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Belma Imamović

Društvene mreže:

A. Elezovic, Amar Elezović, Miroslav Hadnađev, Adna Dzemat, Emina Hrnčić, B. Imamović, E. Becic, V. Krstonošić

The extent and rate of release of active substances from topical products must be sufficient to ensure their effectiveness, which depends on selecting the most appropriate formulation. This study examined allantoin emulsions and gel formulations. In water-in-oil (W/O) and oil-in-water (O/W) emulsions, the main emulsifier was varied, while the same gelling agent was used in all formulations to test the effects of oil phase presence and emulsifier type on allantoin release, as well as the formulations' rheological and textural characteristics. O/W emulsions exhibited similar release rates and the overall amount released over six hours (11-14.8%), while the highest amount of allantoin (20.9%) was released from the gel formulation. Conversely, the amount of allantoin released from the W/O emulsion (0.77%) was insufficient. Experimental data generally fit best with the Higuchi model kinetics. The formulations demonstrated shear-thinning thixotropic behavior. The greatest deviation from the Newtonian type of flow, with the smallest value of constant n (0.106-0.13) and the largest thixotropic loop area (6602.67-8140 Pas-1) were shown by O/W emulsions. The W/O emulsion exhibited the highest constant n (0.70) and smaller hysteresis area (991.23 Pas-1). Firmness and consistency values increased in the order: gel < W/O emulsion  < O/W emulsions. The O/W emulsions showed similarity in microstructure and textural characteristics, likely explaining their similar release behavior.

Paediatric and geriatric populations, as well as other special patient populations with swallowing problems, require patient-tai-lored dosage forms. One promising dosage form for these specific populations is orodispersible films. When preparing orodispersible films using sodium carboxymethyl cellulose as the film-forming polymer and glycerine as the plasticizer, it is essential to determine the optimal mixing time and mixing speed of the casting solution to achieve the desired transparency/opacity of the orodispersible films. In this paper, the primary focus is on mixing time and mixing speed, and determining how these two parameters can influence optical characteristics. All tested parameters are supported by FTIR anal - ysis. The obtained results show that either a mixing speed of 7000 rpm on a high-shear mixer for 15 min or a mixing speed of 9000 rpm for 5 min can produce films with optimal optical characteristics.

E. Becic, M. Salihović, B. Tüzün, Elma Omeragić, B. Imamović, M. Dedić, S. Roca, S. Špirtović-Halilović

BACKGROUND Computational research plays an important role in predicting the chemical and physical properties of biologically active compounds important in future structural modifications to improve or modify biological activity. OBJECTIVE This research focuses on quantum chemical and spectroscopic investigations properties of synthesized 4-hydroxycoumarin derivatives. METHODS Quantum chemical calculations were obtained using B3LYP, HF, and M06-2x level methods with the 6-31++G (d,p) basis set. Afterward, IR, 1H, 13C, UV-Visible experimentally parameters were compared with the results obtained using the B3LYP/6-31+G*(d) basis set of the molecules to be able to characterize the structures. RESULTS Based on the quantum chemical calculations compound with acetamido group on the phenyl ring is the most reactive, and compound with nitro substituent is the least reactive and the the strongest electrophile among tested compounds. With the exception of compounds with dimethylamino group, all other compounds have a pronounced tautomer between between OH and C = O group. The calculated and experimental values are in agreement with each other. CONCLUSION The molecular structure in the ground state of six 3-cinnamoyl 4-hydroxycoumarin derivatives was optimized using density functional theory. The observed and computed values were compared and it can be concluded that the theoretical results were in good linear agreement with the experimental data.

M. Dedić, Elma Omeragić, B. Imamović, Esma Bilajac, Lejla Mahmutović, Una Glamočlija, E. Becic

BACKGROUND Preclinical drug testing requires in vitro and in vivo assessments that are vital for studying drug pharmacokinetics and toxicity. Distinct factors that play an important role in drug screening, such as hydrophobicity, solubility of the substance and serum protein binding can be challenging by inducing result inconsistencies. Hence, establishing accurate methods to quantify drug concentrations in cell cultures becomes pivotal for reliable and reproducible results important for in vivo dosing predictions. OBJECTIVE This research focuses on developing an optimized analytical approach via high-pressure liquid chromatography (HPLC) to determine thymoquinone (TQ) levels in monolayer cell cultures. METHODS The method's validation adheres to the International Council for Harmonisation (ICH) guideline M10, ensuring its acceptance and applicability. Using an HPLC system with a Diode Array Detector (DAD), the study fine-tuned various parameters to achieve an efficient separation of TQ. Validation covered specificity, sensitivity, matrix effects, linearity, precision, and accuracy, alongside assessing TQ stability in RPMI-1640 medium. RESULTS The HPLC method exhibited remarkable TQ specificity, free from interfering peaks at the analyte retention. Sensitivity analysis at the lower limit of quantification (LLOQ) revealed 5.68% %CV and 98.37% % mean accuracy. Matrix effect evaluation showcased accuracy within 85-115%. Linearity spanned in the concentration range of 2-10 μM with a correlation coefficient (r2) of 0.9993. Precision and accuracy were aligned with acceptance criteria. The proposed method was found to be greener in terms of usage of persistent, bioaccumulative, and toxic chemicals and solvents, corrosive samples, and waste production. CONCLUSION The developed HPLC-DAD method emerges as specific, accurate, sensitive, and reliable for TQ determination in cell cultures. It ensures robust TQ quantification, enhancing precise in vitro assessments and dependable dosing predictions for in vivo studies. Further research is advocated to investigate TQ's stability across diverse environmental conditions.

E. Becic, M. Dedić, B. Imamović, S. Špirtović-Halilović, Elma Omeragić

Solvent and substitution effects on the UV/Vis spectroscopic and fluorescence behaviour of seven synthesized 3-substituted 4-hydroxycoumarin derivatives were tested. The tested compounds were dissolved in ethyl acetate, acetonitrile, and dimethyl sulfoxide. Absorption and emission spectra were recorded in the range of 200–800 nm. All tested 4-hydroxycoumarin derivatives showed good absorption in a wide range of 200–550 nm, depending on the properties of the substituents on the benzene ring of the cinnamoyl moiety and the type of solvent. In comparison to the unsubstituted analogue, compounds with an electron-donating group exhibited bathochromically shifted UV/Vis absorption and emission spectra. The highest fluorescence quantum yield was observed for compounds with dimethylamino and acetamido groups as substituents at the benzene ring. Considering that both substitution and solvent affect the absorption and emission spectra of the tested compounds, it can be concluded that judiciously selecting these parameters can improve their absorption and fluorescence properties, making them suitable for various analytical uses.

Abstract Four natural sweeteners (sucrose, xylitol, fructose, and isomalt) were selected to examine the influence of their qualities and amounts on the characteristics of orodispersible films. Sodium carboxymethylcellulose (2% w/w) was utilized as the film-forming polymer and 1% w/w glycerol as a plasticizer. Films were produced through the solvent casting method, rendering them suitable for convenient application in community or hospital pharmacy settings. The physicochemical and optical properties of the films were analyzed, and Fourier-transform infrared analysis was carried out. All films exhibited acceptable disintegration time, uniformity of mass, thickness, and optical characteristics, with significant dependence (p<0.05) on both sweetener type and quantity. Disintegration time varied based on the employed method, as well as the characteristics and amount of sweetener. Additionally, all films maintained pH values within the oral cavity range, suggesting no potential irritancy upon administration. Fourier-transform infrared analysis confirmed the formation of the film and demonstrated compatibility between its components.

Elma Omeragić, B. Imamović, M. Dedić, Indira Mujezin, E. Becic

Skin sensitization is a crucial endpoint in the safety assessment of chemicals, with the Direct Peptide Reactivity Assay (DPRA) emerging as a valuable in chemico method for evaluating a substance's sensitization potential. This review delves into the principles, applicability, and limitations of the DPRA within the context of the Adverse Outcome Pathway (AOP) framework for skin sensitization. We examine the DPRA'srole in addressing the molecular initiating event of skin sensitization, its integration into Integrated Approaches to Testing and Assessment (IATA), and its performance in predicting sensitizers. The review also highlights the challenges in testing certain categories of chemicals and the importance of considering the DPRA's results alongside other complementary methods. By providing a comprehensive overview of the DPRA, this review aims to inform researchers, regulators, and clinicians about its utility and limitations in the context of skin sensitization testing.

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