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UĞURLU, TİMUÇİN

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TİMUÇİN

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2020 - 202410
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    PublicationOpen Access
    Managing allergic conjunctivitis via ophthalmic microemulsions: Formulation, characterization, in vitro irritation studies based on EpiOcular™ eye irritation assay and in vivo studies in rabbit eye
    (2023-01-01) UĞURLU, TİMUÇİN; Yozgatlı V., Üstündağ Okur N., Okur M. E., Sipahi H., Charehsaz M., Aydın A., UĞURLU T.
    The purpose of this work was the development of an alternative ocular tetrahydrozoline hydrochloride (THZ) microemulsion for the management of allergic conjunctivitis. Pseudo-ternary phase diagrams were used to produce the microemulsions. For the formulation of the microemulsions, isopropyl myristate was selected as oil. Furthermore, various surfactants were applied for the determination of their suitability; ME-1 and ME-4 were developed using Sorbitan monolaurate 80 and Polysorbate 80, for ME-2 and ME-5 Sorbitan monolaurate 80 and macrogolglycerol ricinoleate while for ME-3 and ME-6 Sorbitan monolaurate 80 and Polysorbate 20. For ME-1, ME-2, and ME-3 propylene glycol and ethanol, for ME-4, ME-5, and ME-6 ethanol and polyethylene glycol were used as co-surfactants. Various characterization parameters of microemulsions were evaluated such as droplet size, conductivity, zeta potential, viscosity, and pH. In addition, the drug release, stability, sterility, safety, ex vivo, and in vivo experiments were studied. The characterization showed that the formulations can act as suitable carriers for eye application. In addition, it was revealed that microemulsions were found stable and sterile. The formulations released the drug in a sustained manner. Ex vivo diffusion studies exhibited that the microemulsions can be used for topical delivery to the eye. Assessment of in vitro ocular irritation was conducted by an in vivo prediction model, EpiOcular™ eye irritation test. Based on the in vivo studies, the chosen ideal microemulsion showed longer contact time to the cornea than the commercial product. Moreover, the developed ocular carrier was found to be safe from the viewpoint of in vitro ocular irritancy and mutagenicity. In conclusion, according to characterization results, the THZ microemulsions can act as a hopeful approach for topical eye application.
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    Preformulation studies of chitosan nanoparticles for intranasal vaccine administration
    (2023-05-31) ÖZER ÖNDER, SETENAY; UĞURLU, TİMUÇİN; Özer Önder S., Uğurlu T.
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    PublicationOpen Access
    Synthesis and characterization of chitosan-PVA hydrogel containing PEGylated recombinant epidermal growth factor on cell culture for wound healing substitute
    (2022-08-01) SEZER, ALİ DEMİR; UĞURLU, TİMUÇİN; ŞAHBAZ, SEVİNÇ; Doğan M., Şahbaz S., Uğurlu T., Sezer A. D.
    The aim of the current study was to assess the physicochemical characteristics and wound healing activity of chitosan-polyvinyl alcohol (PVA) crosslinked hydrogel containing recombinant human epidermal growth factor (rh-EGF) or recombinant mouse epidermal growth factor (rm-EGF). The hydrogels were prepared and analyses were made of the morphological properties, viscosity, water absorption capacity, mechanical and bio-adhesive properties. The viscosity of the formulations varied between 14.400 - 48.500 cPs, with the greatest viscosity values determined in K2 formulation. F2 formulation showed the highest water absorption capacity. According to the studies of the mechanical properties, H2 formulation (0.153±0.018 N.mm) showed the greatest adhesiveness and E2 (0.245±0.001 mj/cm2 ) formulation, the highest bio-adhesion values. Hydrogels were cytocompatible considering in vitro cell viability values of over 76% on human keratinocyte cells (HaCaT, CVCL-0038) and of over 84% on human fibroblast cells (NIH 3T3, CRL-1658) used as a model cell line. According to the BrdU cell proliferation results, B1 (197.82±2.48%) formulation showed the greatest NIH 3T3 and C1 (167.43±5.89%) formulation exhibited the highest HaCaT cell proliferation ability. In addition, the scratch closure assay was performed to assess the wound healing efficiency of formulation and the results obtained in the study showed that F2 formulation including PEGylated rh-EGF had a highly effective role. Keywords: Chitosan. rh-EGF. Hydrogel. Texture analyzer. Cell culture.
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    Development and In Vitro Evaluation of a Novel Pulsatile Drug Delivery System Containing Dexketoprofen Trometamol
    (SPRINGER, 2021) UĞURLU, TİMUÇİN; Ugurlu, Timucin; Ilhan, Ezgi
    Purpose A pulsatile drug delivery system containing dexketoprofen trometamol was designed by combining immediate release and colon-targeted mini tablets into a capsule. Methods Both immediate release and colon-targeted mini tablets were prepared by wet granulation. Furthermore, colon-targeted mini tablets were coated with Eudragit L 100, Eudragit S 100, Eudragit RS 30D, and ethylcellulose (Surelease (R)) using Wurster and pan coating methods. Results The optimum drug release of the system developed in the study was found to be mini tablets coated with 30% Eudragit S 100 on a 20% Surelease (R) subcoating for the purpose of colon targeting. Conclusion In the finished product, the immediate release part released the drug within the first hour, and less than 5% release was observed from the colon-targeted tablets in a 0.1 N HCl in 2 h. Then, less than 20% release occurred in the colon-targeted tablets up to 6 h in pH 6.8 phosphate buffer solution. The cumulative release rate reached 100% for up to 12 h. To our knowledge, it was the first time dexketoprofen trometamol was designed by combining both immediate release and colon-targeted mini tablets in a one dosage form.
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    Aseklofenak içeren ağızda dağılan tablet formülasyonlarının hazırlanması ve in-vitro değerlendirilmesi
    (2021-01-12) UĞURLU, TİMUÇİN; ŞAHBAZ, SEVİNÇ; Erdoğan K. O., Uğurlu T., Şahbaz S.
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    Probiyotik tablet formülasyonlarında kullanılan yardımcı maddelerin bakteri sağ kalımına etkisinin değerlendirilmesi
    (2023-03-19) ŞAHBAZ, SEVİNÇ; RAYAMAN, ERKAN; UĞURLU, TİMUÇİN; Kandur B., Şahbaz S., Rayaman E., Uğurlu T.
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    PublicationOpen Access
    Preparation and characterization of poly(lactic-co-glycolic acid) nanoparticles containing TGF-beta 1 and evaluation of in vitro wound healing effect
    (MARMARA UNIV, 2020-03-12) SEZER, ALİ DEMİR; Soysal, Aysun Celik; Sahbaz, Sevinc; Ugurlu, Timucin; Sezer, Ali Demir
    ( )Wound healing involves many complex mechanisms, and many growth factors are effective in this process. Growth factors are biologically active polypeptides. They perform activities such as cell growth, differentiation, proliferation and migration with molecular cascades by binding to specific receptors. Transforming growth factor stimulates (TGF-beta) different cell types in the wound healing process. Poly(lactic-co-glycolic acid) (PLGA) degradation produces lactate that expedites angiogenesis, activates pro-collagen factors. Therewith, we hypothesized to combine the therapeutic effect of the TGF-beta 1with the positive effect of the drug delivery system including PLGA nanoparticles (TGF beta-PLGA NP). The burst effect decreases as the polymer concentration increases in PLGA nanoparticles. The inhibitory effect of TGF-beta 1 on keratinocytes was reduced by the improved nanoparticle formulations. It showed a proliferative effect of up to 92.5 per cent on fibroblast cells involved in wound healing. Although TGF-beta 1 has an inhibitory effect on keratinocytes, it induces migration both NIH-3T3 and HaCaT cell lines in the scratch assay.
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    PublicationOpen Access
    Development of a multiple-unit system: Tablets containing amlodipine besylate which have different release kinetics
    (MARMARA UNIV, 2020-07-16) TEKDEMİR, OZAN; Tekdemir, Ozan; Tilki, Gizem; Ugurlu, Timucin
    Multiple-unit systems may include tablets, capsules, pellets in a single administration. Once-a-day administration of Amlodipine Besylate (AML) accounts for fluctuation of plasma drug concentrations between dosing intervals. The aim of this study is to develop an extended-release (ER) and an immediate-release (IR) tablet to overcome the fluctuation of plasma drug concentrations. To achieve this purpose, 9 IR tablets and 6 ER tablet formulations were developed. The dissolution media for IR tablets was pH 2 for 1 hour and the dissolution media for ER tablets was pH 2 for 2 hours, and afterwards was pH 6.8 for 10 hours. The amount of AML released into the dissolution media was measured by Mettler Toledo UV 5 at a wavelength of 238 nm. The dissolution data of IR and ER tablets were statically evaluated. The highest dissolution rate for IR tablets (93%) was achieved with the IR-5 formulation. For ER tablets, a 50% drug release was achieved with the ER-1 and ER-4 formulation. The drug release kinetics of all ER tablets were calculated and subsequently the ER-1 formulation, which has Higuchi drug release kinetics, was chosen as the ER tablet. Lastly, a dissolution study of the selected formulations (IR-5 and ER-1) was conducted in the same vessel. After 12 hours of the dissolution study, drug release was found to be 79% +/- 0,92 (close to 75% which was targeted). Multiple-unit systems that have different tablet formulations in one administration could be used to enhance drug release kinetics that cannot be achieved with conventional tablets.
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    PublicationOpen Access
    Application of Box-Behnken design in the optimization of chitosan nanoparticles prepared by the ionic gelationultrasonication method and evaluation of dispersion stability
    (2024-01-01) ÖZER ÖNDER, SETENAY; UĞURLU, TİMUÇİN; ÖZER ÖNDER S., UĞURLU T.
    The main objective of this study was to optimize chitosan nanoparticles by exploring the relationship between design factors and experimental data through response surface methodology. A Box-Behnken design was employed, considering chitosan: tripolyphosphate ratio (X1), pH of the chitosan solution (X2), and ultrasonication amplitude (X3) as independent factors. Particle size, polydispersity index (PDI), and zeta potential served as the dependent variables. Nanoparticles were successfully prepared using a modified ionic gelation method incorporating an ultrasonic homogenizer and evaluated by models according to Box-Behnken Design. Surface plots were utilized to enhance the understanding of interactions between different variables. Results indicated that the chitosan ratio played the most significant role on both particle size and polydispersity, while the ultrasonic homogenizer amplitude predominantly influenced zeta potential. The models for particle size and polydispersity exhibited high accuracy (R², 0.9992 and 0.9955, respectively), whereas the zeta potential model demonstrated a lower R² value (0.7857) and lack of statistical significance. Comparison of predicted and actual data revealed larger error% values in the zeta potential model, exceeding the acceptable 15% threshold. Consequently, it was concluded that the ionic gelation-ultrasonic homogenizer technique, coupled with the Box-Behnken Design, is a rapid and effective approach for chitosan nanoparticle preparation and optimization. Additionally, aqueous dispersions of nanoparticles exhibited significant changes in particle size, polydispersity, and zeta potential values over one month at temperature and relative humidity conditions in accordance with ICH stability guidelines. This reinforced the recommendation that nanoparticles should be lyophilized and stored in a dry form. KEYWORDS: Chitosan; nanoparticle; Box-Behnken design; DoE, stability.
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    PublicationOpen Access
    A recent review of the utilization of 3D printing in the development and manufacturing of pharmaceutical dosage forms
    (2024-01-01) KERİMOĞLU, OYA; UĞURLU, TİMUÇİN; Alenezi E. E., KERİMOĞLU O., UĞURLU T.
    Three-dimensional (3D) printing has paved the way in pharmaceutical applications. This innovative methodology presents novel and inventive remedies for patients and the pharmaceutical sector. Moreover, the benefits of this approach encompass the mitigation of adverse effects, customization of formulations for patients with rare medical conditions, and enhancement of therapeutic effectiveness. The objective of our review was to offer a comprehensive survey of the advancements observed in the drug delivery systems that were produced. A thorough inspection has assessed the diverse dosage forms developed using the three-dimensional printing technique (3DP), especially in the last five years. The pharmaceutical industry places significant emphasis on the benefits of developing dosage forms with intricate designs and geometries, incorporating multiple active ingredients, and tailored release profiles due to their versatility and related advantages. Drug delivery systems can be classified into different modalities, tablets, capsules, suppositories, transdermal delivery systems, microneedles, vaginal delivery systems, and nanoscale dosage forms. The utilization of our classification system facilitates researchers\" task of evaluating publications and effectively pinpointing further opportunities for research exploration.