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Papers by Dilyana Georgieva
Journal of Applied Polymer Science, Mar 12, 2018
Crosslinked carriers based on cationic monomer [2-(acryloyloxy)ethyl]trimethylammonium chloride o... more Crosslinked carriers based on cationic monomer [2-(acryloyloxy)ethyl]trimethylammonium chloride or 2-(dimethylamino)ethyl methacrylate were developed and investigated as new platform for ibuprofen transdermal delivery. Series of networks of varied composition and structure were synthesized and characterized by FTIR spectroscopy and following swelling kinetics in different solvents. Dermal safety tests to examine the skin irritation and sensitization potential of the network films were performed in vivo. Chosen network compositions were loaded with ibuprofen by swelling in its ethanol solution. The structures of the drug carriers were investigated by scanning electron microscopy. Ibuprofen release from the developed drug delivery systems was followed in phosphate buffer solution at 37 8C. The investigation proved the feasibility of the developed cationic copolymer networks as effective platforms with modified ibuprofen release for potential dermal application.
Pharmaceutics, Mar 3, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Gels
Dexamethasone (DXM) is a highly potent and long-acting synthetic glucocorticoid with anti-inflamm... more Dexamethasone (DXM) is a highly potent and long-acting synthetic glucocorticoid with anti-inflammatory, anti-allergic, and immunosuppressive effects. However, the systemic application of DXM can cause undesirable side effects: sleep disorders, nervousness, heart rhythm disorders, heart attack, and others. In the present study, multicomponent polymer networks were developed as potential new platforms for the dermal application of dexamethasone sodium phosphate (DSP). First, a copolymer network (CPN) comprising hydrophilic segments of different chemical structures was synthesized by applying redox polymerization of dimethyl acrylamide onto poly(ethylene glycol) in the presence of poly(ethylene glycol) diacrylate (PEGDA) as a crosslinker. On this basis, an interpenetrating polymer network structure (IPN) was obtained by introducing a second network of PEGDA-crosslinked poly(N-isopropylacrylamide). Multicomponent networks obtained were characterized by FTIR, TGA, and swelling kinetics i...
Pharmaceutics
Natural alkaloid galantamine is widely used for the treatment of mild to moderate Alzheimer’s dem... more Natural alkaloid galantamine is widely used for the treatment of mild to moderate Alzheimer’s dementia. Galantamine hydrobromide (GH) is available as fast-release tablets, extended-release capsules, and oral solutions. However, its oral delivery can cause some unwanted side effects, such as gastrointestinal disturbances, nausea, and vomiting. Intranasal administration is one possible way to avoid such unwanted effects. In this work, chitosan-based nanoparticles (NPs) were studied as potential GH delivery vehicles for nasal application. The NPs were synthesized via ionic gelation and studied using dynamic light scattering (DLS) as well as by spectroscopic and thermal methods. The GH-loaded chitosan–alginate complex particles were also prepared as a way to modify the release of GH. The high loading efficiency of the GH was confirmed for both types of particles, at 67% for the GH-loaded chitosan NPs and 70% for the complex chitosan/alginate GH-loaded particles. The mean particle size o...
Gels
Nowadays, modern pharmaceutical investigations are directed toward the design and production of d... more Nowadays, modern pharmaceutical investigations are directed toward the design and production of drug delivery systems for achieving prolonged and controlled drug delivery. In this respect, the use of interpenetrating polymer networks (IPNs) is an opportunity in the preparation of polymer drug delivery systems with desired characteristics. This paper describes the synthesis and characterization of novel poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) and polyacrylamide (PAAm)-based IPNs with different compositions and their application as diclofenac sodium delivery systems. The prepared IPNs were shown to possess phase-separated structures at the nano level, as revealed by SEM and TM-DSC. The IPNs’ composition was shown to determine the swelling behavior of these novel materials, and the inclusion of the charged IPN component (PDMAEMA) has changed the water molecules type diffusion from Fickian to non-Fickian, as revealed by the swelling kinetics study. Loading efficiency of dic...
Macromolecular Chemistry and Physics, 2021
Aripiprazole is a second‐generation atypical antipsychotic used for the treatment of schizophreni... more Aripiprazole is a second‐generation atypical antipsychotic used for the treatment of schizophrenia, bipolar disorder, tic disorders, major depressive disorder, etc. However, aripiprazole is poorly soluble in water and many efforts are focused on developing delivery systems which can improve the solubility and the therapeutic activity of aripiprazole. In this contribution, the fabrication of novel cryogel carriers comprising β‐cyclodextrin (β‐CD) moieties for improved solubilization of aripiprazole is reported. Cryogels are synthesized by photochemical crosslinking of N,N‐dimethylacrylamide (DMA) and β‐CD triacrylate (β‐CD‐Ac3) in frozen aqueous system using H2O2 as initiator. The effect of DMA/β‐CD‐Ac3 mass ratio on the reaction efficiency, physico‐mechanical properties of cryogel, and drug loading efficiency is evaluated. The cryogel carriers are loaded with aripiprazole via procedure favoring inclusion of drug molecules into the hydrophobic cavity of β‐CD. The release of aripipraz...
Journal of Applied Polymer Science, 2018
ABSTRACTCrosslinked carriers based on cationic monomer [2‐(acryloyloxy)ethyl]trimethylammonium ch... more ABSTRACTCrosslinked carriers based on cationic monomer [2‐(acryloyloxy)ethyl]trimethylammonium chloride or 2‐(dimethylamino)ethyl methacrylate were developed and investigated as new platform for ibuprofen transdermal delivery. Series of networks of varied composition and structure were synthesized and characterized by FTIR spectroscopy and following swelling kinetics in different solvents. Dermal safety tests to examine the skin irritation and sensitization potential of the network films were performed in vivo. Chosen network compositions were loaded with ibuprofen by swelling in its ethanol solution. The structures of the drug carriers were investigated by scanning electron microscopy. Ibuprofen release from the developed drug delivery systems was followed in phosphate buffer solution at 37 °C. The investigation proved the feasibility of the developed cationic copolymer networks as effective platforms with modified ibuprofen release for potential dermal application. © 2018 Wiley Pe...
AAPS PharmSciTech, 2016
Nowadays, the modern pharmaceutical investigations are directed toward obtaining of new polymer m... more Nowadays, the modern pharmaceutical investigations are directed toward obtaining of new polymer micro- and nano-sized drug delivery carriers. In this respect, the use of hydrogel carriers based on polyzwitterions (PZIs) is an opportunity in the preparation of polymer drug delivery systems with desired characteristics. This paper describes the synthesis and characterization of micro-structured p(VA-co-DMAPS) systems with different compositions in situ loaded with Ibuprofen by emulsifier-free emulsion copolymerization (EEC) in water. The mean size of the prepared microparticles was measured by SEM and particles have been visualized by AFM. The inclusion of Ibuprofen in the polyzwitterionic copolymer microgel systems was established by using DSC. In vitro drug release experiments were carried out in order to estimate the ability of the obtained microgels to modify the release of water-insoluble Ibuprofen.
Journal of pharmaceutical sciences, 2014
This paper describes the synthesis and characterization of cationic copolymers with different mac... more This paper describes the synthesis and characterization of cationic copolymers with different macromolecular architecture and drug delivery properties of the corresponding dexamethasone sodium phosphate (DSP)-loaded systems. Copolyelectrolytes comprising poly[2-(acryloyloxy)ethyl] trimethylammonium chloride (PAETMAC) and poly(ethylene glycol) blocks as well as a tri-arm star-shaped PAETMAC were synthesized using cerium(IV) ion-mediated polymerization method. The obtained copolyelectrolytes and corresponding ionic associates with DSP have been characterized by (1)H NMR, Fourier Transform Infrared spectroscopy, and differential scanning calorimetry. The average diameter, size distribution, and ζ-potential of the copolymers and DSP-copolymer ionic associates were determined by dynamic light scattering, and particles were visualized by scanning electron microscopy and transmission electron microscopy. The biocompatibility and cytotoxicity of obtained copolymers were determined. In vitro...
Pharmacia
The paediatric population is composed of several very different subgroups, each with its own spec... more The paediatric population is composed of several very different subgroups, each with its own specific characteristics. For this reason, children cannot be considered “small adults”. The development of formulations suitable for children is a complex process, as it must consider the physiological changes that occur during childhood and the impact they have on the absorption of drugs. Sildenafil citrate is a drug with a narrow therapeutic index used in paediatrics to treat pulmonary hypertension. In the present work, technological approaches for extemporaneous preparation of paediatric oral forms containing sildenafil citrate for personalized therapy in children were studied. The prepared formulations were tested for physical and microbiological stability, in-use stability, and determination of active substance content. All tested oral formulations remained unchanged in terms of appearance during the entire period of stability monitoring at the selected storage conditions – room temper...
Pharmacia
3D printing is an innovative technology for building three-dimensional objects by laying down suc... more 3D printing is an innovative technology for building three-dimensional objects by laying down successive layers of material under the control of a computer software. It is entering pharmacy mainly because of its revolutionary potential to provide individualized dosage forms that meet the needs of each patient, due to the possibility to produce objects of many different sizes and shapes. An important aspect of personalized 3D tablets is the possibility to include several active substances in one dosage form, which would reduce the daily number of medications and the frequency of their administration and improve patient compliance. Another advantage of 3D printing is the possibility of producing small batches or even individual drugs for each patient. Despite the many advantages, 3D printing has several technological challenges to overcome before it becomes widely applicable in pharmacy. Five basic technologies are currently applied in pharmaceutical practice: powder-based printing, s...
Pharmaceutics
Three-dimensional (3D) printing has emerged as a new promising technique for the production of pe... more Three-dimensional (3D) printing has emerged as a new promising technique for the production of personalized dosage forms and medical devices. Polyvinyl alcohol is prominently used as a source material to produce 3D-printed medicines via fused deposition modeling (FDM)—a technology that combines hot melt extrusion and 3D printing. A preliminary screening of three grades of PVA indicated that partially hydrolyzed PVA with a molecular weight (MW) of 31,000–50,000 and plasticized with sorbitol was most suitable for 3D printing. Paracetamol was used as a model drug. The materials and the produced filaments were characterized by X-ray powder diffraction (XRPD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The complex viscosity (η*) of the polymer melts was determined as a function of the angular frequency (ω) at the printing temperature to assess their printability. Three-dimensional printlets with a 40% infill exhibited an immediate release of the API, w...
Pharmaceutics, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Journal of Applied Polymer Science, Mar 12, 2018
Crosslinked carriers based on cationic monomer [2-(acryloyloxy)ethyl]trimethylammonium chloride o... more Crosslinked carriers based on cationic monomer [2-(acryloyloxy)ethyl]trimethylammonium chloride or 2-(dimethylamino)ethyl methacrylate were developed and investigated as new platform for ibuprofen transdermal delivery. Series of networks of varied composition and structure were synthesized and characterized by FTIR spectroscopy and following swelling kinetics in different solvents. Dermal safety tests to examine the skin irritation and sensitization potential of the network films were performed in vivo. Chosen network compositions were loaded with ibuprofen by swelling in its ethanol solution. The structures of the drug carriers were investigated by scanning electron microscopy. Ibuprofen release from the developed drug delivery systems was followed in phosphate buffer solution at 37 8C. The investigation proved the feasibility of the developed cationic copolymer networks as effective platforms with modified ibuprofen release for potential dermal application.
Pharmaceutics, Mar 3, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Gels
Dexamethasone (DXM) is a highly potent and long-acting synthetic glucocorticoid with anti-inflamm... more Dexamethasone (DXM) is a highly potent and long-acting synthetic glucocorticoid with anti-inflammatory, anti-allergic, and immunosuppressive effects. However, the systemic application of DXM can cause undesirable side effects: sleep disorders, nervousness, heart rhythm disorders, heart attack, and others. In the present study, multicomponent polymer networks were developed as potential new platforms for the dermal application of dexamethasone sodium phosphate (DSP). First, a copolymer network (CPN) comprising hydrophilic segments of different chemical structures was synthesized by applying redox polymerization of dimethyl acrylamide onto poly(ethylene glycol) in the presence of poly(ethylene glycol) diacrylate (PEGDA) as a crosslinker. On this basis, an interpenetrating polymer network structure (IPN) was obtained by introducing a second network of PEGDA-crosslinked poly(N-isopropylacrylamide). Multicomponent networks obtained were characterized by FTIR, TGA, and swelling kinetics i...
Pharmaceutics
Natural alkaloid galantamine is widely used for the treatment of mild to moderate Alzheimer’s dem... more Natural alkaloid galantamine is widely used for the treatment of mild to moderate Alzheimer’s dementia. Galantamine hydrobromide (GH) is available as fast-release tablets, extended-release capsules, and oral solutions. However, its oral delivery can cause some unwanted side effects, such as gastrointestinal disturbances, nausea, and vomiting. Intranasal administration is one possible way to avoid such unwanted effects. In this work, chitosan-based nanoparticles (NPs) were studied as potential GH delivery vehicles for nasal application. The NPs were synthesized via ionic gelation and studied using dynamic light scattering (DLS) as well as by spectroscopic and thermal methods. The GH-loaded chitosan–alginate complex particles were also prepared as a way to modify the release of GH. The high loading efficiency of the GH was confirmed for both types of particles, at 67% for the GH-loaded chitosan NPs and 70% for the complex chitosan/alginate GH-loaded particles. The mean particle size o...
Gels
Nowadays, modern pharmaceutical investigations are directed toward the design and production of d... more Nowadays, modern pharmaceutical investigations are directed toward the design and production of drug delivery systems for achieving prolonged and controlled drug delivery. In this respect, the use of interpenetrating polymer networks (IPNs) is an opportunity in the preparation of polymer drug delivery systems with desired characteristics. This paper describes the synthesis and characterization of novel poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) and polyacrylamide (PAAm)-based IPNs with different compositions and their application as diclofenac sodium delivery systems. The prepared IPNs were shown to possess phase-separated structures at the nano level, as revealed by SEM and TM-DSC. The IPNs’ composition was shown to determine the swelling behavior of these novel materials, and the inclusion of the charged IPN component (PDMAEMA) has changed the water molecules type diffusion from Fickian to non-Fickian, as revealed by the swelling kinetics study. Loading efficiency of dic...
Macromolecular Chemistry and Physics, 2021
Aripiprazole is a second‐generation atypical antipsychotic used for the treatment of schizophreni... more Aripiprazole is a second‐generation atypical antipsychotic used for the treatment of schizophrenia, bipolar disorder, tic disorders, major depressive disorder, etc. However, aripiprazole is poorly soluble in water and many efforts are focused on developing delivery systems which can improve the solubility and the therapeutic activity of aripiprazole. In this contribution, the fabrication of novel cryogel carriers comprising β‐cyclodextrin (β‐CD) moieties for improved solubilization of aripiprazole is reported. Cryogels are synthesized by photochemical crosslinking of N,N‐dimethylacrylamide (DMA) and β‐CD triacrylate (β‐CD‐Ac3) in frozen aqueous system using H2O2 as initiator. The effect of DMA/β‐CD‐Ac3 mass ratio on the reaction efficiency, physico‐mechanical properties of cryogel, and drug loading efficiency is evaluated. The cryogel carriers are loaded with aripiprazole via procedure favoring inclusion of drug molecules into the hydrophobic cavity of β‐CD. The release of aripipraz...
Journal of Applied Polymer Science, 2018
ABSTRACTCrosslinked carriers based on cationic monomer [2‐(acryloyloxy)ethyl]trimethylammonium ch... more ABSTRACTCrosslinked carriers based on cationic monomer [2‐(acryloyloxy)ethyl]trimethylammonium chloride or 2‐(dimethylamino)ethyl methacrylate were developed and investigated as new platform for ibuprofen transdermal delivery. Series of networks of varied composition and structure were synthesized and characterized by FTIR spectroscopy and following swelling kinetics in different solvents. Dermal safety tests to examine the skin irritation and sensitization potential of the network films were performed in vivo. Chosen network compositions were loaded with ibuprofen by swelling in its ethanol solution. The structures of the drug carriers were investigated by scanning electron microscopy. Ibuprofen release from the developed drug delivery systems was followed in phosphate buffer solution at 37 °C. The investigation proved the feasibility of the developed cationic copolymer networks as effective platforms with modified ibuprofen release for potential dermal application. © 2018 Wiley Pe...
AAPS PharmSciTech, 2016
Nowadays, the modern pharmaceutical investigations are directed toward obtaining of new polymer m... more Nowadays, the modern pharmaceutical investigations are directed toward obtaining of new polymer micro- and nano-sized drug delivery carriers. In this respect, the use of hydrogel carriers based on polyzwitterions (PZIs) is an opportunity in the preparation of polymer drug delivery systems with desired characteristics. This paper describes the synthesis and characterization of micro-structured p(VA-co-DMAPS) systems with different compositions in situ loaded with Ibuprofen by emulsifier-free emulsion copolymerization (EEC) in water. The mean size of the prepared microparticles was measured by SEM and particles have been visualized by AFM. The inclusion of Ibuprofen in the polyzwitterionic copolymer microgel systems was established by using DSC. In vitro drug release experiments were carried out in order to estimate the ability of the obtained microgels to modify the release of water-insoluble Ibuprofen.
Journal of pharmaceutical sciences, 2014
This paper describes the synthesis and characterization of cationic copolymers with different mac... more This paper describes the synthesis and characterization of cationic copolymers with different macromolecular architecture and drug delivery properties of the corresponding dexamethasone sodium phosphate (DSP)-loaded systems. Copolyelectrolytes comprising poly[2-(acryloyloxy)ethyl] trimethylammonium chloride (PAETMAC) and poly(ethylene glycol) blocks as well as a tri-arm star-shaped PAETMAC were synthesized using cerium(IV) ion-mediated polymerization method. The obtained copolyelectrolytes and corresponding ionic associates with DSP have been characterized by (1)H NMR, Fourier Transform Infrared spectroscopy, and differential scanning calorimetry. The average diameter, size distribution, and ζ-potential of the copolymers and DSP-copolymer ionic associates were determined by dynamic light scattering, and particles were visualized by scanning electron microscopy and transmission electron microscopy. The biocompatibility and cytotoxicity of obtained copolymers were determined. In vitro...
Pharmacia
The paediatric population is composed of several very different subgroups, each with its own spec... more The paediatric population is composed of several very different subgroups, each with its own specific characteristics. For this reason, children cannot be considered “small adults”. The development of formulations suitable for children is a complex process, as it must consider the physiological changes that occur during childhood and the impact they have on the absorption of drugs. Sildenafil citrate is a drug with a narrow therapeutic index used in paediatrics to treat pulmonary hypertension. In the present work, technological approaches for extemporaneous preparation of paediatric oral forms containing sildenafil citrate for personalized therapy in children were studied. The prepared formulations were tested for physical and microbiological stability, in-use stability, and determination of active substance content. All tested oral formulations remained unchanged in terms of appearance during the entire period of stability monitoring at the selected storage conditions – room temper...
Pharmacia
3D printing is an innovative technology for building three-dimensional objects by laying down suc... more 3D printing is an innovative technology for building three-dimensional objects by laying down successive layers of material under the control of a computer software. It is entering pharmacy mainly because of its revolutionary potential to provide individualized dosage forms that meet the needs of each patient, due to the possibility to produce objects of many different sizes and shapes. An important aspect of personalized 3D tablets is the possibility to include several active substances in one dosage form, which would reduce the daily number of medications and the frequency of their administration and improve patient compliance. Another advantage of 3D printing is the possibility of producing small batches or even individual drugs for each patient. Despite the many advantages, 3D printing has several technological challenges to overcome before it becomes widely applicable in pharmacy. Five basic technologies are currently applied in pharmaceutical practice: powder-based printing, s...
Pharmaceutics
Three-dimensional (3D) printing has emerged as a new promising technique for the production of pe... more Three-dimensional (3D) printing has emerged as a new promising technique for the production of personalized dosage forms and medical devices. Polyvinyl alcohol is prominently used as a source material to produce 3D-printed medicines via fused deposition modeling (FDM)—a technology that combines hot melt extrusion and 3D printing. A preliminary screening of three grades of PVA indicated that partially hydrolyzed PVA with a molecular weight (MW) of 31,000–50,000 and plasticized with sorbitol was most suitable for 3D printing. Paracetamol was used as a model drug. The materials and the produced filaments were characterized by X-ray powder diffraction (XRPD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The complex viscosity (η*) of the polymer melts was determined as a function of the angular frequency (ω) at the printing temperature to assess their printability. Three-dimensional printlets with a 40% infill exhibited an immediate release of the API, w...
Pharmaceutics, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY