pharmacy, Zarqa University, Jordan. She graduated from Jordan University, College of Pharmacy in 2006. Then she obtained her MSc Degree in Pharmaceutical Science from Jordan University in 2010. After that she completed her PhD in Drug Delivery and Pharmaceutical Technology at the Faculty of Pharmacy, Queen’s University of Belfast, United Kingdom in 2013. Her research interests in the field of Transdermal Drug Delivery, Microneedle, Controlled Release, Formulations and Iontophoresis. She has presented her work at many international conferences such as, Proceedings of the 2nd International Conference on Microneedles, Cork, Ireland; Proceedings of the 2013 UKICRS Symposium, Belfast; UK, Proceedings of the UK PharmSci Conference, Nottingham.UK; Stratum Corneum VIII Conference, Cardiff, UK; 8th International Conference and Exhibition on Pharmaceutics and Novel Drug Delivery Systems 2016, Madrid, Spain and 6th FIP Pharmaceutical Sciences World Congress 2017, Stockholm, Sweden.

Hydrogels that are used for biomedical purposes such as controlled drug delivery systems should be biocompatible and often biodegradable. Depending upon the hydrogel type, their swelling ratios are dramatically changed, due to changes in external pH, temperature, ionic strength and electromagnetic radiation. This study describes the effect of hydrogel crosslink density upon the swelling kinetics and electro-responsive nature of the hydrogel, such that a formulation with the highest degree of swelling and greatest enhancement in solute permeation following the application of an electric current could be identified for subsequent microneedle (MN) production. The intention is to obtain electrically responsive hydrogel systems suitable for the production of a novel hydrogel forming, MN mediated iontophoretic transdermal drug delivery. In order to achieve hydrogels with good mechanical properties to be used as MN, network parameters, ionic conductivity, solute permeation, the mechanical and electrical properties of hydrogel films were investigated. Based upon the equilibrium swelling and ionic conductivity studies, a formulation producing a hydrogel of high swelling and conductivity at F7 6 hrs, F16 6 hrs, and F18 were identified to investigate the effect of electric current upon the electro-responsive nature of these hydrogel systems. In conclusion, the more open network structure of low crosslink density hydrogels enables solute permeation to occur more readily and the greater ionic conductivity of these formulations allows a greater solute permeation enhancement to occur when subjected to an external electric field.

Y S Chu is a Pharmacist working on improving patients’ health through patient safety management and system improvement since four years at the Seoul VHS Hospital, the largest veteran’s hospital in Korea. She has 15 years of experience both in hospitals and pharmacies, contributing to social healthcare and education.

Statement of the Problem: Antimicrobial resistance in major bacterial pathogens has become a serious medical health problem. To provide reference data or guideline for treatment of antimicrobial therapy, we studied a change pattern in the antimicrobial resistance rates of clinically important microorganisms at a veteran’s hospital. In general, higher resistance rates are observed among intensive-care-unit (ICU) isolates than non-ICU isolates. Antimicrobial resistance is an emerging problem for ICU. Therefore, we also studied the trend of antibiotic consumption in ICU at the same hospital between 2012 and 2016. Methodology & Theoretical Orientation: Susceptibility data were collected from Seoul VHS Hospital’s EMR (Electronic Medical Record) system and antimicrobial resistance monitoring system annual report between 2012 and 2016. We used days of therapy (DOT) to calculate the annual antibiotic consumption for 17 antibiotic groups, retrospectively. Findings: Total number of detected bacteria in the medical center was 96,410. Frequently isolated organisms in decreasing order were Staphylococcus aureus (12%), Pseudomonas spp. (10%), Acinetobacter spp. (10%), Klebsiella spp. (9%). Methicillin-resistant S. aureus (MRSA), vancomycin-resistant S. aureus (VRSA), vancomycin-resistant Enterococcus spp. (VRE), multidrug-resistant P. aeruginosa (MRPA), multidrug-resistant Acinetobacter baumannii (MRAB) and carbapenem-resistant Enterobaterceae (CRE, Klebsiela pneumoniae) were isolated at 75~80%, 0%, 12~37%, 10~15%, 55~68% and 2~15%, respectively; the resistance rate increased gradually. Average annual antibiotic consumption during 2012–2016 was 18002 DOT/year. The prescription rates of injection antibiotics are in the order of glycopeptide, carbapenem, β-Lactam/β-Lactamase inhibitor, 3rd generation cephalosporin, 1st generation cephalosporin and quinolone. However, no statistically significant change in the total amount of antibiotics was observed during the study period. Consumption of 2nd generation cephalosporin, lincosamide, monobactam and aminoglycoside was significantly decreased, while that of β -lactam/β -lactamase inhibitor, 3rd and 4th generation cephalosporin, carbapenem, quinolone, polymyxin, glycycline and oxazolidinone with broad spectrum increased significantly. Conclusion & Significance: High rates of antibiotic consumption were associated with high resistance rates of microorganisms. The increase of multidrug-resistant microorganisms requires an update of guidelines and a more strict control of antibiotics.

Hajar Owji completed her PharmD from Shiraz University of Medical Sciences. She is now working as a Research Pharmacist affiliated to the Department of Pharmaceutical Biotechnology. Her research interests are focused on Bioinformatics, Molecular Biology, and Biomolecular Pharmaceutical Sciences.

Statement of the Problem: Day by day, the demand for biotherapeutics and recombinant proteins is increasing. Herein, cytoplasmic expression in prokaryotic and eukaryotic hosts has been widely accepted. However, there are several obstacles in the large-scale production of recombinant proteins. Recombinant proteins might form inclusion bodies or be degraded by proteases. Endogenous proteins might also interfere with the folding of a recombinant secretory protein. These factors, as well as the complicated downstream purification process, will result in loss of protein yield. Moreover, the yield of recombinant protein is not only related to expression levels, but also to translocation efficiency. Thus, the translocation efficiency could be increased by using signal peptides. Phenylalanine ammonialyase (PAL), involved in the first step of the phenylpropanoid pathway, catalyzes the deamination of phenylalanine to cinnamate and ammonia. PALs are ubiquitous in plants and also commonly found in fungi; however, animal lacks it. They are of special interest in several medical and industrial applications, including preparation of low phenylalanine diet, treatment of phenylketonuria and certain neoplastic tumors. Although several methods have been applied in the production of PAL, the final titers of PAL are still low, thereby impeding considerable industrialization of this enzyme. Objective: This study aims to evaluate a vast number of signal peptides, previously deposited in databases (1168 signal peptides), in order to select the most appropriate ones for secretory production of PAL. Methodology & Theoretical Orientation: Herein, the SignalP tool was applied to determine the secretion efficiency as well as cleavage sites. Moreover, various physiochemical properties of signal peptides linked to the protein as well as secretory pathways were identified. Effects of signal peptide addition on antigenicity, allergenicity, and mRNA secondary structure of PAL were evaluated. Findings: The appropriate candidates for high yield and efficient production of phenylalanine ammonia-lyse in E. coli were identified.

Elaheh Entezar-Almahdi completed her PharmD at Shiraz University of Medical Sciences in 2016. Currently, she is a PhD student of Pharmaceutics. Her research interests include, designing novel smart DDS, targeted drug/gene delivery system for cancers, and nanoparticulate DDS.

Among various dedicated nanoparticles for drug delivery applications, hydrogels have been mostly studied. Hydrogels are 3D structures with high water-content capacity that is made up of hydrophilic polymers. In addition, hydrogels have significant physicochemical properties, such as permeability, porosity, physical interactions and some smart ones are capable of responding to environmental stimuli like temperature, pH and ionic strength. Poly vinyl caprolactam (PVCL) as one of the most extensively studied thermoresponsive polymers, has a continuous coil-to-globule phase transition behavior with the lower critical solution temperature (LCST) ranging from 32 to 50°C, which depends on PVCL molecular weight and concentration. In this study, novel temperature responsive hydrogel based on poly(vinylcaprolactam) (PVCL) were prepared via reversible addition-fragmentation chain-transfer (RAFT) polymerization, where PEG- diacrylate served as cross-linker, and lysine was used as linking agent and applied for drug delivery. First, PVCL-PEG nano-hydrogel was prepared by RAFT polymerization in dioxane solvent, and then lysine was added to PVCL-PEG. After that, doxorubicin as an anti-cancer drug, was conjugated to lysine moiety of a prepared structure via Schiff-base reaction. Obtained nano-gels were characterized by FT-IR, 1H-NMR and their effective sizes were checked by dynamic light scattering analysis. LCST were determined and the drug release profile was tested in vitro. The 1H-NMR analysis of PVCL-PEG and PVCL-PEG-lysine confirmed the synthetic steps. DLS analysis represents the particles hydrodynamic size with average diameter of 20 nm. The LCST behavior was measured to lie at 37°C. Synthesized PVCL-PEG-lysine were observed to disperse well in aqueous solution without precipitation which show their high potential as a nanocarrier for drug delivery.

P Vergara-Aragón is an MD and PhD in Psychological Research and has worked in the Faculty of Medicine, UNAM in Mexico for more than 30 years. She collaborates with the Physics Institute of the National Polytechnique Institute. Her research is focused in the field of Parkinson’s disease (PD), study of the nigrostriatal pathway degeneration, and involved mechanism caused by rotenone and 6-OHDA; stabilization of dopamine and its use as treatment for PD; the study of the effects produced in vivo of a TiO2 amorphous matrix as a reservoir for dopamine in a PD model in rats; description of the cognitive implications of PD in patients; toxicity and biological implications of rotenone exposure in animal models.

The development of formulations based on titanium dioxide to store dopamine (TiO2/DA) minimizes the oxidation of it by protecting it from direct exposure to natural light and air. It also fulfills a second function that is the release of dopamine (DA) for long periods in a rat model of hemiparkinsonism. A critical point is the toxicity of these materials that has led us to perform biocompatibility tests on these TiO2/DA implants. The first biocompatibility studies on TiO2/DA implant are presented here. Presterilized samples of the matrix were implanted subcutaneously and intraperitoneally in male Wistar rats. Scanning electron microscopy and histological examination of implanted samples and surrounding tissues were performed; subcutaneous implant was 0.095 g/DA per 20 ml of TiO2. Histological examination of implanted samples and surrounding tissues revealed no evidence of acute or chronic foreign body inflammatory response. The fibrous capsules surrounding the implant remained thin (<100 μm) after more than three months in situ, while the surrounding tissue remained well vascularized; intraperitoneal implant was 0.02 ml/DA per 20 ml of TiO2. The histological analysis for the liver, heart, lung, kidney, spleen, muscles and brain did not show structural macroscopic changes. It did not show an inflammatory response either (TNF-a, IL -6 and cellular infiltration), between the control group and the experimental groups. Also, the implants lingered encapsulated on tissue after three months; intraperitoneal implant was 0.13 g/DA per 20 ml of TiO2. It was observed that a mild inflammatory effect and the presence of mononucleocytes within the group which received the highest dose of TiO2/DA. The results of this analysis suggest that there is no contamination across the organs due to the implants. It is possible to suggest the compatibility of the TiO2/DA implant with the rat tissue, and thus, justify a further investigation about its potential use as biomaterial for storing and releasing drugs.

B Hernández-Téllez is a Biology graduate and has worked in the Faculty of Medicine UNAM in Mexico for more than 20 years. Her research is focused in the field of Tissue Engineering and collaborates in toxicity and biological implications of rotenone exposure in animal models. She is a Professor of Histology in the Biology Cellular and Tisular Department, Faculty of Medicine, National Autonomous University of Mexico, Mexico

The aim of the present study was to establish the relation that exists between the striatal dopamine levels and urine dopamine content in hemiparkinsonism rat model. 20 Wistar rats were used and were randomized into two groups as follows: a) control group and b) lessoned injured group induced by (6-OHDA). All animals were re-tested on the same battery of motor tests that before lesion. The rotation test behavior test was assessed and striatal DA levels and urine DA were determined by HPLC, motor behavior fine tests were done and finally immunohistochemical (Hir+) striatum was done. We found a positive correlation between the dopamine levels in the striatum and the content dopamine in urine of rats (control vs. 6-OHDA group). Respect motor performance, the 6-OHDA group showed a significant fine motor impairment (grasp and advance) vs. control group (p<0.01). Immunostaining for tyrosine hydroxylase (TH) expression revealed no TH-immunoreactive (THir) neurons in any 6-OHDA animals vs. control group (p<0.01). Positive correlation between the dopamine levels in the striatum and the content dopamine in urine could be talking also, about a major proportion of urinary dopamine could be derived from the renal decarboxylation of circulating dopa and not dopaminergic system disturbance. The other hand, alterations of a forelimb motor function in rats could be only due to more vulnerability of striatal dopaminergic depletion and not to low periphery dopamine levels.