83 results on '"Ibric S"'
Search Results
2. Opinions of Romanian Dental Students Toward Tobacco Use Interventions in the Dental Setting
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Dumitrescu, A. L., Ibric, S., and Ibric-Cioranu, V.
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- 2016
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- View/download PDF
3. Assessing Oral Cancer Knowledge in Romanian Undergraduate Dental Students
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Dumitrescu, A. L., Ibric, S., and Ibric-Cioranu, V.
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- 2014
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- View/download PDF
4. Application of D-optimal experimental design method to optimize the formulation of O/W cosmetic emulsions
- Author
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Djuris, J., Vasiljevic, D., Jokic, S., and Ibric, S.
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- 2014
- Full Text
- View/download PDF
5. Mathematical modeling of diclofenac sodiumʼs release from polyethylene oxide matrices
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Petrovic, J., Jockovic, J., Ibric, S., Parojcic, J., and Djuric, Z.
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- 2008
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6. Mixture design evaluation of drug release from matrix tablets containing carbomer and HPMC
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Petrovic, A., Cvetkoviæ, N., Trajkovic, S., Ibric, S., Popadic, D., and Djuric, Z.
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- 2006
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7. Lignocellulosic biomass as a source of microcrystalline cellulose - chemical and technological characterization and future perspectives
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Krstic, M., Maksimovic, Z., Ibric, S., Bakic, T., Prodanovic, J., and Razic, S.
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corn stover ,wheat straw ,employment of agricultural residues ,compactibility ,compressibility ,food and beverages ,microcrystalline cellulose - Abstract
In this paper, agricultural waste (corn stover and wheat straw) was used for isolation of microcrystalline cellulose (MCC). Lignocellulosic biomass is widely available and applying smart technologies to valorise it will have a double benefit through environmental protection and achieving high-performance materials for targeted applications. The obtained MCC showed excellent features in terms of purity, physical-chemical properties and safety, as well. The methods applied for characterizing the materials were as follows: FT-IR, SEM, ICP-AAE and IC. Then, tablets were made by the compression method, using the isolated and purified MCC, as well as its commercially available counterpart. Excellent technological characteristics were confirmed by testing material compaction, compactibility, compressibility and drug release. This was one of the first tests in which Gamlen Tableting D was applied, especially in the case of using biomass, in the first phase, with prospects of application at a large scale, particularly, in the pharmaceutical industry.
- Published
- 2018
8. Chemometrical Evaluation of Metoprolol Tartarate Enantiomers Separation Applying Conventional Achiral Chromatography
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Vujic Z, Ivkovic B, Karljikovic-Rajic K, and Ibric S
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chemistry.chemical_compound ,Chromatography ,Materials science ,Resolution (mass spectrometry) ,chemistry ,Particle size ,Response surface methodology ,Enantiomer ,Acetonitrile ,Selectivity ,High-performance liquid chromatography ,Volumetric flow rate - Abstract
In this paper, the separation of metoprolol tartarate enantiomers using conventional achiral chromatography was followed employing experimental design 24. Design was useful tool in evaluation of chromatographic behavior of enantiomers. For the separation, Supelcosil LC18 4.6 mm × 250 mm, 5 m particle size column was used. UV detection was performed at 275 nm. Because of the large number of factors which can influence chromatographic separation, in preliminary study ″one factor at a time″ method was applied to define values of important factors. As outputs, retention factor, selectivity factor and resolution factors were chosen. Chromatographic behavior of investigated enantiomers was affected by acetonitrile content, chiral modificator content in the mobile phase and flow rate the most, demonstrated by obtained linear models. On the basis of results from screening of experiment, factors with strong influence on the separation, were analyzed in method optimization applying response surface methodology (RSM). The appropriate region of chromatographic behavior of metoprolol tartarate enantiomers was defined using three-D graphs and analysis of variance. The methodology proposed represents an efficient approach in resolving the problem of searching for optimal HPLC chromatographic conditions via experimental design.
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- 2016
9. Digital light processing (DLP) 3D printing technique applied in the fabrication of two-layered tablets: The concept of a combined polypill
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Adamov Ivana, Medarević Đorđe, Ivković Branka, Ivković Aleksandar, and Ibrić Svetlana
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dlp technique ,hydrochlorothiazide ,warfarin sodium ,combined two-layered 3d tablets ,personalized medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
Ever since 3D printing was introduced to the field of pharmacy, it has caused a paradigm shift from the manufacturing of large-scale to small batches of medicines tailored accordingly to the specific needs of patients. This study aimed to formulate and fabricate two-layered 3D tablets using the digital light processing (DLP) technique. Hydrochlorothiazide (HHT,5%,w/w) and warfarin sodium (WS,5%,w/w) were selected as model drugs. The printing process was initiated with 0.1% of photoinitiator, at a constant ratio of poly(ethylene glycol)diacrylate and poly(ethylene glycol) 400, 1:1, with the addition of water (10%,w/w). Single-layered tablets of 8.00 mm diameter and 1.50 mm thickness, containing HHT and WS respectively, were successfully printed, as well as combined two-layered 3D tablets, with each of the active substances in separate layers. Dissolution tests of single-layered tablets showed immediate, but incomplete release of WS (81.47±1.47%, after 45min), and prolonged and complete release of HHT (98.17±3.11%, after 8h), while significantly slower and incomplete release of both drugs from the combined two-layered 3D tablets was observed. The absence of drug-polymer interaction and presence of a layered cross-sectional tablet structure were confirmed. DLP technique enables simple and rapid fabrication of combined two-layered 3D tablets, while further optimization of formulation factors is necessary to achieve complete drug release.
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- 2022
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10. Application of text-mining techniques for extraction and analysis of paracetamol and ibuprofen marketed products' qualitative composition
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Đuriš Jelena, Pilović Jovana, Džunić Marina, Cvijić Sandra, and Ibrić Svetlana
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text mining ,dosage forms ,qualitative analysis ,excipients ,paracetamol ,ibuprofen ,Pharmacy and materia medica ,RS1-441 - Abstract
Text mining (TM) applications in the field of biomedicine are gaining great interest. TM tools can facilitate formulation development by analyzing textual information from patent databases, scientific articles, summary of products characteristics, etc. The aim of this study was to utilize TM tools to perform qualitative analysis of paracetamol (PAR) and ibuprofen (IBU) formulations, in terms of identifying and evaluating the presence of excipients specific to the active pharmaceutical ingredient (API) and/or dosage form. A total of 152 products were analyzed. Web-scraping was used to retrieve the data, and Python-based open-source software Orange 3.31.1 was used for TM and statistical analysis (ANOVA) of the obtained results. The majority of marketed products for both APIs were tablets. The predominant excipients in all tablet formulations were povidone, starch, microcrystalline cellulose and hypromellose. Povidone, stearic acid, potassium sorbate, maize starch and pregelatinized starch occurred more frequently in PAR tablets. On the other hand, titanium dioxide, lactose, shellac, sucrose and ammonium hydroxide were specific to IBU tablets. PAR oral suspensions more frequently contained dispersible cellulose; liquid sorbitol; methyl and propyl parahydroxybenzoate, glycerol and acesulfame potassium. Specific excipients in other PAR dosage forms, such as effervescent tablets, hard capsules, oral powders, solutions and suspensions, as well as IBU gels and soft capsules, were also evaluated.
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- 2022
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11. Preparation and characterization of 3D printed bone scaffold for ibuprofen delivery
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Jovanović Marija, Petrović Miloš, Stojanović Dušica, Ibrić Svetlana, and Uskoković Petar
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semi-solid extrusion 3d printing ,gelatin-based bone scaffold ,in vitro ibuprofen release and kinetics ,microindentation ,hardness ,Pharmacy and materia medica ,RS1-441 - Abstract
In this work, a blend of gelatin A (GA) and polyvinylpyrrolidone (PVP K30) was used for semi-solid 3D printing of bone scaffold for ibuprofen (IBU) delivery. The cross-linking of the obtained scaffold was performed with a 1% glutaraldehyde (GTA) solution, followed by lyophilization. The thermal and mechanical properties, as well as drug release profiles, and drug kinetics of prepared scaffolds were investigated. The cross-linked and lyophilized scaffold has shown good thermal stability, mechanical properties, and prolonged release of IBU following the Fickian diffusion process.
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- 2022
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12. Usage of compaction simulators for the powder compression characterization: Advantages and limitations
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Nikolić Nenad, Miletić Tijana, Kovačević Jovana, Medarević Đorđe, and Ibrić Svetlana
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compaction simulator ,tablet-press instrumentation ,scale-up ,compressibility ,compression block deformation ,Pharmacy and materia medica ,RS1-441 - Abstract
Compaction simulators are designed as machines which can provide an in-depth analysis of the powder compaction process. Characterization of the powder compression and compaction process, as well as material characterization, play an important role in the formulation and manufacturing process design and development, as well as in creating a strong knowledge basis for the scale-up of the tablet compression and troubleshooting in further stages of the product lifecycle. Although compaction simulators are designed to simulate the compression process on high-speed tablet-presses, with the advantages of a small quantity of material needed and highly sophisticated instrumentation, there are certain limitations in the extrapolation of the process parameters from these machines to high-speed rotary tablet presses. However, the advantage of the use of compaction simulators for studying basic compression and compaction mechanisms, identification of critical material attributes and critical process parameters ranges, and their relations with tablet characteristics and critical quality attributes of pharmaceutical products is clear, compared to the use of small excentre tablet presses, and complementary to the use of small rotary tablet presses. This scientific paper provides an overview and examples of the different advantages provided by the instrumentation of compaction simulators, including certain limitations in their exploitation.
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- 2022
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13. Data mining techniques applied in the analysis of historical data
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Kovačević Jovana, Kovačević Aleksandar, Miletić Tijana, Đuriš Jelena, and Ibrić Svetlana
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drug manufacturing ,gastro-resistant pellets ,modelling ,release profile ,acid-resistance ,Pharmacy and materia medica ,RS1-441 - Abstract
Understanding the effect of the characteristics of formulation and process parameters on the physicochemical properties of a pharmaceutical product is very significant for the development of solid dosage forms, as the knowledge gained on small scale batches in the early phase of development is used in the later phases of product lifecycle or in the development of other products. One of the approaches for gaining a better understanding of the effects of the formulation and production process on the quality of the finished product is to apply a systematical approach which concerns performing experiments according to a predefined factorial or fractional factorial experimental plan. However, often it is the case that there are available data gathered in a non-systematic way, because experiments were not performed according to a predetermined experimental plan. In such a case, data mining techniques could be used to extract useful data from the historical data set. In this research, the possibility of using several data mining techniques to build models that describe the effect of formulation characteristics on acid resistance and dissolution profile of a model drug from gastro-resistant pellets. The model drug used in the research is duloxetine hydrochloride from the group of antidepressants. It belongs to the BCS 2 class of active pharmaceutical ingredients, and it is therefore necessary for the release profile of duloxetine to be characterized by a higher number of tested time points. The developed models can be used for planning future laboratory trials, or in the development of other products.
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- 2022
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14. SUN-PP251: Preparation and Characterization of O/W Nanoemulsion for the total Parenteral Nutrition
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Mirkovic, D., primary, Isailovic, B., additional, and Ibric, S., additional
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- 2015
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15. Opinions of Romanian Dental Students Toward Tobacco Use Interventions in the Dental Setting
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Dumitrescu, A. L., primary, Ibric, S., additional, and Ibric-Cioranu, V., additional
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- 2015
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16. Multiparticulate oral formulations as a viable strategy for precise drug dosing in pediatrics: Propranolol case study
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Kurćubić Ivana, Cvijić Sandra, Lukić Milica, Ibrić Svetlana, and Đuriš Jelena
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propranolol ,pediatric dosage forms ,multiparticulates ,mini tablets ,uniformity of content ,Pharmacy and materia medica ,RS1-441 - Abstract
The development of solid dosage forms that are both convenient for administration and allow precise drug dosing for pediatric patients is one of the great challenges in contemporary pharmaceutical technology. The presented study has utilized propranolol hydrochloride, as one of the most frequently prescribed drugs that require manipulation of the conventional dosage forms to be administered to children. Multiparticulate oral formulations, powderand granulefilled capsules, as well as mini tablets, were prepared and characterized in terms of their mass and content uniformity and compared to conventional marketed tablets split into halves and quarters. The obtained results have demonstrated the superiority of the multiparticulate formulations, in terms of their average mass and drug content uniformity. It has also been demonstrated that, due to improved flowability, granule-filled capsules are more conveniently compounded and provide higher content uniformity compared to powder-filled capsules. The presented compounding method could be easily employed in community pharmacy settings. Mini tablets with high and uniform content of propranolol hydrochloride have been successfully prepared, thereby presenting a viable strategy for efficient drug dose adjustment.
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- 2021
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17. Review of machine learning algorithms' application in pharmaceutical technology
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Đuriš Jelena, Kurćubić Ivana, and Ibrić Svetlana
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machine learning ,artificial neural networks ,quality by design ,pharmaceutical development ,process analytical technologies ,Pharmacy and materia medica ,RS1-441 - Abstract
Machine learning algorithms, and artificial intelligence in general, have a wide range of applications in the field of pharmaceutical technology. Starting from the formulation development, through a great potential for integration within the Quality by design framework, these data science tools provide a better understanding of the pharmaceutical formulations and respective processing. Machine learning algorithms can be especially helpful with the analysis of the large volume of data generated by the Process analytical technologies. This paper provides a brief explanation of the artificial neural networks, as one of the most frequently used machine learning algorithms. The process of the network training and testing is described and accompanied with illustrative examples of machine learning tools applied in the context of pharmaceutical formulation development and related technologies, as well as an overview of the future trends. Recently published studies on more sophisticated methods, such as deep neural networks and light gradient boosting machine algorithm, have been described. The interested reader is also referred to several official documents (guidelines) that pave the way for a more structured representation of the machine learning models in their prospective submissions to the regulatory bodies.
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- 2021
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18. The emerging role of physiologically-based pharmacokinetic/biopharmaceutics modeling in formulation development
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Cvijić Sandra, Ignjatović Jelisaveta, Parojčić Jelena, and Ibrić Svetlana
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physiologically-based pharmacokinetic modeling (pbpk) ,physiologically-based biopharmaceutics modeling (pbbm) ,model informed drug development (midd) ,drug bioperformance ,Pharmacy and materia medica ,RS1-441 - Abstract
Computer-based (in silico) modeling & simulation tools have been embraced in different fields of pharmaceutics for a variety of applications. Among these, physiologically-based pharmacokinetic/biopharmaceutics modeling (PBPK/PBBM) emerged as a particularly useful tool in formulation development. PBPK/PBBM facilitated strategies have been increasingly evaluated over the past few years, as demonstrated by several reports from the pharmaceutical industry, and a number of research and review papers on this subject. Also, the leading regulatory authorities have recently issued guidance on the use of PBPK modeling in formulation design. In silico PBPK models can comprise different dosing routes (oral, intraoral, parenteral, inhalation, ocular, dermal etc.), although the majority of published examples refer to modeling of oral drugs performance. In order to facilitate the use of PBPK modeling tools, a couple of companies have launched commercially available software such as GastroPlus™, Simcyp™ PBPK Simulator and PK-Sim®. This paper highlights various application fields of PBPK/PBBM modeling, along with the basic principles, advantages and limitations of this approach, and provides relevant examples to demonstrate the practical utility of modeling & simulation tools in different stages of formulation development.
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- 2021
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19. The protective effect of thiola against the genotoxic action of benzo(a)pyrene
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Galdean, D., Petrasincu, D., Alangiu, P., Ibric, S., and Voiculetz, N.
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- 1986
- Full Text
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20. Application of D-optimal experimental design method to optimize the formulation of O/W cosmetic emulsions
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Djuris, J., primary, Vasiljevic, D., additional, Jokic, S., additional, and Ibric, S., additional
- Published
- 2013
- Full Text
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21. Integrated biopharmaceutical approach in pharmaceutical development and drug characterization: General concept and application
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Cvijić Sandra V., Ibrić Svetlana R., and Parojčić Jelena V.
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biowaiver ,clinical performance ,dissolution testing ,in vitro-in vivo correlation ,physiologically based pharmacokinetic/biopharmaceutics modeling ,Chemical technology ,TP1-1185 - Abstract
The importance of biopharmaceutical considerations in pharmaceutical development and drug characterization has been well recognized both by pharmaceutical industry and regulatory authorities as a tool to establish predictive relationships between drug product quality attributes (in vitro data) and its clinical performance (in vivo data). In the present paper, contemporary biopharmaceutics toolkit including in vivo predictive dissolution testing, Biopharmaceutics Classification System, physiologically based pharmacokinetic and biopharmaceutics modeling and simulation, in vitro-in vivo correlation and biowaiver, are reviewed with regards to relevant general principles and applicability. The recently introduced innovative strategy for patient-centric drug development using an integrated systems approach grounded in fundamental biopharmaceutics concepts, clinical insights and therapeutic drug delivery targets, described as Biopharmaceutics Risk Assessment Roadmap (BioRAM) is also presented. Further development in the field will benefit from joint efforts and exchange of knowledge and experiences between pharmaceutical industry and regulatory authorities for the common goal to accelerate development of effective and safe drug products designed in accordance with patients’ needs and expectations.
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- 2020
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22. Determination of the percolation thresholds for polyethylene oxide and polyacrylic acid matrix tablets
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Petrović, J., Ibrić, S., Jocković, J., Parojčić, J., and Đurić, Z.
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- 2009
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23. Machine learning modelling of wet granulation scale-up using compressibility, compactibility and manufacturability parameters
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Millen Nada, Kovačević Aleksandar, Khera Lalit, Đuriš Jelena, and Ibrić Svetlana
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quality by design ,artificial intelligence ,compaction work ,decompaction work ,elastic recovery ,Chemical technology ,TP1-1185 - Abstract
The purpose of this extensive study is to use a quality by design (QbD) approach and multiple machine learning algorithms in facilitating wet granulation process scale-up. This study investigated the extent of influence of both formulation and process variables. Furthermore, measured responses covered compressibility, compactibility and manufacturability of a powder blend. Finally, the models developed on laboratory scale samples were tested on pilot and commercial scale runs. Tablet detachment and ejection work were calculated from force-displacement measurements. Significant numerical and categorical input variables were identified by using a stepwise regression model and their importance evaluated by using a boosted trees model. Pilot scale runs resulted in the highest tablet tensile strength and compaction work as well as the highest detachment and ejection work. Critical quality attributes (CQAs) that were the most successfully predicted were the compaction, decompaction, and net work, as well as the tablet height. The most important input variable influencing all CQAs was the compaction force. Application of the boosted regression trees model resulted in the lowest Root Mean Square Error (RMSE) values for all of the responses. This work demonstrates reliability of predictions of developed models that can be successfully used as a part of a QbD approach for wet granulation scale-up.
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- 2019
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24. Estrogenic metabolites of alkylphenol polyethoxylates in secondary sewage effluents and rivers
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Ahel, M., primary, Molnar, E., primary, Ibric, S., primary, and Giger, W., primary
- Published
- 2000
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25. Application of D-optimal experimental design method to optimize the formulation of O/ W cosmetic emulsions.
- Author
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Djuris, J., Vasiljevic, D., Jokic, S., and Ibric, S.
- Subjects
EMULSIONS ,BIODEGRADABLE products ,COSMETICS ,EXPERIMENTAL design ,GLUCOSIDES ,STEARIC acid ,CETYL alcohol - Abstract
Copyright of International Journal of Cosmetic Science is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2014
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26. The Influence of Processing Variables on Performance of O/W Emulsion Gels Based on Polymeric Emulsifier (Pemulen RTR-2NF)
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Simovic, S., primary, Milic-Askrabic, J., additional, Vuleta, G., additional, Ibric, S., additional, and Stupar, M., additional
- Published
- 1999
- Full Text
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27. Characterization of orodispersible tablets and orodispersible films
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Drašković Milica, Cvijić Sandra, Ibrić Svetlana, and Parojčić Jelena
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orodispersible tablets ,orodispersible films ,disintegration ,mechanical properties ,taste-masking ,Pharmacy and materia medica ,RS1-441 - Abstract
Orodispersible dosage forms are intended to be placed on tongue where, in contact with limited saliva volume, fast disintegration, followed by facilitated swallowing, occurred. Intraoral disintegration might be accompanied by drug release and dissolution in oral cavity. Dissolved drug could interact with receptors on taste buds causing taste sensation. The most important critical quality attributes of orodispersible dosage forms are acceptable mechanical resistance, fast disintegration and pleasant taste which have to be monitored and evaluated during formulation development and production. However, compendial methods for orodispersible dosage forms characterization are still lacking, while many authors attempt to develop different, more suitable approaches. The highest variability during determination of disintegration properties is observed. It can be concluded that for the proper disintegration assessment influence of tongue force have to be considered, especially in the case of different polymeric orodispersible films. For reliable development of in vivo study for evaluation of tastemasking efficacy, proper selection and training of panelists accompanied by bitterness threshold determination are of the utmost importance. In order to correlate in vitro and in vivo data, it is necessary to develop analytical method for evaluation of taste-masking efficacy that mimic, in great extent, physiological intraoral conditions.
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- 2018
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28. An investigation into the effects of excipients on quality characteristics of a dry herbal extract containing capsule
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Grujić Branka, Vuković Zdenka, Veljković-Giga Jelena, Ibrić Svetlana, and Dekanski Dragana
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dry herbal extracts ,olive leaf ,vine leaf ,capsules ,Chemical technology ,TP1-1185 - Abstract
Nutrition and dietary supplements have a significant role in the prevention and treatment of cardiovascular disease. Olive and vine leaves, thanks to their constituents, represent powerful natural antioxidants exhibiting cardioprotective activity. High concentrations of active ingredients can be provided by means of extraction. Dry herbal extracts are highly sensitive to moisture and elevated temperature and from the pharmaceutical and technological point of view these are raw materials with inadequate technological properties. The aim of this study was to investigate and to compare the influence of different excipients in capsule formulation of these two dry extracts i.e. the selection of excipients that will ensure appropriate critical process parameters in the manufacturing procedure. The monitored quality characteristics include flowability, bulk density and tapped density that are critical for technological feasibility of the capsule-filling operation. The effects of excipients on the above parameters have been experimentally studied and the appropriate capsule formulations have been developed based on the obtained results, which will ensure homogeneity and stability of the preparation. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. TR34007]
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- 2018
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29. Interactions of chromium(III) complexes with hydrous .delta.-alumina: rearrangements in the coordination sphere studied by electron spin resonanace and electron spin-echo spectroscopies
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Karthein, R., primary, Motschi, H., additional, Schweiger, A., additional, Ibric, S., additional, Sulzberger, B., additional, and Stumm, W., additional
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- 1991
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30. Properties and potential application of modern adsorbents in formulation of solid drug delivery systems
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Krstić Marko, Milović Mladen, and Ibrić Svetlana
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adsorbents ,specific surface area ,drug release ,Pharmacy and materia medica ,RS1-441 - Abstract
In latest years, many natural and synthetic solid carriers attract increasing attention, due to theirs biocompatibility, acceptable ecological and toxicological properties, possible modification of physico-chemical properties, simple production, high stability and relatively low price. These carriers have similar chemical structure, mostly based on silicon-dioxide, magnesium aluminometasilicate and calcium phosphate, and differ from each other in structure porosity, specific surface area, size, volume and shape of pores, and possibility of surface functionalization. Ordered mesoporous materials like MCM - 41 and SBA - 15, as well as porous materials from Neusilin® and Sylysia® groups, represent the most common adsorbents evaluated in order to increase drug dissolution rate, and its bioavailability, and also in modifiedand targeted drug release formulations. Also, natural silica material, isolated from diatomites, diatom microshells, with its unique characteristics, represents relatively cheap solid carrier used in formulation of oral dosage forms and implants. Modern adsorbents are mostly used in formulations of solid dispersions with low water-soluble drugs, or as solid carriers for lipid formulations. In latest years, modern porous carriers are evaluated for possible surface functionalization in order to achieve prolonged or signal-initiated drug release.
- Published
- 2016
- Full Text
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31. Application of mixture experimental design in formulation and characterization of solid self-nanoemulsifying drug delivery systems containing carbamazepine
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Krstić Marko Z. and Ibrić Svetlana R.
- Subjects
dissolution rate ,mixture design ,Polisorbat 80 ,Labrasol® ,Transcutol® HP ,Neusilin® UFl2 ,Neusilin® FL2 ,Sylysia® 320 ,diatomite ,carbamazepine ,Chemical technology ,TP1-1185 - Abstract
One of the problems with orally used drugs is their poor solubility, which can be overcame by creating solid self-nanoemulsifying drug delivery systems (SNEDDS). Aim is choosing appropriate SNEDDS using mixture design and adsorption of SNEDDS on a solid carrier to improve the dissolution rate of carbamazepine. Self-emulsifying drug delivery systems (SEDDS) consisting of oil phase (caprilic-capric triglycerides), a surfactant (Polisorbat 80 and Labrasol® (1:1)) and cosurfactant (Transcutol® HP) are formed by applying mixture design. 16 formulations were formulated, where proportion of lipids, surfactant and cosurfactant were varied (input parameters) in the following ranges: 10-30%, 40-60%, 30-50%, respectively. After dilution of SEDDS with water (90% water), the droplet size and polydispersity index (PdI) of the obtained emulsions (output parameters) were measured using photon correlation spectroscopy. After processing data, appropriate mathematical models that describe the dependence of input and output parameters were selected. The optimized SNEDDS was adsorbed on the carbamazepine and solid carrier physical mixture, containing 20% carbamazepine. Neusilin® UFl2, Neusilin® FL2, Sylysia® 320, diatomite were used as the carriers. The ratio of SNEDDS:carrier varied (1:1, 2:1). Dissolution testing was carried out in the rotation paddles apparatus. Caracterization of solid SNEDDS was performed using the hot stage microscopy (HSM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), infrared spectrophotometry with Fourier transformation (FT-IR), scanning electron microscopy (SEM) and X-ray diffraction (PXRD). Selected SNEDDS consisting of lipids (21.12%), surfactant (42.24%) and cosurfactant (36.64%) had a droplet size 157.02±34.09 nm and PDI 0.184±0.021. Drug release profiles showed that in all formulations dissolution rate increased (the fastest drug release was observed in formulations with Sylysia® 320). It can be concluded that in all formulations carbamazepine is present in the thermodynamically most stable polymorphic form III. Formulation of solid SNEDDS can significantly increase dissolution rate carbamazepine, with conservation of the polymorphic form III CBZ and potentially increased bioavailability. [Projekat Ministarstva nauke Republike Srbije, br. TR 34007]
- Published
- 2016
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32. Diatoms - nature materials with great potential for bioapplications
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Medarević Đorđe P., Lošić Dušan, and Ibrić Svetlana R.
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diatoms ,drug delivery systems ,biosensors ,gas sensors ,biomolecules immobilization ,target drug delivery ,Chemical technology ,TP1-1185 - Abstract
Diatoms are widespread unicellular photosynthetic algae that produce unique highly ordered siliceous cell wall, called frustule. Micro- to nanoporous structure with high surface area that can be easily modified, high mechanical resistance, unique optical features (light focusing and luminescence) and biocompatibility make diatom frustule as a suitable raw material for the development of devices such as bio- and gas sensors, microfluidic particle sorting devices, supercapacitors, batteries, solar cells, electroluminescent devices and drug delivery systems. Their wide availability in the form of fossil remains (diatomite or diatomaceous earth) as well as easy cultivation in the artificial conditions further supports use of diatoms in many different fields of application. This review focused on the recent achievements in the diatom bioapplications such as drug delivery, biomolecules immobilization, bio- and gas sensing, since great progress was made in this field over the last several years.
- Published
- 2016
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33. The Influence of Processing Variables on Performance of O/W Emulsion Gels Based on Polymeric Emulsifier (Pemulen ®TR-2NF).
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Simovic, S., Milic-Askrabic, J., Vuleta, G., Ibric, S., and Stupar, M.
- Published
- 1999
- Full Text
- View/download PDF
34. Melt granulation as an alternative technique in solid dosage forms manufacture
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Aleksić Ivana, Đuriš Jelena, Cvijić Sandra, Ibrić Svetlana, and Parojčić Jelena
- Subjects
melt granulation ,agglomeration mechanisms ,fluid bed granulator ,Pharmacy and materia medica ,RS1-441 - Abstract
Conventional granulation methods are associated with significant disadvantages which have led to increased interest and investment in the development of alternative techniques. Melt granulation is an alternative technique with significant potential for the application in production of solid dosage forms. Melt granulation involves the use of binders with relatively low melting point (50 to 100°C) that act as a molten binding liquid in agglomeration process. Considering that solvent is not required, drying phase is avoided, and number of processing steps and costs is reduced in comparison with the traditional wet granulation process. Process is suitable for moisture-sensitive drugs, and by selecting the suitable binder, it can be used to prepare modified or immediate release dosage forms, with improved bioavailability of poorly water soluble drugs, as well as to achieve taste masking. Melt granulation can be performed in the equipment commonly used for wet granulation, such as high shear mixers, fluid bed granulators, and extruders. Numerous formulation variables, process parameters, and equipment-related factors can affect the agglomeration mechanism and characteristics of the granules obtained. Well controlled melt granulation process requires thorough knowledge and understanding of the influence of these factors. Therefore, this research area still requires an intense and often multidisciplinary research.
- Published
- 2015
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35. Evaluation of formulation and effects of process parameters on drug release and mechanical properties of tramadol hydrocloride sustained release matrix tablets
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Nikolić Nenad D., Medarević Đorđe P., Ibrić Svetlana R., and Đurić Zorica R.
- Subjects
tramadol HCl ,matrix tablets ,PEO WSR Coagulant ,drug release ,mechanical properties of tablets ,Chemical technology ,TP1-1185 - Abstract
This study investigates using of high molecular weight polyethylene oxide (PEO WSR Coagulant) for the preparation of sustained release matrix tablets containing high dose, highly water soluble drug, tramadol HCl. Proportion of PEO polymer, type of insoluble filler, proportion of tramadol HCl, amount of drug in tablet, tablet diameter and compression pressure were recognized as critical formulation and process parameters and their influence on drug release and tablet mechanical properties was evaluated. Percentages of tramadol HCl released after 30 and 240 minutes were selected for evaluation of drug release, while tensile strength was used as indicator of tablet mechanical properties. Only proportion of tramadol HCl exhibits statistically significant effect on percentages of tramadol HCl released after 30 and 240 minutes, with higher, wherein increasing of the tramadol HCl proportion increased its release rate among the evaluated variables in selected ranges. All of the investigated factors exhibit statistically significant effect on tablets tensile strength, with the largest influence of filler type. Tablets prepared with highly compressible filler (microcrystalline celullose) exhibit higher tensile strength and therefore better mechanical properties to those prepared with partially pregelatinised starch (Strach 1500). [Projekat Ministarstva nauke Republike Srbije, br. TR 34007]
- Published
- 2015
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36. Application of experimental design in examination of the dissolution rate of carbamazepine from formulations: Characterization of the optimal formulation by DSC, TGA, FT-IR and PXRD analysis
- Author
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Krstić Marko, Ražić Slavica, Vasiljević Dragana, Spasojević Đurđija, and Ibrić Svetlana
- Subjects
poloxamer ,neusilin ,diatomite ,solid surfactant drug delivery systems ,polymorphous transition ,Chemistry ,QD1-999 - Abstract
Poor solubility is one of the key reasons for the poor bioavailability of these drugs. This paper displays a formulation of a solid surfactant system with carbamazepine, in order to increase its dissolution rate. Solid state surfactant systems are formed by application of fractal experimental design. Poloxamer 237 and Poloxamer 338 were used as surfactants and Brij® 35 was used as the co-surfactant. The ratios of the excipients and carbamazepine were varied and their effects on the dissolution rate of carbamazepine were examined. Moreover, the effects of the addition of natural (diatomite) and a synthetic adsorbent carrier (Neusiline UFL2) on the dissolution rate of carbamazepine were also tested. The prepared surfactant systems were characterized and the influence of the excipients on possible changes of the polymorphous form of carbamazepine examined by application of analytical techniques (DSC, TGA, FT-IR, PXRD). It was determined that an appropriate selection of the excipient type and ratio could provide a significant increase in the carbamazepine dissolution rate. By application of analytical techniques, it was found that that the employed excipients induce a transition of carbamazepine into the amorphous form and that the selected sample was stable for three months, when kept under ambient conditions. [Projekat Ministarstva nauke Republike Srbije, br. TR34007]
- Published
- 2015
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37. Quality assessment of total parenteral nutrition admixtures by the use of fractional factorial design
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Mirković Dušica, Ibrić Svetlana, and Antunović Mirjana
- Subjects
parenteral nutrition ,particle size ,fat emulsions, intravenous ,electrolytes ,quality control ,Medicine (General) ,R5-920 - Abstract
Background/Aim. Parenteral nutrition as a specific aspect of providing nutritients still remains a permanent topic of both theoretical and experimental research. Total parenteral nutrition (TPN) admixtures have complex contents making difficult to maintain their stability. The most critical parameter is the diameter of a lipid droplet, i.e. droplet size distribution. It is recommended that droplet size should not be more than 5
- Published
- 2013
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38. In silico methods in stability testing of hydrocortisone, powder for injections: Multiple regression analysis versus dynamic neural network
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Vujić Zorica B., Jocković Jelena M., Stankovic Predrag D., Solomun Ljiljana N., Ibrić Svetlana R., Pejanović Vjera M., and Đuriš Jelena D.
- Subjects
hydrocortisone ,stability ,multiple regression analysis ,dynamic neural network ,Chemical technology ,TP1-1185 - Abstract
This article presents the possibility of using of multiple regression analysis (MRA) and dynamic neural network (DNN) for prediction of stability of Hydrocortisone 100 mg (in a form of hydrocortisone sodium succinate) freeze-dried powder for injection packed into a dual chamber container. Degradation products of hydrocortisone sodium succinate: free hydrocortisone and related substances (impurities A, B, C, D and E; unspecified impurities and total impurities) were followed during stress and formal stability studies. All data obtained during stability studies were used for in silico modeling; multiple regression models and dynamic neural networks as well, in order to compare predicted and observed results. High values of coefficient of determination (0.950.99) were gained using MRA and DNN, so both methods are powerful tools for in silico stability studies, but superiority of DNN over mathematical modeling of degradation was also confirmed.
- Published
- 2012
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39. Potential application of surfactant systems in formulation of dosage forms with slightly soluble substances
- Author
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Ibrić Svetlana R., Đurić Zorica R., Vasiljević Dragana D., Đuriš Jelena D., and Milović Mladen R.
- Subjects
PEG-40 hydrogenated castor oil ,diethylene glycol monoethyl ether ,surfactant systems ,magnesium aluminometasilicate ,ibuprofen ,Chemical technology ,TP1-1185 - Abstract
In order to achieve fast release of ibuprofen, slightly soluble model substance (0.52104 mol/l), surfactant systems for oral use with different PEG-40 hydrogenated castor oil (C)/diethylene glycol monoethyl ether (T) ratios were investigated. Comparison between dissolution profiles for ibuprofen from formulated systems and from two commercial products, film tablets and soft capsules, is presented in this paper. Photon correlation spectroscopy has shown that after high dilution with water, surfactant systems were able to form micellar solutions. The size of micelles varies from 14.8 ± 0,075 nm to 16.2 ± 0,021 nm with increasing C/T ratio from 1:2 to 2:1. Although with increasing content of PEG-40 hydrogenated castor oil larger micelles have formed, lower values of polydispersity index indicated that more homogeneous distribution of micelles size was gained. Conductometric analysis has demonstrated that system composing of C/T ratio 2:1, has shown most pronounced interaction between droplets, which can be seen as high rise of electrical conductivity with increasing water content (% (wwater/wtotal)) in the sample. No significant difference in percolation threshold between formulations with different C/T ratios was observed. Different surfactant systems were adsorbed on magnesium aluminometasilicate, as adsorbent with high specific active surface (≈300 m2/g), in order to investigate potential influence of adsorbent on ibuprofen dissolution rate. Formulated systems, with or without adsorbent were filled in hard gelatin capsules. The dissolution profiles of ibuprofen from different formulations were obtained in 30 minutes by dissolution apparatus with rotating baskets and compared with dissolution profiles of ibuprofen from commercial products. For formulations without adsorbent faster release of ibuprofen in first minutes of dissolution test, showed formulations with C/T ratio 2:1 and 1:1. Magnesium aluminometasilicate, as adsorbent with high specific surface area, significantly improved release rate of ibuprofen from formulation with C/T ratio 2:1, but, for formulation with C/T ratio 1:1, significantly lower release of ibuprofen was observed. Formulations with other C/T ratios in terms of fast ibuprofen release did not give satisfying results. Obtained results show that in comparison to dissolution profile of ibuprofen from commercial products proper C/T ratio as well as magnesium aluminometasilicate, as adsorbent with high specific surface area, can significantly increase release of ibuprofen.
- Published
- 2012
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40. Retraction notice to: Artificial intelligence in pharmaceutical product formulation: Neural computing [Chem. Ind. Chem. Eng. Q. 15(4) (2009) 227-236]
- Author
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Ibrić Svetlana, Đurić Zorica, Parojčić Jelena, and Petrović Jelena
- Subjects
nema ,Chemical engineering ,TP155-156 ,Chemical industries ,HD9650-9663 - Abstract
This article has been retracted at the request of the authors. The retraction has been made because the authors admitted that they took the text and rawings from the review article written by R. Rowe and E. Colbourn, Future Medicinal Chemistry 1(4) (2009) 713-726, without their permission and even did not include this article in the list of references. One of the conditions of submission of a paper for publication are that authors confirm that their work is entirely originally written, someone else’s data and/or text are appropriately cited or quoted and permission has been obtained for use of copyrighted material from other sources. Therefore, the retracted article represents a severe improperly usage of the scientific publishing system. Apologies are offered to readers of the Chem. Ind. Chem. Eng. Q. that this abuse was not detected during the submission process. Link to the retracted article 10.2298/CICEQ0904227I
- Published
- 2011
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41. Solid self-emulsifying phospholipid suspension (SSEPS) with diatom as a drug carrier
- Author
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Andriy Dashevskiy, Dusan Losic, Svetlana Ibrić, Spomenka Simovic, Mladen Milović, Milovic, M, Simovic, Spomenka, Losic, Dusan, Dashevskiy, A, and Ibric, S
- Subjects
food.ingredient ,Surface Properties ,Pharmaceutical Science ,Lecithin ,Polyvinyl alcohol ,Suspension (chemistry) ,Crystallinity ,chemistry.chemical_compound ,Drug Delivery Systems ,food ,Adsorption ,Suspensions ,Particle Size ,Dissolution ,Phospholipids ,Diatoms ,Drug Carriers ,Chromatography ,Molecular Structure ,fungi ,Labrasol (R) ,Silicon Dioxide ,labrasol® ,Solid self-emulsifying phospholipid suspension ,Carbamazepine ,chemistry ,Emulsions ,Dispersion (chemistry) ,Drug carrier ,Porosity ,Nuclear chemistry - Abstract
We report the application of diatom as a solid carrier for water insoluble drugs applied in oral drug delivery system based on the self-emulsifying drug delivery system (SEDDS) caprylocaproyl macrogol-8 glycerides/lecithin/propylene glycol/caprylic/capric triglyceride. Diatoms are fossilized skeletons of photosynthetic algae with complex 3-dimensional (3D), porous structure consisting of amorphous silica, obtained by purification of diatomaceous earth. Different solid samples of carbamazepine (CBZ) suspension in SEDDS, called solid self-emulsifying phospholipid suspension (SSEPS), were prepared using two methods: adsorption of CBZ dispersion in SEDDS by gentle mixing with diatoms in mortar with pestle (Method A) or dispersion of diatoms in ethanol solution of CBZ and SEDDS components, followed by ethanol evaporation (Method B). Release rate of CBZ from SSEPS was significantly higher in comparison to pure drug, physical mixture of diatoms and CBZ as well as solid dispersion of pure CBZ and diatoms obtained by ethanol evaporation. The dissolution of CBZ from SSEPS sample prepared using method B was faster than from the sample prepared by the method A. Higher dissolution for sample prepared by the method B can be attributed to the partial adsorption (deeper localization) of liquid material inside the pores of diatoms. Upon storage of the samples under accelerated conditions (40 °C and 70% RH) for 10 weeks no significant changes in CBZ crystallinity and dissolution was in case of SSEPS, contrary to solid dispersion with increased crystallinity, indicating that diatoms with adsorbed liquid CBZ-loaded SEPS can maintain initial CBZ characteristics. Refereed/Peer-reviewed
- Published
- 2014
42. Application of Machine-Learning Algorithms for Better Understanding of Tableting Properties of Lactose Co-Processed with Lipid Excipients.
- Author
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Djuris J, Cirin-Varadjan S, Aleksic I, Djuris M, Cvijic S, and Ibric S
- Abstract
Co-processing (CP) provides superior properties to excipients and has become a reliable option to facilitated formulation and manufacturing of variety of solid dosage forms. Development of directly compressible formulations with high doses of poorly flowing/compressible active pharmaceutical ingredients, such as paracetamol, remains a great challenge for the pharmaceutical industry due to the lack of understanding of the interplay between the formulation properties, process of compaction, and stages of tablets' detachment and ejection. The aim of this study was to analyze the influence of the compression load, excipients' co-processing and the addition of paracetamol on the obtained tablets' tensile strength and the specific parameters of the tableting process, such as (net) compression work, elastic recovery, detachment, and ejection work, as well as the ejection force. Two types of neural networks were used to analyze the data: classification (Kohonen network) and regression networks (multilayer perceptron and radial basis function), to build prediction models and identify the variables that are predominantly affecting the tableting process and the obtained tablets' tensile strength. It has been demonstrated that sophisticated data-mining methods are necessary to interpret complex phenomena regarding the effect of co-processing on tableting properties of directly compressible excipients.
- Published
- 2021
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- View/download PDF
43. An Integrative in silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS-CoV-2 Main Protease.
- Author
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Djokovic N, Ruzic D, Djikic T, Cvijic S, Ignjatovic J, Ibric S, Baralic K, Buha Djordjevic A, Curcic M, Djukic-Cosic D, and Nikolic K
- Subjects
- Antiviral Agents chemistry, Computer Simulation, Drug Design, Humans, Molecular Docking Simulation, Protease Inhibitors chemistry, SARS-CoV-2 drug effects, Viral Matrix Proteins metabolism, Antiviral Agents pharmacology, Drug Repositioning methods, Protease Inhibitors pharmacology, SARS-CoV-2 enzymology, Viral Matrix Proteins antagonists & inhibitors, COVID-19 Drug Treatment
- Abstract
Considering the urgent need for novel therapeutics in ongoing COVID-19 pandemic, drug repurposing approach might offer rapid solutions comparing to de novo drug design. In this study, we designed an integrative in silico drug repurposing approach for rapid selection of potential candidates against SARS-CoV-2 Main Protease (M
pro ). To screen FDA-approved drugs, we implemented structure-based molecular modelling techniques, physiologically-based pharmacokinetic (PBPK) modelling of drugs disposition and data mining analysis of drug-gene-COVID-19 association. Through presented approach, we selected the most promising FDA approved drugs for further COVID-19 drug development campaigns and analysed them in context of available experimental data. To the best of our knowledge, this is unique in silico study which integrates structure-based molecular modeling of Mpro inhibitors with predictions of their tissue disposition, drug-gene-COVID-19 associations and prediction of pleiotropic effects of selected candidates., (© 2021 Wiley-VCH GmbH.)- Published
- 2021
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- View/download PDF
44. Tableting of hot-melt coated paracetamol granules: Material tableting properties and quality characteristics of the obtained tablets.
- Author
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Milanovic A, Aleksic I, Ibric S, Parojcic J, and Cvijic S
- Subjects
- Delayed-Action Preparations chemistry, Drug Delivery Systems methods, Drug Liberation physiology, Excipients chemistry, Hot Melt Extrusion Technology methods, Lipids chemistry, Solubility drug effects, Tensile Strength drug effects, Acetaminophen chemistry, Tablets chemistry
- Abstract
Hot-melt coating (HMC) has been recognized as a promising technique in the production of solid dosage forms e.g., HMC of granules can be applied prior to compression in order to obtain modified drug release or taste masking. However, tableting properties of HMC granules have not been studied yet. In this work, we explored the influence of the lipid coating on granules tableting properties, and assessed quality attributes of the obtained tablets. Paracetamol granules, previously coated with the lipid excipient Precirol® ATO 5 using a hot-melt coating technique in modified fluidized-bed system, were evaluated in terms of work of compression, elastic recovery, tablets tensile strength, detachment stress and ejection stress. Regarding the product quality, tablets content uniformity, friability, disintegration time and drug release properties were tested. Our results demonstrated that tablets made of coated granules exhibited more pronounced elastic behaviour, and increased tensile strength in comparison to tablets made of uncoated granules, suggesting that lipid coating promotes elastic deformation and forms lipid matrix within the tablets. Additionally, low detachment and ejection stresses for tablets made of HMC granules indicated no need to add lubricant prior to tableting process. Evaluation of tablets properties revealed that tablets friability was not influenced by the presence of lipid coating on the compressed granules. However, formation of lipid matrix within the tablets made of HMC granules resulted in prolonged tablet disintegration time, and sustained drug release. Moreover, the performance of lipid matrix tablets, in terms of drug dissolution rate, was relatively insensitive to compression pressure variations in 104-173 MPa range. The obtained results indicate that tableting of HMC granules is a promising technique to obtain sustained release lipid matrix tablets of suitable pharmaceutical-technical properties., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2020
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- View/download PDF
45. Optimization and Prediction of Ibuprofen Release from 3D DLP Printlets Using Artificial Neural Networks.
- Author
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Madzarevic M, Medarevic D, Vulovic A, Sustersic T, Djuris J, Filipovic N, and Ibric S
- Abstract
The aim of this work was to investigate effects of the formulation factors on tablet printability as well as to optimize and predict extended drug release from cross-linked polymeric ibuprofen printlets using an artificial neural network (ANN). Printlets were printed using digital light processing (DLP) technology from formulations containing polyethylene glycol diacrylate, polyethylene glycol, and water in concentrations according to D-optimal mixture design and 0.1% w / w riboflavin and 5% w/w ibuprofen. It was observed that with higher water content longer exposure time was required for successful printing. For understanding the effects of excipients and printing parameters on drug dissolution rate in DLP printlets two different neural networks were developed with using two commercially available softwares. After comparison of experimental and predicted values of in vitro dissolution at the corresponding time points for optimized formulation, the R
2 experimental vs. predicted value was 0.9811 (neural network 1) and 0.9960 (neural network 2). According to difference f1 and similarity factor f2 ( f1 = 14.30 and f2 = 52.15) neural network 1 with supervised multilayer perceptron, backpropagation algorithm, and linear activation function gave a similar dissolution profile to obtained experimental results, indicating that adequate ANN is able to set out an input-output relationship in DLP printing of pharmaceutics., Competing Interests: The authors declare no conflict of interest- Published
- 2019
- Full Text
- View/download PDF
46. Selection of the suitable polymer for supercritical fluid assisted preparation of carvedilol solid dispersions.
- Author
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Djuris J, Milovanovic S, Medarevic D, Dobricic V, Dapčević A, and Ibric S
- Subjects
- Calorimetry, Differential Scanning, Carbon Dioxide chemistry, Carvedilol chemistry, Drug Compounding methods, Drug Liberation, Microscopy, Electrochemical, Scanning, Solubility, Spectroscopy, Fourier Transform Infrared, Tablets, Carvedilol administration & dosage, Chemistry, Pharmaceutical methods, Drug Carriers chemistry, Polymers chemistry
- Abstract
Solid dispersions production is one of the substantial approaches for improvement of poor drug solubility. Additionally, supercritical fluid assisted method for preparation of solid dispersions can offer many advantages in comparison to the conventional melting or solvent-evaporation methods. Miscibility analysis provides valuable guidance for selection of the most appropriate polymeric carrier for dispersion of the drug of interest. In addition to the increased drug release rate, solid dispersions should have proper mechanical attributes in order to be successfully formulated in the final solid dosage form such as tablet. Therefore, several pharmaceutical grade polymers have been selected for development of BCS Class II drug carvedilol (CARV) solid dispersions. They were compared based on behavior in supercritical CO
2 and affinity towards CARV calculated from the miscibility analysis. By utilization of the supercritical CO2 assisted method, solid dispersions of CARV with the selected (co)polymers (polyvinylpyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC), Soluplus® and Eudragit®) were obtained. Properties of the prepared CARV-polymer dispersions were observed by the polarizing and scanning electron microscopy and analyzed by differential scanning calorimetry and Fourier transform infrared spectroscopy. CARV was additionally characterized by X-ray powder diffraction. Furthermore, in vitro dissolution studies and dynamic compaction analysis were performed on the selected samples of solid dispersions. Among the studied polymers, PVP and HPMC have been identified as polymers with the highest affinity towards CARV, based on the calculated δp values. This has been also confirmed with the highest dissolution efficiency of CARV-PVP and CARV-HPMC solid dispersions. Solid state characterization indicated that CARV was dispersed either molecularly, or in the amorphous form, depending on interactions with each polymer. Determination of CARV-PVP and CARV-HPMC mechanical properties revealed that CARV-PVP solid dispersion has superior compactibility and tabletability. Therefore, CARV-PVP solid dispersion has been highlighted as the most appropriate for the further development of tablets as the final dosage form. Presented study provides an example for efficient approach for development of poorly soluble drug solid dispersion with satisfactory tableting properties., (Copyright © 2018 Elsevier B.V. All rights reserved.)- Published
- 2019
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- View/download PDF
47. Application of the design of experiments in optimization of drug layering of pellets with an insight into drug polymer interactions.
- Author
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Kovacevic J, Ibric S, Djuris J, and Kleinebudde P
- Subjects
- Calorimetry, Differential Scanning, Duloxetine Hydrochloride chemistry, Chemistry, Pharmaceutical methods, Duloxetine Hydrochloride administration & dosage, Excipients chemistry, Polymers chemistry
- Abstract
This study consists of two experimental designs. Within the first one, suitable technique for application of model drug onto inactive pellets was evaluated and formulation and process parameters with greatest impact to process efficency and useful yield were determined. Results of experiments showed that formulation characteristics were the ones with the greatest impact on coating efficiency and that suspension layering technique was significantly better for drug application onto inactive pellets in comparison to solution layering during which pronounced agglomeration of pellets occurred. Analysis of drug-polymer interactions by differential scanning calorimetry was performed to explain the results of experiments. The reason for agglomeration of pellets during solution layering was formation of low Tg amorphous form of model drug. The second set of experiments was performed according to central composite design experimental plan in order to optimize level of binder and concentration of solids in the coating liquid which were found to have greatest positive impact on process efficiency and useful yield in the screening study. Statistically significant models were obtained by response surface methodology and it was possible to use them to define optimal levels of excipients in the formulation., (Copyright © 2016. Published by Elsevier B.V.)
- Published
- 2016
- Full Text
- View/download PDF
48. Evaluation of powder, solution and suspension layering for the preparation of enteric coated pellets.
- Author
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Kovacevic J, Mladenovic A, Djuris J, and Ibric S
- Subjects
- Chemistry, Pharmaceutical methods, Drug Compounding methods, Drug Stability, Excipients chemistry, Polymers chemistry, Solubility, Drug Implants chemistry, Powders chemistry, Solutions chemistry, Suspensions chemistry, Tablets, Enteric-Coated chemistry
- Abstract
Gastro-resistant pellets were prepared by use of three different drug loading techniques (powder layering, solution layering and suspension layering) and two different enteric coating techniques (powder layering and suspension layering). Pellets produced by different layering techniques were compared in terms of morphological characteristics, content of drug, release properties and stability. Drug loaded pellets produced by the use of powder layering had much more pronounced surface roughness in comparison to other tested techniques. Higher weight gains of enteric polymer were needed to achieve the same level of gastric resistance when powder layering was employed to apply enteric layer than when it was applied by suspension layering. Both tested techniques of enteric coating application enabled complete dissolution of drug in buffer stage of dissolution test. Suspension layering proved to be superior to other techniques both in drug loading and enteric layering phase., (Copyright © 2016. Published by Elsevier B.V.)
- Published
- 2016
- Full Text
- View/download PDF
49. Effect of composition in the development of carbamazepine hot-melt extruded solid dispersions by application of mixture experimental design.
- Author
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Djuris J, Ioannis N, Ibric S, Djuric Z, and Kachrimanis K
- Subjects
- Carbamazepine administration & dosage, Chemistry, Pharmaceutical, Drug Carriers standards, Drug Stability, Freezing, Hardness, Humans, Plasticizers chemistry, Solubility, Solutions, Carbamazepine chemistry, Drug Carriers chemistry, Drug Compounding methods, Hot Temperature, Poloxamer chemistry, Polyethylene Glycols chemistry, Polyvinyls chemistry
- Abstract
Objectives: This study investigates the application of hot-melt extrusion for the formulation of carbamazepine (CBZ) solid dispersions, using polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus, BASF, Germany) and polyoxyethylene-polyoxypropylene block copolymer (Poloxamer 407). In agreement with the current Quality by Design principle, formulations of solid dispersions were prepared according to a D-optimal mixture experimental design, and the influence of formulation composition on the properties of the dispersions (CBZ heat of fusion and release rate) was estimated., Methods: Prepared solid dispersions were characterized using differential scanning calorimetry, attenuated total reflectance infrared spectroscopy and hot stage microscopy, as well as by determination of the dissolution rate of CBZ from the hot-melt extrudates., Key Findings: Solid dispersions of CBZ can be successfully prepared using the novel copolymer Soluplus. Inclusion of Poloxamer 407 as a plasticizer facilitated the processing and decreased the hardness of hot-melt extrudates. Regardless of their composition, all hot-melt extrudates displayed an improvement in the release rate compared to the pure CBZ, with formulations having the ratio of CBZ : Poloxamer 407 = 1 : 1 showing the highest increase in CBZ release rate., Conclusions: Interactions between the mixture components (CBZ and polymers), or quadratic effects of the components, play a significant role in overall influence on the CBZ release rate., (© 2013 Royal Pharmaceutical Society.)
- Published
- 2014
- Full Text
- View/download PDF
50. Spray-dried voriconazole-cyclodextrin complexes: solubility, dissolution rate and chemical stability.
- Author
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Miletic T, Kyriakos K, Graovac A, and Ibric S
- Subjects
- 2-Hydroxypropyl-beta-cyclodextrin, Carbohydrate Conformation, Drug Stability, Molecular Docking Simulation, Solubility, Temperature, Voriconazole, Pyrimidines chemistry, Triazoles chemistry, beta-Cyclodextrins chemistry
- Abstract
The present work investigates the effect of complexation with hydroxypropyl-beta-cyclodextrin (HPBCD) and 2-O-methyl-beta-cyclodextrin (2-O-MBCD), on voriconazole solubility, dissolution rate and chemical stability. Drug-cyclodextrin complexes were prepared as aqueous solutions, which were spray-dried, and their properties were compared to wet ground samples and physical mixtures. DSC analysis revealed absence of crystalline voriconazole from spray-dried complexes. FTIR spectroscopy indicated changes in the H-bonding network of the hydroxyl groups of cyclodextrin following drug inclusion. Dissolution rate of voriconazole was significantly higher from spray-dried complexes with either cyclodextrin in comparison with free drug, physical mixtures, or wet ground mixtures. However, two degradation impurities were found in aged samples, with slightly higher impurity level with HPBCD. Performed solubility studies suggested that 2-O-MBCD is more efficient solubilizer. Molecular docking simulations showed a difference in the 1:1 binding affinities and sites, with HPBCD surprisingly forming complexes of much lower energy, thus suggesting a multiple rather than a 1:1 complexation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
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