TY  - THES
AU  - Milanović, Ana
PY  - 2021
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=8469
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:24857/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=48963593
UR  - https://nardus.mpn.gov.rs/handle/123456789/18887
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4040
AB  - Oblaganje topljenjem je proces u kom se supstanca za oblaganje nanosi na supstrat u rastopljenom obliku i najčešće se sprovodi u uređaju tipa fluidizirajućeg sistema. Zbog velikog broja procesnih parametara i kompleksnosti procesa, optimizacija postupka oblaganja topljenjem u ovakvim uređajima predstavlja poseban izazov. Cilj ovog rada je ispitivanje uticaja procesnih parametara na karakteristike granula obloženih topljenjem i optimizacija postupka oblaganja topljenjem u uređaju tipa fluidizirajućeg sistema laboratorijskog kapaciteta. Na osnovu rezultata ispitivanja dobijenih primenom eksperimentalnog dizajna, uočene su dve oblasti koje definišu optimalne uslove procesa oblaganja topljenjem, odnosno, definisan je prostor za dizajn.Komprimovanjem granula obloženih topljenjem mogu se izraditi tablete sa produženim oslobađanjem lekovite supstance. Ispitivanje tabletabilnih karakteristika materijala obloženog topljenjem do sada nije opisano u literaturi. Dobijeni rezultati su pokazali da obložene granule poseduju zadovoljavajuće karakteristike u smislu kompaktibilnosti i pogodnosti za proizvodnju, a da farmaceutsko-tehnološke karakteristike izrađenih tableta odgovaraju zahtevima Ph. Eur. 10.0. Takođe, ispitivanja su pokazala da je brzina rastvaranja paracetamola iz tableta izrađenih od obloženih granula nezavisna do pritiska kompresije primenjenog u postupku izrade tableta.Granule obložene topljenjem i tablete izrađene od obloženih granula predstavljaju pogodne farmaceutske oblike lekova za pedijatrijske pacijente, pre svega zbog primene bezbednih pomoćnih supstanci za oblaganje i mogućnosti maskiranja ukusa, a smanjena učestalost doziranja zbog produženog oslobađanjа lekovite supstance može dodatno povećati komplijansu pacijenata. Rezultati in silico modelovanja i simulacija pokazali su da se primenom obloženih granula paracetamola i tableta izrađenih od obloženih granula, kod dece različitog uzrasta, može postići odgovarajuća sistemska raspoloživost uz istovremeno smanjenje učestalosti uzimanja leka.
AB  - Hot-melt coating is a process in which the coating excipient is applied on a substrate in a molten state. Generally, fluidized-bed systems are preferred for hot-melt coating. Optimization of hot-met coating in a fluidized-bed apparatus is often a challenge due to the numerous process parameters and the process complexity. The aim of this study was to evaluate the effects of process parameters on the coated granules characteristics and to optimize the hot-melt coating process in the laboratory-scale fluidized-bed apparatus. Based on the experimental design results, two discrete areas defining optimal values of the process parameters were observed i.e., design space was established.Hot-melt coated granules can be compressed to yield prolonged-release tablets. Evaluation of hot-melt coated material tableting properties has not been described in literature so far. The results obtained in this study revealed that hot-melt coated paracetamol granules have suitable tableting properties, in terms of compactibility and manufacturability. In addition, pharmaceutical-technical properties of the tablets made of hot-melt coated granules are within the limits described in the Ph. Eur. 10.0. Dissolution testing showed that the applied range of compression loads during tableting process did not influence the drug dissolution rate from tablets made of hot-melt coated paracetamol granules.Hot-melt coated granules and tablets made of hot-melt coated granules can be a suitable dosage forms for paediatric patients because the presence of the coat can provide taste masking, the coating excipients are generally recognized as safe, and prolonged drug release can reduce the dosing frequency, and consequently, improve patients compliance. In silico modelling and simulation results indicated that administration of hot-melt coated paracetamol granules or tablets made of hot-melt coated granules in different paediatric subgroups can provide suitable drug systemic availability with reduced daily dosing.
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Optimizacija postupka oblaganja topljenjem u uređaju tipa fluidizirajućeg sistema: izrada i karakterizacija granula sa modifikovanim oslobađanjem paracetamola
UR  - https://hdl.handle.net/21.15107/rcub_nardus_18887
ER  - 

@phdthesis{
author = "Milanović, Ana",
year = "2021",
abstract = "Oblaganje topljenjem je proces u kom se supstanca za oblaganje nanosi na supstrat u rastopljenom obliku i najčešće se sprovodi u uređaju tipa fluidizirajućeg sistema. Zbog velikog broja procesnih parametara i kompleksnosti procesa, optimizacija postupka oblaganja topljenjem u ovakvim uređajima predstavlja poseban izazov. Cilj ovog rada je ispitivanje uticaja procesnih parametara na karakteristike granula obloženih topljenjem i optimizacija postupka oblaganja topljenjem u uređaju tipa fluidizirajućeg sistema laboratorijskog kapaciteta. Na osnovu rezultata ispitivanja dobijenih primenom eksperimentalnog dizajna, uočene su dve oblasti koje definišu optimalne uslove procesa oblaganja topljenjem, odnosno, definisan je prostor za dizajn.Komprimovanjem granula obloženih topljenjem mogu se izraditi tablete sa produženim oslobađanjem lekovite supstance. Ispitivanje tabletabilnih karakteristika materijala obloženog topljenjem do sada nije opisano u literaturi. Dobijeni rezultati su pokazali da obložene granule poseduju zadovoljavajuće karakteristike u smislu kompaktibilnosti i pogodnosti za proizvodnju, a da farmaceutsko-tehnološke karakteristike izrađenih tableta odgovaraju zahtevima Ph. Eur. 10.0. Takođe, ispitivanja su pokazala da je brzina rastvaranja paracetamola iz tableta izrađenih od obloženih granula nezavisna do pritiska kompresije primenjenog u postupku izrade tableta.Granule obložene topljenjem i tablete izrađene od obloženih granula predstavljaju pogodne farmaceutske oblike lekova za pedijatrijske pacijente, pre svega zbog primene bezbednih pomoćnih supstanci za oblaganje i mogućnosti maskiranja ukusa, a smanjena učestalost doziranja zbog produženog oslobađanjа lekovite supstance može dodatno povećati komplijansu pacijenata. Rezultati in silico modelovanja i simulacija pokazali su da se primenom obloženih granula paracetamola i tableta izrađenih od obloženih granula, kod dece različitog uzrasta, može postići odgovarajuća sistemska raspoloživost uz istovremeno smanjenje učestalosti uzimanja leka., Hot-melt coating is a process in which the coating excipient is applied on a substrate in a molten state. Generally, fluidized-bed systems are preferred for hot-melt coating. Optimization of hot-met coating in a fluidized-bed apparatus is often a challenge due to the numerous process parameters and the process complexity. The aim of this study was to evaluate the effects of process parameters on the coated granules characteristics and to optimize the hot-melt coating process in the laboratory-scale fluidized-bed apparatus. Based on the experimental design results, two discrete areas defining optimal values of the process parameters were observed i.e., design space was established.Hot-melt coated granules can be compressed to yield prolonged-release tablets. Evaluation of hot-melt coated material tableting properties has not been described in literature so far. The results obtained in this study revealed that hot-melt coated paracetamol granules have suitable tableting properties, in terms of compactibility and manufacturability. In addition, pharmaceutical-technical properties of the tablets made of hot-melt coated granules are within the limits described in the Ph. Eur. 10.0. Dissolution testing showed that the applied range of compression loads during tableting process did not influence the drug dissolution rate from tablets made of hot-melt coated paracetamol granules.Hot-melt coated granules and tablets made of hot-melt coated granules can be a suitable dosage forms for paediatric patients because the presence of the coat can provide taste masking, the coating excipients are generally recognized as safe, and prolonged drug release can reduce the dosing frequency, and consequently, improve patients compliance. In silico modelling and simulation results indicated that administration of hot-melt coated paracetamol granules or tablets made of hot-melt coated granules in different paediatric subgroups can provide suitable drug systemic availability with reduced daily dosing.",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Optimizacija postupka oblaganja topljenjem u uređaju tipa fluidizirajućeg sistema: izrada i karakterizacija granula sa modifikovanim oslobađanjem paracetamola",
url = "https://hdl.handle.net/21.15107/rcub_nardus_18887"
}

Milanović, A.. (2021). Optimizacija postupka oblaganja topljenjem u uređaju tipa fluidizirajućeg sistema: izrada i karakterizacija granula sa modifikovanim oslobađanjem paracetamola. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_18887

Milanović A. Optimizacija postupka oblaganja topljenjem u uređaju tipa fluidizirajućeg sistema: izrada i karakterizacija granula sa modifikovanim oslobađanjem paracetamola. in Универзитет у Београду. 2021;.
https://hdl.handle.net/21.15107/rcub_nardus_18887 .

Milanović, Ana, "Optimizacija postupka oblaganja topljenjem u uređaju tipa fluidizirajućeg sistema: izrada i karakterizacija granula sa modifikovanim oslobađanjem paracetamola" in Универзитет у Београду (2021),
https://hdl.handle.net/21.15107/rcub_nardus_18887 .

TY  - JOUR
AU  - Milanović, Ana
AU  - Aleksić, Ivana
AU  - Ibrić, Svetlana
AU  - Parojčić, Jelena
AU  - Cvijić, Sandra
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3508
AB  - 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.
PB  - Elsevier B.V.
T2  - European Journal of Pharmaceutical Sciences
T1  - Tableting of hot-melt coated paracetamol granules: Material tableting properties and quality characteristics of the obtained tablets
VL  - 142
DO  - 10.1016/j.ejps.2019.105121
ER  - 

@article{
author = "Milanović, Ana and Aleksić, Ivana and Ibrić, Svetlana and Parojčić, Jelena and Cvijić, Sandra",
year = "2020",
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.",
publisher = "Elsevier B.V.",
journal = "European Journal of Pharmaceutical Sciences",
title = "Tableting of hot-melt coated paracetamol granules: Material tableting properties and quality characteristics of the obtained tablets",
volume = "142",
doi = "10.1016/j.ejps.2019.105121"
}

Milanović, A., Aleksić, I., Ibrić, S., Parojčić, J.,& Cvijić, S.. (2020). Tableting of hot-melt coated paracetamol granules: Material tableting properties and quality characteristics of the obtained tablets. in European Journal of Pharmaceutical Sciences
Elsevier B.V.., 142.
https://doi.org/10.1016/j.ejps.2019.105121

Milanović A, Aleksić I, Ibrić S, Parojčić J, Cvijić S. Tableting of hot-melt coated paracetamol granules: Material tableting properties and quality characteristics of the obtained tablets. in European Journal of Pharmaceutical Sciences. 2020;142.
doi:10.1016/j.ejps.2019.105121 .

Milanović, Ana, Aleksić, Ivana, Ibrić, Svetlana, Parojčić, Jelena, Cvijić, Sandra, "Tableting of hot-melt coated paracetamol granules: Material tableting properties and quality characteristics of the obtained tablets" in European Journal of Pharmaceutical Sciences, 142 (2020),
https://doi.org/10.1016/j.ejps.2019.105121 . .

TY  - JOUR
AU  - Milanović, Ana
AU  - Aleksić, Ivana
AU  - Ibrić, Svetlana
AU  - Parojčić, Jelena
AU  - Cvijić, Sandra
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3034
AB  - Hot-melt coating is a novel and cost-effective solvent-free coating technique. Commonly used excipients for hot-melt coating are lipid substances. In this work, modified fluidized-bed system was applied for coating, and additional components were used to melt and convey the excipient to the fluidized-bed apparatus. Granules containing 20% (w/w) paracetamol were coated with Precirol((R)) ATO 5 at 9.1% (w/w) coating level. The aims of this study were to define a relationship between the three process parameters (fluidization airflow, atomization air pressure and spray rate) and characteristics of the coated granules using Box-Behnken experimental design, and to identify the design space for hot-melt coating of granules with desired mechanical and drug release properties. Response surface methodology was used for data analysis and modeling. We have found that interactions between the selected input parameters have pronounced influence on coated granules size, flowability and initial drug release rate. In addition, granules size distribution is strongly influenced by fluidization airflow and atomization air pressure. Granules flowability, and total and partial areas under the drug release curve were recognized as critical quality attributes of the coated granules. Design space was determined by all three process parameters which can be referred to as critical process parameters.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Drug Delivery Science and Technology
T1  - Hot-melt coating with Precirol ATO 5 in a fluidized-bed apparatus: Application of experimental design in the optimization of process parameters
VL  - 46
SP  - 274
EP  - 284
DO  - 10.1016/j.jddst.2018.05.030
ER  - 

@article{
author = "Milanović, Ana and Aleksić, Ivana and Ibrić, Svetlana and Parojčić, Jelena and Cvijić, Sandra",
year = "2018",
abstract = "Hot-melt coating is a novel and cost-effective solvent-free coating technique. Commonly used excipients for hot-melt coating are lipid substances. In this work, modified fluidized-bed system was applied for coating, and additional components were used to melt and convey the excipient to the fluidized-bed apparatus. Granules containing 20% (w/w) paracetamol were coated with Precirol((R)) ATO 5 at 9.1% (w/w) coating level. The aims of this study were to define a relationship between the three process parameters (fluidization airflow, atomization air pressure and spray rate) and characteristics of the coated granules using Box-Behnken experimental design, and to identify the design space for hot-melt coating of granules with desired mechanical and drug release properties. Response surface methodology was used for data analysis and modeling. We have found that interactions between the selected input parameters have pronounced influence on coated granules size, flowability and initial drug release rate. In addition, granules size distribution is strongly influenced by fluidization airflow and atomization air pressure. Granules flowability, and total and partial areas under the drug release curve were recognized as critical quality attributes of the coated granules. Design space was determined by all three process parameters which can be referred to as critical process parameters.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Drug Delivery Science and Technology",
title = "Hot-melt coating with Precirol ATO 5 in a fluidized-bed apparatus: Application of experimental design in the optimization of process parameters",
volume = "46",
pages = "274-284",
doi = "10.1016/j.jddst.2018.05.030"
}

Milanović, A., Aleksić, I., Ibrić, S., Parojčić, J.,& Cvijić, S.. (2018). Hot-melt coating with Precirol ATO 5 in a fluidized-bed apparatus: Application of experimental design in the optimization of process parameters. in Journal of Drug Delivery Science and Technology
Elsevier Science BV, Amsterdam., 46, 274-284.
https://doi.org/10.1016/j.jddst.2018.05.030

Milanović A, Aleksić I, Ibrić S, Parojčić J, Cvijić S. Hot-melt coating with Precirol ATO 5 in a fluidized-bed apparatus: Application of experimental design in the optimization of process parameters. in Journal of Drug Delivery Science and Technology. 2018;46:274-284.
doi:10.1016/j.jddst.2018.05.030 .

Milanović, Ana, Aleksić, Ivana, Ibrić, Svetlana, Parojčić, Jelena, Cvijić, Sandra, "Hot-melt coating with Precirol ATO 5 in a fluidized-bed apparatus: Application of experimental design in the optimization of process parameters" in Journal of Drug Delivery Science and Technology, 46 (2018):274-284,
https://doi.org/10.1016/j.jddst.2018.05.030 . .