Ivana Kurcubic - Academia.edu (original) (raw)

Papers by Ivana Kurcubic

Research paper thumbnail of Assessment of mucoadhesive buccal tablets with propranolol hydrochloride using principal component analysis

Makedonsko farmacevtski bilten, Aug 31, 2023

Research paper thumbnail of Review of machine learning algorithms' application in pharmaceutical technology

Arhiv za farmaciju, 2021

Machine learning algorithms, and artificial intelligence in general, have a wide range of applica... more 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.

Research paper thumbnail of Multiparticulate oral formulations as a viable strategy for precise drug dosing in pediatrics: Propranolol case study

Arhiv za farmaciju, 2021

The development of solid dosage forms that are both convenient for administration and allow preci... more 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, powder-and 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.

Research paper thumbnail of Influence of experimental model, active substance and polymer type on mucoadhesive properties of buccal tablets

Research paper thumbnail of Mucoadhesive buccal tablets with propranolol hydrochloride: Formulation development and in vivo performances in experimental essential hypertension

International Journal of Pharmaceutics, Dec 1, 2021

The objective of this study was to formulate extended-release mucoadhesive buccal tablets of prop... more The objective of this study was to formulate extended-release mucoadhesive buccal tablets of propranolol hydrochloride in order to provide a prolonged absorption of propranolol hydrochloride from the buccal mucosa and to reduce presystemic metabolism and thus provide a better therapeutic effect. Besides, the aim was to perform comparative in vivo pharmacokinetic and hemodynamic studies of the developed extended-release (ER) propranolol hydrochloride 10 mg mucoadhesive buccal tablets and commercial immediate-release (IR) propranolol hydrochloride 10 mg tablets in spontaneously hypertensive rats. Formulation with 15% polyethylene oxide showed the highest degree of propranolol hydrochloride permeation, satisfactory mucoadhesiveness, and extended-release of propranolol hydrochloride, thus it was selected for further in vivo study. The pharmacokinetic study in rats showed the superiority of ER mucoadhesive buccal tablets over IR tablets in terms of propranolol hydrochloride absorption extent (AUC values: 70.32 ± 19.56 versus 31.69 ± 6.97 µg·h/mL), although lower maximum plasma propranolol hydrochloride concentration (Cmax) was achieved. However, no statistically significant difference was observed in Cmax between these treatments. The hemodynamic study showed that ER mucoadhesive buccal tablets provide a more pronounced decrease primarily in heart rate, but also in systolic and diastolic arterial pressure, as well as a longer heart rate reduction compared to IR tablets.

Research paper thumbnail of Chemometric methods in pharmaceutical technology

Computer-Aided Applications in Pharmaceutical Technology

Research paper thumbnail of Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films

Journal of Drug Delivery Science and Technology

Research paper thumbnail of Višečestične formulacije lekova za oralnu primenu kao strategija za precizno doziranje kod pedijatrijskih pacijenata - studija slučaja propranolola

The development of solid dosage forms that are both convenient for administration and allow preci... more 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, powder- and granule-filled 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-fill...

Research paper thumbnail of Development of Lipid-Based Gastroretentive Delivery System for Gentian Extract by Double Emulsion–Melt Dispersion Technique

Pharmaceutics, 2021

Gentian (Gentiana lutea L., Gentianaceae) root extract (GRE) is used for the treatment of gastroi... more Gentian (Gentiana lutea L., Gentianaceae) root extract (GRE) is used for the treatment of gastrointestinal disorders. However, its bioactive potential is limited in conventional forms due to the low bioavailability and short elimination half-life of the dominant bioactive compound, gentiopicroside. The aim of study was to encapsulate GRE in the lipid-based gastroretentive delivery system that could provide high yield and encapsulation efficiency, as well as the biphasic release of gentiopicroside from the tablets obtained by direct compression. Solid lipid microparticles (SLM) loaded with GRE were prepared by freeze-drying double (W/O/W) emulsions, which were obtained by a multiple emulsion–melt dispersion technique, with GRE as the inner water phase, Gelucire® 39/01 or 43/01, as lipid components, with or without the addition of porous silica (Sylysia® 350) in the outer water phase. Formulated SLM powders were examined by SEM and mercury intrusion porosimetry, as well as by determin...

Research paper thumbnail of Influence of experimental model, active substance and polymer type on mucoadhesive properties of buccal tablets

Research paper thumbnail of Multiparticulate oral formulations as a viable strategy for precise drug dosing in pediatrics: Propranolol case study

The development of solid dosage forms that are both convenient for administration and allow preci... more 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 ...

Research paper thumbnail of Development of propranolol hydrochloride bilayer mucoadhesive buccal tablets supported by in silico physiologically-based modeling

Reactive and Functional Polymers, 2020

Research paper thumbnail of Assessment of mucoadhesive buccal tablets with propranolol hydrochloride using principal component analysis

Makedonsko farmacevtski bilten, Aug 31, 2023

Research paper thumbnail of Review of machine learning algorithms' application in pharmaceutical technology

Arhiv za farmaciju, 2021

Machine learning algorithms, and artificial intelligence in general, have a wide range of applica... more 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.

Research paper thumbnail of Multiparticulate oral formulations as a viable strategy for precise drug dosing in pediatrics: Propranolol case study

Arhiv za farmaciju, 2021

The development of solid dosage forms that are both convenient for administration and allow preci... more 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, powder-and 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.

Research paper thumbnail of Influence of experimental model, active substance and polymer type on mucoadhesive properties of buccal tablets

Research paper thumbnail of Mucoadhesive buccal tablets with propranolol hydrochloride: Formulation development and in vivo performances in experimental essential hypertension

International Journal of Pharmaceutics, Dec 1, 2021

The objective of this study was to formulate extended-release mucoadhesive buccal tablets of prop... more The objective of this study was to formulate extended-release mucoadhesive buccal tablets of propranolol hydrochloride in order to provide a prolonged absorption of propranolol hydrochloride from the buccal mucosa and to reduce presystemic metabolism and thus provide a better therapeutic effect. Besides, the aim was to perform comparative in vivo pharmacokinetic and hemodynamic studies of the developed extended-release (ER) propranolol hydrochloride 10 mg mucoadhesive buccal tablets and commercial immediate-release (IR) propranolol hydrochloride 10 mg tablets in spontaneously hypertensive rats. Formulation with 15% polyethylene oxide showed the highest degree of propranolol hydrochloride permeation, satisfactory mucoadhesiveness, and extended-release of propranolol hydrochloride, thus it was selected for further in vivo study. The pharmacokinetic study in rats showed the superiority of ER mucoadhesive buccal tablets over IR tablets in terms of propranolol hydrochloride absorption extent (AUC values: 70.32 ± 19.56 versus 31.69 ± 6.97 µg·h/mL), although lower maximum plasma propranolol hydrochloride concentration (Cmax) was achieved. However, no statistically significant difference was observed in Cmax between these treatments. The hemodynamic study showed that ER mucoadhesive buccal tablets provide a more pronounced decrease primarily in heart rate, but also in systolic and diastolic arterial pressure, as well as a longer heart rate reduction compared to IR tablets.

Research paper thumbnail of Chemometric methods in pharmaceutical technology

Computer-Aided Applications in Pharmaceutical Technology

Research paper thumbnail of Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films

Journal of Drug Delivery Science and Technology

Research paper thumbnail of Višečestične formulacije lekova za oralnu primenu kao strategija za precizno doziranje kod pedijatrijskih pacijenata - studija slučaja propranolola

The development of solid dosage forms that are both convenient for administration and allow preci... more 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, powder- and granule-filled 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-fill...

Research paper thumbnail of Development of Lipid-Based Gastroretentive Delivery System for Gentian Extract by Double Emulsion–Melt Dispersion Technique

Pharmaceutics, 2021

Gentian (Gentiana lutea L., Gentianaceae) root extract (GRE) is used for the treatment of gastroi... more Gentian (Gentiana lutea L., Gentianaceae) root extract (GRE) is used for the treatment of gastrointestinal disorders. However, its bioactive potential is limited in conventional forms due to the low bioavailability and short elimination half-life of the dominant bioactive compound, gentiopicroside. The aim of study was to encapsulate GRE in the lipid-based gastroretentive delivery system that could provide high yield and encapsulation efficiency, as well as the biphasic release of gentiopicroside from the tablets obtained by direct compression. Solid lipid microparticles (SLM) loaded with GRE were prepared by freeze-drying double (W/O/W) emulsions, which were obtained by a multiple emulsion–melt dispersion technique, with GRE as the inner water phase, Gelucire® 39/01 or 43/01, as lipid components, with or without the addition of porous silica (Sylysia® 350) in the outer water phase. Formulated SLM powders were examined by SEM and mercury intrusion porosimetry, as well as by determin...

Research paper thumbnail of Influence of experimental model, active substance and polymer type on mucoadhesive properties of buccal tablets

Research paper thumbnail of Multiparticulate oral formulations as a viable strategy for precise drug dosing in pediatrics: Propranolol case study

The development of solid dosage forms that are both convenient for administration and allow preci... more 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 ...

Research paper thumbnail of Development of propranolol hydrochloride bilayer mucoadhesive buccal tablets supported by in silico physiologically-based modeling

Reactive and Functional Polymers, 2020