ESSP Volume 10 Edition 1

Table of contents

4 Amidrazones as substrates for the synthesis of compounds with multidirectional therapeutic activity

6 Structure-activity relationships for several series of Janus Kinase Inhibitors using principal component analysis

8 GAIT analysis of the transgenic mice, carriers of the human CYP2C19 gene

10 The application of 3D tablet printing into personalised medicine to provide patient-tailored therapy: a review of the recent progress and advances

14 Effect of dimethyl fumarate treatment on cognitive functions: Research in Dark Agouti rat experimental autoimmune encephalomyelitis model

16 Development of directly compressible formulations by mechanical properties’ simulations

Dear readers,

I am pleased to welcome you to the first edition of EPSA Students’ Science Publication (ESSP) Volume 10. ESSP is an EPSA periodic publication that aims to spread knowledge and research projects conducted by motivated pharmacy students all around Europe in the form of abstracts.

In this edition, there are six abstracts on a collection of topics. The first abstract will give insights into the future of amidrazones in therapeutics. Will the upcoming antibacterial be an amidrazone derivative? You can find the answer in this abstract. Janus Kinases are potential targets for anticancer drugs. The second abstract tells how the physicochemical properties of a set of compounds reflect on their capacities to inhibit Janus Kinases.

Transgenic animals, animals with a foreign gene purposely inserted in their genome, are an essential part of many research projects. The third group investigated whether transgenic mice are good models for studying cerebellar ataxia. The fourth abstract is about 3D printing and its importance in personalised medicine.

Furthermore, a group of young researchers from Serbia investigated whether experimental autoimmune encephalomyelitis (EAE) leads to a cognitive deficit. To know the answer, do not skip the fourth abstract. Lastly, you will read about the development of directly compressible formulations by mechanical properties simulations.

Ultimately, I would like to express my sincerest gratefulness and gratitude to the European Federation for Pharmaceutical Sciences (EUFEPS) for the availability and invaluable feedback. Your efforts are highly appreciated by the authors and by EPSA. I would also like to thank everyone who contributed to the success and publication of this edition, particularly EPSA’s public relations department.

Enjoy your reading, Yours in EPSA

Rahaf Alsayyed EPSA Science Coordinator 2022-2023

Amidrazones as substrates for the synthesis of compounds with multidirectional therapeutic activity

Author: Daria Frisch (e-mail: daria.frisch@wp.pl)

Scientific Coordinators: Renata Paprocka, Bożena Modzelewska-Banachiewicz Institution: Department of Organic Chemistry, Faculty of Pharmacy, Nicolaus Copernicus University, Poland

INTRODUCTION: Chemical compounds classified as amidrazones contain a specific group within which the hydrazone and amide parts can be recognised. Amidrazones and their derivatives have been the subject of scientific interest for at least 75 years and the subject of original publications published by research teams of many countries from different continents, including South Korea, India, Jordan, Taiwan, China, Brazil, Tunisia, Egypt, Portugal, Germany, Russia, Italy, and Poland. These compounds are characterised by significant biological activity that can meet the needs of modern pharmacy.

THE AIM: The study aimed to systematise the knowledge of the biological activity of amidrazone derivatives, contained in publications from 2010 to 2021, and to select and characterise those compounds in in vivo and in vitro studies that proved to have the most therapeutically desirable properties.

MATERIALS AND METHODS: The research material consisted of about 80 original publications, available in bibliographic databases, including Medline (PubMed), Scopus or Web of Science.

RESULTS: The analysis of the available scientific sources allowed for identifying 131 significant, in terms of biological activity, derivatives of amidrazones. Among them, both cyclic and acyclic compounds, as well as complexes with transition metals, have been identified. The most frequently documented properties were as follows: anticancer activity (in over 30% of compounds), antibacterial activity (in 20% of compounds) and anti-inflammatory activity (in 14% of compounds). Moreover, antifungal, antioxidant, antiviral and antiparasitic activities have been demonstrated, as well as a beneficial effect on the central nervous system and supporting effect in the therapy of diseases such as rheumatoid arthritis (RA), diabetes and obesity.

14 amidrazone derivatives were classified as the

most promising drug candidates. 70% of them are compounds with anti-cancer and/or antiinflammatory properties. Currently, delpazolid, i.e. a derivative containing cyclic amidrazone, which has shown antibacterial (including antituberculosis) activity and is in the second phase of clinical trials, has the greatest chance of being granted the status of a drug. In addition, interesting biological activities have been reported for a large number of the described derivatives: selectivity towards the cellular target or low toxicity towards healthy cells of the organism.

CONCLUSION: Amidrazone derivatives meet many requirements for new therapeutic substances, and further research on their therapeutic usefulness may result in new drug registrations.

KEYWORDS: amidrazone, delpazolid, antitumor activity, antibacterial activity, antiinflammatory activity.

Questions & answers

Please, tell us a little bit more about yourself.

I am a final 6th-year student of Pharmacy. This year I’m doing an apprenticeship in a community pharmacy and a hospital pharmacy. So far, I have also gained experience in other places, such as the Department of Health. Currently, I am a Coordinator for Educational Materials at the Polish Pharmaceutical Students’ Association (PPSA -Bydgoszcz branch) and a member of the Polish Editorial Group and the Polish Educational Group of the PPSA. In my spare time, I read crime novels and articles on psychology. I am also a fan of rock music.

Tell us a bit more about your research and its significance.

My research focused on the potential use of amidrazone derivatives in pharmacotherapy. I analysed the biological activity documented in original publications, and on this basis, I selected the most promising compounds. Such analyses are very valuable considering the large number of chemical compounds that are synthesised every year and tested for their therapeutic properties. Thanks to my research, scientists dealing with this group of chemical compounds will find out which specific compounds are worth dealing with in the future.

What was the biggest challenge while carrying out the research, and how did you overcome that?

The culmination of my research was the selection of over a hundred compounds and then fourteen compounds that, to the best of

my knowledge, are the best drug candidates. It was time-consuming and required much patience, but the results I achieved were worth it. My recipe for effective data analysis turned out to be a mind map, which I created by hand with paper and felt-tip pens. :)

In your opinion, what is the benefit of joining ESSP, and what advice do you have for students undertaking research in the future?

Membership in ESSP allows you to acquire professional skills useful not only in a scientific career, which increases self-confidence. My advice to all future scientists is: Do not be afraid to act. Only those who do nothing do not make mistakes. :)

Structure-activity relationships for several series of Janus Kinase Inhibitors using principal component analysis

Authors: Dominika Nádaská*

Scientific Coordinator: Assoc. Prof. PharmDr. Ivan Malík, PhD.

Institution: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University Bratislava, Odbojárov 10, SK-832 32, Slovak Republic

*Author to whom correspondence should be addressed: nadaska11@uniba.sk

INTRODUCTION: Janus kinases (JAKs) are intracellular tyrosine kinases which mediate the signalling of many cytokines and growth factors regulating a wide range of biochemical processes. Isoenzymes JAKs (JAK1–JAK3, TYK2) are very attractive biological targets for treating cancer and autoimmune diseases.

AIM: The current research aimed structure–activity relationships within the groups of inhibitors containing a purinone, pyrazolopyrimidine as well as benzimidazole structural motif (number of analysed compounds (n) = 74) considering possible connections between their in silico properties and ability to inhibit JAK1–JAK3 employing Principal Component Analysis (PCA).

MATERIALS AND METHODS: The in vitro JAK1–JAK3 inhibitory activity constants (IC50 values) for investigated sets were adopted from the research papers already published. The physicochemical descriptors generated in silico and used in a current PCA were as follows: molecular weight (MW), number of carbon atoms in sp3 hybridisation (csp3), molecular volume (MV), molar refractivity (MR), lipophilicity parameters (log P values) calculated by an iLOGP, XLOGP3, WLOGP, MLOGP, LOGP (SILICOS-IT), CLOGP, log PCf, log PVf and miLogP 2.2 method, respectively, water solubility, i.e., log S descriptors predicted by a log S (ESOL), log S (Ali) and log S (SILICOSIT) method, respectively, employing various software packages. PCA was performed by XLSTAT software ver. 2022 (Addinsoft Inc., New York, N.Y., USA).

RESULTS: Positive correlation defined by a Pearson’s correlation coefficient (r) was found between lipophilicity (LOGP (SILICOS-IT)) and

the ability of the ligands to inhibit JAK1 (r = 0.694). The most valuable positive correlation was calculated for purinone derivatives (n = 29; r = 0.765). Neither the JAK2 nor JAK3 inhibition was significantly directly proportional to the lipophilicity of evaluated ligands. The csp3 descriptor of purinone ligands inversely correlated with both JAK1 (r = -0.670) and JAK2 (r = -0.706) inhibitory efficiency. However, the findings observed for other sets showed that a given conclusion could not be applied in general.

CONCLUSION: The performed PCA indicated a positive linear correlation between in silico lipophilicity (LOGP (SILICOS-IT)) of purinone scaffold-based ligands and their in vitro JAK1 inhibitory efficiency as well as the inverse linear correlation between number of carbon atoms in sp3 hybridisation of the ligands (csp3) and their JAK1/JAK2 inhibitory potency. In addition, the research revealed a real possibility that analysed ligands inhibited both JAK1 and JAK2 with similar mechanisms; the JAK3 inhibition may be due to the interference with other targets in the structure of the given isoenzyme.

Questions & answers

Please, tell us a little bit more about yourself.

My name is Dominika Nádaská, and I am a 23-year-old Pharmacy student at the Faculty of Pharmacy, Comenius University Bratislava (Slovak Republic). I have just finished my fourth year at the faculty, so I am heading into the final year of my study. Currently, I am Vice President of the Slovak Pharmaceutical Students’ Association. I am a passionately curious student, and my field of interest is Pharmaceutical Chemistry. After the Master of Pharmacy graduation, I would like to continue my study to obtain an academic Philosophy Doctor degree and become a drug design and development researcher.

Tell us a bit more about your research and its significance.

Structural characteristics and physicochemical properties of drugs are closely related to their biological activities or toxicity. The structures of the drugs hide a lot of information that will make it possible to understand the reasons why a particular compound is soluble in aqueous or lipophilic compartments of the human body, able to permeate blood–brain barrier, biologically effective, selective towards its biological target(s) or toxic. The main goal of our research was to investigate structure–activity relationships within several groups of structurally different inhibitors of biologically exceptionally significant Janus kinase (JAK) isoenzymes, explore and define possible connections/relationships between several in silico physicochemical descriptors of these molecules and their JAK inhibitory activities.

What was the biggest challenge while carrying out the research, and how did you overcome that?

A significant part of our research was calculating a vast amount of data and numbers as well as their reasonable interpretation, so I needed to be precise and careful, making no mistakes. The biggest challenge for me was learning how to choose and properly use appropriate software packages as well as interactive prediction tools, how to understand and correctly interpret the results of Principal Component Analysis. Although it was not always easy, I learned a lot and overcame that, thanks to my supervisor.

In your opinion, what is the benefit of joining ESSP, and what advice do you have for students undertaking research in the future?

Indeed, it was an honour to submit the abstract describing our research, which was reviewed by European Federation for Pharmaceutical Sciences and published in EPSA Students’ Science Publication (ESSP). ESSP is a remarkable way to share your research ideas via an international platform. In addition, you can improve your writing skills and gain unique experience describing precisely the most significant findings and conclusions from the research. Overall, this unique opportunity strengthens my determination to engage in scientific activity in my professional life.

My advice is maybe cliché, but I would like to bequeath, never give up and strongly believe in yourself. Although it may seem difficult at first, it is worth it. Be persistent. Above all, listen to your supervisor. Well, if you are afraid of anything, it is all right. We do not grow when we stay inside our comfort zone.

GAIT analysis of the transgenic mice, carriers of the human CYP2C19 gene

Author: Pavle Sitarica

Scientific Coordinators: Assoc. Prof. Marin Jukić, TA Andrea Atanasov Institution: Department of Physiology, Faculty of Pharmacy, University of Belgrade

INTRODUCTION: Animal models are essential for understanding the aetiology and pathophysiology of movement disorders. Transgenic mice carriers of the human CYP2C19 gene, expressed in the liver and developing brain, exhibit complex emotional and motor phenotype and may be useful in investigating the potential role of the CYP2C19 enzyme in neurodevelopment.

AIM: Characterization of gait in the CYP2C19 mice by footprint test and evaluation of potential usefulness of the CYP2C19 mice as an animal model for cerebellar ataxia.

MATERIAL AND METHODS: Transgenic (TG) and control mice were involved in the experiment. Body weight was measured from the 21st to the 42nd postnatal day (P21-P42). From 5-8 postnatal weeks, the hindpaw elevation height was quantified, a footprint test was performed, and stride lengths for every paw, the width of the front and hind base, and the overlap of the steps were measured.

RESULTS: TG mice exhibited a statistically significant reduction in body weight of 13.54% (CI 95%: 7,71-19,35%; p<0,001) in P21 and 4.60% (CI 95%: 0,32-8,88%; p=0,036) in P32; after which there wasn’t a significant difference. The hindpaw elevation was approximately twice higher in the TG compared to control mice, and this difference did not change over time. TG mice exhibited an increase in elevation of both hindpaws in the 5th postnatal week, after which TG mice gradually started exhibiting unilateral elevation, which is equally present on the right and left hindpaw. Footprint analysis showed no significant difference between TG and control mice in any of the analysed parameters, accounting for all examined time points. There was a trend towards the wider hind base in transgenic mice at the 5th postnatal week (-7% [95%CI: -13%, -0.3%], p=0.042), but the effect was no longer significant after the correction for animal sex (p=0.15).

CONCLUSION: No significant changes were observed in the gait of TG mice compared to control mice, aside from substantially more pronounced hindpaw elevation. CYP2C19 mice do not present a prototypical model of cerebellar ataxia since they do not exhibit greater hind base widths as animal models of ataxia do.

KEYWORDS: CYP2C19; gait disorder; footprint test; cerebellar ataxia

Questions & answers

Please, tell us a little bit more about yourself.

My name is Pavle Sitarica, and I am a thirdyear student at the Faculty of Pharmacy, University of Belgrade, Serbia. I started my research work one year ago. I’m very interested in neuroscience and pharmacology and very motivated to continue my research in those fields. Also, I am a part of the Student Research Centre (CNIRS) at my faculty.

Tell us a bit more about your research and its significance.

CYP2C19 is an enzyme expressed mainly in the liver, but the expression is also detected in the fetal brain. CYP2C19 transgenic mice contain the human CYP2C19 gene, which is not present in a mouse genome, and exhibit the same CYP2C19 organ distribution as humans. Transgenic mice exhibit abnormal walking, diminished balance, and loss of fine dexterity, which are the most common symptoms of cerebellar ataxia. However, this model possesses a few unique properties not previously observed in other models of movement disorders. Transgenic mice spontaneously improve motoric phenotype over time, only one side of the body is affected with motoric impairment in their later adulthood, and this animal model nearly does not exhibit abnormalities in footprint test parameters. Understanding the exact molecular mechanisms involved in TG mouse motoric phenotype could provide insight into new drug targets for the treatment of cerebellar disorders.

What was the biggest challenge while carrying out the research, and how did you overcome

that?

The biggest challenge was processing all experimentally obtained data. At the same time, I spent many hours reading literature and writing my research paper. The time given for the project was very limited, so it wasn’t easy to balance my research with a lot of work during the academic year. I got much support from my mentors during the research project, so everything became much easier.

In your opinion, what is the benefit of joining ESSP, and what advice do you have for students undertaking research in the future?

The benefit of joining ESSP is an excellent opportunity to present your research and get in touch with other students and people with similar interests. Research during studies could provide you with a lot of knowledge and skills and help you become a better pharmacist. The results won’t always be as expected, but that’s not the reason to give up. Working in a research group gives you unique experiences outside the regular faculty program.

The application of 3D tablet printing into personalised medicine to provide patient-tailored therapy: a

review of the recent progress and advances

Author: Abanoub Soliman (Bh56ui@student.sunderland.ac.uk)

Scientific Coordinator: Dr. Ahmed

Faheem

Institution: University of Sunderland, United Kingdom

INTRODUCTION: For decades, prescribers have relied on the “One size fits all” prescribing approach, considering the same first-line treatment to all patients diagnosed with the same disease, with the anticipation that they would respond in a similar way to the drug. It drives the pharmaceutical industry to operate through mass production, manufacturing physically and chemically identical drug tablets. It has left patients with poor therapeutic responses and unwanted side effects, leading to poor patient compliance and treatment adherence. The current tablet manufacturing approaches, including tablet compression, have served the pharmaceutical industry for years with well-established quality control pathways. However, these methods have demonstrated weak production flexibility, process capability and adaptability to specific individual needs for the desired therapeutic outcome. It urges the unmet need to incorporate 3D printing technology to provide patient-tailored treatment regimens.

AIM: The review focuses on the investigation and evaluation of the suitability to incorporate the novel 3D printing technology of fused deposition modelling (FDM) into the pharmaceutical industry to revolutionise the tablet manufacturing sector. It addresses the different filament drug loading techniques, including impregnation (IMP) and hot-melt extrusion (HME) and their offered capability to individualise produced drug tablets for a unique and promising clinical outcome.

MATERIALS AND METHODS: The research was based on a quantitative approach to evaluate the pharmaceutical characteristics of printlets, including tablet strength, drug loading capability, and dissolution studies. A qualitative approach was considered to assess the impact of the novel technology on patient care regarding disease management, medication accessibility and patient acceptability of the new formulations. Eight articles were retrieved for analysis through advanced research using databases, including PubMed and ScienceDirect. The main eligibility criteria were the focus on the FDM technique for drug tablet manufacturing. Some articles were

excluded due to the focus on other 3D printing techniques; others were discarded due to using more than one type of polymer to produce a filament. The use of a single polymeric material provides the ability to individually assess the impact of each type of polymer on the printability and the printlets’ physicochemical properties.

RESULTS: FDM uses a filament fed through a heating extruder head and then deposited on a build platform. Different drug-loading techniques have been identified. Their implications are demonstrated in the different studies shown in the Table below.

CONCLUSION: The versatility of the novel tabletting technology promotes its ability to reinforce the concept behind precision medicine, accounting for unique patient requirements. The HME technique demonstrated the ability to incorporate high-risk drugs due to the increased dosing accuracy. Future considerations include incorporating the Human Genome Project to study the differences in pharmacodynamic and pharmacokinetic outcomes between patients.

In combination with the 3D printing strategy, it will provide the ability to accommodate dose-specific tablets such as warfarin to ease the burden of its frequent monitoring requirement. On the other hand, the print and fill approach showed the capability to produce polypills to compete against polypharmacy, easing complex regimens. Such bright results elucidated the significance of

the novel tablet manufacturing approach. The promising adaptability points to the potential integration of a dispensing system outside the clinical environment, such as patient homes, enhancing medication accessibility. Quality control regulations are yet to be established. Hence, a Quality by Design model is compulsory for further investigation.

Study & Aim Outcomes & conclusions

Goyanes et al. (2014)

Assess the extent of the filament drug loading through IMP.

Goyanes et al. (2015)

Assess the extent of the filament 4-ASA and 5-ASA loading through IMP.

Ibrahim et al. (2019)

Assess the ability to load a hydrophilic drug into a hydrophilic filament through IMP.

Skowyra et al. (2015)

Assess the ability to produce extended-release prednisolone tablets using IMP.

Thanawuth et al. (2021) Compare the effect of IMP and HME on the drug release.

Arafat et al. (2018)

Analyse the drug loading accuracy of printed warfarin tablets using HME.

Beatrix et al. (2020)

Assess the ability to produce a 3D-printed polypill to compete against polypharmacy.

IMP allows for low and unpredictable drug loading (0.29 %w/w), which restricts its use to drugs that require low therapeutic doses.

The higher the drug solubility in the solvent the higher the filament drug-loading. Thermolabile drugs can undergo serious degradation during the printing process, restricting the number of drugs suitable for incorporation.

It is important to maintain good solubility of the drug in the solvent while minimising the solubility of the filament in the solvent to maintain the integrity of the filament. In this case, this could be done by using an ethanol-water mixture instead of an absolute ethanolic solution or water.

Methanol allows the physical stability of the filament to be maintained during the drug loading, as compared to ethanol. A constant fluctuation was revealed in the dosing accuracy, ranging between 87.12% and 117.67%, which questions the reproducibility of tablets.

HME allows for higher, more accurate and predictable drug loading (27.93 %w/w), as compared to IMP, reserving its use to high-risk drugs requiring high accuracy in reproducibility.

A fairly acceptable dosing accuracy of 91.5 – 102.4% was demonstrated. The implementation of the HME technique provides the ability to precisely control the drug content of the tablets, targeting high risk-drugs with a small therapeutic index.

It is possible to take the concept of a capsule to the next level, by printing an empty shell with different compartments to accommodate different drugs. The thickness of the walls determines the rate of drug release. It provides the ability to ease complex treatments, providing a single formulation with several APIs.

Questions & answers

Please, tell us a little bit more about yourself.

My name is Abanoub Soliman. I’m a finalyear pharmacy student at the University of Sunderland, United Kingdom. I’m very enthusiastic about the innovation and enhancement of drug development approaches to revolutionise the pharmaceutical industry. This drives my motivation to positively impact patient care, ensuring ideal clinical outcomes.

As a future healthcare professional, my vision is to focus not only on the appropriate medication and its route of administration for the patient but how we can personalise the drug formulations to optimise the clinical management of a disease.

Tell us a bit more about your research and its significance.

As a laboratory technician, I’ve seen many cases where patients present with side effects and adverse drug reactions to newly prescribed drugs. Also, sometimes it would require patients to try several medications with different doses until an appropriate regimen is established for their chronic disease. Genetic variations are crucial to understanding the differences in pharmacological responses of drugs between patients. If unique patient needs and requirements are identified, we can take advantage of the versatility and flexibility of the 3D printing technology to manufacture patient-customised solid oral formulations.

In the future, 3D printers could serve as transportable dispensing stations to facilitate drug accessibility. This way, implementing such innovative devices would target optimal therapeutic results and ease the burden of medicine availability seen in developing cities.

What was the biggest challenge while conducting the research, and how did you overcome that?

During my research, I was required to read and analyse a lot of literature about not only 3D printing and its application, but also about the concept of precision medicine and further criticise and analyse the implementation of the novel technology into the pharmaceutical field. The main challenge is that it required a lot of time and effort to eventually organise the retrieved data and information to present a well-structured systematic review. I found it beneficial to divide the work into several stages, looking at every aspect of 3D tablet printing individually. In return, it eased the ability to relate and compare findings to come up with clear and concise conclusions.

In your opinion, what is the benefit of joining ESSP, and what advice do you have for students undertaking research in the future?

ESSP provides a fabulous opportunity for young researchers to share their work and knowledge while connecting with other future scientists in their areas of interest to fulfil their scientific curiosity. My advice is that it might seem like there is no progress but always keep the big picture in front of you. The results may not correlate with your expectations, but your contribution brings value to your area of research.

Effect of dimethyl fumarate treatment on cognitive functions: Research in Dark Agouti rat experimental autoimmune encephalomyelitis model

Authors: Strahinja Đurić, Maja Skočić, Aleksandar Stojadinović; Scientific Coordinators: Full Prof. Zorica Stojić-Vukanić, Assist. Prof. Ivan Jančić Institute: Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade

INTRODUCTION: Neurocognitive deficit is seen in 40-65% of patients with multiple sclerosis (MS). Experimental autoimmune encephalomyelitis (EAE) is an umbrella term for the spectrum of the most commonly used MS models. Neurocognitive dysfunction has also been described in some EAE models. Dimethyl fumarate (DMF), an agent for MS therapy, can improve the cognitive capacity of MS patients and mice in one EAE model. This indicates differences in the pathogenesis of this deficiency in EAE animal models and human MS.

AIM: To examine whether there is a cognitive deficit in EAE-induced Dark Agouti (DA) rats and, if so, whether it can be improved by DMF treatment.

MATERIAL AND METHODS: EAE was induced by injection of spinal cord homogenate and complete Freund’s adjuvant at the tail base, intradermally. EAE rats developed protracted disease with a peak on the 14th day post immunisation (d.p.i.) and by the spontaneous recovery of most animals on the 38th d.p.i. One group of animals was treated orally with DMF from the appearance of motor signs of EAE, while the other received a vehicle. A number of rats were not immunised and were later used as a control group. Motor signs of the disease were scored daily, and body weight was measured weekly. From the 35th to the 39th-day postimmunization short-term memory and wellbeing of diseased animals were examined. Novel object recognition test (NORT) was used for short-term memory evaluation. This test is based on the natural proclivity of rodents towards exploring unknown objects. The well-being of diseased animals was assessed through the Burrowing test, which exploits the rodent’s inherent evolutionary instinct to burrow.

RESULTS: DMF treatment significantly reduced the motor deficit at the disease peak (p<0.01)

and during the recovery (p<0.05). It also significantly decreased the duration of motor symptoms (p<0.05). The animal weight loss corresponded with the severity of the disease. Since DMF has gastrointestinal adverse effects, it slightly increases weight loss. EAE induction negatively affected short-term memory, while DMF led to improvement, but it did not reach statistical significance.

CONCLUSION: DA rats developed neurocognitive deficit in the EAE relapsingremittent model; hence it can be used for further studies of the effects of DMF, and other drugs, on cognition in EAE/MS.

Questions & answers

Please, tell us a little bit more about yourself.

I’m Strahinja Đurić, a fourth-year student at the University of Belgrade, faculty of pharmacy. Though ageing research will be my main area of interest in the future, I am now learning a lot about immunological and behavioural in vivo trials. I participate in our University’s Center for Student Scientific Research as well.

I’m Aleksandar Stojadinović, a fourth-year student at the University of Belgrade, Faculty of Pharmacy. My research interests are pharmacology and immunology-related in vivo studies. I also promote awareness about air pollution as an environmental activist.

My name is Maja Skočić. I am a fourth-year student at Belgrade University, faculty of pharmacy. My studies are mainly directed towards medical biochemistry, but I am also interested in immunology and pharmacology. Research and volunteering are two ways to channel my desire to make people’s lives better.

Tell us a bit more about your research and its significance.

Our initial objective was to determine whether Dark Agouti rats, a strain noted for being anxious, are suitable as experimental animals to be used in EAE models. The second objective was to assess the disease’s progression over a 40-day period while consistently administering DMF to a group of animals. Our ultimate objective was to evaluate DMF’s impact on motor and cognition impairments. Given the prevalence of cognitive abnormalities in multiple sclerosis (MS) patients and how

easily they might be missed throughout the diagnostic and treatment processes, the neurocognitive deficits were the main emphasis, and they were assessed using the novel object recognition test.

It’s critical to spread knowledge about the cognitive deficits these individuals may experience, given the rising prevalence of MS.

3. What was the biggest challenge while carrying out the research, and how did you overcome that?

The challenging nature of the in vivo experiments was the most difficult aspect of this research. Also, the statistical calculations were even more complicated than anticipated because there were three comparable groups of animals.

It is critical to be organised appropriately. We also received a lot of help from our mentor, who trained us and was there for us every step of the way.

4. In your opinion, what is the benefit of joining ESSP, and what advice do you have for students undertaking research in the future?

The value of joining ESSP is the ability to publish your research and connect with students who share your interests and exploratory spirit. Our advice to other colleagues who want to pursue a scientific career is to persevere and never give up on their goals.

Development of directly compressible formulations by mechanical properties’ simulations

Author: Teodora Micić, MPharm Scientific Coordinator: Prof. Jelena Đuriš Institution: Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade

INTRODUCTION: Due to its simplicity and profitability, direct compression has become important for tablet manufacturing. The challenge in this process is to optimise a formulation that contains an active substance with poor mechanical properties to produce tablets with satisfactory mechanical characteristics by direct compression.

AIM: This work aims to investigate the impact of different parameters on the tabletability of a powder blend that contains paracetamolan active substance with limited mechanical properties, by combining laboratory experiments with software tools.

MATERIAL AND METHODS: The tests were performed on the tablets with 25% and 35% paracetamol fractions. The remaining parts of the formulations consisted of a coprocessed excipient containing alpha-lactose monohydrate and microcrystalline cellulose in a 3:1 ratio (MicroceLac® 100). The software used to predict the characteristics of tablets and compression conditions is ZoomLab™. The tablets were made by direct compression, with variable compression force, i.e., load (from 275 to 483.90 kg) and punch speed (30-120 mm/ min).

RESULTS: The focus of the analysis was to determine the tablets’ tensile strength, a potential correlation between the software and the experimental results, and the influence of significant parameters on tabletability. The significance of the following parameters has been demonstrated (R ≥ 0,90): fraction of the active substance, particle size distribution, density, tensile strength, and flowability. It was proven that tabletability deteriorates by increasing the fraction of paracetamol in the mixture, which consequently increases the difference in particle size and the number of

particles smaller than 50 µm, reduces the value of bulk angle and flowability, as well as tensile strength and compatibility.

CONCLUSION: The use of software tools in developing new formulations can benefit accessibility and time effectiveness, as software can facilitate decision-making. However, examining mechanical characteristics and developing new formulations should be based on the combination of software simulations, experiments and literature data.

Questions & answers

Please, tell us a little bit more about yourself. My name is Teodora Micić, and I am a recently graduated Master of Pharmacy. Currently, I am working in a community pharmacy as an intern. During my studies, I participated in a short-term exchange programme in Poland. I also completed an Erasmus+ hospital pharmacy traineeship in Germany. My future professional interests include industrial and clinical pharmacy.

Tell us a bit more about your research and its significance.

This research work was a part of my master’s thesis. It aimed to test the reliability of software used in formulating pharmaceutical forms. Another goal was to investigate the impact of different parameters on the tabletability of a powder blend that contains an active substance with limited mechanical properties. The software we worked with utilises advanced algorithms to predict the most effective excipients and production parameters for a given active ingredient and a pharmaceutical dosage form. According to the developer, implementing such tools would decrease time and cost in the research and development of new drugs.

What was the biggest challenge while conducting the research, and how did you overcome that?

The biggest challenge was to find a proper critical approach towards the results of software simulations. To be more precise, it was demanding to understand how the algorithm predicted specific process parameters. But with meticulous research of the available literature, I managed to make an adequate comparison between the software and laboratory results. In your opinion, what is the benefit of joining

ESSP, and what advice do you have for students undertaking research in the future?

By participating in the ESSP, students receive professional reviews of their research abstracts, which can be a tremendous educational opportunity.

My advice is never to give up. Undertaking research work can be challenging, but on the other hand, it can be very beneficial. Students don’t only gain knowledge which often exceeds the regular university curriculum but also get a chance to develop valuable soft skills (e.g., critical thinking, decision-making, problemsolving and teamwork